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Sample records for affects vegf distribution

  1. Formation of VEGF isoform-specific spatial distributions governing angiogenesis: computational analysis

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    Mac Gabhann Feilim

    2011-05-01

    Full Text Available Abstract Background The spatial distribution of vascular endothelial growth factor A (VEGF is an important mediator of vascular patterning. Previous experimental studies in the mouse hindbrain and retina have suggested that VEGF alternative splicing, which controls the ability of VEGF to bind to heparan sulfate proteoglycans (HSPGs in the extracellular matrix (ECM, plays a key role in controlling VEGF diffusion and gradients in tissues. Conversely, proteolysis notably by matrix metalloproteinases (MMPs, plays a critical role in pathological situations by releasing matrix-sequestered VEGF and modulating angiogenesis. However, computational models have predicted that HSPG binding alone does not affect VEGF localization or gradients at steady state. Results Using a 3D molecular-detailed reaction-diffusion model of VEGF ligand-receptor kinetics and transport, we test alternate models of VEGF transport in the extracellular environment surrounding an endothelial sprout. We show that differences in localization between VEGF isoforms, as observed experimentally in the mouse hindbrain, as well as the ability of proteases to redistribute VEGF in pathological situations, are consistent with a model where VEGF is endogenously cleared or degraded in an isoform-specific manner. We use our predictions of the VEGF distribution to quantify a tip cell's receptor binding and gradient sensing capacity. A novel prediction is that neuropilin-1, despite functioning as a coreceptor to VEGF165-VEGFR2 binding, reduces the ability of a cell to gauge the relative steepness of the VEGF distribution. Comparing our model to available in vivo vascular patterning data suggests that vascular phenotypes are most consistently predicted at short range by the soluble fraction of the VEGF distributions, or at longer range by matrix-bound VEGF detected in a filopodia-dependent manner. Conclusions Isoform-specific VEGF degradation provides a possible explanation for numerous examples

  2. Anti-VEGF-A affects the angiogenic properties of tumor-derived microparticles.

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    Munster, Michal; Fremder, Ella; Miller, Valeria; Ben-Tsedek, Neta; Davidi, Shiri; Scherer, Stefan J; Shaked, Yuval

    2014-01-01

    Tumor derived microparticles (TMPs) have recently been shown to contribute to tumor re-growth partially by inducing the mobilization and tumor homing of specific bone marrow derived pro-angiogenic cells (BMDCs). Since antiangiogenic drugs block proangiogenic BMDC mobilization and tumor homing, we asked whether TMPs from cells exposed to an antiangiogenic drug may affect BMDC activity and trafficking. Here we show that the level of VEGF-A is reduced in TMPs from EMT/6 breast carcinoma cells exposed to the anti-VEGF-A antibody, B20. Consequently, these TMPs exhibit reduced angiogenic potential as evaluated by a Matrigel plug and Boyden chamber assays. Consistently, BMDC mobilization, tumor angiogenesis, microvessel density and BMDC-colonization in growing tumors are reduced in mice inoculated with TMPs from B20-exposed cells as compared to mice inoculated with control TMPs. Collectively, our results suggest that the neutralization of VEGF-A in cultured tumor cells can block TMP-induced BMDC mobilization and colonization of tumors and hence provide another mechanism of action by which antiangiogenic drugs act to inhibit tumor growth and angiogenesis.

  3. Anti-VEGF-A affects the angiogenic properties of tumor-derived microparticles.

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    Michal Munster

    Full Text Available Tumor derived microparticles (TMPs have recently been shown to contribute to tumor re-growth partially by inducing the mobilization and tumor homing of specific bone marrow derived pro-angiogenic cells (BMDCs. Since antiangiogenic drugs block proangiogenic BMDC mobilization and tumor homing, we asked whether TMPs from cells exposed to an antiangiogenic drug may affect BMDC activity and trafficking. Here we show that the level of VEGF-A is reduced in TMPs from EMT/6 breast carcinoma cells exposed to the anti-VEGF-A antibody, B20. Consequently, these TMPs exhibit reduced angiogenic potential as evaluated by a Matrigel plug and Boyden chamber assays. Consistently, BMDC mobilization, tumor angiogenesis, microvessel density and BMDC-colonization in growing tumors are reduced in mice inoculated with TMPs from B20-exposed cells as compared to mice inoculated with control TMPs. Collectively, our results suggest that the neutralization of VEGF-A in cultured tumor cells can block TMP-induced BMDC mobilization and colonization of tumors and hence provide another mechanism of action by which antiangiogenic drugs act to inhibit tumor growth and angiogenesis.

  4. Antiangiogenic VEGF Isoform in Inflammatory Myopathies

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    Nila Volpi

    2013-01-01

    Full Text Available Objective. To investigate expression of vascular endothelial growth factor (VEGF antiangiogenic isoform A-165b on human muscle in idiopathic inflammatory myopathies (IIM and to compare distribution of angiogenic/antiangiogenic VEGFs, as isoforms shifts are described in other autoimmune disorders. Subjects and Methods. We analyzed VEGF-A165b and VEGF-A by western blot and immunohistochemistry on skeletal muscle biopsies from 21 patients affected with IIM (polymyositis, dermatomyositis, and inclusion body myositis and 6 control muscle samples. TGF-β, a prominent VEGF inductor, was analogously evaluated. Intergroup differences of western blot bands density were statistically examined. Endomysial vascularization, inflammatory score, and muscle regeneration, as pathological parameters of IIM, were quantitatively determined and their levels were confronted with VEGF expression. Results. VEGF-A165b was significantly upregulated in IIM, as well as TGF-β. VEGF-A was diffusely expressed on unaffected myofibers, whereas regenerating/atrophic myofibres strongly reacted for both VEGF-A isoforms. Most inflammatory cells and endomysial vessels expressed both isoforms. VEGF-A165b levels were in positive correlation to inflammatory score, endomysial vascularization, and TGF-β. Conclusions. Our findings indicate skeletal muscle expression of antiangiogenic VEGF-A165b and preferential upregulation in IIM, suggesting that modulation of VEGF-A isoforms may occur in myositides.

  5. BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.

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    Nowacka, Marta; Obuchowicz, Ewa

    2013-01-01

    Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

  6. Reinstate the Damaged VEGF Signaling Pathway with VEGF-activating Transcription Factor

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    Yao-guo Yang; Heng Guan; Chang-wei Liu; Yong-jun Li

    2009-01-01

    Objective To investigate the role of vascular endothelial growth factor-activating transcriptional factor(VEGF-ATF)on the VEGF signaling pathway in diabetes mellitus.Methods Totally,20 C57BL/6 mice fed with high fat diet was induced into diabetes mellitus.Ten diabetes mellitus mice received a lower limb muscle injection with VEGF-ATF plasmid,and another ten were as control.VEGF-ATF is an engineered transcription factor designed to increase VEGF expression.Three days later,mice were sacrificed and the injected gastrocnemius was used for analysis.VEGF mRNA and protein expressions were examined by real-time PCR and ELISA respectively.VEGF receptor 2 mRNA expression was tested with RT-PCR.Phosphorylated Akt,Akt,endothelial nitric oxide synthase(eNOS),and phosphorylated eNOS were assessed by western blot.Results At 3 days post-injection,in mice with diabetes mellitus,VEGF gene transfer increased VEGF mRNA copies and VEGF protein expression in injected muscles compared with control;and reinstated the impaired VEGF signaling pathway with increasing the ratios of phosphorylated Akt/Akt and phosphorylated eNOS/eNOS.However,it did not affect the expression of VEGF receptor 2 mRNA.Conclusion Gene transfer with VEGF-ATF is able to reinstate the impaired VEGF downstream pathway,and potentially promote therapeutic angiogenesis in mice with diabetes mcllitus.

  7. Expression of vascular endothelial growth factor (VEGF) and VEGF-C in serum and tissue of Wilms tumor

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    WANG Lei; ZHANG Da; CHEN Xin-rang; FAN Yu-xia; WANG Jia-xiang

    2011-01-01

    Background Angiogenesis and lymphogenesis which were promoted by vascular endothelial growth factor (VEGF)and VEGF-C are important in the growth and metastasis of solid tumors.The high level of VEGF and VEGF-C were distributed in numerous types of cancers,but their distribution and expression in Wilms tumor,the most common pediatric tumor of the kidney,was unclear.Methods To learn about the distribution,mass spectroscopy and immunohistochemistry were used to measure the level of VEGF and VEGF-C in serum and tissue of Wilms tumor.Results The expression level of VEGF in serum of Wilms tumor was the same as in pre-surgery and control,so it was the same case of VEGF-C.Both of these factors were chiefly located in Wilms tumor tissue,but not in borderline and normal.In addition,the higher clinical staging and histopathologic grading were important elements in high expression of VEGF and VEGF-C.Gender,age and the size of tumor have not certainly been implicated in expression level of VEGF and VEGF-C.Conclusions The lymph node metastasis and growth of tumors resulted from angiogenesis and lymphogenesis which were promoted by VEGF and VEGF-C in Wilms tumor.The autocrine and paracrine process of VEGF and VEGF-C were the principal contributor to specific tissues of Wilms tumor but not to the entire body.

  8. DISTRIBUTION OF VEGF mRNA IN BREAST CANCER WITH NONRADIOACTIVE IN SITU HYBRIDIZATION AT ELECTRON MICROSCOPIC LEVELS

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    王医术; 林; 王心蕊; 李一雷; 吴珊; 张丽红

    2002-01-01

    Object: To localize the mRNA coding for VEGF at Ultrastractural level in human breast cancer by using digoxigenin-labeled cDNA probes. Methods: Nonradio- active in situ hybridization at electron microscopic level was employed to detected VEGF mRNA in breast cancer. Result: Cancer cells and endothelial cell of angiogensis show dark color in experiment sections. No dark color can be found in control sections. Positive hybridization signals showed dark dot and were locatedin various compartments of the breast cancer cell and endothelial cell in experiment section. No labeling was observed in control sections. In experiment sections, the staining appeared concentrated in cytoplasm and nucleus of the breast cancer cell and endothelial cell. Conclusion: Nonradioactive in situ hybridization at electron microscopic level is efficient for direct observation of the target site mRNA of VEGF in the cytoplasm and nucleus.

  9. Miniaturizing VEGF: Peptides mimicking the discontinuous VEGF receptor-binding site modulate the angiogenic response.

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    De Rosa, Lucia; Finetti, Federica; Diana, Donatella; Di Stasi, Rossella; Auriemma, Sara; Romanelli, Alessandra; Fattorusso, Roberto; Ziche, Marina; Morbidelli, Lucia; D'Andrea, Luca Domenico

    2016-08-08

    The angiogenic properties of VEGF are mediated through the binding of VEGF to its receptor VEGFR2. The VEGF/VEGFR interface is constituted by a discontinuous binding region distributed on both VEGF monomers. We attempted to reproduce this discontinuous binding site by covalently linking into a single molecular entity two VEGF segments involved in receptor recognition. We designed and synthesized by chemical ligation a set of peptides differing in length and flexibility of the molecular linker joining the two VEGF segments. The biological activity of the peptides was characterized in vitro and in vivo showing a VEGF-like activity. The most biologically active mini-VEGF was further analyzed by NMR to determine the atomic details of its interaction with the receptor.

  10. Circulating VEGF as a biological marker in patients with rheumatoid arthritis? Preanalytical and biological variability in healthy persons and in patients

    DEFF Research Database (Denmark)

    Hetland, Merete Lund; Christensen, Ib Jarle; Lottenburger, Tine

    2008-01-01

    and contamination of plasma with cellular elements lead to significant increases in VEGF levels, whereas storage for up to 2 years at -80 degrees C or up to 10 freeze/thaw cycles did not affect VEGF levels. Serum VEGF levels were 7-10 fold higher than plasma VEGF levels. Reference intervals for VEGF (plasma: 45 pg...

  11. VEGF: a potential target for hydrocephalus.

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    Shim, Joon W; Sandlund, Johanna; Madsen, Joseph R

    2014-12-01

    Growth factors are primarily responsible for the genesis, differentiation and proliferation of cells and maintenance of tissues. Given the central role of growth factors in signaling between cells in health and in disease, it is understandable that disruption of growth factor-mediated molecular signaling can cause diverse phenotypic consequences including cancer and neurological conditions. This review will focus on the specific questions of enlarged cerebral ventricles and hydrocephalus. It is also well known that angiogenic factors, such as vascular endothelial growth factor (VEGF), affect tissue permeability through activation of receptors and adhesion molecules; hence, recent studies showing elevations of this factor in pediatric hydrocephalus led to the demonstration that VEGF can induce ventriculomegaly and altered ependyma when infused in animals. In this review, we discuss recent findings implicating the involvement of biochemical and biophysical factors that can induce a VEGF-mimicking effect in communicating hydrocephalus and pay particular attention to the role of the VEGF system as a potential pharmacological target in the treatment of some cases of hydrocephalus. The source of VEGF secretion in the cerebral ventricles, in periventricular regions and during pathologic events including hydrocephalus following hypoxia and hemorrhage is sought. The review is concluded with a summary of potential non-surgical treatments in preclinical studies suggesting several molecular targets including VEGF for hydrocephalus and related neurological disorders.

  12. Relationship between Expression of beta-catenin and VEGFs(VEGFA,VEGF-C),VEGF Receptors-2(VEGFR-2)in Medulloblastoma

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    ZHANG Hong-mei; ZHANG Xiong; LI Yu; MI Can

    2008-01-01

    Objective:To investigate the expression of beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGF receptor-2(VEGFR-2)protein in medulloblastoma.Methods:Immunohistochemical staining with SP method Was conducted to determine the expression of beta-eatenin and VEGFs(VEGF-A,VEGF-C)and VEGFR-2 in 33 cases of medulloblastoma and 10 normal cerebellar tissues. Results:The expression rate of beta-catenin,and VEGFs (VEGF-A,VEGF-C)and VEGFR-2 in medulloblastoma were significantly higher than that in normal tissue.A significant positive correlation was found between beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGFR-2 protein in medulloblastoma. Conclusion:There was a correlation between beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGFR-2 in medulloblastoma,which may play a role in the pathogenesis and development of medulloblastoma.

  13. Relationship of VEGF/VEGFR with immune and cancer cells:staggering or forward?

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    Yu-Ling Li; Hua Zhao; Xiu-Bao Ren

    2016-01-01

    Vascular endothelial growth factor (VEGF) is primarily known as a proangiogenic factor and is one of the most important growth and survival factors affecting the vascular endothelium. However, recent studies have shown that VEGF also plays a vital role in the immune environment. In addition to the traditional growth factor role of VEGF and VEGF receptors (VEGFRs), they have a complicated relationship with various immune cells. VEGF also reportedly inhibits the differentiation and function of immune cells during hematopoiesis. Dendritic cells (DCs), macrophages, and lymphocytes further express certain types of VEGF receptors. VEGF can be secreted as well by tumor cells through the autocrine pathway and can stimulate the function of cancer stemness. This review will provide a paradigm shift in our understanding of the role of VEGF/VEGFR signaling in the immune and cancer environment.

  14. Physicochemical conditions in affecting the distribution of spring phytoplankton community

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    Wei, Yuqiu; Liu, Haijiao; Zhang, Xiaodong; Xue, Bing; Munir, Sonia; Sun, Jun

    2017-03-01

    To better understand the physicochemical conditions in affecting regional distribution of phytoplankton community, one research cruise was carried out in the Bohai Sea and Yellow Sea during 3rd and 23th May, 2010. The phytoplankton community, including Bacillariophyta (105 taxa), Pyrrophyta (54 taxa), Chrysophyta (1 taxon) and Chlorophyta (2 taxa), had been identified and clearly described from six ecological provinces. And, the six ecological provinces were partitioned based on the top twenty dominant species related with notable physicochemical parameters. In general, the regional distributions of phytoplankton ecological provinces were predominantly influenced by the physicochemical properties induced by the variable water masses and circulations. The predominant diatoms in most of water samples showed well adaptability in turbulent and eutrophic conditions. However, several species of dinoflagellates e.g., Protoperidinium conicum, Protoperidinium triestinum, Protoperidinium sp. and Gymnodinium lohmanni preferred warmer, saltier and nutrient-poor environment. Moreover, the dinoflagellates with high frequency in the Yellow Sea might be transported from the Yellow Sea Warm Current. The horizontal distribution of phytoplankton was depicted by diatoms and controlled by phosphate concentration, while the vertical distribution was mainly supported by light and nutrients availability in the subsurface and bottom layers, respectively.

  15. VEGF121b and VEGF165b are weakly angiogenic isoforms of VEGF-A

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    Pio Ruben

    2010-12-01

    Full Text Available Abstract Background Different isoforms of VEGF-A (mainly VEGF121, VEGF165 and VEGF189 have been shown to display particular angiogenic properties in the generation of a functional tumor vasculature. Recently, a novel class of VEGF-A isoforms, designated as VEGFxxxb, generated through alternative splicing, have been described. Previous studies have suggested that these isoforms may inhibit angiogenesis. In the present work we have produced recombinant VEGF121/165b proteins in the yeast Pichia pastoris and constructed vectors to overexpress these isoforms and assess their angiogenic potential. Results Recombinant VEGF121/165b proteins generated either in yeasts or mammalian cells activated VEGFR2 and its downstream effector ERK1/2, although to a lesser extent than VEGF165. Furthermore, treatment of endothelial cells with VEGF121/165b increased cell proliferation compared to untreated cells, although such stimulation was lower than that induced by VEGF165. Moreover, in vivo angiogenesis assays confirmed angiogenesis stimulation by VEGF121/165b isoforms. A549 and PC-3 cells overexpressing VEGF121b or VEGF165b (or carrying the PCDNA3.1 empty vector, as control and xenotransplanted into nude mice showed increased tumor volume and angiogenesis compared to controls. To assess whether the VEGFxxxb isoforms are differentially expressed in tumors compared to healthy tissues, immunohistochemical analysis was conducted on a breast cancer tissue microarray. A significant increase (p xxxb and total VEGF-A protein expression in infiltrating ductal carcinomas compared to normal breasts was observed. A positive significant correlation (r = 0.404, p = 0.033 between VEGFxxxb and total VEGF-A was found. Conclusions Our results demonstrate that VEGF121/165b are not anti-angiogenic, but weakly angiogenic isoforms of VEGF-A. In addition, VEGFxxxb isoforms are up-regulated in breast cancer in comparison with non malignant breast tissues. These results are to be taken

  16. VEGF Inhibitors for Cancer Therapy

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    Prakash S. Sukhramani; Maulik P. Suthar

    2010-01-01

    Despite significant advances in systemic therapies, radiation oncology, and surgical techniques, many patients with cancer are still incurable. A novel therapeutic approach has been to target the vascular endothelial growth factors (VEGFs) which are often mutated and/or over-expressed in many tumors. The ligands and receptors of VEGF family are well established as key regulators of angiogenesis and vasculogenesis processes. VEGF is a homodimeric, basic, 45 kDa glycoprotein specific for vascul...

  17. Mental training affects distribution of limited brain resources.

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    Heleen A Slagter

    2007-06-01

    Full Text Available The information processing capacity of the human mind is limited, as is evidenced by the so-called "attentional-blink" deficit: When two targets (T1 and T2 embedded in a rapid stream of events are presented in close temporal proximity, the second target is often not seen. This deficit is believed to result from competition between the two targets for limited attentional resources. Here we show, using performance in an attentional-blink task and scalp-recorded brain potentials, that meditation, or mental training, affects the distribution of limited brain resources. Three months of intensive mental training resulted in a smaller attentional blink and reduced brain-resource allocation to the first target, as reflected by a smaller T1-elicited P3b, a brain-potential index of resource allocation. Furthermore, those individuals that showed the largest decrease in brain-resource allocation to T1 generally showed the greatest reduction in attentional-blink size. These observations provide novel support for the view that the ability to accurately identify T2 depends upon the efficient deployment of resources to T1. The results also demonstrate that mental training can result in increased control over the distribution of limited brain resources. Our study supports the idea that plasticity in brain and mental function exists throughout life and illustrates the usefulness of systematic mental training in the study of the human mind.

  18. Mental training affects distribution of limited brain resources.

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    Slagter, Heleen A; Lutz, Antoine; Greischar, Lawrence L; Francis, Andrew D; Nieuwenhuis, Sander; Davis, James M; Davidson, Richard J

    2007-06-01

    The information processing capacity of the human mind is limited, as is evidenced by the so-called "attentional-blink" deficit: When two targets (T1 and T2) embedded in a rapid stream of events are presented in close temporal proximity, the second target is often not seen. This deficit is believed to result from competition between the two targets for limited attentional resources. Here we show, using performance in an attentional-blink task and scalp-recorded brain potentials, that meditation, or mental training, affects the distribution of limited brain resources. Three months of intensive mental training resulted in a smaller attentional blink and reduced brain-resource allocation to the first target, as reflected by a smaller T1-elicited P3b, a brain-potential index of resource allocation. Furthermore, those individuals that showed the largest decrease in brain-resource allocation to T1 generally showed the greatest reduction in attentional-blink size. These observations provide novel support for the view that the ability to accurately identify T2 depends upon the efficient deployment of resources to T1. The results also demonstrate that mental training can result in increased control over the distribution of limited brain resources. Our study supports the idea that plasticity in brain and mental function exists throughout life and illustrates the usefulness of systematic mental training in the study of the human mind.

  19. Cancer-derived VEGF plays no role in malignant ascites formation in the mouse

    Institute of Scientific and Technical Information of China (English)

    Bayasi Guleng; Tsuneo Ikenoue; Yasushi Fukushima; Keita Morikane; Makoto Miyagishi; Kazunari Taira; Takao Kawabe; Masao Omata; Keisuke Tateishi; Fumihiko Kanai; Amarsanaa Jazag; Miki Ohta; Yoshinari Asaoka; Hideaki Ijichi; Yasuo Tanaka; Jun Imamura

    2005-01-01

    AIM: Vascular endothelial growth factor (VEGF) is a potent mediator of peritoneal fluid accumulation following tumor progression. This study investigated the role of VEGF secreted by cancerous cells in the formation of malignant ascites.METHODS: VEGF expression was eliminated byknockdown in the pancreas cancer cell-line PancO2 using vector-based short-hairpin type RNA interference (RNAi).Malignant ascites formation in the mouse was analyzed by intraperitoneal injection of PancO2 cells expressing VEGF or with expression knockdown.RESULTS: The VEGF knockdown PancO2 cell was successfully established. Knockdown of VEGF did not affect cancer cell proliferation in vitro or in vivo. The volume of ascites following peritoneal expansion of the tumor in VEGF knockdown cells and control cells did not differ statistically in this in vivo study. Moreover, the VEGF concentration in the ascites did not differ statistically.CONCLUSION: Malignant ascites formation might be mediated by VEGF production in noncancerous tissues,such as stromal compartments. An anti-VEGF strategy against malignant ascites could be applied to various tumors regardless of whether they secrete VEGF.

  20. Identification and function analysis of a novel vascular endothelial growth factor, LvVEGF3, in the Pacific whiteleg shrimp Litopenaeus vannamei.

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    Wang, Zhiwei; Li, Shihao; Li, Fuhua; Xie, Shijun; Xiang, Jianhai

    2016-10-01

    VEGF signaling pathway is first discovered in mammals and proved to play important roles in the biological processes of angiogenesis, tumor migration, cell differentiation, apoptosis, host-virus interaction etc. Three members in the VEGF signaling pathway, including LvVEGFR, LvVEGF1 and LvVEGF2 in shrimp have been proved to be related with WSSV infection in our previous studies. Currently, another member of VEGF family, LvVEGF3, was isolated and its function during the WSSV infection of shrimp was studied. The deduced amino acid sequence of LvVEGF3 contained a signal peptide, a typical PDGF/VEGF domain and a cysteine-knot motif (CXCXC). Tissue distribution analysis showed that LvVEGF3 was predominantly expressed in hemocytes. The transcriptional level of LvVEGF3 in hemocytes was apparently up-regulated during WSSV infection. Silencing of LvVEGF3 with double-stranded RNA caused a reduction of the cumulative mortality rate of shrimp during WSSV infection. The expression of LvVEGFR was apparently down-regulated after LvVEGF3 silencing and up-regulated after injection of recombinant LvVEGF3 protein, suggesting an interaction between LvVEGF3 and LvVEGFR. Furthermore, the interaction between LvVEGFR and LvVEGF3 was confirmed using the yeast two-hybrid system. The results provided new insights into understanding the role of VEGF signaling pathway during virus infection.

  1. Response to anti-VEGF-A treatment of endothelial cells in vitro.

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    Puddu, Alessandra; Sanguineti, Roberta; Traverso, Carlo Enrico; Viviani, Giorgio L; Nicolò, Massimo

    2016-05-01

    This study was conducted to compare the effects of two anti-VEGF-A drugs, Ranibizumab and Aflibercept, on the expression and secretion of VEGFs family members, and on their influence in proliferation and migration of endothelial cells (HECV) in vitro. HECV cells were exposed 24 h (T1), 4 days (T2) and 6 days (T3) to Ranibizumab or Aflibercept at pharmacodynamically relevant concentrations (Ranibizumab: 12.5 μg/ml and 125 μg/ml; Aflibercept: 50 μg/ml and 500 μg/ml). Cell viability and then expression and secretion of VEGF-A, VEGF-B, VEGF-C and PlGF were evaluated respectively by Real Time-PCR and ELISA. Intracellular signaling activated by VEGF-A and VEGF-C was investigated evaluating phosphorylation of VEGFR2. Influence in would healing was evaluated through scratch assay. In general no differences were observed among the tested concentrations of anti-vegf drugs. Ranibizumab and Aflibercept did not affect HECV cell viability in all experimental times. At T1, Ranibizumab decreased mRNA levels of VEGF-A, induced VEGF-C secretion, abrogated phosphorylation of VEGFR2 stimulated by VEGF-A, and impaired ability of HECV cells to repair wound healing. Aflibercept decreased mRNA levels of VEGF-A, -B and PlGF; slightly increased basal level of phVEGFR2, and completely abrogated phosphorylation stimulated by VEGF-A and VEGF-C. No effects on secretion of VEGF-B and on would healing were observed after exposure to Aflibercept. Prolonged exposure to anti-VEGFs decreased expression and secretion of VEGF-A and VEGF-B, up-regulated VEGF-C mRNA levels and its secretion, and increased basal phosphorylation of VEGFR2. Acute treatment with Ranibizumab or Aflibercept evoked different responses on endothelial cells, however these differences were lost after prolonged exposure. Scratch test results suggest that treatment with Ranibizumab may be more effective than Aflibercept in reducing angiogenic potential of endothelial cells in vitro.

  2. How Required Reserve Ratio Affects Distribution and Velocity of Money

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    Xi, N; Wang, Y; Xi, Ning; Ding, Ning; Wang, Yougui

    2005-01-01

    In this paper the dependence of wealth distribution and the velocity of money on the required reserve ratio is examined based on a random transfer model of money and computer simulations. A fractional reserve banking system is introduced to the model where money creation can be achieved by bank loans and the monetary aggregate is determined by the monetary base and the required reserve ratio. It is shown that monetary wealth follows asymmetric Laplace distribution and latency time of money follows exponential distribution. The expression of monetary wealth distribution and that of the velocity of money in terms of the required reserve ratio are presented in a good agreement with simulation results.

  3. How required reserve ratio affects distribution and velocity of money

    Science.gov (United States)

    Xi, Ning; Ding, Ning; Wang, Yougui

    2005-11-01

    In this paper the dependence of wealth distribution and the velocity of money on the required reserve ratio is examined based on a random transfer model of money and computer simulations. A fractional reserve banking system is introduced to the model where money creation can be achieved by bank loans and the monetary aggregate is determined by the monetary base and the required reserve ratio. It is shown that monetary wealth follows asymmetric Laplace distribution and latency time of money follows exponential distribution. The expression of monetary wealth distribution and that of the velocity of money in terms of the required reserve ratio are presented in a good agreement with simulation results.

  4. Rainfall and temperature affect tree species distributions in Ghana

    NARCIS (Netherlands)

    Amissah, L.; Mohren, G.M.J.; Bongers, F.; Hawthorne, W.D.; Poorter, L.

    2014-01-01

    We evaluated the relative importance of annual rainfall, temperature and their seasonality to tree species distribution in Ghana. We used species presence/absence data from 2505 1-ha plots systematically distributed over Ghana's forests. Logistic regression was used to determine species responses to

  5. Humidity distribution affected by freely exposed water surfaces

    DEFF Research Database (Denmark)

    Hygum, Morten Arnfeldt; Popok, Vladimir

    2014-01-01

    Accurate models for the water vapor flux at a water-air interface are required in various scientific, reliability and civil engineering aspects. Here, a study of humidity distribution in a container with air and freely exposed water is presented. A model predicting a spatial distribution and time...

  6. How Required Reserve Ratio Affects Distribution and Velocity of Money

    OpenAIRE

    Ning Xi; Ning Ding; Yougui Wang

    2005-01-01

    In this paper the dependence of wealth distribution and the velocity of money on the required reserve ratio is examined based on a random transfer model of money and computer simulations. A fractional reserve banking system is introduced to the model where money creation can be achieved by bank loans and the monetary aggregate is determined by the monetary base and the required reserve ratio. It is shown that monetary wealth follows asymmetric Laplace distribution and latency time of money fo...

  7. Factors affecting distribution of airflow in a human tracheobronchial cast.

    Science.gov (United States)

    Cohen, B S; Sussman, R G; Lippmann, M

    1993-09-01

    Air velocity was measured at end airways of hollow replicate casts of the human tracheobronchial tree in order to determine the flow distribution within casts extending to 3 mm diameter airways. Measurements were made by hot-wire anemometry for constant inspiratory flow rates of 7.5, 15, 30 and 60 L.min-1. Average flow distribution among the lung lobes was as follows: right upper, 18.5%; right middle, 9.2%; right lower, 32.3%; left upper, 15.7%; and left lower, 24.3%. An empirical model derived from the experimental flow distribution data demonstrated the effect of various morphometric parameters of the hollow cast on the distribution of airflow. Airway cross-sectional area, branching angle and total path-length were found to have the greatest influence. As the tracheal flow rate decreased from 60 to 7.5 L.min-1, the influence of branching angle was reduced, while total path-length became more influential. These results provide evidence for the transition of flow regimes within the TB tree within normal physiological flow ranges.

  8. Factors Affecting Bacterial Growth in Drinking Water Distribution System

    Institute of Scientific and Technical Information of China (English)

    WEI LU; XIAO-JIAN ZHANG

    2005-01-01

    Objective To define the influence of some parameters, including assimilable organic carbon (AOC), chloramine residual, etc. on the bacterial growth in drinking water distribution systems. Methods Three typical water treatment plants in a northern city (City T) of China and their corresponding distribution systems were investigated. Some parameters of the water samples, such as heterotrophic plate content (HPC), AOC, CODMn, TOC, and phosphate were measured. Results The AOC in most water samples were more than 100 μg/L, or even more than 200 μg/L in some cases. The HPC in distribution systems increased significantly with the decrease of residual chlorine. When the residual chlorine was less than 0.1 mg/L, the magnitude order of HPC was 104 CFU/mL; when it was 0.5-0.7 mg/L, the HPC was about 500 CFU/mL. Conclusion For controlling the biostability of drinking water, the controlling of AOC and residual chlorine should be considered simultaneously. The influence of phosphors on the AOC tests of water is not significant. Phosphors may not be the limiting nutrient in the water distribution systems.

  9. Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.

    Science.gov (United States)

    Honek, Jennifer; Seki, Takahiro; Iwamoto, Hideki; Fischer, Carina; Li, Jingrong; Lim, Sharon; Samani, Nilesh J; Zang, Jingwu; Cao, Yihai

    2014-10-14

    Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.

  10. Enhanced effect of VEGF165 on L-type calcium currents in guinea-pig cardiac ventricular myocytes.

    Science.gov (United States)

    Xing, Wenlu; Gao, Chuanyu; Qi, Datun; Zhang, You; Hao, Peiyuan; Dai, Guoyou; Yan, Ganxin

    2017-01-01

    The mechanisms of vascular endothelial growth factor 165 (VEGF165) on electrical properties of cardiomyocytes have not been fully elucidated. The aim of this study is to test the hypothesis that VEGF165, an angiogenesis-initiating factor, affects L-type calcium currents (ICa,L) and cell membrane potential in cardiac myocytes by acting on VEGF type-2 receptors (VEGFR2). ICa,L and action potentials (AP) were recorded by the whole-cell patch clamp method in isolated guinea-pig ventricular myocytes treated with different concentrations of VEGF165 proteins. Using a VEGFR2 inhibitor, we also tested the receptor of VEGF165 in cardiomyocytes. We found that VEGF165 increased ICa,L in a concentration-dependent manner. SU5416, a VEGFR2 inhibitor, almost completely eliminated VEGF165-induced ICa,L increase. VEGF165 had no significant influence on action potential 90 (APD90) and other properties of AP. We conclude that in guinea-pig ventricular myocytes, ICa,L can be increased by VEGF165 in a concentration-dependent manner through binding to VEGFR2 without causing any significant alteration to action potential duration. Results of this study may further expound the safety of VEGF165 when used in the intervention of heart diseases.

  11. Spinal vascular endothelial growth factor (VEGF) and erythropoietin (EPO) induced phrenic motor facilitation after repetitive acute intermittent hypoxia.

    Science.gov (United States)

    Dale, Erica A; Mitchell, Gordon S

    2013-02-01

    Vascular endothelial growth factor (VEGF) and erythropoietin (EPO) exert neurotrophic and neuroprotective effects in the CNS. We recently demonstrated that VEGF, EPO and their receptors (VEGF-R2, EPO-R) are expressed in phrenic motor neurons, and that cervical spinal VEGF-R2 and EPO-R activation elicit long-lasting phrenic motor facilitation (pMF). Since VEGF, VEGF-R, EPO, and EPO-R are hypoxia-regulated genes, and repetitive exposure to acute intermittent hypoxia (rAIH) up-regulates these molecules in phrenic motor neurons, we tested the hypothesis that 4 weeks of rAIH (10 episodes per day, 3 days per week) enhances VEGF- or EPO-induced pMF. We confirm that cervical spinal VEGF and EPO injections elicit pMF. However, neither VEGF- nor EPO-induced pMF was affected by rAIH pre-conditioning (4 wks). Although our data confirm that spinal VEGF and EPO may play an important role in respiratory plasticity, we provide no evidence that rAIH amplifies their impact. Further experiments with more robust protocols are warranted.

  12. Network Regulation and Support Schemes - How Policy Interactions Affect the Integration of Distributed Generation

    DEFF Research Database (Denmark)

    Ropenus, Stephanie; Jacobsen, Henrik; Schröder, Sascha Thorsten

    2011-01-01

    This article seeks to investigate the interactions between the policy dimensions of support schemes and network regulation and how they affect distributed generation. Firstly, the incentives of distributed generators and distribution system operators are examined. Frequently there exists a trade......-off between the incentives for these two market agents to facilitate the integration of distributed generation. Secondly, the interaction of these policy dimensions is analyzed, including case studies based on five EU Member States. Aspects of operational nature and investments in grid and distributed...

  13. Wnt3a upregulates transforming growth factor-β-stimulated VEGF synthesis in osteoblasts.

    Science.gov (United States)

    Natsume, Hideo; Tokuda, Haruhiko; Matsushima-Nishiwaki, Rie; Kato, Kenji; Yamakawa, Kengo; Otsuka, Takanobu; Kozawa, Osamu

    2011-07-01

    It is recognized that Wnt3a affects bone metabolism via the canonical Wnt/β-catenin signalling pathway. We have previously shown that transforming growth factor-β (TGF-β) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Wnt3a on TGF-β-stimulated VEGF synthesis in these cells. Wnt3a, which alone had little effect on the VEGF levels, significantly enhanced the TGF-β-stimulated VEGF release. Lithium chloride and SB216763, inhibitors of glycogen synthase kinase 3β, markedly amplified the TGF-β-stimulated VEGF release. Wnt3a failed to affect the TGF-β-induced phosphorylation of Smad2, p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. Wnt3a and lithium chloride strengthened the VEGF mRNA expression induced by TGF-β. These results strongly suggest that Wnt3a upregulates VEGF synthesis stimulated by TGF-β via activation of the canonical pathway in osteoblasts.

  14. Evidence for Pro-angiogenic Functions of VEGF-Ax.

    Science.gov (United States)

    Xin, Hong; Zhong, Cuiling; Nudleman, Eric; Ferrara, Napoleone

    2016-09-22

    The VEGF-A isoforms play a crucial role in vascular development, and the VEGF signaling pathway is a clinically validated therapeutic target for several pathological conditions. Alternative mRNA splicing leads to the generation of multiple VEGF-A isoforms, including VEGF165. A recent study reported the presence of another isoform, VEGF-Ax, arising from programmed readthrough translation. Compared to VEGF165, VEGF-Ax has a 22-amino-acid extension in the COOH terminus and has been reported to function as a negative regulator of VEGF signaling in endothelial cells, with potent anti-angiogenic effects. Here, we show that, contrary to the earlier report, VEGF-Ax stimulates endothelial cell mitogenesis, angiogenesis, as well as vascular permeability. Accordingly, VEGF-Ax induces phosphorylation of key tyrosine residues in VEGFR-2. Notably, VEGF-Ax was less potent than VEGF165, consistent with its impaired binding to the VEGF co-receptor neuropilin-1.

  15. Circulating VEGF as a biological marker in patients with rheumatoid arthritis? Preanalytical and biological variability in healthy persons and in patients

    DEFF Research Database (Denmark)

    Hetland, Merete Lund; Christensen, Ib Jarle; Lottenburger, Tine

    2008-01-01

    -analytical factors were investigated. A reference interval for VEGF was established in serum and plasma from 306 healthy persons. Diurnal, day-to-day, week-to-week, long-term variability, and impact of exercise were evaluated. RESULTS: Delayed processing time, room temperature, low centrifugal force...... and contamination of plasma with cellular elements lead to significant increases in VEGF levels, whereas storage for up to 2 years at -80 degrees C or up to 10 freeze/thaw cycles did not affect VEGF levels. Serum VEGF levels were 7-10 fold higher than plasma VEGF levels. Reference intervals for VEGF (plasma: 45 pg....../ml (range: non-detectable to 352); serum: 328 pg/ml (53-1791)) were independent of gender and age. Short- and long-term biologic variability included diurnal variation (sampling should take place after 7 AM) and impact of exercise (increased VEGF immediately after bicycling normalised within 1 hour...

  16. 2-Deoxy Glucose Modulates Expression and Biological Activity of VEGF in a SIRT-1 Dependent Mechanism.

    Science.gov (United States)

    Kunhiraman, Haritha; Edatt, Lincy; Thekkeveedu, Sruthi; Poyyakkara, Aswini; Raveendran, Viji; Kiran, Manikantan Syamala; Sudhakaran, Perumana; Kumar, Sameer V B

    2017-02-01

    Reprogramming of energy metabolism particularly switching over of cells to aerobic glycolysis leading to accumulation of lactate is a hallmark of cancer. Lactate can induce angiogenesis, an important process underlying tumor growth and metastasis. VEGF is one of the most important cytokines which regulate this process and the present study was designed to examine if blocking glycolytic pathway in tumor cells can affect its angiogenic potency with respect to VEGF. For this, the expression and biological activity of VEGF synthesized and secreted by tumor derived cell lines in the presence or absence of 2-deoxy glucose (2-DG), an inhibitor of glycolysis was determined. The results suggested that inhibition of glycolysis using sub-lethal doses of 2-DG down-regulated the expression of VEGF and also significantly reduced its biological activity. Further mechanistic studies revealed that the down regulation of VEGF gene expression by 2-DG was due to an increase in SIRT-1 activity and the reduced biological activity was found to be due to an increase in the PAR modification of VEGF. Activity of SIRT-1 and PAR modification of VEGF in turn, was found to be correlated to the cellular NAD(+) levels. The results presented here therefore suggest that treatment of cancer cells with 2-DG can significantly reduce its overall angiogenic potency through transcriptional and post-translational mechanisms. J. Cell. Biochem. 118: 252-262, 2017. © 2016 Wiley Periodicals, Inc.

  17. VEGF165-induced vascular permeability requires NRP1 for ABL-mediated SRC family kinase activation

    Science.gov (United States)

    Lampropoulou, Anastasia; Senatore, Valentina; Brash, James T.; Liyanage, Sidath E.; Raimondi, Claudio; Bainbridge, James W.

    2017-01-01

    The vascular endothelial growth factor (VEGF) isoform VEGF165 stimulates vascular growth and hyperpermeability. Whereas blood vessel growth is essential to sustain organ health, chronic hyperpermeability causes damaging tissue edema. By combining in vivo and tissue culture models, we show here that VEGF165-induced vascular leakage requires both VEGFR2 and NRP1, including the VEGF164-binding site of NRP1 and the NRP1 cytoplasmic domain (NCD), but not the known NCD interactor GIPC1. In the VEGF165-bound receptor complex, the NCD promotes ABL kinase activation, which in turn is required to activate VEGFR2-recruited SRC family kinases (SFKs). These results elucidate the receptor complex and signaling hierarchy of downstream kinases that transduce the permeability response to VEGF165. In a mouse model with choroidal neovascularisation akin to age-related macular degeneration, NCD loss attenuated vessel leakage without affecting neovascularisation. These findings raise the possibility that targeting NRP1 or its NCD interactors may be a useful therapeutic strategy in neovascular disease to reduce VEGF165-induced edema without compromising vessel growth. PMID:28289053

  18. The correlation analysis of the expression of VEGF and the DCs’ infiltration density of gastric cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Feng Yang; Ai-Mei Li; De-Huai Jing

    2016-01-01

    Objective:To investigate the correlation of the expression of vascular endothecial growth factor (VEGF) and the dendritic cells (DCs) infiltration density of tumor tissues in patients with gastric cancer and the correlation of the frequency of DCs of VEGF in gastric cancer tissues and the clinic stages; and to analyze the expressions of HLA-DR and CD86 on peripheral blood monocyte-derived DCs.Methods:Immuno fluorescence method was applied to test the expressions of CD11c and VEGF in gastric cancer tissues and para-carcinoma tissues and enzyme-linked immune sorbent assay was used to detect the concentration of serum VEGF. Peripheral blood mononuclear cells of the gastric cancer patients and healthy people were separated and induced DCs by GM-CSF and IL-4in vitro. Then, the expressions of HLA-DR and CD86 on DCs were tested by flow cytometry. Finally, the recombinant VEGF protein was added into DCs cultures to explore how VEGF affected the expression of CD86. Results: There was a negative correlation between the expression intensity of VEGF on gastric cancer cells and the tumor-infiltrating density of DCs; while there was a certain positive correlation between the frequency of DCs of VEGF and the development of the disease. The concentration of serum VEGF had no association with the density of tumor-infiltrating DCs. As for peripheral blood mononuclear cell, it had a certain induced effect on the decrease of DCs, the expressions of HLA-DR and CD86 and the expression of CD86 on DCs’ cell surface by VEGF.Conclusions:The activities of DCs were inhibited by VEGF secretion of gastric cancer tissues so as to mediate immune escape of the cancer cells. In addition, DCs infiltrated in gastric cancer tissues may secrete VEGF to participate the development of the disease.

  19. VEGF internalization is not required for VEGFR-2 phosphorylation in bioengineered surfaces with covalently linked VEGF

    Science.gov (United States)

    Anderson, Sean M.; Shergill, Bhupinder; Barry, Zachary T.; Manousiouthakis, Eleana; Chen, Tom T.; Botvinick, Elliot; Platt, Manu O.; Iruela-Arispe, M. Luisa; Segura, Tatiana

    2011-01-01

    Vascular endothelial growth factor (VEGF) is known to activate proliferation, migration, and survival pathways in endothelial cells through phosphorylation of VEGF receptor-2 (VEGFR-2). VEGF has been incorporated into biomaterials through encapsulation, electrostatic sequestration, and covalent attachment, but the effect of these immobilization strategies on VEGF signaling has not been thoroughly investigated. Further, although growth factor internalization along with the receptor generally occurs in a physiological setting, whether this internalization is needed for receptor phosphorylation is not entirely clear. Here we show that VEGF covalently bound through a modified heparin molecule elicits an extended response of pVEGFR-2 in human umbilical vein endothelial cells (HUVECs) and that the covalent linkage reduces internalization of the growth factor during receptor endocytosis. Optical tweezer measurements show that the rupture force required to disrupt the heparin-VEGF-VEGFR-2 interaction increases from 3–8 pN to 6–12 pN when a covalent bond is introduced between VEGF and heparin. Importantly, by covalently binding VEGF to a heparin substrate, the stability (half-life) of VEGF is extended over three-fold. Here, mathematical models support the biological conclusions, further suggesting that VEGF internalization is significantly reduced when covalently bound, and indicating that VEGF is available for repeated phosphorylation events. PMID:21826315

  20. VEGF-C Is a Thyroid Marker of Malignancy Superior to VEGF-A in the Differential Diagnostics of Thyroid Lesions.

    Directory of Open Access Journals (Sweden)

    Kosma Woliński

    Full Text Available Thyroid nodular goiter is one of the most common medical conditions affecting even over a half of adult population. The risk of malignancy is rather small but noticeable-estimated by numerous studies to be about 3-10%. The definite differentiation between benign and malignant ones is a vital issue in endocrine practice. The aim of the current study was to assess the expression of vascular endothelial growth factor A (VEGF-A and VEGF-C on the mRNA level in FNAB washouts in case of benign and malignant thyroid nodules and to evaluate the diagnostic value of these markers of malignancy.Patients undergoing fine-needle aspiration biopsy (FNAB in our department between January 2013 and May 2014 were included. In case of all patients who gave the written consent, after ultrasonography (US and fine-needle aspiration biopsy (FNAB performed as routine medical procedure the needle was flushed with RNA Later solution, the washouts were frozen in -80 Celsius degrees. Expression of VEGF-A and VEGF-C and GADPH (reference gene was assessed in washouts on the mRNA level using the real-time PCR technique. Probes of patients who underwent subsequent thyroidectomy and were diagnosed with differentiated thyroid cancer (DTC; proved by post-surgical histopathology were analyzed. Similar number of patients with benign cytology were randomly selected to be a control group.Thirty one DTCs and 28 benign thyroid lesions were analyzed. Expression of VEGF-A was insignificantly higher in patients with DTCs (p = 0.13. Expression of VEGF-C was significantly higher in patients with DTC. The relative expression of VEGF-C (in comparison with GAPDH was 0.0049 for DTCs and 0.00070 for benign lesions, medians - 0.0036 and 0.000024 respectively (p<0.0001.Measurement of expression VEGF-C on the mRNA level in washouts from FNAB is more useful than more commonly investigated VEGF-A. Measurement of VEGF-C in FNAB washouts do not allow for fully reliable differentiation of benign and

  1. Rho-kinase limits FGF-2-stimulated VEGF release in osteoblasts.

    Science.gov (United States)

    Natsume, Hideo; Tokuda, Haruhiko; Adachi, Seiji; Takai, Shinji; Matsushima-Nishiwaki, Rie; Kato, Kenji; Minamitani, Chiho; Niida, Shunpei; Mizutani, Jun; Kozawa, Osamu; Otsuka, Takanobu

    2010-04-01

    We previously reported that basic fibroblast growth factor (FGF-2) stimulates the release of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates the VEGF release in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether Rho-kinase is involved in FGF-2-stimulated VEGF release in MC3T3-E1 cells. FGF-2 induced the phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a substrate of Rho-kinase. Y27632, a specific inhibitor of Rho-kinase, which attenuated the MYPT-1 phosphorylation, significantly enhanced the FGF-2-stimulated VEGF release. Fasudil, another Rho-kinase inhibitor, also amplified the VEGF release. FGF-2 significantly stimulated VEGF accumulation and fasudil enhanced FGF-2-stimulated VEGF accumulation also in whole cell lysates. Neither Y27632 nor fasudil affected the phosphorylation levels of p44/p42 MAP kinase or p38 MAP kinase. Y27632 and fasudil markedly strengthened the FGF-2-induced phosphorylation of SAPK/JNK. Y27632 as well as fasudil enhanced FGF-2-stimulated VEGF release and Y27632 enhanced the FGF-2-induced phosphorylation levels of SAPK/JNK also in human osteoblasts. These results strongly suggest that Rho-kinase negatively regulates FGF-2-stimulated VEGF release in osteoblasts.

  2. Abnormal expression of vascular endothelial growth factor (VEGF) and its clinical features in tissues of human lung cancer

    Institute of Scientific and Technical Information of China (English)

    Xinhua Wu; Dengfu Yao; Gongshen Shi; Liwei Qiu; Wei Wu; Songshi Ni; Xueguang Zhang

    2005-01-01

    Objective: Angiogennesis, the formation of new blood vessels from the existing vascular bed, is essential step for growth and invasion of primary tumor. Vascular endothelial growth-factor (VEGF) is known to play crucial role in tumor angiogenesis. In the present study, we investigate the expression of VEGF and VEGF-mRNA in the angiogennesis, metastasis and prognosis of lung cancer.Methods: The VEGF cellular distributions and expression in 38 specimens of patients with lung cancer were investigated with immunohistochemistry stain technology. The total RNAs in 38 tissues of lung cancer was measured, then the levels of VEGF-mRNA expression were analyzed by a reverse-transcription polymerase chain reaction (RT-PCR) assay. The levels of VEGF in sera of patients with lung cancer, benign lung diseases and healthy controls were detected through Enzyme linked immunosorbent assay (ELISA) method. Results: The VEGF positive stain was 76% in 38 cases of lung cancer specimens. The 89% rate of VEGF stain was found for clinical stage Ⅲ cases and 92%for stage Ⅳ lung cancers. The significantly higher expression of VEGF was evidenced in patients with lymph node metastasis (84 % ), distant metastasis (90%), and lung cancers with lower histological differentiation (89%), respectively. The expression level of total RNA was significantly higher in patients with lung cancers than that in their paracancerous or distant lung tissues. The VEGF expressions were tightly correlated with total RNA concentration of lung carcinoma ( P < 0.01 ). The predominant expressions of VEGF121 and VEGF165 gene fragments were found in lung cancer specimens by RT-PCR analysis. No significant difference of serum VEGF levels was detected between cases with lung cancer and patients with benign diseases. However, the VEGF level of cases with benign diseases was decreased significantly after patients with anti-inflammation medication. Conclusion: The present data suggested that the tumor tissue VEGF

  3. Distributed Speech Recognition Systems and Some Key Factors Affecting It's Performance

    Institute of Scientific and Technical Information of China (English)

    YE Lei; YANG Zhen

    2003-01-01

    In this paper we first analyze the Distributed Speech Recognition (DSR) system and the key factors that affect it's performance and then focus on the research on the relationship between the length of testing speech and the recognition accuracy of the system. Some experimental results are given at last.

  4. Thematic and spatial resolutions affect model-based predictions of tree species distribution.

    Directory of Open Access Journals (Sweden)

    Yu Liang

    Full Text Available Subjective decisions of thematic and spatial resolutions in characterizing environmental heterogeneity may affect the characterizations of spatial pattern and the simulation of occurrence and rate of ecological processes, and in turn, model-based tree species distribution. Thus, this study quantified the importance of thematic and spatial resolutions, and their interaction in predictions of tree species distribution (quantified by species abundance. We investigated how model-predicted species abundances changed and whether tree species with different ecological traits (e.g., seed dispersal distance, competitive capacity had different responses to varying thematic and spatial resolutions. We used the LANDIS forest landscape model to predict tree species distribution at the landscape scale and designed a series of scenarios with different thematic (different numbers of land types and spatial resolutions combinations, and then statistically examined the differences of species abundance among these scenarios. Results showed that both thematic and spatial resolutions affected model-based predictions of species distribution, but thematic resolution had a greater effect. Species ecological traits affected the predictions. For species with moderate dispersal distance and relatively abundant seed sources, predicted abundance increased as thematic resolution increased. However, for species with long seeding distance or high shade tolerance, thematic resolution had an inverse effect on predicted abundance. When seed sources and dispersal distance were not limiting, the predicted species abundance increased with spatial resolution and vice versa. Results from this study may provide insights into the choice of thematic and spatial resolutions for model-based predictions of tree species distribution.

  5. Anti-VEGF Anticancer Drugs: Mind the Hypertension.

    Science.gov (United States)

    Katsi, Vasiliki; Zerdes, Ioannis; Manolakou, Stavroula; Makris, Thomas; Nihoyannopoulos, Petros; Tousoulis, Dimitris; Kallikazaros, Ioannis

    2014-01-01

    The introduction of therapies that inhibit tumor angiogenesis and particularly target to vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR) (VEGF inhibitors/VEGFi) have revolutionized the treatment of various cancer types. Although their clinical benefit can be optimal for cancer-affected patients, the safety of these targeted agents is of special concern especially for longer-term adjuvant or maintenance treatment. Importantly, VEGFi therapy has been significantly associated with hypertension (HTN) as an adverse effect and therefore the control of blood pressure (BP) after the administration of these drugs remains a challenging matter to be faced. The aim of this review is to summarize studies which investigate the association of VEGFi agents with HTN manifestation and the possible risks associated with this complication. Additionally, given that the optimal management of HTN caused by VEGFi remains obscure, this review will focus on prevention strategies including BP monitoring plans and propose potential therapeutic approaches.

  6. [Spatial distribution pattern of soil nitrogen in Huanghuadianzi watershed and related affecting factors].

    Science.gov (United States)

    Li, Long; Yao, Yun-feng; Qin, Fu-cang; Gao, Yu-han; Zhang, Mei-li

    2015-05-01

    This research was conducted in Huanghuadianzi watershed in Aohan, Chifeng, Inner Mongolia. Geostatistic was used to study the spatial distribution of soil nitrogen and their affecting factors. The results showed that the soil nitrogen contents in all layers distributed as an island shape, and the high value areas were mainly distributed in the northwest of the watershed as an obvious fertile island shape, while the low value areas were mainly distributed in the south of the watershed. Nitrogen was mainly concentrated in the surface soil, and its content decreased with the increase of soil depth. The soil nitrogen content at first increased then decreased with the altitude, decreased with the slope, and showed the order of shady slope>semi-shady slope>semi-sunny slope> sunny slope in different aspects. The average soil nitrogen contents in different land use types ranked as cropland >woodland > grassland.

  7. [Spatiotemporal distribution of negative air ion concentration in urban area and related affecting factors: a review].

    Science.gov (United States)

    Huang, Xiang-Hua; Wang, Jian; Zeng, Hong-Da; Chen, Guang-Shui; Zhong, Xian-Fang

    2013-06-01

    Negative air ion (NAI) concentration is an important indicator comprehensively reflecting air quality, and has significance to human beings living environment. This paper summarized the spatiotemporal distribution features of urban NAI concentration, and discussed the causes of these features based on the characteristics of the environmental factors in urban area and their effects on the physical and chemical processes of NAI. The temporal distribution of NAI concentration is mainly controlled by the periodic variation of solar radiation, while the spatial distribution of NAI concentration along the urban-rural gradient is mainly affected by the urban aerosol distribution, underlying surface characters, and urban heat island effect. The high NAI concentration in urban green area is related to the vegetation life activities and soil radiation, while the higher NAI concentration near the water environment is attributed to the water molecules that participate in the generation of NAI through a variety of ways. The other environmental factors can also affect the generation, life span, component, translocation, and distribution of NAI to some extent. To increase the urban green space and atmospheric humidity and to maintain the soil natural attributes of underlying surface could be the effective ways to increase the urban NAI concentration and improve the urban air quality.

  8. VEGFR2-mediated vascular dilation as a mechanism of VEGF-induced anemia and bone marrow cell mobilization.

    Science.gov (United States)

    Lim, Sharon; Zhang, Yin; Zhang, Danfang; Chen, Fang; Hosaka, Kayoko; Feng, Ninghan; Seki, Takahiro; Andersson, Patrik; Li, Jingrong; Zang, Jingwu; Sun, Baocun; Cao, Yihai

    2014-10-23

    Molecular mechanisms underlying tumor VEGF-induced host anemia and bone marrow cell (BMC) mobilization remain unknown. Here, we report that tumor VEGF markedly induced sinusoidal vasculature dilation in bone marrow (BM) and BMC mobilization to tumors and peripheral tissues in mouse and human tumor models. Unexpectedly, anti-VEGFR2, but not anti-VEGFR1, treatment completely blocked VEGF-induced anemia and BMC mobilization. Genetic deletion of Vegfr2 in endothelial cells markedly ablated VEGF-stimulated BMC mobilization. Conversely, deletion of the tyrosine kinase domain from Vegfr1 gene (Vegfr1(TK-/-)) did not affect VEGF-induced BMC mobilization. Analysis of VEGFR1(+)/VEGFR2(+) populations in peripheral blood and BM showed no significant ratio difference between VEGF- and control tumor-bearing animals. These findings demonstrate that vascular dilation through the VEGFR2 signaling is the mechanism underlying VEGF-induced BM mobilization and anemia. Thus, our data provide mechanistic insights on VEGF-induced BMC mobilization in tumors and have therapeutic implications by targeting VEGFR2 for cancer therapy.

  9. VEGF receptor-2 (Flk-1 overexpression in mice counteracts focal epileptic seizures.

    Directory of Open Access Journals (Sweden)

    Litsa Nikitidou

    Full Text Available Vascular endothelial growth factor (VEGF was first described as an angiogenic agent, but has recently also been shown to exert various neurotrophic and neuroprotective effects in the nervous system. These effects of VEGF are mainly mediated by its receptor, VEGFR-2, which is also referred to as the fetal liver kinase receptor 1 (Flk-1. VEGF is up-regulated in neurons and glial cells after epileptic seizures and counteracts seizure-induced neurodegeneration. In vitro, VEGF administration suppresses ictal and interictal epileptiform activity caused by AP4 and 0 Mg(2+ via Flk-1 receptor. We therefore explored whether increased VEGF signaling through Flk-1 overexpression may regulate epileptogenesis and ictogenesis in vivo. To this extent, we used transgenic mice overexpressing Flk-1 postnatally in neurons. Intriguingly, Flk-1 overexpressing mice were characterized by an elevated threshold for seizure induction and a decreased duration of focal afterdischarges, indicating anti-ictal action. On the other hand, the kindling progression in these mice was similar to wild-type controls. No significant effects on blood vessels or glia cells, as assessed by Glut1 and GFAP immunohistochemistry, were detected. These results suggest that increased VEGF signaling via overexpression of Flk-1 receptors may directly affect seizure activity even without altering angiogenesis. Thus, Flk-1 could be considered as a novel target for developing future gene therapy strategies against ictal epileptic activity.

  10. VEGF regulates TRPC6 channels in podocytes

    DEFF Research Database (Denmark)

    Thilo, Florian; Liu, Ying; Loddenkemper, Christoph;

    2012-01-01

    BACKGROUND: Both, increased plasma concentrations of vascular endothelial growth factor (VEGF) and increased expression of transient receptor potential canonical type 6 (TRPC6) channels in podocytes have been associated with proteinuric kidney diseases. Now, we investigated the hypothesis that VE...

  11. Amount and distribution of dietary protein affects clinical response to levodopa in Parkinson's disease.

    Science.gov (United States)

    Carter, J H; Nutt, J G; Woodward, W R; Hatcher, L F; Trotman, T L

    1989-04-01

    Reducing dietary protein improves the effectiveness of levodopa (LD) but the most effective distribution of a low-protein diet (0.8 g/kg) is unclear. We compared a 1.6 g/kg protein diet, a 0.8 g/kg diet with protein evenly distributed between meals, and a 0.8 g/kg diet with protein restricted to the evening meal in 5 parkinsonian patients with motor fluctuations. We monitored clinical response, plasma LD, and plasma large amino acids (LNAAs) hourly throughout the day. Mean "on" times were 51% (1.6 g/kg diet), 67% (0.8 g/kg evenly distributed), and 77% (0.8 g/kg restricted). Hourly averages of plasma LD did not differ between the diets. The mean plasma LNAAs were 732 nmol/ml (1.6 g/kg diet), 640 (0.8 g/kg distributed), and 542 (0.8 g/kg restricted), and the diurnal pattern reflected the distribution of protein intake. In conclusion, the amount and distribution of dietary protein affect clinical response to LD. These effects are not related to LD absorption but are explained by the variation in plasma LNAAs.

  12. VEGF and prostatic cancer: a systematic review.

    Science.gov (United States)

    Botelho, Francisco; Pina, Francisco; Lunet, Nuno

    2010-09-01

    Elevated vascular endothelial growth factor (VEGF) blood concentration reflects its prostatic production, making this a potentially interesting tumour marker to support the decision of submitting a patient for prostatic biopsy. The objective was to review systematically the evidence on the role of VEGF blood concentration in prostate cancer detection. Published studies addressing the relation between serum or plasma VEGF levels and prostate cancer were identified by searching Pubmed, ISI Web of Knowledge, SCOPUS and LILACS up to January 2010, and reviewed following a standardized protocol. Three studies reported higher plasma VEGF (pg/ml) in patients with localized prostate cancer than in healthy controls (7.0 vs. 0.0, 9.9 vs. 2.2, and 210 vs. 26.5, Pprostate cancer patients than in patients with benign prostate hypertrophy (518.9 vs. 267.9, Pbenign prostate hypertrophy, localized or metastatic prostate cancer. The three studies that used controls with previous suspicion of prostatic cancer but a negative biopsy reported non-statistically significant difference in VEGF serum levels (pg/ml) between controls and localized prostate cancer patients (241 vs. 206; 69.5 vs. 55; 215.2 vs. 266.4). Higher VEGF plasma levels are observed in prostatic cancer patients compared with healthy controls, but serum levels do not appear to be useful in differentiating benign from malignant prostatic disease using, as controls, individuals with high risk of prostate cancer and negative biopsy.

  13. Slit2/Robo4 Signaling: Potential Role of a VEGF-Antagonist Pathway to Regulate Luteal Permeability

    Science.gov (United States)

    Bekes, I.; Haunerdinger, V.; Sauter, R.; Holzheu, I.; Janni, W.; Wöckel, A.; Wulff, C.

    2017-01-01

    Introduction The corpus luteum (CL) is dependent on luteal vascular permeability, which is controlled by human chorionic gonadotropin (hCG) via vascular endothelial growth factor (VEGF). In this study we investigated the role of a potential VEGF antagonist pathway – Slit2/Robo4 – and its influence on endothelial cell adhesion. Materials and Methods Luteinized granulosa cells (LGCs) were stimulated with hCG in the absence or presence of a VEGF inhibitor. The expression of VEGF and Slit2 were measured. Human umbilical vein endothelial cells (HUVECs) were stimulated with Slit2 or VEGF, and gene expressions of cadherin 5 (CDH5) and claudin 5 (CLDN5) were measured. Following Robo4 knockdown, CDH5, CLDN5 and endothelial permeability were measured. Results Stimulation of human LGCs with hCG significantly increased VEGF while Slit2 expression was significantly suppressed. Inhibition of VEGF action after hCG stimulation did not change Slit2 suppression. Slit2 knockdown did not affect VEGF expression. While VEGF stimulation of HUVECs significantly suppressed CDH5 and CLDN5 gene expression, stimulation of HUVECs with Slit2 resulted in a significant increase in CDH5 and CLDN5. Robo4 knockdown was done, leading to downregulation of CDH5 and CLDN5 which resulted in significantly increased permeability. Conclusions Our results indicate the existence of a VEGF-antagonist pathway in the CL that decreases vascular permeability. During the functional life of the CL the pathway is suppressed by hCG. It is possible that stimulation of this pathway could be used to treat ovarian hyperstimulation syndrome. PMID:28190892

  14. Effect of combined VEGF165/ SDF-1 gene therapy on vascular remodeling and blood perfusion in cerebral ischemia.

    Science.gov (United States)

    Hu, Guo-Jie; Feng, Yu-Gong; Lu, Wen-Peng; Li, Huan-Ting; Xie, Hong-Wei; Li, Shi-Fang

    2016-12-16

    OBJECTIVE Therapeutic neovascularization is a promising strategy for treating patients after an ischemic stroke; however, single-factor therapy has limitations. Stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) proteins synergistically promote angiogenesis. In this study, the authors assessed the effect of combined gene therapy with VEGF165 and SDF-1 in a rat model of cerebral infarction. METHODS An adenoviral vector expressing VEGF165 and SDF-1 connected via an internal ribosome entry site was constructed (Ad- VEGF165-SDF-1). A rat model of middle cerebral artery occlusion (MCAO) was established; either Ad- VEGF165-SDF-1 or control adenovirus Ad- LacZ was stereotactically microinjected into the lateral ventricle of 80 rats 24 hours after MCAO. Coexpression and distribution of VEGF165 and SDF-1 were examined by reverse-transcription polymerase chain reaction, Western blotting, and immunofluorescence. The neurological severity score of each rat was measured on Days 3, 7, 14, 21, and 28 after MCAO. Angiogenesis and vascular remodeling were evaluated via bromodeoxyuridine and CD34 immunofluorescence labeling. Relative cerebral infarction volumes were determined by T2-weighted MRI and triphenyltetrazolium chloride staining. Cerebral blood flow, relative cerebral blood volume, and relative mean transmit time were assessed using perfusion-weighted MRI. RESULTS The Ad- VEGF165-SDF-1 vector mediated coexpression of VEGF165 and SDF-1 in multiple sites around the ischemic core, including the cortex, corpus striatum, and hippocampal granular layer. Coexpression of VEGF165 and SDF-1 improved neural function, reduced cerebral infarction volume, increased microvascular density and promoted angiogenesis in the ischemic penumbra, and improved cerebral blood flow and perfusion. CONCLUSIONS Combined VEGF165 and SDF-1 gene therapy represents a potential strategy for improving vascular remodeling and recovery of neural function after cerebral

  15. Social information affects adults' evaluation of fairness in distributions: An ERP approach.

    Science.gov (United States)

    Ishikawa, Mitsuhiko; Park, Yun-Hee; Kitazaki, Michiteru; Itakura, Shoji

    2017-01-01

    The sense of fairness has been observed in early infancy. Because many studies of fairness in adults have used economic games such as the Ultimatum Game, it has been difficult to compare fairness between adults and infants. Further, recent studies have suggested that social information about actors who behave fairly or unfairly may influence the judgement of fairness in infants. Therefore, to compare the sense of fairness between infants and adults, the study using paradigm in infant research is required. We examined how social information about two characters, either prosocial or antisocial, affects the event-related potential response (ERP) to fair or unfair resource distributions in adults. In the habituation phase, participants were informed about characters' social information through their actions. One character then distributed resources fairly or unfairly, and ERP was measured at the end of the distribution. Data from eighteen adult participants were analysed. A significant interaction of social information and fairness was found for late positive potential (LPP), but a post-hoc t test revealed a significant difference between fair and unfair conditions only for actions of the antisocial character. We found that LPP can reflect the sense of fairness affected by social information. Comparison with infant studies suggests that the sense of fairness may change during development.

  16. Social information affects adults’ evaluation of fairness in distributions: An ERP approach

    Science.gov (United States)

    Ishikawa, Mitsuhiko; Park, Yun-hee; Kitazaki, Michiteru; Itakura, Shoji

    2017-01-01

    The sense of fairness has been observed in early infancy. Because many studies of fairness in adults have used economic games such as the Ultimatum Game, it has been difficult to compare fairness between adults and infants. Further, recent studies have suggested that social information about actors who behave fairly or unfairly may influence the judgement of fairness in infants. Therefore, to compare the sense of fairness between infants and adults, the study using paradigm in infant research is required. We examined how social information about two characters, either prosocial or antisocial, affects the event-related potential response (ERP) to fair or unfair resource distributions in adults. In the habituation phase, participants were informed about characters’ social information through their actions. One character then distributed resources fairly or unfairly, and ERP was measured at the end of the distribution. Data from eighteen adult participants were analysed. A significant interaction of social information and fairness was found for late positive potential (LPP), but a post-hoc t test revealed a significant difference between fair and unfair conditions only for actions of the antisocial character. We found that LPP can reflect the sense of fairness affected by social information. Comparison with infant studies suggests that the sense of fairness may change during development. PMID:28235082

  17. Factors affecting the distribution of natural and anthropogenic radionuclides in the coastal Burullus Lake.

    Science.gov (United States)

    El-Reefy, H I; Badran, H M; Sharshar, T; Hilal, M A; Elnimr, T

    2014-08-01

    In the present study, measurements of naturally occurring radioactive materials and (137)Cs activity in sediment were conducted for locations covering the entire Burullus Lake in order to gather information about radionuclides mobility and distribution. Low-background γ-spectrometry was employed to determine the activity concentrations of water and sediment samples. The activity concentrations of (226)Ra and (232)Th are close to uniform distribution in the lake environment. Among the different physical and chemical characteristics measured for water and sediment, only salinity and total organic matter content have the potential to affect the mobility of (137)Cs and (40)K. The results suggest that these two radionuclides are attached to different mobile particulates. Increasing salinity tends to strengthen the adsorption of (137)Cs and solubilization of (40)K in sediment. On the other hand, sediment with high organic matter content traps (137)Cs and (40)K associated particulates to bottom sediment.

  18. Probability distribution functions of turbulence in seepage-affected alluvial channel

    Science.gov (United States)

    Sharma, Anurag; Kumar, Bimlesh

    2017-02-01

    The present experimental study is carried out on the probability distribution functions (PDFs) of turbulent flow characteristics within near-bed-surface and away-from-bed surfaces for both no seepage and seepage flow. Laboratory experiments were conducted in the plane sand bed for no seepage (NS), 10% seepage (10%S) and 15% seepage (15%) cases. The experimental calculation of the PDFs of turbulent parameters such as Reynolds shear stress, velocity fluctuations, and bursting events is compared with theoretical expression obtained by Gram-Charlier (GC)-based exponential distribution. Experimental observations follow the computed PDF distributions for both no seepage and seepage cases. Jensen-Shannon divergence (JSD) method is used to measure the similarity between theoretical and experimental PDFs. The value of JSD for PDFs of velocity fluctuation lies between 0.0005 to 0.003 while the JSD value for PDFs of Reynolds shear stress varies between 0.001 to 0.006. Even with the application of seepage, the PDF distribution of bursting events, sweeps and ejections are well characterized by the exponential distribution of the GC series, except that a slight deflection of inward and outward interactions is observed which may be due to weaker events. The value of JSD for outward and inward interactions ranges from 0.0013 to 0.032, while the JSD value for sweep and ejection events varies between 0.0001 to 0.0025. The theoretical expression for the PDF of turbulent intensity is developed in the present study, which agrees well with the experimental observations and JSD lies between 0.007 and 0.015. The work presented is potentially applicable to the probability distribution of mobile-bed sediments in seepage-affected alluvial channels typically characterized by the various turbulent parameters. The purpose of PDF estimation from experimental data is that it provides a complete numerical description in the areas of turbulent flow either at a single or finite number of points.

  19. A decrease in phytic acid content substantially affects the distribution of mineral elements within rice seeds.

    Science.gov (United States)

    Sakai, Hiroaki; Iwai, Toru; Matsubara, Chie; Usui, Yuto; Okamura, Masaki; Yatou, Osamu; Terada, Yasuko; Aoki, Naohiro; Nishida, Sho; Yoshida, Kaoru T

    2015-09-01

    Phytic acid (myo-inositol hexakisphosphate; InsP6) is the storage compound of phosphorus and many mineral elements in seeds. To determine the role of InsP6 in the accumulation and distribution of mineral elements in seeds, we performed fine mappings of mineral elements through synchrotron-based X-ray microfluorescence analysis using developing seeds from two independent low phytic acid (lpa) mutants of rice (Oryza sativa L.). The reduced InsP6 in lpa seeds did not affect the translocation of mineral elements from vegetative organs into seeds, because the total amounts of phosphorus and the other mineral elements in lpa seeds were identical to those in the wild type (WT). However, the reduced InsP6 caused large changes in mineral localization within lpa seeds. Phosphorus and potassium in the aleurone layer of lpa greatly decreased and diffused into the endosperm. Zinc and copper, which were broadly distributed from the aleurone layer to the inner endosperm in the WT, were localized in the narrower space around the aleurone layer in lpa mutants. We also confirmed that similar distribution changes occurred in transgenic rice with the lpa phenotype. Using these results, we discussed the role of InsP6 in the dynamic accumulation and distribution patterns of mineral elements during seed development.

  20. Evaluating how species niche modelling is affected by partial distributions with an empirical case

    Science.gov (United States)

    Carretero, Miguel A.; Sillero, Neftalí

    2016-11-01

    Ecological niche models (ENMs) will successfully identify a species' ecological niche, provided that important assumptions are fulfilled, namely environment equilibrium and niche equality across the distribution. Violations may seriously affect ENM reliability, leading to erroneous biogeographic conclusions and inappropriate conservation prioritisation. We evaluate the robustness of ENMs against incomplete knowledge of distribution with a real example, the threatened Iberian lizard Podarcis carbonelli, whose distribution was gradually discovered over a long time period. We used several ENM methods for presence-only data (Maxent, ENFA, Bioclim, and Domain) to infer the realised ecological niche at two spatial resolutions (1 km and 200 m). The distribution data were split into four partial datasets corresponding to separate subranges: Central System (CS); Viseu-Aveiro (VA); Atlantic coast (AC); and Doñana (DO). We then accumulated the datasets following the species discovery sequence: CS + VA, CS + VA + AC, and CS + VA + AC + DO. Niche equivalence and similarity between partial models were compared using Ecospat. ENMs were strongly affected by the violation of niche equilibrium; only the VA subrange forecasts the complete species range. ENMs were also sensitive to the violation of niche equality: only VA models were similar to the Iberian model, altitude being the most important variable followed by annual precipitation, maximum temperature in July, and annual radiation. When the ENMs were applied only to the first subrange discovered (CS), only the VA area was predicted, while the other subranges might have remained unknown, thus compromising conservation strategies. As assumptions of niche equilibrium and equality were violated, likely owing to the species' ecological multimodality, the models generated were biased and of limited predictive value. ENMs are useful tools in biogeography and conservation, but only if their basal assumptions are achieved. Partial

  1. Geographic distance affects dispersal of the patchy distributed greater long-tailed hamster (Tscherskia triton).

    Science.gov (United States)

    Xue, Huiliang; Zhong, Min; Xu, Jinhui; Xu, Laixiang

    2014-01-01

    Dispersal is a fundamental process in ecology influencing the genetic structure and the viability of populations. Understanding how variable factors influence the dispersal of the population is becoming an important question in animal ecology. To date, geographic distance and geographic barriers are often considered as main factors impacting dispersal, but their effects are variable depending on different conditions. In general, geographic barriers affect more significantly than geographic distance on dispersal. In rapidly expanding populations, however, geographic barriers have less effect on dispersal than geographic distance. The effects of both geographic distance and geographic barriers in low-density populations with patchy distributions are poorly understood. By using a panel of 10 microsatellite loci we investigated the genetic structure of three patchy-distributed populations of the Greater long-tailed hamster (Tscherskia triton) from Raoyang, Guan and Shunyi counties of the North China Plain. The results showed that (i) high genetic diversity and differentiation exist in three geographic populations with patchy distributions; (ii) gene flow occurs among these three populations with physical barriers of Beijing city and Hutuo River, which potentially restricted the dispersal of the animal; (iii) the gene flow is negatively correlated with the geographic distance, while the genetic distance shows the positive correlation. Our results suggest that the effect of the physical barriers is conditional-dependent, including barrier capacity or individual potentially dispersal ability. Geographic distance also acts as an important factor affecting dispersal for the patchy distributed geographic populations. So, gene flow is effective, even at relatively long distances, in balancing the effect of geographic barrier in this study.

  2. Statistical analysis of factors affecting landslide distribution in the new Madrid seismic zone, Tennessee and Kentucky

    Science.gov (United States)

    Jibson, R.W.; Keefer, D.K.

    1989-01-01

    More than 220 large landslides along the bluffs bordering the Mississippi alluvial plain between Cairo, Ill., and Memphis, Tenn., are analyzed by discriminant analysis and multiple linear regression to determine the relative effects of slope height and steepness, stratigraphic variation, slope aspect, and proximity to the hypocenters of the 1811-12 New Madrid, Mo., earthquakes on the distribution of these landslides. Three types of landslides are analyzed: (1) old, coherent slumps and block slides, which have eroded and revegetated features and no active analogs in the area; (2) old earth flows, which are also eroded and revegetated; and (3) young rotational slumps, which are present only along near-river bluffs, and which are the only young, active landslides in the area. Discriminant analysis shows that only one characteristic differs significantly between bluffs with and without young rotational slumps: failed bluffs tend to have sand and clay at their base, which may render them more susceptible to fluvial erosion. Bluffs having old coherent slides are significantly higher, steeper, and closer to the hypocenters of the 1811-12 earthquakes than bluffs without these slides. Bluffs having old earth flows are likewise higher and closer to the earthquake hypocenters. Multiple regression analysis indicates that the distribution of young rotational slumps is affected most strongly by slope steepness: about one-third of the variation in the distribution is explained by variations in slope steepness. The distribution of old coherent slides and earth flows is affected most strongly by slope height, but the proximity to the hypocenters of the 1811-12 earthquakes also significantly affects the distribution. The results of the statistical analyses indicate that the only recently active landsliding in the area is along actively eroding river banks, where rotational slumps formed as bluffs are undercut by the river. The analyses further indicate that the old coherent slides

  3. Glucose and TGF β2 Modulate the Viability of Cultured Human Retinal Pericytes and Their VEGF Release

    Science.gov (United States)

    Vidro, Eileen K.; Gee, Stephen; Unda, Richard; Ma, Jian-xing; Tsin, Andrew

    2015-01-01

    Purpose Determine the effects of glucose and exogenous TGFβ2 on viability and VEGF release by human retinal pericytes (HRP). Methods Human retinal pericytes (HRP) were cultured in 5 mM (physiologic) or high (18 mM) glucose with or without added TGFβ2. Viable cells were counted; TGFβ2 and VEGF in the conditioned media (CM) were measured by ELISA. Results High glucose significantly reduced viable cell number and increased the levels of TGFβ2 and VEGF. TGFβ2 caused a significant dose-dependent effect on viable cell number and on the level of VEGF secreted into the CM by HRP in physiologic glucose, decreasing viable cell number, and increasing VEGF release per 1000 cells at a low concentration (0.1 ng/ml) and increasing viable cell number and decreasing VEGF release per 1000 cells at higher concentrations (1.0 and 10 ng/ml). TGFβ2 affected neither parameter in high glucose. Conclusions Elevated glucose decreased HRP viability and modulated changes in TGFβ2 and VEGF release. This suggests a novel mechanism for HRP dropout in diabetic retinopathy. PMID:19085381

  4. VEGF-A/NRP1 stimulates GIPC1 and Syx complex formation to promote RhoA activation and proliferation in skin cancer cells

    Directory of Open Access Journals (Sweden)

    Ayumi Yoshida

    2015-09-01

    Full Text Available Neuropilin-1 (NRP1 has been identified as a VEGF-A receptor. DJM-1, a human skin cancer cell line, expresses endogenous VEGF-A and NRP1. In the present study, the RNA interference of VEGF-A or NRP1 suppressed DJM-1 cell proliferation. Furthermore, the overexpression of the NRP1 wild type restored shNRP1-treated DJM-1 cell proliferation, whereas NRP1 cytoplasmic deletion mutants did not. A co-immunoprecipitation analysis revealed that VEGF-A induced interactions between NRP1 and GIPC1, a scaffold protein, and complex formation between GIPC1 and Syx, a RhoGEF. The knockdown of GIPC1 or Syx reduced active RhoA and DJM-1 cell proliferation without affecting the MAPK or Akt pathway. C3 exoenzyme or Y27632 inhibited the VEGF-A-induced proliferation of DJM-1 cells. Conversely, the overexpression of the constitutively active form of RhoA restored the proliferation of siVEGF-A-treated DJM-1 cells. Furthermore, the inhibition of VEGF-A/NRP1 signaling upregulated p27, a CDK inhibitor. A cell-penetrating oligopeptide that targeted GIPC1/Syx complex formation inhibited the VEGF-A-induced activation of RhoA and suppressed DJM-1 cell proliferation. In conclusion, this new signaling pathway of VEGF-A/NRP1 induced cancer cell proliferation by forming a GIPC1/Syx complex that activated RhoA to degrade the p27 protein.

  5. Computational model of vascular endothelial growth factor spatial distribution in muscle and pro-angiogenic cell therapy.

    Directory of Open Access Journals (Sweden)

    Feilim Mac Gabhann

    2006-09-01

    Full Text Available Members of the vascular endothelial growth factor (VEGF family of proteins are critical regulators of angiogenesis. VEGF concentration gradients are important for activation and chemotactic guidance of capillary sprouting, but measurement of these gradients in vivo is not currently possible. We have constructed a biophysically and molecularly detailed computational model to study microenvironmental transport of two isoforms of VEGF in rat extensor digitorum longus skeletal muscle under in vivo conditions. Using parameters based on experimental measurements, the model includes: VEGF secretion from muscle fibers; binding to the extracellular matrix; binding to and activation of endothelial cell surface VEGF receptors; and internalization. For 2-D cross sections of tissue, we analyzed predicted VEGF distributions, gradients, and receptor binding. Significant VEGF gradients (up to 12% change in VEGF concentration over 10 mum were predicted in resting skeletal muscle with uniform VEGF secretion, due to non-uniform capillary distribution. These relative VEGF gradients were not sensitive to extracellular matrix composition, or to the overall VEGF expression level, but were dependent on VEGF receptor density and affinity, and internalization rate parameters. VEGF upregulation in a subset of fibers increased VEGF gradients, simulating transplantation of pro-angiogenic myoblasts, a possible therapy for ischemic diseases. The number and relative position of overexpressing fibers determined the VEGF gradients and distribution of VEGF receptor activation. With total VEGF expression level in the tissue unchanged, concentrating overexpression into a small number of adjacent fibers can increase the number of capillaries activated. The VEGF concentration gradients predicted for resting muscle (average 3% VEGF/10 mum is sufficient for cellular sensing; the tip cell of a vessel sprout is approximately 50 mum long. The VEGF gradients also result in heterogeneity in

  6. Main Factors Affecting the Distribution of the Macroscopic Destruction Field of Earthquake

    Institute of Scientific and Technical Information of China (English)

    Li Minfeng; Li Shengqiang; Chen Yong; Mi Hongliang

    2001-01-01

    It is proposed that some possible macroseismic epicenters can be determined quickly from the relationship that the microseismic epicenters located by instruments bear with faults. Based on these so-called macroseismic epicenters, we can make fast seismic hazard estimation after a shock by use of the empirical distribution model of seismic intensity. In comparison with the method that uses the microseismic epicenters directly, this approach can increase the precision of fast seismic hazard estimation. Statistical analysis of 133 main earthquakes in China was made. The result shows that the deviation distance between the microseismic epicenter and macroseismic epicenter falls within the range of 35 km for 88 % earthquakes of the total and within the range of 35 to 75 km for the remaining ones. Then, we can take the area that has the microseismic epicenter as its center and is 35 km in radius as the area for emphatic analysis, and take the area within 75 km around the microseismic epicenter as the area for general analysis. The relation between the 66 earthquake cases on the N-S Seismic Belt in China and the spatial distribution characteristics of faults and the results of focal mechanism solution were analyzed in detail. We know from the analysis that the error of instrumental epicenter determination is not the only factor that gives effects to the deviation of the macroseismic epicenter. In addition to it, the fault size, fault distribution, fault activity, fault intersection types, earthquake magnitude, etc. are also main affecting factors. By sorting out,processing and analyzing these affecting factors, the principle and procedures for quickly determining the possible position of the macroseismic epicenter were set up. Taking these as a basis and establishing a nationwide database of faults that contains relevant factors, it is possible to apply this method in practical fast estimation of seismic hazard.

  7. Hypoxia Affects Nitrogen Uptake and Distribution in Young Poplar (Populus × canescens Trees.

    Directory of Open Access Journals (Sweden)

    Bin Liu

    Full Text Available The present study with young poplar trees aimed at characterizing the effect of O2 shortage in the soil on net uptake of NO3- and NH4+ and the spatial distribution of the N taken up. Moreover, we assessed biomass increment as well as N status of the trees affected by O2 deficiency. For this purpose, an experiment was conducted in which hydroponically grown young poplar trees were exposed to hypoxic and normoxic (control conditions for 14 days. 15N-labelled NO3- and NH4+ were used to elucidate N uptake and distribution of currently absorbed N and N allocation rates in the plants. Whereas shoot biomass was not affected by soil O2 deficiency, it significantly reduced root biomass and, consequently, the root-to-shoot ratio. Uptake of NO3- but not of NH4+ by the roots of the trees was severely impaired by hypoxia. As a consequence of reduced N uptake, the N content of all poplar tissues was significantly diminished. Under normoxic control conditions, the spatial distribution of currently absorbed N and N allocation rates differed depending on the N source. Whereas NO3- derived N was mainly transported to the younger parts of the shoot, particularly to the developing and young mature leaves, N derived from NH4+ was preferentially allocated to older parts of the shoot, mainly to wood and bark. Soil O2 deficiency enhanced this differential allocation pattern. From these results we assume that NO3- was assimilated in developing tissues and preferentially used to maintain growth and ensure plant survival under hypoxia, whereas NH4+ based N was used for biosynthesis of storage proteins in bark and wood of the trees. Still, further studies are needed to understand the mechanistic basis as well as the eco-physiological advantages of such differential allocation patterns.

  8. Radiation-induced VEGF-C expression and endothelial cell proliferation in lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yu-Hsuan [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University, Pharmacological Institute, College of Medicine, Taipei (China); Pan, Shiow-Lin; Wang, Jing-Chi; Teng, Che-Ming [National Taiwan University, Pharmacological Institute, College of Medicine, Taipei (China); Kuo, Sung-Hsin [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University College of Medicine, Department of Internal Medicine, Taipei (China); Cheng, Jason Chia-Hsien [National Taiwan University Hospital, Department of Oncology, Taipei (China); National Taiwan University College of Medicine, Graduate Institute of Clinical Medicine, Taipei (China)

    2014-12-15

    The present study was undertaken to investigate whether radiation induces the expression of vascular endothelial growth factor C (VEGF-C) through activation of the PI3K/Akt/mTOR pathway,subsequently affecting endothelial cells. Radiotherapy-induced tumor micro-lymphatic vessel density (MLVD) was determined in a lung cancer xenograft model established in SCID mice. The protein expression and phosphorylation of members of the PI3K/Akt/mTOR pathway and VEGF-C secretion and mRNA expression in irradiated lung cancer cells were assessed by Western blot analysis, enzyme-linked immunosorbent assays (ELISAs), and reverse transcriptase-polymerase chain reaction (RT-PCR). Moreover, specific chemical inhibitors were used to evaluate the role of the PI3K/Akt/mTOR signaling pathway. Conditioned medium (CM) from irradiated control-siRNA or VEGF-C-siRNA-expressing A549 cells was used to evaluate the proliferation of endothelial cells by the MTT assay. Radiation increased VEGF-C expression in a dose-dependent manner over time at the protein but not at the mRNA level. Radiation also up-regulated the phosphorylation of Akt, mTOR, 4EBP, and eIF4E, but not of p70S6K. Radiation-induced VEGF-C expression was down-regulated by LY294002 and rapamycin (both p < 0.05). Furthermore, CM from irradiated A549 cells enhanced human umbilical vein endothelial cell (HUVEC) and lymphatic endothelial cell (LEC) proliferation, which was not observed with CM from irradiated VEGF-C-siRNA-expressing A549 cells. Radiation-induced activation of the PI3K/Akt/mTOR signaling pathway increases VEGF-C expression in lung cancer cells, thereby promoting endothelial cell proliferation. (orig.) [German] Die vorliegende Studie untersucht, ob die Strahlung die Expression von VEGF-C (vascular endothelial growth factor C) mittels Aktivierung des PI3K/Akt/mTOR-Signalwegs induziert und anschliessend die endothelialen Zellen beeinflusst. Die durch Strahlentherapie induzierte Mikrolymphgefaessdichte (MLVD) im Tumor wurde in

  9. DC electric stimulation upregulates angiogenic factors in endothelial cells through activation of VEGF receptors.

    Science.gov (United States)

    Bai, Huai; Forrester, John V; Zhao, Min

    2011-07-01

    Small direct current (DC) electric fields direct some important angiogenic responses of vascular endothelial cells. Those responses indicate promising use of electric fields to modulate angiogenesis. We sought to determine the regulation of electric fields on transcription and expression of a serial of import angiogenic factors by endothelial cells themselves. Using semi-quantitative PCR and ELISA we found that electric stimulation upregulates the levels of mRNAs and proteins of a number of angiogenic proteins, most importantly VEGF165, VEGF121 and IL-8 in human endothelial cells. The up-regulation of mRNA levels might be specific, as the mRNA encoding bFGF, TGF-beta and eNOS are not affected by DC electric stimulation at 24h time-point. Inhibition of VEGF receptor (VEGFR1 or VEGFR2) signaling significantly decreased VEGF production and completely abolished IL-8 production. DC electric stimulation selectively regulates production of some growth factors and cytokines important for angiogenesis through a feed-back loop mediated by VEGF receptors.

  10. A peptide fusion protein in hibits angiogenesis and tumorgrowth by blocking VEGF binding to KDR

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Vascular endothelial growth factor (VEGF) binding to its tyrosine kinase receptors (KDR/FLK1, Flt-1) induces angiogenesis. In search of the peptides blocking VEGF binding to its receptor KDR/FLK1 to inhibit tumor- angiogenesis and growth, we screened a phage display peptide library with KDR as target protein, and some candidate peptides were isolated. In this study, we cloned the DNA fragment coding the peptide K237 from the library, into a vector pQE42 to express fusion protein DHFR-K237 in E. coli M15. The affection of fusion protein DHFR-K237 on endothelial cell proliferation and angiogenesis was investigated. In vitro, DHFR-K237 could completely block VEGF binding to KDR and significantly inhibit the VEGF-medi- ated proliferation of the human vascular endothelial cells. In vivo, DHFR-K237 inhibited angiogenesis in chick embryo chorioa- llantoric membrane and tumor growth in nude mice. These results suggest that K237 is an effective antagonist of VEGF binding to KDR, and could be a potential agent for cancer biotherapy.

  11. Angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium

    Institute of Scientific and Technical Information of China (English)

    DONG Shu-qiang; ZHANG Bao-ren; MEI Ju; XU Zhi-yun; ZOU Liang-jian; HUANG Sheng-dong

    2002-01-01

    Objective: To study the angiogenesis effects of adenovirus-mediated gene transfer of VEGF-B on chronic ischemic myocardium. Methods: Domestic pigs underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, Ad. VEGF-B, Ad. LacZ or PBS were administrated directly into the myocardium at 10 sites in the circumflex distribution (109 PFU or 100 μl) according to groups. Echocardiography and ex vivo coronary angiography were performed. The injection sites around myocardium were harvested and subjected to histological analysis and immunochemical staining. Results: Echocardiography assessment 4 weeks after vector administration demonstrated significant improvement of regional wall systolic function. Collateral vesseldevelopment assessed by angiography was also significantly greater in Ad. VEGF-B animals than that in control animals. Vascular density analysis revealed a mean of 43±5 neovessels per high-power field in Ad.VEGF-B group versus 19±4 and 17±6 in Ad.LacZ and PBS group. Conclusion:Direct intramyocardial administration of Ad.VEGF-B can induce focal angiogenesis and result in improvement in regional myocardial function, which may be useful in patients with ischemic heart disease who are not eligible for conventional therapies.

  12. The role of VEGF and KDR polymorphisms in moyamoya disease and collateral revascularization.

    Directory of Open Access Journals (Sweden)

    Young Seok Park

    Full Text Available We conducted a case-control study to investigate whether vascular endothelial growth factor (VEGF -2578, -1154, -634, and 936 and kinase insert domain containing receptor (KDR -604, 1192, and 1719 polymorphisms are associated with moyamoya disease. Korean patients with moyamoya disease (n = 107, mean age, 20.9±15.9 years; 66.4% female and 243 healthy control subjects (mean age, 23.0±16.1 years; 56.8% female were included. The subjects were divided into pediatric and adult groups. Among the 64 surgical patients, we evaluated collateral vessel formation after 2 years and divided patients into good (collateral grade A or poor (collateral grade B and C groups. The frequencies and distributions of four VEGF (-2578, -1154, -634, and 936 and KDR (-604, 1192, and 1719 polymorphisms were assessed from patients with moyamoya disease and compared to the control group. No differences were observed in VEGF -2578, -1154, -634, and 936 or KDR -604, 1192, and 1719 polymorphisms between the control group and moyamoya disease group. However, we found the -634CC genotype occurred less frequently in the pediatric moyamoya group (p = 0.040 whereas the KDR -604C/1192A/1719T haplotype increased the risk of pediatric moyamoya (p = 0.024. Patients with the CC genotype of VEGF -634 had better collateral vessel formation after surgery. Our results suggest that the VEGF -634G allele is associated with pediatric moyamoya disease and poor collateral vessel formation.

  13. Flooding affects uptake and distribution of carbon and nitrogen in citrus seedlings.

    Science.gov (United States)

    Martínez-Alcántara, Belén; Jover, Sara; Quiñones, Ana; Forner-Giner, María Ángeles; Rodríguez-Gamir, Juan; Legaz, Francisco; Primo-Millo, Eduardo; Iglesias, Domingo J

    2012-08-15

    Soil flooding has been widely reported to affect large areas of the world. In this work, we investigated the effect of waterlogging on citrus carbon and nitrogen pools and partitioning. Influence on their uptake and translocation was also studied through ¹⁵N and ¹³C labeling to provide insight into the physiological mechanisms underlying the responses. The data indicated that flooding severely reduced photosynthetic activity and affected growth and biomass partitioning. Total nitrogen content and concentration in the plant also progressively decreased throughout the course of the experiment. After 36 days of treatment, nitrogen content of flooded plants had decreased more than 2.3-fold compared to control seedlings, and reductions in nitrogen concentration ranged from 21 to 55% (in roots and leaves, respectively). Specific absorption rate and transport were also affected, leading to important changes in the distribution of this element inside the plant. Additionally, experiments involving labeled nitrogen revealed that ¹⁵N uptake rate and accumulation were drastically decreased at the end of the experiment (93% and 54%, respectively). ¹³CO₂ assimilation into the plant was strongly reduced by flooding, with δ¹³C reductions ranging from 22 to 37% in leaves and roots, respectively. After 36 days, the relative distribution of absorbed ¹³C was also altered. Thus, ¹³C recovery in flooded leaves increased compared to controls, whereas roots exhibited the opposite pattern. Interestingly, when carbohydrate partitioning was examined, the data revealed that sucrose concentration was augmented significantly in roots (37-56%), whereas starch was reduced. In leaves, a marked increase in sucrose was detected from the first sampling onwards (36-66%), and the same patter was observed for starch. Taken together, these results indicate that flooding altered carbon and nitrogen pools and partitioning in citrus. On one hand, reduced nitrogen concentration appears to

  14. How Are Distributed Groups Affected by an Imposed Structuring of their Decision-Making Process?

    DEFF Research Database (Denmark)

    Lundell, Anders Lorentz; Hertzum, Morten

    2011-01-01

    Groups often suffer from ineffective communication and decision making. This experimental study compares distributed groups solving a preference task with support from either a communication system or a system providing both communication and a structuring of the decision-making process. Results...... show that groups using the latter system spend more time solving the task, spend more of their time on solution analysis, spend less of their time on disorganized activity, and arrive at task solutions with less extreme preferences. Thus, the type of system affects the decision-making process as well...... as its outcome. Notably, the task solutions arrived at by the groups using the system that imposes a structuring of the decision-making process show limited correlation with the task solutions suggested by the system on the basis of the groups’ explicitly stated criteria. We find no differences in group...

  15. Fish in shallow areas in Moreton Bay, Queensland and factors affecting their distribution

    Science.gov (United States)

    Weng, H. T.

    1990-06-01

    Five shallow areas (sea grass, river mouth, mangrove fringe and sewage outlet. A total of 86 fish species were recorded. Five species (6%) were regarded as true marine fish but these were of rare occurrence (0·5%). Four species (5%) were highly abundant (51%) and 57 species (66%) were represented by low numbers of fish (5%). The sewage outlet and the river mouth sites were found to contain the highest number of fish with relatively low numbers of species. The sand-drifting and the sea grass sites were different in fish fauna, and both were different from the remaining three sites which were of high similarity in fish faunal groups. Food availability, preference for habitats, sea grass vegetation, juvenile/adult segregation, season of juvenile recruitment and hydrological characteristics were thought to be important factors affecting the distribution of these species of fish.

  16. Does day length affect winter bird distribution? Testing the role of an elusive variable.

    Directory of Open Access Journals (Sweden)

    Luis M Carrascal

    Full Text Available Differences in day length may act as a critical factor in bird biology by introducing time constraints in energy acquisition during winter. Thus, differences in day length might operate as a main determinant of bird abundance along latitudinal gradients. This work examines the influence of day length on the abundance of wintering crested tits (Lophophanes cristatus in 26 localities of Spanish juniper (Juniperus thurifera dwarf woodlands (average height of 5 m located along a latitudinal gradient in the Spanish highlands, while controlling for the influence of food availability, minimum night temperature, habitat structure and landscape characteristics. Top regression models in the AIC framework explained 56% of variance in bird numbers. All models incorporated day length as the variable with the highest magnitude effect. Food availability also played an important role, although only the crop of ripe juniper fruits, but not arthropods, positively affected crested tit abundance. Differences in vegetation structure across localities had also a strong positive effect (average tree height and juniper tree density. Geographical variation in night temperature had no influence on crested tit distribution, despite the low winter temperatures reached in these dwarf forests. This paper demonstrates for the first time that winter bird abundance increases with day length after controlling for the effect of other environmental variables. Winter average difference in day length was only 10.5 minutes per day along the 1°47' latitudinal interval (190 km included in this study. This amount of time, which reaches 13.5 h accumulated throughout the winter season, appears to be large enough to affect the long-term energy budget of small passerines during winter and to shape the distribution of winter bird abundance under restrictive environmental conditions.

  17. The governance of natural resources: Issues affecting better management of revenues and distribution of benefits within Papua New Guinea

    Directory of Open Access Journals (Sweden)

    Hitelai Polume-Kiele

    2014-09-01

    The focus of the article’s discussion is on governance and management issues that affect the distribution of benefits, delivery of essential services to rural areas of PNG, stability within government, and the expectations of landowners.

  18. Coal fly ash effluent affects the distributions of Brachionus calyciflorus sibling species.

    Science.gov (United States)

    Zhang, Gen; Xi, Yi-Long; Xue, Ying-Hao; Xiang, Xian-Ling; Wen, Xin-Li

    2015-02-01

    Fly ash, a coal combustion residue of thermal power plants and a source of multiple pollutants, has been recognized as an environmental hazard all over the world. Although it is known that fly ash effluent affects density, diversity and distribution of rotifers in drainage systems and receiving water bodies, the effect of fly ash effluent on the distributions of highly similar rotifer species remains unknown. In this study, the mtDNA COI genes of 90 individuals in Brachionus calyciflorus complex from Lake Hui (as a fly ash discharge water pond) and other two neighboring lakes (Lake Fengming and Lake Tingtang) were sequenced and analyzed, and the responses in selected life table demographic parameters (life expectancy at hatching, net reproductive rate, intrinsic rate of population increase and proportion of sexual offspring) of different rotifer populations to fly ash effluent were investigated. Overall, 72 mtDNA haplotypes were defined, and were split into two clades by the phylogenetic trees. The divergence of COI gene sequences between the two clades ranged from 11.8% to17.8%, indicating the occurrence of two sibling species (sibling species I and sibling species II). Sibling species I distributed in all the three lakes, showing strong capabilities for dispersal and colonization, which were supported by its higher level of gene flow (2.60-4.04) between the populations from Lake Hui and each of the other two lakes, longer life expectancy at hatching (101.6-148.2 h), and higher net reproductive rate (4.4-16.4 offspring/female) and intrinsic rate of population increase (0.60-0.98/d) when cultured in aerated tap water and fly ash effluent. Sibling species II distributed in both Lake Tingtang and Lake Fengming, showing that its dispersal existed between the two lakes. Considering that the distance between Lake Hui and Lake Fengming is shorter than that between Lake Tingtang and Lake Fengming, sibling species II is able to disperse at least from Lake Fengming to Lake

  19. Scale-dependent factors affecting North American river otter distribution in the midwest

    Science.gov (United States)

    Jeffress, Mackenzie R.; Paukert, C.P.; Whittier, Joanna B.; Sandercock, B.K.; Gipson, P.S.

    2011-01-01

    The North American river otter (Lontra canadensis) is recovering from near extirpation throughout much of its range. Although reintroductions, trapping regulations and habitat improvements have led to the reestablishment of river otters in the Midwest, little is known about how their distribution is influenced by local- and landscape-scale habitat. We conducted river otter sign surveys from Jan. to Apr. in 2008 and 2009 in eastern Kansas to assess how local- and landscape-scale habitat factors affect river otter occupancy. We surveyed three to nine 400-m stretches of stream and reservoir shorelines for 110 sites and measured local-scale variables (e.g., stream order, land cover types) within a 100 m buffer of the survey site and landscape-scale variables (e.g., road density, land cover types) for Hydrological Unit Code 14 watersheds. We then used occupancy models that account for the probability of detection to estimate occupancy as a function of these covariates using Program PRESENCE. The best-fitting model indicated river otter occupancy increased with the proportion of woodland cover and decreased with the proportion of cropland and grassland cover at the local scale. Occupancy also increased with decreased shoreline diversity, waterbody density and stream density at the landscape scale. Occupancy was not affected by land cover or human disturbance at the landscape scale. Understanding the factors and scale important to river otter occurrence will be useful in identifying areas for management and continued restoration. ?? 2011, American Midland Naturalist.

  20. Evaluating How Circle of Willis Topology Affects Embolus Distribution in the Brain

    Science.gov (United States)

    Jani, Neel; Mukherjee, Debanjan; Shadden, Shawn

    2016-11-01

    Embolic stroke occurs when fragmented cellular or acellular material (emboli) travels to the brain to occlude an artery. Understanding the transport of emboli across unsteady, pulsatile flow in complex arterial geometries is challenging and influenced by a range of factors, including patient anatomy. The work herein develops the modeling and mechanistic understanding of how embolus transport is affected by the arterial connections at the base of the brain known as the Circle of Willis (CoW). A majority of the human population has an incomplete CoW anatomy, with connections either missing or ill-developed. We employ numerical simulations combining image-based modeling, computational fluid dynamics, discrete particle dynamics, and a sampling based analysis to compare collateral flow through the most prevalent CoW topologies, to determine embolus distribution fractions among vessels in the CoW, and to investigate the role of inertial effects in causing differences in flow and embolus distribution. The computational framework developed enables characterization of the complex interplay of anatomy, hemodynamics, and embolus properties in the context of embolic stroke as well as statistical analysis of embolism risks across common CoW variations.

  1. Factors affecting continued use of ceramic water purifiers distributed to Tsunami-affected Communities in Sri Lanka

    OpenAIRE

    Casanova, Lisa M.; Walters, Adam; Naghawatte, Ajith; Sobsey, Mark D.

    2012-01-01

    Objectives  There is little information about continued use of point-of-use technologies after disaster relief efforts. After the 2004 tsunami, the Red Cross distributed ceramic water filters in Sri Lanka. This study determined factors associated with filter disuse and evaluate the quality of household drinking water. Methods  A cross-sectional survey of water sources and treatment, filter use and household characteristics was administered by in-person oral interview, and household water qual...

  2. Different tree species affect soil respiration spatial distribution in a subtropical forest of southern Taiwan

    Science.gov (United States)

    Chiang, Po-Neng; Yu, Jui-Chu; Wang, Ya-nan; Lai, Yen-Jen

    2014-05-01

    Global forests contain 69% of total carbon stored in forest soil and litter. But the carbon storage ability and release rate of warming gases of forest soil also affect global climate change. Soil carbon cycling processes are paid much attention by ecological scientists and policy makers because of the possibility of carbon being stored in soil via land use management. Soil respiration contributed large part of terrestrial carbon flux, but the relationship of soil respiration and climate change was still obscurity. Most of soil respiration researches focus on template and tropical area, little was known that in subtropical area. Afforestation is one of solutions to mitigate CO2 increase and to sequestrate CO2 in tree and soil. Therefore, the objective of this study is to clarify the relationship of tree species and soil respiration distribution in subtropical broad-leaves plantation in southern Taiwan. The research site located on southern Taiwan was sugarcane farm before 2002. The sugarcane was removed and fourteen broadleaved tree species were planted in 2002-2005. Sixteen plots (250m*250m) were set on 1 km2 area, each plot contained 4 subplots (170m2). The forest biomass (i.e. tree height, DBH) understory biomass, litter, and soil C were measured and analyzed at 2011 to 2012. Soil respiration measurement was sampled in each subplot in each month. The soil belongs to Entisol with over 60% of sandstone. The soil pH is 5.5 with low base cations because of high sand percentage. Soil carbon storage showed significantly negative relationship with soil bulk density (p<0.001) in research site. The differences of distribution of live tree C pool among 16 plots were affected by growth characteristic of tree species. Data showed that the accumulation amount of litterfall was highest in December to February and lowest in June. Different tree species planted in 16 plots, resulting in high spatial variation of litterfall amount. It also affected total amount of litterfall

  3. Neutralization of schwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy.

    Directory of Open Access Journals (Sweden)

    Michela M Taiana

    Full Text Available The pathogenetic role of vascular endothelial growth factor (VEGF in long-term retinal and kidney complications of diabetes has been demonstrated. Conversely, little is known in diabetic neuropathy. We examined the modulation of VEGF pathway at mRNA and protein level on dorsal root ganglion (DRG neurons and Schwann cells (SC induced by hyperglycaemia. Moreover, we studied the effects of VEGF neutralization on hyperglycemic DRG neurons and streptozotocin-induced diabetic neuropathy. Our findings demonstrated that DRG neurons were not affected by the direct exposition to hyperglycaemia, whereas showed an impairment of neurite outgrowth ability when exposed to the medium of SC cultured in hyperglycaemia. This was mediated by an altered regulation of VEGF and FLT-1 receptors. Hyperglycaemia increased VEGF and FLT-1 mRNA without changing their intracellular protein levels in DRG neurons, decreased intracellular and secreted protein levels without changing mRNA level in SC, while reduced the expression of the soluble receptor sFLT-1 both in DRG neurons and SC. Bevacizumab, a molecule that inhibits VEGF activity preventing the interaction with its receptors, restored neurite outgrowth and normalized FLT-1 mRNA and protein levels in co-cultures. In diabetic rats, it both prevented and restored nerve conduction velocity and nociceptive thresholds. We demonstrated that hyperglycaemia early affected neurite outgrowth through the impairment of SC-derived VEGF/FLT-1 signaling and that the neutralization of SC-secreted VEGF was protective both in vitro and in vivo models of diabetic neuropathy.

  4. The VEGF signaling pathway in cancer: the road ahead

    Institute of Scientific and Technical Information of China (English)

    Steven A.Stacker; Marc G.Achen

    2013-01-01

    The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology.The members of the family,VEGF-A (also known as VEGF),VEGF-B,VEGF-C,VEGF-D,and placenta growth factor (PIGF),play important roles in vascular biology in both normal physiology and pathology.The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab,also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target.Other members of the VEGF family are now being targeted,and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic.Here,we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.

  5. Geohelminths distribution as affected by soil properties, physicochemical factors and climate in Sharkyia governorate Egypt.

    Science.gov (United States)

    Etewa, Samia E; Abdel-Rahman, Sara A; Abd El-Aal, Naglaa F; Fathy, Ghada M; El-Shafey, Mahmoud A; Ewis, A M G

    2016-06-01

    Soil-transmitted helminths are mainly a group of parasitic nematodes causing human infection through contact with parasite eggs or larvae; they survive in the warm and moist soil of the tropical and subtropical countries. This study was carried out in Sharkyia governorate from October, 2011 to October, 2013, to correlate between the prevalence and distribution of these parasites in the soil and the physicochemical factors affecting the examined samples of the soil. One hundred and twenty samples of different types of soil (clay, silt, sand) from different localities were collected and examined. Diagnosis of geohelminths was confirmed by the recovery of their eggs and larvae with other protozoa by different parasitological methods. The modified baermann method was found to be more efficient in detection of geohelminths larvae than charcoal culture method. Among the examined sites geohelminths were much more numerous in the soil of rural areas especially in the spring and summer seasons, while the contamination of canal banks by geohelminths was the worst (80 %). An insignificant correlation was reported between the soil texture and the number of positive samples in the examined areas while the relationship was directly proportional among (moisture, PH, organic). It appeared that the most common geohelminthic stage was Toxocara spp. eggs besides other types of protozoa especially Balantidium coli cysts. This suggests that factors other than soil texture are important in the prevalence of geohelminths in the soil e.g. temperature, moisture, PH and organic matter. So, to change some of these factors in a trial to control geoparasites transmission but with keeping the environment should be tried. These results also open the way to further studies to highlight the mutual affection between inhabitants of these sites and the prevalence of these geoparasites.

  6. Distribution of CO2 in Soil Air Affected by Vegetation in the Shilin National Park

    Institute of Scientific and Technical Information of China (English)

    宋林华; 梁福源

    2001-01-01

    This paper studies the CO2 distribution of soil atmosphere in the Shilin National Park. The measurement sites were chosen according to different topographic features and different vegetations. Seven measurement sites on 3 cross sections were chosen to pass through 3 karstic depressions or on the slopes of depressions. All measurement results show soils with pH values lower than 7.0 (from 5.4 to 6.6). There are 2 cases for the pH values of soil in different topographic features: the pH values of 2 profiles on the ridges or upper slopes of depressions are lower than those in the depressions;and the pH values of 2 soil profiles on the slopes of depressions are higher than those in the depressions. Most samples show relatively low humidity and CO2 contents on the ridges or slopes of depressions compared with soil profiles in the depressions. High CO2 contents occur at depths from -40 to -80 cm and high and dense grassland shows high CO2 contents in the soil atmosphere. Grass roots may grow and are distributed mainly at depths from -20 to -40 cm; while tree roots predominantly as deep as -60 cm even -80 cm. The influences of pine, cypress and eucalyptus on soil CO2 have been studied. Soil CO2 influenced by pine and cypress are generally concentrated in an area surrounding the tree with a diameter of 1 m and the strongly influenced distance is 50 cm. Eucalyptus will strongly affect the CO2 contents in an area with a diameter of 2 m, especially 1 m distant from the tree. The highest concentration of soil CO2 at a depth of-30 and 100 cm from the tree reaches 92000 ppm.``

  7. Factors Affecting the Spatial Distribution of Oviposition Sites for Tandem Black Saddlebags Dragonflies (Odonata: Libellulidae)

    Science.gov (United States)

    Thornton, Jessica L.; Switzer, Paul V.

    2015-01-01

    Oviposition site location may be affected by (1) factors influencing the costs and benefits to the offspring (e.g., resource availability, competition, predation risk) and (2) factors influencing the costs and benefits to the female (e.g., predation risk or mate harassment). In cases in which both the male and female are involved in locating a site, costs and benefits may differ for each parent and the resulting oviposition site location may represent the outcome of selection pressures on one or both of them. We studied oviposition behavior in the black saddlebags dragonfly (Tramea lacerata Hagen), a species in which the male and female typically remain together (i.e., in tandem) while traveling among potential oviposition locations. Oviposition sites tended to be away from pond shoreline at the outer edge of the vegetation on the water’s surface. We found that tandems distributed their oviposition locations widely around the pond, and interactions with other dragonflies (typically other T. lacerata, either territorial males or tandems) led to a larger distance between consecutive oviposition locations. Interestingly, for 10% of the tandems, the female became separated from the male and oviposited solitarily multiple times. These solitary females spent significantly less time and traveled significantly smaller distances between successive oviposition sites than when in tandem. Our results indicate that while some aspects of oviposition behavior and site selection may be consistent between the male and female (e.g., the characteristics that make a site suitable), other aspects, such as the distribution of sites, may be a result of a differing benefits and costs for the two sexes, perhaps as a consequence of potential sperm competition.

  8. A VEGF delivery system targeting MI improves angiogenesis and cardiac function based on the tropism of MSCs and layer-by-layer self-assembly.

    Science.gov (United States)

    Liu, Ge; Li, Li; Huo, Da; Li, Yanzhao; Wu, Yangxiao; Zeng, Lingqing; Cheng, Panke; Xing, Malcolm; Zeng, Wen; Zhu, Chuhong

    2017-05-01

    Myocardial infarction (MI) is a serious ischemic condition affecting many individuals around the world. Vascular endothelial growth factor (VEGF) is considered a promising factor for enhancing cardiac function by promoting angiogenesis. However, the lack of a suitable method of VEGF delivery to the MI area is a serious challenge. In this study, we screened a suitable delivery carrier with favorable biocompatibility that targeted the MI area using the strategy of an inherent structure derived from the body and that was based on characteristics of the MI. Mesenchymal stem cells (MSCs) are important infiltrating cells that are derived from blood and have an inherent tropism for the MI zone. We hypothesized that VEGF-encapsulated MSCs targeting MI tissue could improve cardiac function by angiogenesis based on the tropism of the MSCs to the MI area. We first developed VEGF-encapsulated MSCs using self-assembled gelatin and alginate polyelectrolytes to improve angiogenesis and cardiac function. In vitro, the results showed that VEGF-encapsulated MSCs had a sustained release of VEGF and tropism to SDF-1. In vivo, VEGF-encapsulated MSCs migrated to the MI area, enhanced cardiac function, perfused the infarcted area and promoted angiogenesis. These preclinical findings suggest that VEGF-loaded layer-by-layer self-assembled encapsulated MSCs may be a promising and minimally invasive therapy for treating MI. Furthermore, other drugs loaded to layer-by-layer self-assembled encapsulated MSCs may be promising therapies for treating other diseases.

  9. Anti-VEGF therapy in the management of retinopathy of prematurity: what we learn from representative animal models of oxygen-induced retinopathy

    Directory of Open Access Journals (Sweden)

    Wang H

    2016-05-01

    Full Text Available Haibo Wang Department of Ophthalmology, John A Moran Eye Center, The University of Utah, Salt Lake City, UT, USA Abstract: Retinopathy of prematurity (ROP remains a leading cause of childhood blindness, affecting infants born prematurely. ROP is characterized by the onset of delayed physiological retinal vascular development (PRVD and followed by pathologic neovascularization into the vitreous instead of the retina, called intravitreal neovascularization (IVNV. Therefore, the therapeutic strategy for treating ROP is to promote PRVD and inhibit or prevent IVNV. Vascular endothelial growth factor (VEGF plays an important role in the pathogenesis of ROP. There is a growing body of studies testing the use of anti-VEGF agents as a treatment for ROP. Intravitreal anti-VEGF treatment for ROP has potential advantages compared with laser photocoagulation, the gold standard for the treatment of severe ROP; however, intravitreal anti-VEGF treatment has been associated with reactivation of ROP and suppression of systemic VEGF that may affect body growth and organ development in preterm infants. Therefore, it is important to understand the role of VEGF in PRVD and IVNV. This review includes the current knowledge of anti-VEGF treatment for ROP from animal models of oxygen-induced retinopathy (OIR, highlighting the importance of VEGF inhibition by targeting retinal Müller cells, which inhibits IVNV and permits PRVD. The signaling events involved in mediating VEGF expression and promoting VEGF-mediated angiogenesis, including hypoxia-dependent signaling, erythropoietin/erythropoietin receptor-, oxidative stress-, beta-adrenergic receptor-, integrin-, Notch/Delta-like ligand 4- and exon guidance molecules-mediated signaling pathways, are also discussed. Keywords: vascular endothelial growth factor, retinopathy of prematurity, intravitreal neovascularization, oxygen-induced retinopathy model, physiological retinal vascular development

  10. Diversity of riceland mosquitoes and factors affecting their occurrence and distribution in Mwea, Kenya.

    Science.gov (United States)

    Muturi, Ephantus J; Shililu, Josephat I; Jacob, Benjamin G; Mwangangi, Joseph M; Mbogo, Charles M; Githure, John I; Novak, Robert J

    2008-09-01

    Knowledge of mosquito species diversity, occurrence, and distribution is an essential component of vector ecology and a guiding principle to formulation and implementation of integrated vector management programs. A 12-month entomological survey was conducted to determine the diversity of riceland mosquitoes and factors affecting their occurrence and distribution at 3 sites targeted for malaria vector control in Mwea, Kenya. Adult mosquitoes were sampled indoors by pyrethrum spray catch and outdoors by the Centers for Disease Control and Prevention light traps. Mosquitoes were then morphologically identified to species using taxonomic keys. The characteristics of houses sampled for indoor resting mosquitoes, including number of people sleeping in each house the night preceding collection, presence of bed nets, location of the house, size of eaves, wall type, presence of cattle and distance of the house to the cowshed, and proximity to larval habitats, were recorded. Of the 191,378 mosquitoes collected, 95% were identified morphologically to species and comprised 25 species from 5 genera. Common species included Anopheles arabiensis (53.5%), Culex quinquefasciatus (35.5%), An. pharoensis (4.7%), An. coustani (2.5%), and An. funestus (1.6%). Shannon's species diversity and evenness indices did not differ significantly among the 3 study sites. There was a marked house-to-house variation in the average number of mosquitoes captured. The number of people sleeping in the house the night preceding collection, size of eaves, distance to the cowshed, and the nearest larval habitat were significant predictors of occurrence of either or both An. arabiensis and Cx. quinquefasciatus. The peak abundance of An. arabiensis coincided with land preparation and the first few weeks after transplanting of rice seedlings, and that of Cx. quinquefasciatus coincided with land preparation, late stage of rice development, and short rains. After transplanting of rice seedlings, the

  11. An increase in vascular endothelial growth factor (VEGF and VEGF soluble receptor-1 (sFlt-1 are associated with early recurrent spontaneous abortion.

    Directory of Open Access Journals (Sweden)

    Lihong Pang

    Full Text Available Recurrent spontaneous abortion (RSA is a health problem that affects approximately 1% to 5% reproductive age woman. Yet, in around half of these patients, the mechanism for RSA is unexplained. Recent studies have indicated that placental ischemia/hypoxia and endothelial dysfunction are important factors in miscarriage. Other studies have indicated that the level and expression of soluble FMS-like tyrosine kinase-1 (sFlt1 is increased under a hypoxic environment. However, decreased sFlt-1 in the maternal circulation during the first trimester has recently been proposed as a potential marker for identifying risk of pregnancy loss. In this prospective study clinical samples were obtained within a short time after the fetal death, protein expression and maternal serum levels of sFlt1 were assessed and compared to samples taken from those with normal pregnancies. Our results indicate that levels of VEGF and sFlt-1 are both increased in women during early pregnancy compared women that are not pregnant (p<0.05 indicating that VEGF and sFlt-1 are both associated with pregnancy. More importantly, we detected a significant (p<0.05 increase in sFlt1 and VEGF levels and expression in the RSA patients who suffered subsequent miscarriages compare to controls. These results demonstrate that there is likely a relationship between VEGF, sFlt-1 and RSA suggesting that the high levels and over expression of sFlt-1 and VEGF might be associated with the pathogenesis of RSA.

  12. Environmental factors affecting the distribution of Chironomid larvae of the Seybouse wadi, North-Eastern Algeria

    Directory of Open Access Journals (Sweden)

    Nadjla Chaib

    2013-03-01

    Full Text Available A survey of the Seybouse wadi (North-Eastern Algeria between 2008 and 2011 was conducted in 26 sampling sites located on the main river and its tributaries using chironomids. From 3264 collected larvae, forty-five chironomid species were identified, and were correlated to 13 environmental variables to predict determinant factors affecting their distribution. Indicator value (IndVal analysis was first performed to determine indicator chironomid species according to several factors (sites, seasons, source distance, granulometry, conductivity, water temperature, dissolved oxygen, water velocity, pollution and the abundance of filamentous algae. Co-inertia analysis (CoIA supported the IndVal results, emphasising an upstream/downstream gradient in the first axis, while a granulometry gradient was emphasised by the second axis. A pollution gradient was also highlighted in the plane of the first two axes, separating tolerant Chironomus sp. 1, Cricotopus bicinctus and Cricotopus (Isocladius sylvestris from intolerant species as Phaenopsectra flavipes, Rheotanytarsus sp.1 and Cladotanytarsus sp. 1.

  13. Particle size distribution of rice flour affecting the starch enzymatic hydrolysis and hydration properties.

    Science.gov (United States)

    de la Hera, Esther; Gomez, Manuel; Rosell, Cristina M

    2013-10-15

    Rice flour is becoming very attractive as raw material, but there is lack of information about the influence of particle size on its functional properties and starch digestibility. This study evaluates the degree of dependence of the rice flour functional properties, mainly derived from starch behavior, with the particle size distribution. Hydration properties of flours and gels and starch enzymatic hydrolysis of individual fractions were assessed. Particle size heterogeneity on rice flour significantly affected functional properties and starch features, at room temperature and also after gelatinization; and the extent of that effect was grain type dependent. Particle size heterogeneity on rice flour induces different pattern in starch enzymatic hydrolysis, with the long grain having slower hydrolysis as indicated the rate constant (k). No correlation between starch digestibility and hydration properties or the protein content was observed. It seems that in intact granules interactions with other grain components must be taken into account. Overall, particle size fractionation of rice flour might be advisable for selecting specific physico-chemical properties.

  14. Distribution of abnormal prion protein in a sheep affected with L-type bovine spongiform encephalopathy.

    Science.gov (United States)

    Matsuura, Y; Iwamaru, Y; Masujin, K; Imamura, M; Mohri, S; Yokoyama, T; Okada, H

    2013-07-01

    To investigate the topographical distribution and patterns of deposition of immunolabelled abnormal prion protein (PrP(Sc)), interspecies transmission of atypical L-type bovine spongiform encephalopathy (BSE) to Cheviot ewes (ARQ/ARQ genotype) was performed. L-type BSE was successfully transmitted via the intracerebral route to a ewe, with an incubation period of 1,562 days. Minimal vacuolar change was detected in the basal ganglia, thalamus and brainstem, and PrP(Sc) accumulated throughout the brain. The L-type BSE-affected sheep was characterized by conspicuous fine particulate deposits in the neuropil, particulate and/or granular intraneuronal and intraglial deposits, and the absence of PrP(Sc) plaques or stellate deposits. In addition, immunohistochemical and western blot analyses revealed that PrP(Sc) accumulation was present in peripheral nervous tissues (including the trigeminal ganglia and dorsal root ganglion) and adrenal glands, but was absent in lymphoid tissues. These results suggest that L-type BSE has distinct and distinguishable characteristics as well as PrP(Sc) tissue tropism in sheep.

  15. Effects of BMP2 and VEGF165 on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Lin, Zhaowei; Wang, Jiang-Sheng; Lin, Lijun; Zhang, Jingwen; Liu, Yunlong; Shuai, Ming; Li, Qi

    2014-03-01

    Bone marrow-derived mesenchymal stem cells (MSCs) are dominant seed cell sources for bone regeneration. Bone morphogenetic proteins (BMPs) initiate cartilage and bone formation in a sequential cascade. Vascular endothelial growth factor (VEGF) is an essential coordinator of extracellular matrix remodeling, angiogenesis and bone formation. In the present study, the effects of the vascular endothelial growth factor 165 (VEGF165) and bone morphogenetic protein 2 (BMP2) genes on bone regeneration were investigated by the lentivirus-mediated cotransfection of the two genes into rat bone marrow-derived MSCs. The successful co-expression of the two genes in the MSCs was confirmed using quantitative polymerase chain reaction (qPCR) and western blot analysis. The results of alizarin red and alkaline phosphatase (ALP) staining at 14 days subsequent to transfection showed that the area of staining in cells transfected with BMP2 alone was higher than that in cells transfected with BMP2 and VEGF165 or untransfected control cells, while the BMP2 + VEGF165 group showed significantly more staining than the untransfected control. This indicated that BMP2 alone exhibited a stronger effect in bone regeneration than BMP2 in combination with VEGF165. Similarly, in inducing culture medium, the ALP activity of the BMP2 + VEGF165 group was notably suppressed compared with that of the BMP2 group. The overexpression of VEGF165 inhibited BMP2-induced MSC differentiation and osteogenesis in vitro. Whether or not local VEGF gene therapy is likely to affect bone regeneration in vivo requires further investigation.

  16. Local controlled release of VEGF and PDGF from a combined brushite-chitosan system enhances bone regeneration.

    Science.gov (United States)

    De la Riva, Beatriz; Sánchez, Esther; Hernández, Antonio; Reyes, Ricardo; Tamimi, Faleh; López-Cabarcos, Enrique; Delgado, Araceli; Evora, Carmen

    2010-04-02

    The two growth factors VEGF and PDGF are involved in the process of bone regeneration. For this reason, we developed a brushite-chitosan system which controls the release kinetics of incorporated VEGF and PDGF to enhance bone healing. PDGF (250 ng) was incorporated in the liquid phase. Alginate microsphere-encapsulated VEGF (350 ng) was pre-included in small cylindrical chitosan sponges. VEGF and PDGF release kinetics and tissue distribution were determined using iodinated ((125)I) growth factor. In vivo, PDGF was more rapidly delivered from these systems implanted in rabbit femurs than VEGF. 80% of PDGF was released by the end of two weeks while only 70% of VEGF was delivered after a period of three weeks. Both GFs released from the brushite-chitosan constructs remained located around the implantation site (5 cm) with negligible systemic exposure. A PDGF bone peak concentration of approximately 5 ng/g was achieved on the 4th day. Thereafter, PDGF concentrations stayed higher than 2 ng/g during the first week. These scaffolds also provided a local VEGF bone concentration above 3 ng/g during a total of 4weeks, with a peak concentration of 5.5 ng/g on the 7th day. The present work demonstrates that our brushite-chitosan system is capable of controlling the release rate and localization of both GFs within a bone defect. The effect on bone formation was considerably enhanced with PDGF loaded brushite-chitosan scaffolds as well as with the PDGF/VEGF combination.

  17. COX-2, VEGF and tumour angiogenesis.

    LENUS (Irish Health Repository)

    Toomey, D P

    2009-06-01

    Epidemiological evidence suggests a protective effective of regular NSAID use against developing cancer. Cyclooxygenase-2, a target of NSAIDs, is upregulated in many cancers and has been associated with increased VEGF production and angiogenesis. Angiogenesis is the formation of new vessels from existing vasculature and as an essential process for tumour development represents an important therapeutic target. Following an extensive review of the literature this article details the current knowledge on the role of COX-2 in tumorigenesis focusing on its relationship to angiogenesis and VEGF production by tumour cells. While COX-2 is clearly detrimental to prognosis and NSAIDs have a beneficial effect, the possibility of COX-2 independent effects being partly or wholly responsible for this benefit cannot be excluded.

  18. Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma.

    Science.gov (United States)

    Pritchard-Jones, R O; Dunn, D B A; Qiu, Y; Varey, A H R; Orlando, A; Rigby, H; Harper, S J; Bates, D O

    2007-07-16

    Malignant melanoma is the most lethal of the skin cancers and the UK incidence is rising faster than that of any other cancer. Angiogenesis - the growth of new vessels from preexisting vasculature - is an absolute requirement for tumour survival and progression beyond a few hundred microns in diameter. We previously described a class of anti-angiogenic isoforms of VEGF, VEGF(xxx)b, that inhibit tumour growth in animal models, and are downregulated in some cancers, but have not been investigated in melanoma. To determine whether VEGF(xxx)b expression was altered in melanoma, PCR and immunohistochemistry of archived human tumour samples were used. In normal epidermis and in a proportion of melanoma samples, VEGF(xxx)b staining was seen. Some melanomas had much weaker staining. Subsequent examination revealed that expression was significantly reduced in primary melanoma samples (both horizontal and vertical growth phases) from patients who subsequently developed tumour metastasis compared with those who did not (analysis of variance (ANOVA) Pxxx)b expression appears to predict metastatic spread in patients with primary melanoma. These results suggest that there is a switch in splicing as part of the metastatic process, from anti-angiogenic to pro-angiogenic VEGF isoforms. This may form part of a wider metastatic splicing phenotype.

  19. Lung perfusion and emphysema distribution affect the outcome of endobronchial valve therapy

    Directory of Open Access Journals (Sweden)

    Thomsen C

    2016-06-01

    Full Text Available Christian Thomsen,1 Dorothea Theilig,2 Dominik Herzog,1 Alexander Poellinger,2 Felix Doellinger,2 Nils Schreiter,3 Vera Schreiter,2 Dirk Schürmann,1 Bettina Temmesfeld-Wollbrueck,1 Stefan Hippenstiel,1 Norbert Suttorp,1 Ralf-Harto Hubner1 1Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, 2Institute of Radiology, 3Institute of Nuclear Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany Abstract: The exclusion of collateral ventilation (CV and other factors affect the clinical success of endoscopic lung volume reduction (ELVR. However, despite its benefits, the outcome of ELVR remains difficult to predict. We investigated whether clinical success could be predicted by emphysema distribution assessed by computed tomography scan and baseline perfusion assessed by perfusion scintigraphy. Data from 57 patients with no CV in the target lobe (TL were retrospectively analyzed after ELVR with valves. Pulmonary function tests (PFT, St George’s Respiratory Questionnaire (SGRQ, and 6-minute walk tests (6MWT were performed on patients at baseline. The sample was grouped into high and low levels at the median of TL perfusion, ipsilateral nontarget lobe (INL perfusion, and heterogeneity index (HI. These groups were analyzed for association with changes in outcome parameters from baseline to 3 months follow-up. Compared to baseline, patients showed significant improvements in PFT, SGRQ, and 6MWT (all P≤0.001. TL perfusion was not associated with changes in the outcome. High INL perfusion was significantly associated with increases in 6MWT (P=0.014, and high HI was associated with increases in forced expiratory volume in 1 second (FEV1, (P=0.012. Likewise, there were significant correlations for INL perfusion and improvement of 6MWT (r=0.35, P=0.03 and for HI and improvement in FEV1 (r=0.45, P=0.001. This study reveals new attributes that associate with positive outcomes for patient selection prior to ELVR

  20. Analysis of geological structure and anthropological factors affecting arsenic distribution in the Lahore aquifer, Pakistan

    Science.gov (United States)

    Muhammad, Akhtar Malik; Zhonghua, Tang; Sissou, Zakari; Mohamadi, Bahaa; Ehsan, Muhsan

    2016-11-01

    This study investigated the potential factors affecting arsenic concentration in the groundwater system of Lahore, Pakistan. The effects of several factors such as population density (PD), pumping rate (PR), impermeable land use (LU), surface elevation (SE), and water-table elevation (WL) on arsenic concentration were studied in 101 union councils of Lahore. Forty single and multi-factor models were established using geographic information system (GIS) techniques to develop an arsenic contamination map and to investigate the most effective combinations among factors. Additionally, statistical tests were used to evaluate arsenic concentration between classes of the same single factor. The arsenic concentration in the Lahore aquifer varied from 0.001 to 0.143 mg L-1. The highest arsenic concentrations were detected in the Walled City and the town of Shahdara. Among the 40 raster models, groundwater arsenic concentration showed the best matching frequency with single-factor models for PD (50.70 %) and SE (47 %). Thus, PD and SE were used to develop an arsenic distribution raster map, and they were also used to study the effect of aquifer depth on arsenic concentration. PD was found to have hidden latent variables such as PR and LU. The shallow aquifer depth was negatively correlated with arsenic concentration ( r = -0.23) and positively with PR ( r = 0.15). Therefore, when there was high PR in wells with smaller aquifer depth, the arsenic concentration was high. The existing water treatment and alternative water resources are good options, which should be developed to deal with Lahore wells contaminated with arsenic at high concentrations.

  1. Expression of VEGF, b-FGF, and their receptors after injection of VEGF on ischemic heart muscle

    Institute of Scientific and Technical Information of China (English)

    XU Xun-yu; SUN Lin; HAN Tao; CHEN Wen-hong; CUI Yong; LI Yan

    2004-01-01

    Objective: To study the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) and their receptors after injection of external VEGF on ischemic heart muscle and to investigate the mechanism of therapeutic myocardial angiogenesis of VEGF. Methods: Standard experimental pigs underwent placement of a left circumflex artery ameroid occluder. Six weeks later, the animals in the experimental group were treated with VEGF (20μg) by direct epicardial injection ( n = 8) and other animals in the control group did not receive any treatment ( n = 8).Four weeks after therapy, the animals were evaluated with regard to mRNA and protein expression of VEGF and b-FGF and their receptors by RT-PCR and Western blotting. Results: The mRNA expression of VEGF and b-FGF and their receptors by RT-PCR expressing as percentage of density ratio to the GAPDH control was increased in experimental group versus control group. The protein expression of VEGF and b-FGF and their receptors by Western blot expressing as percentage of density ratio to the Commassie Blue control was increased in experimental group versus control Group. Conclusion: Exogenous VEGF can induce the expression of endogenous VEGF, b-FGF, and their receptors; b-FGF may play a role in the angiogenesis of VEGF.

  2. VEGF Deficit is Involved in Endothelium Dysfunction in Preeclampsia

    Institute of Scientific and Technical Information of China (English)

    周琼; 刘海意; 乔福元; 吴媛媛; 徐京晶

    2010-01-01

    This study examined the association of expression of vascular endothelial growth factor(VEGF),a promoter of angiogenesis,with endothelium dysfunction in preeclampsia.The level of VEGF protein and mRNA in the placenta and peripheral blood samples of 30 preeclampsia patients and 30 normotensive pregnant women was measured by immunohistochemistry,real-time reverse transcriptase-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA),respectively.VEGF expression in the human umbilical vei...

  3. Anti-VEGF Cancer Therapy in Nephrology Practice

    Directory of Open Access Journals (Sweden)

    Hassan Izzedine

    2014-01-01

    Full Text Available Expanded clinical experience with the antivascular endothelial growth factor (VEGF agents has come with increasing recognition of their renal adverse effects. Although renal histology is rarely sought in antiangiogenic-treated cancer patients, kidney damage related to anti-VEGF is now established. Its manifestations include hypertension, proteinuria, and mainly glomerular thrombotic microangiopathy. Then, in nephrology practice, should we continue to perform kidney biopsy, and what should be done with the anti-VEGF agents in case of renal toxicity?

  4. Does vertebroplasty affect radiation dose distribution?: comparison of spatial dose distributions in a cement-injected vertebra as calculated by treatment planning system and actual spatial dose distribution.

    Science.gov (United States)

    Komemushi, Atsushi; Tanigawa, Noboru; Kariya, Shuji; Yagi, Rie; Nakatani, Miyuki; Suzuki, Satoshi; Sano, Akira; Ikeda, Koshi; Utsunomiya, Keita; Harima, Yoko; Sawada, Satoshi

    2012-01-01

    Purpose. To assess differences in dose distribution of a vertebral body injected with bone cement as calculated by radiation treatment planning system (RTPS) and actual dose distribution. Methods. We prepared two water-equivalent phantoms with cement, and the other two phantoms without cement. The bulk density of the bone cement was imported into RTPS to reduce error from high CT values. A dose distribution map for the phantoms with and without cement was calculated using RTPS with clinical setting and with the bulk density importing. Actual dose distribution was measured by the film density. Dose distribution as calculated by RTPS was compared to the dose distribution measured by the film dosimetry. Results. For the phantom with cement, dose distribution was distorted for the areas corresponding to inside the cement and on the ventral side of the cement. However, dose distribution based on film dosimetry was undistorted behind the cement and dose increases were seen inside cement and around the cement. With the equivalent phantom with bone cement, differences were seen between dose distribution calculated by RTPS and that measured by the film dosimetry. Conclusion. The dose distribution of an area containing bone cement calculated using RTPS differs from actual dose distribution.

  5. Genetic variations in VEGF and VEGFR2 and glioblastoma outcome

    DEFF Research Database (Denmark)

    Sjöström, S; Wibom, C; Andersson, U

    2010-01-01

    Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases...... collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs...

  6. Genetic variations in VEGF and VEGFR2 and glioblastoma outcome

    DEFF Research Database (Denmark)

    Sjöström, S; Wibom, C; Andersson, U

    2011-01-01

    Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) are central components in the development and progression of glioblastoma. To investigate if genetic variation in VEGF and VEGFR2 is associated with glioblastoma prognosis, we examined blood samples from 154 glioblastoma cases...... collected in Sweden and Denmark between 2000 and 2004. Seventeen tagging single nucleotide polymorphisms (SNPs) in VEGF and 27 in VEGFR2 were genotyped and analysed, covering 90% of the genetic variability within the genes. In VEGF, we found no SNPs associated with survival. In VEGFR2, we found two SNPs...

  7. Hypoxia promotes adipose-derived stem cell proliferation via VEGF

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2016-01-01

    Full Text Available Adipose-derived stem cells (ADSCs are a promising mesenchymal stem cell source with therapeutic applications. Recent studies have shown that ADSCs could be expanded in vitro without phenotype changes. This study aimed to evaluate the effect of hypoxia on ADSC proliferation in vitro and to determine the role of vascular endothelial growth factor (VEGF in ADSC proliferation. ADSCs were selectively cultured from the stromal vascular fraction obtained from adipose tissue in DMEM/F12 medium supplemented with 10% fetal bovine serum and 1% antibiotic-antimycotic. ADSCs were cultured under two conditions: hypoxia (5% O2 and normal oxygen (21% O2. The effects of the oxygen concentration on cell proliferation were examined by cell cycle and doubling time. The expression of VEGF was evaluated by the ELISA assay. The role of VEGF in ADSC proliferation was studied by neutralizing VEGF with anti-VEGF monoclonal antibodies. We found that the ADSC proliferation rate was significantly higher under hypoxia compared with normoxia. In hypoxia, ADSCs also triggered VEGF expression. However, neutralizing VEGF with anti-VEGF monoclonal antibodies significantly reduced the proliferation rate. These results suggest that hypoxia stimulated ADSC proliferation in association with VEGF production. [Biomed Res Ther 2016; 3(1.000: 476-482

  8. [VEGF gene expression in transfected human multipotent stromal cells].

    Science.gov (United States)

    Smirnikhina, S A; Lavrov, A V; Bochkov, N P

    2011-01-01

    Dynamics of VEGF gene expression in transfected multipotent stromal cells from adipose tissue was examined using electroporation and lipofection. Differences in the potency and dynamics of plasmid elimination (up to day 9) between cell cultures were observed. All cultures were divided into fast and slow plasmid-eliminating ones. Interculture differences in VEGF expression were detected. The possibility of a 5-6-fold increase of VEGF expression was shown. There were no differences in transfection potency, plasmid elimination dynamics, and VEGF expression after transfection by both nonviral methods.

  9. Distribution and abundance of predators that affect duck production--prairie pothole region

    Science.gov (United States)

    Sargeant, A.B.; Greenwood, R.J.; Sovada, M.A.; Shaffer, T.L.

    1993-01-01

    During 1983-88, the relative abundance of 18 species and species-groups of mammalian and avian predators affecting duck production in the prairie pothole region was determined in 33 widely scattered study areas ranging in size from 23-26 km2. Accounts of each studied species and species-group include habitat and history, population structure and reported densities, and information on distribution and abundance from the present study. Index values of undetected, scarce, uncommon, common, or numerous were used to rate abundance of nearly all species in each study area. Principal survey methods were livetrapping of striped skunks (Mephitis mephitis) and Franklin's ground squirrels (Spermophilus franklinii), systematic searches for carnivore tracks in quarter sections (0.65 km2), daily records of sightings of individual predator species, and systematic searches for occupied nests of tree-nesting avian predators. Abundances of predators in individual areas were studied 1-3 years.The distribution and abundance of predator species throughout the prairie pothole region have undergone continual change since settlement of the region by Europeans in the late 1800's. Predator populations in areas we studied differed markedly from those of pristine times. The changes occurred from habitat alterations, human-inflicted mortality of predators, and interspecific relations among predator species. Indices from surveys of tracks revealed a decline in the abundance of red foxes (Vulpes vulpes) and an albeit less consistent decline in the abundance of raccoons (Procyon lotor) with an increase in the abundance of coyotes (Canis latrans). Records of locations of occupied nests revealed great horned owls (Bubo virginianus) and red-tailed hawks (Buteo jamaicensis) tended to nest 0.5 km apart, and American crows (Corvus brachyrhynchos) tended to avoid nesting 0.5 km of nests of red-tailed hawks. Excluding large gulls, for which no measurements of abundance were obtained, the number of

  10. Factors affecting the occurrence and distribution of entomopathogenic fungi in natural and cultivated soils.

    Science.gov (United States)

    Quesada-Moraga, Enrique; Navas-Cortés, Juan A; Maranhao, Elizabeth A A; Ortiz-Urquiza, Almudena; Santiago-Alvarez, Cándido

    2007-08-01

    Factors affecting the occurrence and distribution of entomopathogenic fungi in 244 soil samples collected from natural and cultivated areas in Spain were studied using an integrated approach based on univariate and multivariate analyses. Entomopathogenic fungi were isolated from 175 of the 244 (71.7%) soil samples, with only two species found, Beauveria bassiana and Metarhizium anisopliae. Of the 244 soil samples, 104 yielded B. bassiana (42.6%), 18 yielded M. anisopliae (7.3%), and 53 soil samples (21.7%) harboured both fungi. Log-linear models indicated no significant effect of habitat on the occurrence of B. bassiana, but a strong association between M. anisopliae and soils from cultivated habitats, particularly field crops. Also, irrespective of habitat type, B. bassiana predominated over M. anisopliae in soils with a higher clay content, higher pH, and lower organic matter content. Logistic regression analyses showed that pH and clay content were predictive variables for the occurrence of B. bassiana, whereas organic matter content was the predictive variable for M. anisopliae. Also, latitude and longitude predicted the occurrence of these same species, but in opposite directions. Altitude was found to be predictive for the occurrence of B. bassiana. Using principal component analysis, four factors (1 to 4) accounted for 86% of the total variance; 32.8, 22.9, 19.6 and 10.4% of the cumulative variance explained, respectively. Factor 1 was associated with high positive weights for soil clay and silt content and high negative weights for soil sand content. Factor 2 was associated with high positive weights for soil organic matter content and high negative weights for soil pH. Factor 3 was associated with high positive weights for latitude and longitude of the sampled localities and factor 4, had high positive weights only for the altitude. Bi-plot displays representing soil samples were developed for different factor combinations and indicated that, irrespective

  11. Determination of vascular endothelial growth factor (VEGF) in circulating blood: significance of VEGF in various leucocytes and platelets

    DEFF Research Database (Denmark)

    Werther, K; Christensen, Ib Jarle; Nielsen, Hans Jørgen

    2002-01-01

    . In corresponding blood samples, automated complete blood count was performed, and the number of each cell type was correlated to VEGF concentrations in plasma, serum and lysed whole blood. Finally, the impact of increasing clotting time on the release of VEGF to serum was analysed. RESULTS: Isolated neutrophils......AIM: The sources of increased vascular endothelial growth factor (VEGF) concentrations in peripheral blood from cancer patients are not known in detail. The aim of the present study was to evaluate correlations between the VEGF content in isolated leucocyte subpopulations and VEGF concentrations...... in plasma, serum and lysed whole blood. METHODS: In 51 colorectal cancer (CRC) patients, circulating T-lymphocytes, B-lymphocytes, monocytes, and granulocytes were isolated by means of immunomagnetic separation. Subsequently, the isolated cells were lysed and VEGF contents in the lysates were determined...

  12. Morphology, chemistry and distribution of neoformed spherulites in agricultural land affected by metallurgical point-source pollution

    NARCIS (Netherlands)

    Leguedois, S.; Oort, van F.; Jongmans, A.G.; Chevalier, P.

    2004-01-01

    Metal distribution patterns in superficial soil horizons of agricultural land affected by metallurgical point-source pollution were studied using optical and electron microscopy, synchrotron radiation and spectroscopy analyses. The site is located in northern France, at the center of a former entry

  13. A Maximum-Entropy Compound Distribution Model for Extreme Wave Heights of Typhoon-Affected Sea Areas

    Institute of Scientific and Technical Information of China (English)

    WANG Li-ping; SUN Xiao-guang; LU Ke-bo; XU De-lun

    2012-01-01

    A new compound distribution model for extreme wave heights of typhoon-affected sea areas is proposed on the basis of the maximum-entropy principle.The new model is formed by nesting a discrete distribution in a continuous one,having eight parameters which can be determined in terms of observed data of typhoon occurrence-frequency and extreme wave heights by numerically solving two sets of equations derived in this paper.The model is examined by using it to predict the N-year return-periodwave height at two hydrology stations in the Yellow Sea,and the predicted results are compared with those predicted by use of some other compound distribution models.Examinations and comparisons show that the model has some advantages for predicting the N-year return-period wave height in typhoon-affected sea areas.

  14. The endogenous anti-angiogenic VEGF isoform, VEGF165b inhibits human tumour growth in mice.

    NARCIS (Netherlands)

    Rennel, E.; Waine, E.; Guan, H.; Schuler, Y.; Leenders, W.P.J.; Woolard, J.; Sugiono, M.; Gillatt, D.; Kleinerman, E.; Bates, D.; Harper, S.

    2008-01-01

    Vascular endothelial growth factor-A is widely regarded as the principal stimulator of angiogenesis required for tumour growth. VEGF is generated as multiple isoforms of two families, the pro-angiogenic family generated by proximal splice site selection in the terminal exon, termed VEGFxxx, and the

  15. Expression of Vascular Endothelial Growth Factor (VEGF) in Human Osteosarcoma Cells Transfected with Adeno-associated Virus-antisense VEGF

    Institute of Scientific and Technical Information of China (English)

    徐卫国; 陈安民; 张衣北; 易成腊

    2004-01-01

    Summary: The expression of protein vascular endothelial growth factor (VEGF) in osteosarcoma cells transfected with adeno-associated virus (rAAV)-antisense VEGF was studied to provide the foundation of osteosarcoma treatment through antivascularization. The rAAV-antisense VEGF at different doses (0, 20, 50, 100, 200, 240 μl) was transfected into osteosarcoma MG-63 cell. The cells and culture supernatants were collected before and after tansfection. The expression of VEGF protein was detected by using immunohistochemical staining (SP) and Western blot. SP and Western-blot tests revealed that the MG-63 Cells transfected with rAAV-antisense VEGF had less staining than those without transfection with rAAV-antisense VEGF, and the staining intensity was negatively correlated with the doses of genes. The corresponding A values of transfected genes with different doses of rAAV-antisense VEGF (0, 20, 50, 100, 200, 240 μA) were 86 614±13 776, 73 245±15 414, 61 078±12 124, 54 657±10 953, 39 802±11 308, 32 014±15 057 respectively,w ith the difference being significant (P<0.05). It was concluded that the expression of VEGF protein in MG-63 cells could be inhibited by rAAV-antisense VEGF.

  16. VEGF and colon cancer growth beyond angiogenesis: does VEGF directly mediate colon cancer growth via a non-angiogenic mechanism?

    Science.gov (United States)

    Ahluwalia, Amrita; Jones, Michael K; Matysiak-Budnik, Tamara; Tarnawski, Andrzej S

    2014-01-01

    In this article we review the role of vascular endothelial growth factor (VEGF) in colon cancer growth and the underlying mechanisms. Angiogenesis, the growth of new capillary blood vessels in the body, is critical for tissue injury healing and cancer growth. In 1971, Judah Folkman proposed the concept that tumor growth beyond 2 mm is critically dependent on angiogenesis. Tumors including colon cancers release angiogenic growth factors that stimulate blood vessels to grow into the tumors thus providing oxygen and nutrients that enable exponential growth. VEGF is the most potent angiogenic growth factor. Several studies have highlighted the role of VEGF in colon cancer, specifically in the stimulation of angiogenesis. This role of VEGF is strongly supported by studies showing that inhibition of VEGF using the blocking antibody, bevacizumab, results in decreased angiogenesis and abrogation of cancer growth. In the United States, bevacizumab in combination with chemotherapy is FDA approved for the treatment of metastatic colon cancer. However, the source of VEGF in colon cancer tissue, the mechanisms of VEGF generation in colon cancer cells and the molecular pathways involved in VEGF mediated angiogenesis in colon cancer are not fully known. The possibility that VEGF directly stimulates cancer cell growth in an autocrine manner has not been explored in depth.

  17. Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF isoforms provide remarkable anti-angiogenesis effect in vivo.

    Directory of Open Access Journals (Sweden)

    Qin Wang

    Full Text Available VEGF family factors are known to be the principal stimulators of abnormal angiogenesis, which play a fundamental role in tumor and various ocular diseases. Inhibition of VEGF is widely applied in antiangiogenic therapy. Conbercept is a novel decoy receptor protein constructed by fusing VEGF receptor 1 and VEGF receptor 2 extracellular domains with the Fc region of human immunoglobulin. In this study, we systematically evaluated the binding affinity of conbercept with VEGF isoforms and PlGF by using anti-VEGF antibody (Avastin as reference. BIACORE and ELISA assay results indicated that conbercept could bind different VEGF-A isoforms with higher affinity than reference. Furthermore, conbercept could also bind VEGF-B and PlGF, whereas Avastin showed no binding. Oxygen-induced retinopathy model showed that conbercept could inhibit the formation of neovasularizations. In tumor-bearing nude mice, conbercept could also suppress tumor growth very effectively in vivo. Overall, our study have demonstrated that conbercept could bind with high affinity to multiple VEGF isoforms and consequently provide remarkable anti-angiogenic effect, suggesting the possibility to treat angiogenesis-related diseases such as cancer and wet AMD etc.

  18. Preparation and in vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double emulsion/solvent evaporation technique.

    Science.gov (United States)

    Karal-Yılmaz, Okşan; Serhatlı, Müge; Baysal, Kemal; Baysal, Bahattin M

    2011-01-01

    Biodegradable Poly(lactic-co-glycolic acid; PLGA), microspheres encapsulating the angiogenic protein recombinant human vascular endothelial growth factor (rhVEGF) were formed to achieve VEGF release in a sustained manner. These microspheres are a promising delivery system which can be used for therapeutic angiogenesis. The PLGA microspheres incorporating two different initial loading amounts of rhVEGF have been prepared by a modified water-in-oil-in-water (w/o/w) double emulsion/solvent evaporation technique. The microspheres have been characterized by particle size distribution, environmental scanning electron microscopy (ESEM), light microscopy, encapsulation efficiency and their degradation was studied in vitro. The rhVEGF released from microspheres was quantified by the competitive enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial cell (HUVEC) proliferation assay was used to assess biological activity of the released VEGF. The microspheres were spherical with diameters of 10-60 µm and the encapsulation efficiency was between 46% and 60%. The release kinetics of rhVEGF was studied for two different amounts: 5 µg VEGF (V5) and 50 µg VEGF (V50) per 500 mg starting polymer. The total protein (VEGF:BSA) release increased up to 4 weeks for two rhVEGF concentrations. The ELISA results showed that the burst release for V5 and V50 microspheres were 4 and 27 ng/mL, respectively. For V5, the microspheres showed an initial burst release, followed by a higher steady-state release until 14 days. VEGF release increased up to 2 weeks for V50 microsphere. HUVEC proliferation assay showed that endothelial cells responded to bioactive VEGF by proliferating and migrating.

  19. Downregulation of VEGF and upregulation of TL1A expression induce HUVEC apoptosis in response to high glucose stimuli.

    Science.gov (United States)

    Yu, Miao; Lu, Guihua; Zhu, Xun; Huang, Zhibin; Feng, Chong; Fang, Rong; Wang, Yesong; Gao, Xiuren

    2016-04-01

    High glucose‑induced endothelial cell apoptosis is considered to be the initiator of diabetes‑associated vascular complications. Experiments in vivo and in vitro have demonstrated that high glucose levels contribute to the apoptosis of endothelial cells by mediating cellular dysfunction and metabolic disorder via the production of various cytokines. As the most important endogenous vascular regulators, the balance between pro‑proliferative effector vascular endothelial growth factor (VEGF) and anti‑proliferative effector tumor necrosis factor‑like cytokine 1A (TL1A) is important in the modulation of endothelial cell survival and proliferation, and neovascularization. The present study aimed to explore whether the imbalance between VEGF and TL1A affected the apoptosis of human umbilical vein endothelial cells (HUVECs) exposed to high glucose conditions and then further investigated the potential mechanism. The results showed that the downregulation of VEGF in combination with the upregulation of TL1A in response to high glucose levels led to enhanced HUVEC apoptosis. Further experiments revealed that silencing high glucose‑induced TL1A expression using TL1A small interfering (si)RNA or the overexpression of VEGF by transfection with VEGF DNA resulted in a reduced HUVEC apoptosis rate compared with the controls. The effects occurred by attenuating and activating the phosphoinositide 3‑kinase/Akt/endothelial nitric oxide synthase pathway, respectively. In addition, VEGF and TL1A inhibited each other in hyperglycemia. In conclusion, these findings provide theoretical support for the further investigation of novel therapeutic strategies designed to maintain the balance between VEGF and TL1A and, thus, to prevent the onset and progression of endothelial cell apoptosis in response to high glucose stimuli.

  20. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature.

    Science.gov (United States)

    Polizzi, Silvio; Mahajan, Vinit B

    2015-12-01

    The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-VEGF," "intravitreal injection," "pregnant," "pregnancy," "abortion," "miscarriage," "preeclampsia," "embryo-fetal toxicity," "fetal malformations," "teratogenesis," "adverse events," and "maternofetal complications" in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients.

  1. TP53 Alterations Correlate with Response to VEGF/VEGFR Inhibitors: Implications for Targeted Therapeutics.

    Science.gov (United States)

    Wheler, Jennifer J; Janku, Filip; Naing, Aung; Li, Yali; Stephen, Bettzy; Zinner, Ralph; Subbiah, Vivek; Fu, Siqing; Karp, Daniel; Falchook, Gerald S; Tsimberidou, Apostolia M; Piha-Paul, Sarina; Anderson, Roosevelt; Ke, Danxia; Miller, Vincent; Yelensky, Roman; Lee, J Jack; Hong, David; Kurzrock, Razelle

    2016-10-01

    TP53 tumor-suppressor gene mutations are among the most frequent abnormalities in cancer, affecting approximately 40% of patients. Yet, there is no accepted way to target these alterations in the clinic. At the same time, antagonists of VEGFR or its ligand are best-selling oncology drugs, with multiple, expensive compounds approved. Although only a subset of patients benefit from these antiangiogenesis agents, no relevant biomarker has been identified. Interestingly, TP53 mutations upregulate VEGF-A and VEGFR2. We prospectively enrolled 500 patients, to be interrogated by comprehensive genomic profiling (CGP) (next-generation sequencing, 236 genes), and to be matched, whenever possible, with targeted agents. Herein, we analyze outcomes based on VEGF/VEGFR inhibitor treatment and presence of TP53 mutations. Of the 500 patients, 188 (37.6%; with ≥1 alteration) were treated; 106 (56% of 188) had tumors that harbored TP53 mutations. VEGF/VEGFR inhibitor therapy was independently associated with improvement in all outcome parameters [rate of stable disease (SD) ≥6 months/partial and complete remission (PR/CR); (31% versus 7%; TP53-mutant patients (who received no other molecular-matched agents) treated with versus without VEGF/VEGFR inhibitors), time-to-treatment failure, and overall survival (multivariate analysis: all P ≤ 0.01)] for the patients harboring TP53-mutant cancers, but improvement was not seen in any of these parameters for patients with TP53 wild-type neoplasms. We conclude that TP53 mutations predict sensitivity to VEGF/VEGFR inhibitors in the clinic. TP53 alterations may therefore be a ready biomarker for treatment with antiangiogenesis agents, a finding of seminal importance across the cancer field. Mol Cancer Ther; 15(10); 2475-85. ©2016 AACR.

  2. Hypothermia reduces VEGF-165 expression, but not osteogenic differentiation of human adipose stem cells under hypoxia

    Science.gov (United States)

    Bakker, Astrid D.; Hogervorst, Jolanda M. A.; Nolte, Peter A.; Klein-Nulend, Jenneke

    2017-01-01

    Cryotherapy is successfully used in the clinic to reduce pain and inflammation after musculoskeletal damage, and might prevent secondary tissue damage under the prevalent hypoxic conditions. Whether cryotherapy reduces mesenchymal stem cell (MSC) number and differentiation under hypoxic conditions, causing impaired callus formation is unknown. We aimed to determine whether hypothermia modulates proliferation, apoptosis, nitric oxide production, VEGF gene and protein expression, and osteogenic/chondrogenic differentiation of human MSCs under hypoxia. Human adipose MSCs were cultured under hypoxia (37°C, 1% O2), hypothermia and hypoxia (30°C, 1% O2), or control conditions (37°C, 20% O2). Total DNA, protein, nitric oxide production, alkaline phosphatase activity, gene expression, and VEGF protein concentration were measured up to day 8. Hypoxia enhanced KI67 expression at day 4. The combination of hypothermia and hypoxia further enhanced KI67 gene expression compared to hypoxia alone, but was unable to prevent the 1.2-fold reduction in DNA amount caused by hypoxia at day 4. Addition of hypothermia to hypoxic cells did not alter the effect of hypoxia alone on BAX-to-BCL-2 ratio, alkaline phosphatase activity, gene expression of SOX9, COL1, or osteocalcin, or nitric oxide production. Hypothermia decreased the stimulating effect of hypoxia on VEGF-165 gene expression by 6-fold at day 4 and by 2-fold at day 8. Hypothermia also decreased VEGF protein expression under hypoxia by 2.9-fold at day 8. In conclusion, hypothermia decreased VEGF-165 gene and protein expression, but did not affect differentiation, or apoptosis of MSCs cultured under hypoxia. These in vitro results implicate that hypothermia treatment in vivo, applied to alleviate pain and inflammation, is not likely to harm early stages of callus formation. PMID:28166273

  3. Anti-VEGF treatment for myopic choroid neovascularization: from molecular characterization to update on clinical application

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-07-01

    Full Text Available Yan Zhang,1 Qian Han,2 Yusha Ru,1 Qiyu Bo,1 Rui Hua Wei1 1Tianjin Medical University Eye Hospital, Tianjin Medical University Eye Institute, College of Optometry and Ophthalmology, Tianjin Medical University, Tianjin, 2Tangshan Eye Hospital, Tangshan, Hebei Province, People’s Republic of China Abstract: Choroidal neovascularization (CNV secondary to pathologic myopia has a very high incidence in global, especially in Asian, populations. It is a common cause of irreversible central vision loss, and severely affects the quality of life in the patients with pathologic myopia. The traditional therapeutic modalities for CNV secondary to pathologic myopia include thermal laser photocoagulation, surgical management, transpupillary thermotherapy, and photodynamic therapy with verteporfin. However, the long-term outcomes of these modalities are disappointing. Recently, intravitreal administration of anti-VEGF biological agents, including bevacizumab, ranibizumab, pegaptanib, aflibercept, and conbercept, has demonstrated promising outcomes for this ocular disease. The anti-VEGF regimens are more effective on improving visual acuity, reducing central fundus thickness and central retina thickness than the traditional modalities. These anti-VEGF agents thus hold the potential to become the first-line medicine for treatment of CNV secondary to pathologic myopia. This review follows the trend of “from bench to bedside”, initially discussing the pathogenesis of myopic CNV, delineating the molecular structures and mechanisms of action of the currently available anti-VEGF drugs, and then systematically comparing the up to date clinical applications as well as the efficacy and safety of the anti-VEGF drugs to the CNV secondary to pathologic myopia. Keywords: formation of new vessels, choroid membrane, pathologic myopia, vascular endothelial growth factor, molecular mechanisms, clinical trials

  4. Anti-VEGF Treatment Strategies for Wet AMD

    Directory of Open Access Journals (Sweden)

    Jaclyn L. Kovach

    2012-01-01

    Full Text Available Over the past few years, antivascular endothelial growth factor (VEGF therapy has become a standard treatment for neovascular age-related macular degeneration (AMD. During this time, treatment strategies have evolved from a monthly dosing schedule to individualized regimens. This paper will review the currently available anti-VEGF agents and evidence-based treatment strategies.

  5. Anti-VEGF Treatment Strategies for Wet AMD.

    Science.gov (United States)

    Kovach, Jaclyn L; Schwartz, Stephen G; Flynn, Harry W; Scott, Ingrid U

    2012-01-01

    Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a standard treatment for neovascular age-related macular degeneration (AMD). During this time, treatment strategies have evolved from a monthly dosing schedule to individualized regimens. This paper will review the currently available anti-VEGF agents and evidence-based treatment strategies.

  6. Changing paradigms of anti-VEGF in the Indian scenario

    Directory of Open Access Journals (Sweden)

    P Mahesh Shanmugam

    2014-01-01

    Full Text Available Anti-vascular endothelial growth factors (VEGF agents have revolutionized the treatment of retinal diseases. Use of anti-VEGF agents in the Indian Scenario present some unique challenges considering the absence of compounding pharmacies, poor penetrance of health insurance and limited affordability of the citizens of a developing economy. To study the changing paradigms of anti-VEGF use in the Indian scenario, all articles published by Indian authors, data from web-based surveys amongst Indian vitreo-retinal specialists were reviewed. In the paucity of compounding pharmacies in India, fractionation and injection techniques differ from those of developed countries. Frequent anti-VEGF monotherapy offers the best anatomical and visual results, but economics of scale do not allow the same in the Indian scenario, resulting in PRN dosing and combination of anti-VEGF with laser photocoagulation, being the commonly employed treatment protocols.

  7. Serial Spike Time Correlations Affect Probability Distribution of Joint Spike Events.

    Science.gov (United States)

    Shahi, Mina; van Vreeswijk, Carl; Pipa, Gordon

    2016-01-01

    Detecting the existence of temporally coordinated spiking activity, and its role in information processing in the cortex, has remained a major challenge for neuroscience research. Different methods and approaches have been suggested to test whether the observed synchronized events are significantly different from those expected by chance. To analyze the simultaneous spike trains for precise spike correlation, these methods typically model the spike trains as a Poisson process implying that the generation of each spike is independent of all the other spikes. However, studies have shown that neural spike trains exhibit dependence among spike sequences, such as the absolute and relative refractory periods which govern the spike probability of the oncoming action potential based on the time of the last spike, or the bursting behavior, which is characterized by short epochs of rapid action potentials, followed by longer episodes of silence. Here we investigate non-renewal processes with the inter-spike interval distribution model that incorporates spike-history dependence of individual neurons. For that, we use the Monte Carlo method to estimate the full shape of the coincidence count distribution and to generate false positives for coincidence detection. The results show that compared to the distributions based on homogeneous Poisson processes, and also non-Poisson processes, the width of the distribution of joint spike events changes. Non-renewal processes can lead to both heavy tailed or narrow coincidence distribution. We conclude that small differences in the exact autostructure of the point process can cause large differences in the width of a coincidence distribution. Therefore, manipulations of the autostructure for the estimation of significance of joint spike events seem to be inadequate.

  8. Contact analysis and load distribution of double-envelop hourglassworm gearing affected by errors and load

    Institute of Scientific and Technical Information of China (English)

    XU Wujiao; QIN Datong; SHI Wankai

    2003-01-01

    An approach for the contact analysis and load distribution of double-envelop hourglass worm gearing is presented,which is based on a 3-D elastic contact finite element method (FEM) model that 3ccommodates the influence of errors and load.As compared with existing tooth contact analysis model that assumes rigidity for the contacting surfaces, the proposed model provides a more realistic analysis on the contact patterns, the distribution of contact load and transmission errors. It is also capable of exploring the influence of different errors on meshing performances, the contact deformation, the shift of the contact zone and load share among the meshing tooth-pairs under different load.

  9. 26 CFR 1.332-5 - Distributions in liquidation as affecting minority interests.

    Science.gov (United States)

    2010-04-01

    ... liquidation as affecting minority interests. Upon the liquidation of a corporation in pursuance of a plan of complete liquidation, the gain or loss of minority shareholders shall be determined without regard to... minority interests. 1.332-5 Section 1.332-5 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF...

  10. 78 FR 32713 - Distribution of Continued Dumping and Subsidy Offset to Affected Domestic Producers

    Science.gov (United States)

    2013-05-31

    ... 504 of the Tax Relief, Unemployment Insurance Reauthorization, and Job Creation Act of 2010... money available for distribution can be expected to continue diminishing over time. It should also be...-337-804......... 731-TA-776........ Preserved LK Bowman. Mushrooms/ Chile. Modern Mushroom...

  11. 76 FR 31019 - Distribution of Continued Dumping and Subsidy Offset to Affected Domestic Producers

    Science.gov (United States)

    2011-05-27

    ..., Unemployment Insurance Reauthorization, and Job Creation Act of 2010. Consequently, the full impact of the... will be continued for an undetermined period; however, the amount of money available for distribution... Preserved Mushrooms/ LK Bowman Chile. Modern Mushroom Farms Monterey Mushrooms Mount Laurel Canning...

  12. Low temperature treatment affects concentration and distribution of chrysanthemum stunt viroid in Argyranthemum

    Directory of Open Access Journals (Sweden)

    Zhibo eZhang

    2016-03-01

    Full Text Available Chrysanthemum stunt viroid (CSVd can infect Argyranthemum and cause serious economic loss. Low temperature treatment combined with meristem culture has been applied to eradicate viroids from their hosts, but without success in eliminating CSVd from diseased Argyranthemum. The objectives of this work were to investigate 1 the effect of low temperature treatment combined with meristem culture on elimination of CSVd, 2 the effect of low temperature treatment on CSVd distribution pattern in shoot apical meristem (SAM, and 3 CSVd distribution in flowers and stems of two infected Argyranthemum cultivars. After treatment with low temperature combined with meristem tip culture, two CSVd-free plants were found in ‘Border Dark Red’, but none in ‘Yellow Empire’. With the help of in situ hybridization, we found that CSVd distribution patterns in the SAM showed no changes in diseased ‘Yellow Empire’ following 5oC treatment, compared with non-treated plants. However, the CSVd-free area in SAM was enlarged in diseased ‘Border Dark Red’ following prolonged 5oC treatment. Localization of CSVd in the flowers and stems of infected ‘Border Dark Red’ and ‘Yellow Empire’ indicated that seeds could not transmit CSVd in these two cultivars, and CSVd existed in phloem. Results obtained in the study contributed to better understanding of the distribution of CSVd in systemically infected plants and the combination of low temperature treatment and meristem tip culture for production of viroid-free plants.

  13. Distributed Modeling of soil erosion and deposition affected by buffer strips

    DEFF Research Database (Denmark)

    Khademalrasoul, Ataalah; Heckrath, Goswin Johann; Iversen, Bo Vangsø

    and dimension of buffer zones in the landscape can be optimized by means of spatially distributed erosion and deposition modeling. During the period from 1998 to 2000 field campaigns were done on a range of agricultural land in Denmark. On 21 slope units and adjacent buffer zones, rill erosion and deposition...

  14. Soil organic matter distribution and microaggregate characteristics as affected by agricultural management and earthworm activity

    NARCIS (Netherlands)

    Pulleman, M.M.; Six, J.; Breemen, van N.; Jongmans, A.G.

    2005-01-01

    Stable microaggregates can physically protect occluded soil organic matter (SOM) against decomposition. We studied the effects of agricultural management on the amount and characteristics of microaggregates and on SOM distribution in a marine loam soil in the Netherlands. Three long-term farming sys

  15. Patchy Distributions of Competitors Affect the Growth of a Clonal Plant When the Competitor Density Is High

    OpenAIRE

    Wei Xue; Lin Huang; Bi-Cheng Dong; Ming-Xiang Zhang; Fei-Hai Yu

    2013-01-01

    Environments are patchy in not only abiotic factors but also biotic ones. Many studies have examined effects of spatial heterogeneity in abiotic factors such as light, water and nutrients on the growth of clonal plants, but few have tested those in biotic factors. We conducted a greenhouse experiment to examine how patchy distributions of competitors affect the growth of a rhizomatous wetland plant Bolboschoenus planiculmis and whether such effects depend on the density of the competitors. We...

  16. Numerical Simulation for Flow Distribution in ACE7 Fuel Assemblies affected by a Spacer Grid Deformation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jongpil; Jeong, Ji Hwan [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    In spite of various efforts to understand hydraulic phenomena in a rod bundle containing deformed rods due to swelling and/or ballooning of clad, the studies for flow blockage due to spacer grid deformation have been limited. In the present work, 3D CFD analysis for flow blockage was performed to evaluate coolant flow within ACE7 fuel assemblies (FAs) containing a FA affected by a spacer grid deformation. The real geometry except for inner grids was used in the simulation and the region including inner grid was replaced by porous media. In the present work, the numerical simulation was performed to predict coolant flow within ACE7 FAs affected by a Mid grid deformation. The 3D CFD result shows that approximately 60 subchannel hydraulic diameter is required to fully recover coolant flow under normal operating condition.

  17. Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution.

    Science.gov (United States)

    Sbardella, Diego; Tundo, Grazia Raffaella; Sciandra, Francesca; Bozzi, Manuela; Gioia, Magda; Ciaccio, Chiara; Tarantino, Umberto; Brancaccio, Andrea; Coletta, Massimo; Marini, Stefano

    2015-01-01

    Insulin-Degrading-Enzyme (IDE) is a Zn2+-dependent peptidase highly conserved throughout evolution and ubiquitously distributed in mammalian tissues wherein it displays a prevalent cytosolic localization. We have recently demonstrated a novel Heat Shock Protein-like behaviour of IDE and its association with the 26S proteasome. In the present study, we examine the mechanistic and molecular features of IDE-26S proteasome interaction in a cell experimental model, extending the investigation also to the effect of IDE on the enzymatic activities of the 26S proteasome. Further, kinetic investigations indicate that the 26S proteasome activity undergoes a functional modulation by IDE through an extra-catalytic mechanism. The IDE-26S proteasome interaction was analyzed during the Heat Shock Response and we report novel findings on IDE intracellular distribution that might be of critical relevance for cell metabolism.

  18. Proteasome Activity Is Affected by Fluctuations in Insulin-Degrading Enzyme Distribution.

    Directory of Open Access Journals (Sweden)

    Diego Sbardella

    Full Text Available Insulin-Degrading-Enzyme (IDE is a Zn2+-dependent peptidase highly conserved throughout evolution and ubiquitously distributed in mammalian tissues wherein it displays a prevalent cytosolic localization. We have recently demonstrated a novel Heat Shock Protein-like behaviour of IDE and its association with the 26S proteasome. In the present study, we examine the mechanistic and molecular features of IDE-26S proteasome interaction in a cell experimental model, extending the investigation also to the effect of IDE on the enzymatic activities of the 26S proteasome. Further, kinetic investigations indicate that the 26S proteasome activity undergoes a functional modulation by IDE through an extra-catalytic mechanism. The IDE-26S proteasome interaction was analyzed during the Heat Shock Response and we report novel findings on IDE intracellular distribution that might be of critical relevance for cell metabolism.

  19. Distribution of elements in needles of Pinus massoniana (Lamb.) was uneven and affected by needle age.

    Science.gov (United States)

    Kuang, Yuan Wen; Wen, Da Zhi; Zhou, Guoyi; Liu, Shi Zhong

    2007-02-01

    Macronutrients (P, S, K, Na, Mg, Ca), heavy metals (Fe, Zn, Mn, Cu, Pb, Cr, Ni, Cd,) and Al concentrations as well as values of Ca/Al in the tip, middle and base sections, and sheaths of current year and previous year needles of Pinus massoniana from Xiqiao Mountain were analyzed and the distribution patterns of those elements were compared. The results indicated that many elements were unevenly distributed among the different components of needles. Possible deficiency of P, K, Ca, Mn and Al toxicity occurred in needles under air pollution. Heavy metals may threaten the health of Masson pine. Needle sheaths were good places to look for particulate pollutants, in this case including Fe, Cu, Zn, Pb, Cr, Cd and Al.

  20. Distribution of elements in needles of Pinus massoniana (Lamb.) was uneven and affected by needle age

    Energy Technology Data Exchange (ETDEWEB)

    Kuang Yuanwen [South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou (China)]. E-mail: kuangyw@scbg.ac.cn; Wen Dazhi [South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou (China)]. E-mail: dzwen@scbg.ac.cn; Zhou Guoyi [South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou (China)]. E-mail: gyzhou@scbg.ac.cn; Liu Shizhong [South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou (China)]. E-mail: lsz@scbg.ac.cn

    2007-02-15

    Macronutrients (P, S, K, Na, Mg, Ca), heavy metals (Fe, Zn, Mn, Cu, Pb, Cr, Ni, Cd,) and Al concentrations as well as values of Ca/Al in the tip, middle and base sections, and sheaths of current year and previous year needles of Pinus massoniana from Xiqiao Mountain were analyzed and the distribution patterns of those elements were compared. The results indicated that many elements were unevenly distributed among the different components of needles. Possible deficiency of P, K, Ca, Mn and Al toxicity occurred in needles under air pollution. Heavy metals may threaten the health of Masson pine. Needle sheaths were good places to look for particulate pollutants, in this case including Fe, Cu, Zn, Pb, Cr, Cd and Al. - Pine needle sections as bioindicator for heavy metals and nutrient deficiency particularly needle sheath for particle pollutants.

  1. Distribution of elements in needles of Pinus massoniana (Lamb.) was uneven and affected by needle age

    Energy Technology Data Exchange (ETDEWEB)

    Kuang Yuanwen [Institute of Ecology, South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou (China)]. E-mail: kuangyw@scbg.ac.cn; Wen Dazhi [Institute of Ecology, South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou (China)]. E-mail: dzwen@scbg.ac.cn; Zhou Guoyi [Institute of Ecology, South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou (China)]. E-mail: gyzhou@scbg.ac.cn; Liu Shizhong [Institute of Ecology, South China Botanical Garden, Chinese Academy of Sciences, 510650 Guangzhou (China)]. E-mail: lsz@scbg.ac.cn

    2007-01-15

    Macronutrients (P, S, K, Na, Mg, Ca), heavy metals (Fe, Zn, Mn, Cu, Pb, Cr, Ni, Cd) and Al concentrations as well as values of Ca/Al in the tip, middle, base sections and sheaths of current year and previous year needles of Pinus massoniana from Xiqiao Mountain were analyzed and the distribution patterns of those elements were compared. The results indicated that many elements were unevenly distributed among the different components of needles. Possible deficiency of P, K, Ca, Mn and Al toxicity occurred in needles under air pollution. Heavy metals may threaten the health of Masson pine. Needle sheaths were good places to look for particulate pollutants, in this case including Fe, Cu, Zn, Pb, Cr, Cd and Al. - Pine needle sections as bioindicator for heavy metals and nutrient deficiency particularly needle sheath for particle pollutants.

  2. Human and environmental factors affecting Aedes aegypti distribution in an arid urban environment.

    Science.gov (United States)

    Walker, Kathleen R; Joy, Teresa K; Ellers-Kirk, Christa; Ramberg, Frank B

    2011-06-01

    Aedes aegypti has reappeared in urban communities in the southwestern U.S.A. in the 1990s after a 40-year absence. In 2003 and 2004, a systematic survey was conducted throughout metropolitan Tucson, AZ, to identify human and environmental factors associated with Ae. aegypti distribution within an arid urban area. Aedes aegypti presence and abundance were measured monthly using the Centers for Disease Control and Prevention enhanced oviposition traps at sampling sites established in a grid at 3- to 4-km intervals across the city. Sampling occurred in the summer rainy season (July through September), the peak of mosquito activity in the region. Multiple regression analyses were conducted to determine relationships between mosquito density and factors that could influence mosquito distribution. House age was the only factor that showed a consistent significant association with Ae. aegypti abundance in both years: older houses had more mosquito eggs. This is the 1st study of Ae. aegypti distribution at a local level to identify house age as an explanatory factor independent of other human demographic factors. Further research into the reasons why mosquitoes were more abundant around older homes may help inform and refine future vector surveillance and control efforts in the event of a dengue outbreak in the region.

  3. Management of Myopic Choroidal Neovascularization: Focus on Anti-VEGF Therapy.

    Science.gov (United States)

    Teo, Kelvin Yi Chong; Ng, Wei Yan; Lee, Shu Yen; Cheung, Chui Ming Gemmy

    2016-07-01

    Myopic choroidal neovascularization (mCNV) is the second most common form of CNV after age-related macular degeneration (AMD). It is a sight-threatening complication of pathologic myopia (PM) and often affects patients in their working years causing significant impact on quality of life. Previous therapies such as photodynamic therapy with verteporfin have shown limited success. Due to the similarities in pathogenesis of mCNV and AMD CNV, anti-vascular endothelial growth factor therapy (anti-VEGF), which has so far been the mainstay of treatment for AMD CNV, has been shown to be effective in the treatment of mCNV and has become the first-line treatment of choice. This article aims to examine briefly the epidemiology and pathophysiology of mCNV, as well as review the evidence for efficacy, safety, and clinical use of anti-VEGF treatment for mCNV.

  4. VEGF inhibition as possible therapy in spondyloarthritis patients: Targeting bone remodelling.

    Science.gov (United States)

    Lacout, Alexis; Carlier, Robert Yves; El Hajjam, Mostafa; Marcy, Pierre Yves

    2017-04-01

    Spondyloarthritis refers to a group of chronic inflammatory rheumatic diseases that predominantly affects the axial skeleton, causing pain and stiffness. Human bone is highly dynamic organ that interacts with a wide array cells and tissues. Process of bone remodelling relies on a delicate balance between bone formation and bone resorption, orchestrated by osteoblasts and osteoclasts. Disruption of this homeostatic balance of bone removal and replacement can manifest as inappropriate new bone formation found in spondylarthritis. We hypothesize that VEGF may promote bone remodelling, stimulate angiogenesis, and both osteoclastic and osteoblastic activity. Anti VEGF may be tested as a dedicated therapy to prevent bone remodelling in spondyloarthritis patients, namely in cases of aggressive disease. Bone remodelling could be monitored by using [18F]Fluoride PET scan.

  5. How the Assumed Size Distribution of Dust Minerals Affects the Predicted Ice Forming Nuclei

    Science.gov (United States)

    Perlwitz, Jan P.; Fridlind, Ann M.; Garcia-Pando, Carlos Perez; Miller, Ron L.; Knopf, Daniel A.

    2015-01-01

    The formation of ice in clouds depends on the availability of ice forming nuclei (IFN). Dust aerosol particles are considered the most important source of IFN at a global scale. Recent laboratory studies have demonstrated that the mineral feldspar provides the most efficient dust IFN for immersion freezing and together with kaolinite for deposition ice nucleation, and that the phyllosilicates illite and montmorillonite (a member of the smectite group) are of secondary importance.A few studies have applied global models that simulate mineral specific dust to predict the number and geographical distribution of IFN. These studies have been based on the simple assumption that the mineral composition of soil as provided in data sets from the literature translates directly into the mineral composition of the dust aerosols. However, these tables are based on measurements of wet-sieved soil where dust aggregates are destroyed to a large degree. In consequence, the size distribution of dust is shifted to smaller sizes, and phyllosilicates like illite, kaolinite, and smectite are only found in the size range 2 m. In contrast, in measurements of the mineral composition of dust aerosols, the largest mass fraction of these phyllosilicates is found in the size range 2 m as part of dust aggregates. Conversely, the mass fraction of feldspar is smaller in this size range, varying with the geographical location. This may have a significant effect on the predicted IFN number and its geographical distribution.An improved mineral specific dust aerosol module has been recently implemented in the NASA GISS Earth System ModelE2. The dust module takes into consideration the disaggregated state of wet-sieved soil, on which the tables of soil mineral fractions are based. To simulate the atmospheric cycle of the minerals, the mass size distribution of each mineral in aggregates that are emitted from undispersed parent soil is reconstructed. In the current study, we test the null

  6. Treatment of Corneal Neovascularization Using Anti-VEGF Bevacizumab

    Directory of Open Access Journals (Sweden)

    Deli Krizova

    2014-01-01

    Full Text Available Purpose. To evaluate antiangiogenic effect of local use of bevacizumab (anti-VEGF antibody in patients with corneal neovascularization. Methods. Patients were divided into two groups. All patients suffered from some form of corneal neovascularization (NV. Patients in group A received 0.2–0.5 mL of bevacizumab solution subconjunctivally (concentration 25 mg/mL in a single dose. Group A included 28 eyes from 27. Patients in group B applied bevacizumab eye drops twice daily (concentration 2.5 mg/mL for two weeks. Group B included 38 eyes from 35 patients. We evaluated the number of corneal segments affected by NV, CDVA, and the incidence of complications and subjective complaints related to the treatment. The minimum follow-up period was six months. Results. By the 6-month follow-up, in group A the percentage reduction of the affected peripheral segments was 21.6% and of the central segments was 9.6%; in group B the percentage reduction of the central segments was 22.7% and of the central segments was 38.04%. In both groups we noticed a statistically significant reduction in the extent of NV. Conclusion. The use of bevacizumab seems to be an effective and safe method in the treatment of corneal neovascularization, either in the subconjunctival or topical application form.

  7. Stability and heavy metal distribution of soil aggregates affected by application of apatite, lime, and charcoal.

    Science.gov (United States)

    Cui, Hongbiao; Ma, Kaiqiang; Fan, Yuchao; Peng, Xinhua; Mao, Jingdong; Zhou, Dongmei; Zhang, Zhongbin; Zhou, Jing

    2016-06-01

    Only a few studies have been reported on the stability and heavy metal distribution of soil aggregates after soil treatments to reduce the availability of heavy metals. In this study, apatite (22.3 t ha(-1)), lime (4.45 t ha(-1)), and charcoal (66.8 t ha(-1)) were applied to a heavy metal-contaminated soil for 4 years. The stability and heavy metal distribution of soil aggregates were investigated by dry and wet sieving. No significant change in the dry mean weight diameter was observed in any treatments. Compared with the control, three-amendment treatments significantly increased the wet mean weight diameter, but only charcoal treatment significantly increased the wet aggregate stability. The soil treatments increased the content of soil organic carbon, and the fraction 0.25-2 mm contained the highest content of soil organic carbon. Amendments' application slightly increased soil total Cu and Cd, but decreased the concentrations of CaCl2 -extractable Cu and Cd except for the fraction 2 and 0.25-2 mm contained the highest concentrations of CaCl2-extractable Cu and Cd, accounted for about 74.5-86.8 % of CaCl2-extractable Cu and Cd in soil. The results indicated that amendments' application increased the wet soil aggregate stability and decreased the available Cu and Cd. The distribution of available heavy metals in wet soil aggregates was not controlled by soil aggregate stability, but possibly by soil organic carbon.

  8. Distribution and prevalence of crown rot pathogens affecting wheat crops in southern Chile

    Directory of Open Access Journals (Sweden)

    Ernesto Moya-Elizondo

    2015-03-01

    Full Text Available Crown rot pathogens are associated with higher losses for wheat crop farmers, but information about the distribution and prevalence of these pathogens in Chile is inadequate. Distribution and prevalence of wheat (Triticum aestivum L. crown rot pathogens were examined in a survey of 48 commercial fields from December 2011 to February 2012 in southern Chile. These fields were located between Collipulli (37°56'00" S; 72°26'39" W and Purranque (40°50'30" S; 73°22'03" W. Severity of crown rot disease was determined through visual assessment of the first internode of 20 tillers obtained from each field. Incidence of crown rot pathogens per field was determined by plating the 20 tillers on Petri plates with 20% potato dextrose agar amended with lactic acid (aPDA medium. Resulting fungal colonies from monoxenic culture were identified by morphological or molecular-assisted identification. Severity of crown rot varied between 11.3% and 80% for individual fields. Culture plate analysis showed 72.2% of stems were infected with some fungus. Fusarium avenaceum, F. graminearum, and F. culmorum, pathogens associated with Fusarium crown rot disease were isolated from 13.5% of tillers. Gaeumannomyces graminis, causal agent of take-all disease in cereals, was isolated from 11.1% of culms. Phaeosphaeria sp., an endophyte and possibly a non-pathogenic fungus, was isolated from 13.9% of tillers. Pathogenic fungi such as Rhizoctonia spp. and Microdochium nivale, other saprophyte, and several unidentified non-sporulating fungi were isolated at frequencies lower than 3% of the total. Fusarium crown rot and take-all were the most prevalent and distributed crown rot diseases present in wheat crops in southern Chile.

  9. VEGF Correlates with Inflammation and Fibrosis in Tuberculous Pleural Effusion

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    Mauo-Ying Bien

    2015-01-01

    Full Text Available Objective. To investigate the relationship among angiogenic cytokines, inflammatory markers, and fibrinolytic activity in tuberculous pleural effusion (TBPE and their clinical importance. Methods. Forty-two patients diagnosed with TBPE were studied. Based on chest ultrasonography, there were 26 loculated and 16 nonloculated TBPE patients. The effusion size radiological scores and effusion vascular endothelial growth factor (VEGF, interleukin- (IL- 8, plasminogen activator inhibitor type-1 (PAI-1, and tissue type plasminogen activator (tPA were measured. Treatment outcome and pleural fibrosis, defined as radiological residual pleural thickening (RPT, were assessed at 6-month follow-up. Results. The effusion size and effusion lactate dehydrogenase (LDH, VEGF, IL-8, PAI-1, and PAI-1/tPA ratio were significantly higher, while effusion glucose, pH value, and tPA were significantly lower, in loculated than in nonloculated TBPE. VEGF and IL-8 correlated positively with LDH and PAI-1/tPA ratio and negatively with tPA in both loculated and nonloculated TBPE. Patients with higher VEGF or greater effusion size were prone to develop RPT (n=14; VEGF, odds ratio 1.28, P=0.01; effusion size, odds ratio 1.01, P=0.02, and VEGF was an independent predictor of RPT in TBPE (receiver operating characteristic curve AUC=0.985, P<0.001. Conclusions. Effusion VEGF correlates with pleural inflammation and fibrosis and may be targeted for adjunct therapy for TBPE.

  10. Is the distribution of Prochlorococcus and Synechococcus ecotypes in the Mediterranean Sea affected by global warming?

    Science.gov (United States)

    Mella-Flores, D.; Mazard, S.; Humily, F.; Partensky, F.; Mahé, F.; Bariat, L.; Courties, C.; Marie, D.; Ras, J.; Mauriac, R.; Jeanthon, C.; Mahdi Bendif, E.; Ostrowski, M.; Scanlan, D. J.; Garczarek, L.

    2011-09-01

    Biological communities populating the Mediterranean Sea, which is situated at the northern boundary of the subtropics, are often claimed to be particularly affected by global warming. This is indicated, for instance, by the introduction of (sub)tropical species of fish or invertebrates that can displace local species. This raises the question of whether microbial communities are similarly affected, especially in the Levantine basin where sea surface temperatures have significantly risen over the last 25 years (0.50 ± 0.11 °C in average per decade, P libraries of the 16S-23S ribosomal DNA Internal Transcribed Spacer (ITS) region, with a focus on the abundance of clades that may constitute bioindicators of warm waters. During both cruises, the dominant Prochlorococcus clade in the upper mixed layer at all stations was HLI, a clade typical of temperate waters, whereas the HLII clade, the dominant group in (sub)tropical waters, was only present at very low concentrations. The Synechococcus community was dominated by clades I, III and IV in the northwestern waters of the Gulf of Lions and by clade III and groups genetically related to clades WPC1 and VI in the rest of the Mediterranean Sea. In contrast, only a few sequences of clade II, a group typical of warm waters, were observed. These data indicate that local cyanobacterial populations have not yet been displaced by their (sub)tropical counterparts.

  11. Planting densities and bird and rodent absence affect size distributions of four dicots in synthetic tallgrass communities.

    Science.gov (United States)

    Martínez-Garza, Cristina; Saha, Sonali; Torres, Veronica; Brown, Joel S; Howe, Henry F

    2004-05-01

    Variability in the size distributions of populations is usually studied in monocultures or in mixed plantings of two species. Variability of size distributions of populations in more complex communities has been neglected. The effects of seeding density (35 or 350 seeds/species/m2) and presence of small vertebrates on the variability of size distributions were studied for a total of 1,920 individuals of 4 species in replicated synthetic communities of 18 species in northern Illinois. End-of season height and above-ground biomass were measured for prairie perennials Dalea purpurea (purple prairie clover), Echinacea purpurea (purple coneflower), Desmanthus illinoensis (Illinois bundleflower) and Heliopsis helianthoides (early sunflower). Variability in biomass distribution of the four target species was twice as great at low than at high densities when small vertebrates were excluded. Our results suggest that inter- and intraspecific competition may affect all individuals more under high-density conditions, thereby reducing the variability in their biomass distributions within this community. This result, a consequence of plant-plant interaction, is obscured when small birds or mammals are present, presumably because either or both add variance that overwhelms the pattern.

  12. From daily movements to population distributions: weather affects competitive ability in a guild of soaring birds.

    Science.gov (United States)

    Shepard, Emily L C; Lambertucci, Sergio A

    2013-11-06

    The ability of many animals to access and exploit food is dependent on the ability to move. In the case of scavenging birds, which use soaring flight to locate and exploit ephemeral resources, the cost and speed of movement vary with meteorological factors. These factors are likely to modify the nature of interspecific interactions, as well as individual movement capacity, although the former are less well understood. We used aeronautical models to examine how soaring performance varies with weather within a guild of scavenging birds and the consequences this has for access to a common resource. Birds could be divided broadly into those with low wing loading that are more competitive in conditions with weak updraughts and low winds (black vultures and caracaras), and those with high wing loading that are well adapted for soaring in strong updraughts and moderate to high winds (Andean condors). Spatial trends in meteorological factors seem to confine scavengers with high wing loading to the mountains where they out-compete other birds; a trend that is borne out in worldwide distributions of the largest species. However, model predictions and carcass observations suggest that the competitive ability of these and other birds varies with meteorological conditions in areas where distributions overlap. This challenges the view that scavenging guilds are structured by fixed patterns of dominance and suggests that competitive ability varies across spatial and temporal scales, which may ultimately be a mechanism promoting diversity among aerial scavengers.

  13. Elevation and stream-size thresholds affect distributions of native and exotic warmwater fishes in Wyoming

    Science.gov (United States)

    Quist, M.C.; Hubert, W.A.; Rahel, F.J.

    2004-01-01

    This study was conducted to assess the influence of elevation and stream width on the occurrence of 28 native and six exotic fish species using data collected (1954-2003) from 1,114 stream reaches in Wyoming. Medians and ranges of elevation and stream width were used to assess how elevation and stream width influenced the occurrence of individual species and to indicate which species had large and small ranges of distribution. Twenty-four species were common at elevations below 1,550 m and 31 species occurred in streams less than 20 m wide. The six exotic species had the potential to overlap all of the native species with regard to both elevation and stream width. In general, species that were collected over a wide range of elevations were also collected over a wide range of stream widths. Red shiner (Cyprinella lutrensis) and river carpsucker (Carpiodes carpio) occurred over the smallest elevation ranges ( 2,500 m). Longnose sucker and white sucker (Catostomus commersoni) occurred over the greatest ranges in stream widths (> 90 m), and brook stickleback (Culaea inconstans), black bullhead (Ameiurus melas), and quillback (Carpiodes cyprinus) were found over the lowest ranges in stream widths (< 12 m). The distributions of native and exotic species in streams that transition from the Rocky Mountains to the Great Plains were largely explained by elevation and stream width.

  14. Retrospective exploratory analysis of VEGF polymorphisms in the prediction of benefit from first-line FOLFIRI plus bevacizumab in metastatic colorectal cancer

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    Manzoni Mariangela

    2011-06-01

    Full Text Available Abstract Background Molecular predictors of bevacizumab efficacy in colorectal cancer have not been identified yet. Specific VEGF polymorphisms may affect gene transcription and therefore indirectly influence the efficacy of bevacizumab. Methods Genomic DNA of 111 consecutive metastatic colorectal cancer patients treated with first-line FOLFIRI plus bevacizumab was obtained from blood samples. VEGF -2578 C/A, -1498 C/T, + 405 C/G, + 936 C/T polymorphisms were analyzed by means of PCR-RFLP. DNA samples from 107 patients treated with FOLFIRI alone served as historical control group. The relation of VEGF polymorphisms with PFS, evaluated through Kaplan-Meier method and log-rank test, was the primary end-point. An interaction test with a Cox model has been performed in order to demonstrate the heterogeneity of the effect of VEGF -1498 C/T polymorphism between bevacizumab-and control group. Results In the bevacizumab-group median PFS and OS of patients carrying VEGF -1498 C/C, C/T and T/T allelic variants were, respectively, 12.8, 10.5, 7.5 months (p = 0.0046, log-rank test and 27.3, 20.5, 18.6 months (p = 0.038, log-rank test. VEGF -1498 T/T genotype was associated with shorter PFS (HR = 2.13, [1.41-5.10], p = 0.0027. In the control group no significant association of VEGF -1498 C/T allelic variants and PFS or OS was found. Interaction between VEGF -1498 C/T variants and treatment effect suggested that the relation of VEGF -1498 T/T genotype with shorter PFS was caused by the effect of bevacizumab (p = 0.011. Other investigated polymorphisms did not affect the outcome. Conclusions These data suggest a possible role for VEGF -1498 C/T variants in predicting the efficacy of bevacizumab in the up-front treatment of metastatic colorectal cancer patients. A molecular tool for selecting subjects candidate to benefit from the anti-VEGF could be important for clinical practice. The retrospective and exploratory design of the present study, coupled with the

  15. Relationship between breast cancer-related lymphoedema and VEGF-C and VEGFR-3%乳腺癌相关淋巴水肿与VEGF-C及VEGFR-3的关系

    Institute of Scientific and Technical Information of China (English)

    贺建业; 吴庆华; 伍冀湘; 钟晨熙; 陈东; 王伟

    2009-01-01

    目的 研究探讨乳腺癌组织中VEGF-C及癌周淋巴管密度(poritumoral lymph vesselsdensity,PLVD)的表达和分布情况及其临床病理学特征,初步探讨其与乳腺癌相关淋巴水肿(breastcancer-related lymphoedema,BCRL)发生间的关系. 方法应用免疫组化技术检测47例乳腺癌组织中VEGF-C及VEGFR-3,观察乳腺癌组织中VEGF-C的表达情况并计数,检测患者双侧上肢周径,判断有无水肿并分级.结果 47例乳腺癌组织中VEGF-C阳性表达者33例,VEGF-C阳性组的PLVD(30.39±10.46)较阴性组(23.16±11.67)明显增高(P<0.05).癌组织内VEGF-C半定量评分与PLVD呈正相关(r=0.334).淋巴结转移组VEGF-C的阳性表达率(42.55%)及半定量评分(3.68±1.59)均高于未转移组(27.66%,2.48±2.31)(P<0.05);淋巴结转移组PLVD高于未转移组(32.12±10.29 vs.24.82±11.06),P<0.05.47例患者中一年内发生BCRL者17例,一年后仍有BCRL的8例.VEGF-C阴性组发生水肿者(5/14)较阳性组(3/33)增加(P<0.05).结论 VEGF-C在乳腺癌组织中有较高的阳性表达率,并且与PLVD呈正相关.乳腺癌组织中VEGF-C高表达可减少BCRL发生的机会.%Objective To study the distribution and clinicopathological characteristics between VEGF-C and pefitumoral lymph vessels density(PLVD) in breast cancer tissue, and to investigate the development and the mechanism of breast cancer-related lymphoedema (BCRL). Methods VEGF-C and VEGFR-3 were detected by using immunohistochemical technique for the detection of VEGF-C and its receptor VEGFR-3 in forty-seven breast cancer specimens. We measured the patients' circumferences of bilateral upper limbs to determine whether there was lymphoedema and made classification in the follow-ups. Results VEGF-C was positive in 33 out of 47 cases. PLVD significantly increased in VEGF-C positive groups (30.39±10. 46) than in negative groups (23.16±11.67) (P<0.05). VEGF-C semi-quantitative score was in a positive correlation with PLVD (r=0.334). The positive

  16. Joint Effect of Urinary Total Arsenic Level and VEGF-A Genetic Polymorphisms on the Recurrence of Renal Cell Carcinoma.

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    Shu-Mei Yang

    Full Text Available The results of our previous study suggested that high urinary total arsenic levels were associated with an increased risk of renal cell carcinoma (RCC. Germline genetic polymorphisms might also affect cancer risk and clinical outcomes. Vascular endothelial growth factor (VEGF plays an important role in vasculogenesis and angiogenesis, but the combined effect of these factors on RCC remains unclear. In this study, we explored the association between the VEGF-A -2578C>A, -1498T>C, -1154G>A, -634G>C, and +936C>T gene polymorphisms and RCC. We also evaluated the combined effects of the VEGF-A haplotypes and urinary total arsenic levels on the prognosis of RCC. This case-control study was conducted with 191 RCC patients who were diagnosed with renal tumors on the basis of image-guided biopsy or surgical resections. An additional 376 age- and gender-matched controls were recruited. Concentrations of urinary arsenic species were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Genotyping was investigated using fluorescent-based TaqMan allelic discrimination. We observed no significant associations between VEGF-A haplotypes and RCC risk. However, the VEGF-A ACGG haplotype from VEGF-A -2578, -1498, -1154, and -634 was significantly associated with an increased recurrence of RCC (OR = 3.34, 95% CI = 1.03-10.91. Urinary total arsenic level was significantly associated with the risk of RCC in a dose-response manner, but it was not related to the recurrence of RCC. The combination of high urinary total arsenic level and VEGF-A risk haplotypes affected the OR of RCC recurrence in a dose-response manner. This is the first study to show that joint effect of high urinary total arsenic and VEGF-A risk haplotypes may influence the risk of RCC recurrence in humans who live in an area without obvious arsenic exposure.

  17. Mangrove forest distributions and dynamics (19752005) of the tsunami-affected region of Asia

    Science.gov (United States)

    Giri, C.; Zhu, Z.; Tieszen, L.L.; Singh, A.; Gillette, S.; Kelmelis, J.A.

    2008-01-01

    Aim: We aimed to estimate the present extent of tsunami-affected mangrove forests and determine the rates and causes of deforestation from 1975 to 2005. Location: Our study region covers the tsunami-affected coastal areas of Indonesia, Malaysia, Thailand, Burma (Myanmar), Bangladesh, India and Sri Lanka in Asia. Methods: We interpreted time-series Landsat data using a hybrid supervised and unsupervised classification approach. Landsat data were geometrically corrected to an accuracy of plus-or-minus half a pixel, an accuracy necessary for change analysis. Each image was normalized for solar irradiance by converting digital number values to the top-of-the atmosphere reflectance. Ground truth data and existing maps and data bases were used to select training samples and also for iterative labelling. We used a post-classification change detection approach. Results: were validated with the help of local experts and/or high-resolution commercial satellite data. Results The region lost 12% of its mangrove forests from 1975 to 2005, to a present extent of c. 1,670,000 ha. Rates and causes of deforestation varied both spatially and temporally. Annual deforestation was highest in Burma (c. 1%) and lowest in Sri Lanka (0.1%). In contrast, mangrove forests in India and Bangladesh remained unchanged or gained a small percentage. Net deforestation peaked at 137,000 ha during 1990-2000, increasing from 97,000 ha during 1975-90, and declining to 14,000 ha during 2000-05. The major causes of deforestation were agricultural expansion (81%), aquaculture (12%) and urban development (2%). Main conclusions: We assessed and monitored mangrove forests in the tsunami-affected region of Asia using the historical archive of Landsat data. We also measured the rates of change and determined possible causes. The results of our study can be used to better understand the role of mangrove forests in saving lives and property from natural disasters such as the Indian Ocean tsunami, and to identify

  18. Glioblastoma-derived Leptin Induces Tube Formation and Growth of Endothelial Cells: Comparison with VEGF Effects

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    Otvos Laszlo

    2011-07-01

    Full Text Available Abstract Background Leptin is a pleiotropic hormone whose mitogenic and angiogenic activity has been implicated in the development and progression of several malignancies, including brain tumors. In human brain cancer, especially in glioblastoma multiforme (GBM, leptin and its receptor (ObR are overexpressed relative to normal tissue. Until present, the potential of intratumoral leptin to exert proangiogenic effects on endothelial cells has not been addressed. Using in vitro models, we investigated if GBM can express leptin, if leptin can affect angiogenic and mitogenic potential of endothelial cells, and if its action can be inhibited with specific ObR antagonists. Leptin effects were compared with that induced by the best-characterized angiogenic regulator, VEGF. Results We found that GBM cell lines LN18 and LN229 express leptin mRNA and LN18 cells secrete detectable amounts of leptin protein. Both lines also expressed and secreted VEGF. The conditioned medium (CM of LN18 and LN 229 cultures as well as 200 ng/mL pure leptin or 50 ng/mL pure VEGF stimulated proliferation of human umbilical vein endothelial cells (HUVEC at 24 h of treatment. Mitogenic effects of CM were ~2-fold greater than that of pure growth factors. Furthermore, CM treatment of HUVEC for 24 h increased tube formation by ~5.5-fold, while leptin increased tube formation by ~ 80% and VEGF by ~60% at 8 h. The mitogenic and angiogenic effects of both CM were blocked by Aca 1, a peptide ObR antagonist, and by SU1498, which inhibits the VEGF receptor. The best anti-angiogenic and cytostatic effects of Aca1 were obtained with 10 nM and 25 nM, respectively, while for SU1498, the best growth and angiogenic inhibition was observed at 5 μM. The combination of 5 μM SU1498 and Aca1 at 25 nM (growth inhibition or at 10 nM (reduction of tube formation produced superior effects compared with single agent treatments. Conclusions Our data provide the first evidence that LN18 and LN 229 human

  19. The pathophysiologic role of VEGF in hematologic malignancies: therapeutic implications.

    Science.gov (United States)

    Podar, Klaus; Anderson, Kenneth C

    2005-02-15

    Besides its role as an essential regulator of physiologic and pathologic angiogenesis, vascular endothelial growth factor (VEGF) triggers growth, survival, and migration of leukemia and multiple myeloma cells; plays a pivotal role in hematopoiesis; inhibits maturation of dendritic cells; and increases osteoclastic bone-resorbing activity as well as osteoclast chemotaxis. Dysregulation of VEGF expression and signaling pathways therefore plays an important role in the pathogenesis and clinical features of hematologic malignancies, in particular multiple myeloma. Direct and indirect targeting of VEGF and its receptors therefore may provide a potent novel therapeutic approach to overcome resistance to therapies and thereby improve patient outcome.

  20. Interrill erosion, runoff and sediment size distribution as affected by slope steepness and antecedent moisture content

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    M. B. Defersha

    2010-08-01

    Full Text Available Soil erosion is a two-phase process consisting of the detachment of individual particles and their transport by erosive agents such as flowing water. The rate at which erosion occurs depends upon the individual as well as interactive effects of different parameters responsible for soil erosion. The study discusses results of a laboratory analysis and evaluates the effect of slope steepness and antecedent moisture content on sediment yield (wash and runoff rate. Interrill sediment yield, splash detachment, runoff, and sediment size distribution were measured in laboratory erosion pans under simulated total duration of 90 min. Rainfall intensity at 120 mm/hr, 70 mm/hr, and 55 mm/hr were applied sequentially at 9, 25, and 45% slope steepness for three soils (Alemaya Black soil, Regosols, and Cambisols varied from clay to sandy clay loam in texture with wet and dry antecedent water contents. As slope steepness increased from 9 to 25% splash increased for five treatments and decreased for the remaining treatment; washed sediment increased for all treatments. As slope increased from 25 to 45% splash decreased for five treatments but increased for one treatment, and washed sediment increased for three treatments but decreased for the other three treatments. Pre-wetting decreased splash detachment for all soil treatments and rate of reduction was high for the highly aggregated soil, Alemaya Black soil and low for the less aggregated soil Regosols. Splash sediment and sediment yield was not correlated. Change in splash with increase in slope steepness was also not correlated with change in sediment yield. Change in runoff rate with increase in slope steepness was correlated (r=0.66 with change in sediment yield. For Alemaya Black soil and Regosols, splashed sediment size distribution was correlated with washed sediment size distribution. Interrill erosion models that include runoff and rainfall intensity parameters were a better fit for these data

  1. Photoperiod affects distribution of dynorphin A in the brain of Siberian hamster.

    Science.gov (United States)

    Meyza, Ksenia Z; Sotowska-Brochocka, Jolanta

    2006-01-01

    Dynorphin A1-77 (DYN A1-17) acting in the CNS is known to affect thermoregulation, water and energy balance in the short time scale. In this study a long-term alteration of these functions induced by changes of day length in the highly photoperiodic species, the Siberian hamster (Phodopus sungorus) was studied using immunohistochemistry for DYN A1-17. We found that in the long day (LD, L:D 16 h:8 h) more brain areas express DYN A1-17 peptide than in the short day (SD, L:D 8 h:16 h) conditions. Structures of the hypothalamo-pituitary axis as well as cells of the ependyma, subcomissural organ and choroid plexus of the lateral and third brain ventricles are immunoreactive to anti-dynorphin IgG only in the LD. This might indicate a seasonal regulatory role of DYN A1-17 in physiological adaptations to severe climate changes.

  2. Alters Intratumoral Drug Distribution and Affects Therapeutic Synergy of Antiangiogenic Organoselenium Compound

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    Youcef M. Rustum

    2010-01-01

    Full Text Available Tumor differentiation enhances morphologic and microvascular heterogeneity fostering hypoxia that retards intratumoral drug delivery, distribution, and compromise therapeutic efficacy. In this study, the influence of tumor biologic heterogeneity on the interaction between cytotoxic chemotherapy and selenium was examined using a panel of human tumor xenografts representing cancers of the head and neck and lung along with tissue microarray analysis of human surgical samples. Tumor differentiation status, microvessel density, interstitial fluid pressure, vascular phenotype, and drug delivery were correlated with the degree of enhancement of chemotherapeutic efficacy by selenium. Marked potentiation of antitumor activity was observed in H69 tumors that exhibited a well-vascularized, poorly differentiated phenotype. In comparison, modulation of chemotherapeutic efficacy by antiangiogenic selenium was generally lower or absent in well-differentiated tumors with multiple avascular hypoxic, differentiated regions. Tumor histomorphologic heterogeneity was found prevalent in the clinical samples studied and represents a primary and critical physiological barrier to chemotherapy.

  3. Is the distribution of Prochlorococcus and Synechococcus ecotypes in the Mediterranean Sea affected by global warming?

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    M. Ostrowski

    2011-05-01

    Full Text Available Biological communities populating the Mediterranean Sea, which is situated at the northern boundary of the subtropics, are often claimed to be particularly affected by global warming. This is indicated, for instance, by the introduction of (subtropical species of fish or invertebrates that can displace local species. This raises the question of whether microbial communities are similarly affected, especially in the Levantine basin where sea surface temperatures have risen in recent years. In this paper, the genetic diversity of the two most abundant members of the phytoplankton community, the picocyanobacteria Prochlorococcus and Synechococcus, was examined on a transect from the South coast of France to Cyprus in the summer of 2008 (BOUM cruise. Diversity was studied using dot blot hybridization with clade-specific 16S rRNA oligonucleotide probes and clone libraries of the 16S–23S ribosomal DNA Internal Transcribed Spacer (ITS region. Data were compared with those obtained during the PROSOPE cruise held almost a decade earlier, with a focus on the abundance of clades that may constitute bioindicators of warm waters. During both cruises, the dominant Prochlorococcus clade in the upper mixed layer at all stations was HLI, a clade typical of temperate waters, whereas the HLII clade, the dominant group in (subtropical waters, was only present at very low concentrations. The Synechococcus community was dominated by clades I, III and IV in the northwestern waters of the Gulf of Lions and by clade III and groups genetically related to clades WPC1 and VI in the rest of the Mediterranean Sea. In contrast, only a few sequences of clade II, a group typical of warm waters, were observed. These data indicate that local cyanobacterial populations have not yet been displaced by their (subtropical counterparts. This is discussed in the context of the low phosphorus concentrations found in surface waters in the eastern Mediterranean basin, as this may

  4. Do arbuscular mycorrhizal fungi affect cadmium uptake kinetics, subcellular distribution and chemical forms in rice?

    Science.gov (United States)

    Li, Hui; Luo, Na; Zhang, Li Jun; Zhao, Hai Ming; Li, Yan Wen; Cai, Quan Ying; Wong, Ming Hung; Mo, Ce Hui

    2016-11-15

    Rice (Oryza sativa L.) plants were inoculated with two species of arbuscular mycorrhizal fungi (AMF) - Rhizophagus intraradices (RI) and Funneliformis mosseae (FM) and grown for 60days to ensure strong colonization. Subsequently, a short-term hydroponic experiment was carried out to investigate the effects of AMF on cadmium (Cd) uptake kinetics, subcellular distribution and chemical forms in rice exposed to six Cd levels (0, 0.005, 0.01, 0.025, 0.05, 0.1mM) for three days. The results showed that the uptake kinetics of Cd fitted the Michaelis-Menten model well (R(2)>0.89). AMF significantly decreased the Cd concentrations both in shoots and roots in Cd solutions. Furthermore, the decrement of Cd concentrations by FM was significantly higher than RI treatment in roots. AMF reduced the Cd concentrations markedly in the cell wall fractions at high Cd substrate (≥0.025mM). The main subcellular fraction contributed to Cd detoxification was cell wall at low Cd substrate (<0.05mM), while vacuoles at high Cd substrate (≥0.05mM). Moreover, the concentrations and proportions of Cd in inorganic and water-soluble form also reduced by AMF colonization at high Cd substrate (≥0.05mM), both in shoots and roots. This suggested that AMF could convert Cd into inactive forms which were less toxic. Therefore, AMF could enhance rice resistance to Cd through altering subcellular distribution and chemical forms of Cd in rice.

  5. Circulating TFH subset distribution is strongly affected in lupus patients with an active disease.

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    Carole Le Coz

    Full Text Available Follicular helper T cells (TFH represent a distinct subset of CD4(+ T cells specialized in providing help to B lymphocytes, which may play a central role in autoimmune diseases having a major B cell component such as systemic lupus erythematosus. Recently, TFH subsets that share common phenotypic and functional characteristics with TFH cells from germinal centers, have been described in the peripheral blood from healthy individuals. The aim of this study was to analyze the distribution of such populations in lupus patients. Circulating TFH cell subsets were defined by multicolor flow cytometry as TFH17 (CXCR3(-CCR6(+, TFH1 (CXCR3 (+ CCR6(- or TFH2 (CXCR3(-CCR6(- cells among CXCR5 (+ CD45RA(-CD4(+ T cells in the peripheral blood of 23 SLE patients and 23 sex and age-matched healthy controls. IL-21 receptor expression by B cells was analyzed by flow cytometry and the serum levels of IL-21 and Igs were determined by ELISA tests. We found that the TFH2 cell subset frequency is strongly and significantly increased in lupus patients with an active disease (SLEDAI score>8, while the TFH1 cell subset percentage is greatly decreased. The TFH2 and TFH1 cell subset frequency alteration is associated with the presence of high Ig levels and autoantibodies in patient's sera. Moreover, the TFH2 cell subset enhancement correlates with an increased frequency of double negative memory B cells (CD27(-IgD(-CD19(+ cells expressing the IL-21R. Finally, we found that IgE levels in lupus patients' sera correlate with disease activity and seem to be associated with high TFH2 cell subset frequency. In conclusion, our study describes for the first time the distribution of circulating TFH cell subsets in lupus patients. Interestingly, we found an increased frequency of TFH2 cells, which correlates with disease activity. Our results suggest that this subset might play a key role in lupus pathogenesis.

  6. Distribution of organic carbon in physical fractions of soils as affected by agricultural management

    Energy Technology Data Exchange (ETDEWEB)

    Sindhu, Jagadamma [Oak Ridge National Laboratory (ORNL); Lal, Dr. Rattan [Ohio State University, The, Columbus

    2010-08-01

    Soil organic carbon (SOC) is distributed heterogeneously among different-sized primary particles and aggregates. Further, the SOC associated with different physical fractions respond differently to managements. Therefore, this study was conducted with the objective to quantify the SOC associated with all the three structural levels of SOC (particulate organic matter, soil separates and aggregate-size fractions) as influenced by long-term change in management. The study also aims at reevaluating the concept that the SOC sink capacity of individual size-fractions is limited. Long-term tillage and crop rotation effects on distribution of SOC among fractions were compared with soil from adjacent undisturbed area under native vegetation for the mixed, mesic, Typic Fragiudalf of Wooster, OH. Forty five years of no-till (NT) management resulted in more SOC accumulation in soil surface (0 7.5 cm) than in chisel tillage and plow tillage (PT) treatments. However, PT at this site resulted in a redistribution of SOC from surface to deeper soil layers. The soils under continuous corn accumulated significantly more SOC than those under corn soybean rotation at 7.5 45 cm depth. Although soil texture was dominated by the silt-sized particles, most of the SOC pool was associated with the clay fraction. Compared to PT, the NT treatment resulted in (i) significantly higher proportion of large macroaggregates (>2,000 m) and (ii) 1.5 2.8 times higher SOC concentrations in all aggregate-size classes. A comparative evaluation using radar graphs indicated that among the physical fractions, the SOC associated with sand and silt fractions quickly changed with a land use conversion from native vegetation to agricultural crops. A key finding of this study is the assessment of SOC sink capacity of individual fractions, which revealed that the clay fraction of agricultural soils continues to accumulate more SOC, albeit at a slower rate, with progressive increase in total SOC concentration

  7. Changing head model extent affects finite element predictions of transcranial direct current stimulation distributions

    Science.gov (United States)

    Indahlastari, Aprinda; Chauhan, Munish; Schwartz, Benjamin; Sadleir, Rosalind J.

    2016-12-01

    Objective. In this study, we determined efficient head model sizes relative to predicted current densities in transcranial direct current stimulation (tDCS). Approach. Efficiency measures were defined based on a finite element (FE) simulations performed using nine human head models derived from a single MRI data set, having extents varying from 60%-100% of the original axial range. Eleven tissue types, including anisotropic white matter, and three electrode montages (T7-T8, F3-right supraorbital, Cz-Oz) were used in the models. Main results. Reducing head volume extent from 100% to 60%, that is, varying the model’s axial range from between the apex and C3 vertebra to one encompassing only apex to the superior cerebellum, was found to decrease the total modeling time by up to half. Differences between current density predictions in each model were quantified by using a relative difference measure (RDM). Our simulation results showed that {RDM} was the least affected (a maximum of 10% error) for head volumes modeled from the apex to the base of the skull (60%-75% volume). Significance. This finding suggested that the bone could act as a bioelectricity boundary and thus performing FE simulations of tDCS on the human head with models extending beyond the inferior skull may not be necessary in most cases to obtain reasonable precision in current density results.

  8. Carbon amendment and soil depth affect the distribution and abundance of denitrifiers in agricultural soils.

    Science.gov (United States)

    Barrett, M; Khalil, M I; Jahangir, M M R; Lee, C; Cardenas, L M; Collins, G; Richards, K G; O'Flaherty, V

    2016-04-01

    The nitrite reductase (nirS and nirK) and nitrous oxide reductase-encoding (nosZ) genes of denitrifying populations present in an agricultural grassland soil were quantified using real-time polymerase chain reaction (PCR) assays. Samples from three separate pedological depths at the chosen site were investigated: horizon A (0-10 cm), horizon B (45-55 cm), and horizon C (120-130 cm). The effect of carbon addition (treatment 1, control; treatment 2, glucose-C; treatment 3, dissolved organic carbon (DOC)) on denitrifier gene abundance and N2O and N2 fluxes was determined. In general, denitrifier abundance correlated well with flux measurements; nirS was positively correlated with N2O, and nosZ was positively correlated with N2 (P soil (GCC) varied in response to carbon type amendment (P soil depth directly affected bacterial, archaeal, and denitrifier abundance, possibly due to changes in soil carbon availability with depth.

  9. How does the preparation of rye porridge affect molecular weight distribution of extractable dietary fibers?

    Science.gov (United States)

    Rakha, Allah; Aman, Per; Andersson, Roger

    2011-01-01

    Extractable dietary fiber (DF) plays an important role in nutrition. This study on porridge making with whole grain rye investigated the effect of rest time of flour slurries at room temperature before cooking and amount of flour and salt in the recipe on the content of DF components and molecular weight distribution of extractable fructan, mixed linkage (1→3)(1→4)-β-d-glucan (β-glucan) and arabinoxylan (AX) in the porridge. The content of total DF was increased (from about 20% to 23% of dry matter) during porridge making due to formation of insoluble resistant starch. A small but significant increase in the extractability of β-glucan (P = 0.016) and AX (P = 0.002) due to rest time was also noted. The molecular weight of extractable fructan and AX remained stable during porridge making. However, incubation of the rye flour slurries at increased temperature resulted in a significant decrease in extractable AX molecular weight. The molecular weight of extractable β-glucan decreased greatly during a rest time before cooking, most likely by the action of endogenous enzymes. The amount of salt and flour used in the recipe had small but significant effects on the molecular weight of β-glucan. These results show that whole grain rye porridge made without a rest time before cooking contains extractable DF components maintaining high molecular weights. High molecular weight is most likely of nutritional importance.

  10. How Does the Preparation of Rye Porridge Affect Molecular Weight Distribution of Extractable Dietary Fibers?

    Directory of Open Access Journals (Sweden)

    Roger Andersson

    2011-05-01

    Full Text Available Extractable dietary fiber (DF plays an important role in nutrition. This study on porridge making with whole grain rye investigated the effect of rest time of flour slurries at room temperature before cooking and amount of flour and salt in the recipe on the content of DF components and molecular weight distribution of extractable fructan, mixed linkage (1→3(1→4-β-D-glucan (β-glucan and arabinoxylan (AX in the porridge. The content of total DF was increased (from about 20% to 23% of dry matter during porridge making due to formation of insoluble resistant starch. A small but significant increase in the extractability of β-glucan (P = 0.016 and AX (P = 0.002 due to rest time was also noted. The molecular weight of extractable fructan and AX remained stable during porridge making. However, incubation of the rye flour slurries at increased temperature resulted in a significant decrease in extractable AX molecular weight. The molecular weight of extractable β-glucan decreased greatly during a rest time before cooking, most likely by the action of endogenous enzymes. The amount of salt and flour used in the recipe had small but significant effects on the molecular weight of β-glucan. These results show that whole grain rye porridge made without a rest time before cooking contains extractable DF components maintaining high molecular weights. High molecular weight is most likely of nutritional importance.

  11. Distribution of Pseudomonas Species in a Dairy Plant Affected by Occasional Blue Discoloration

    Science.gov (United States)

    Lomonaco, Sara; Nucera, Daniele; Garoglio, Davide; Dalmasso, Alessandra; Civera, Tiziana

    2014-01-01

    During 2010 many cases of discoloration in mozzarella, popularly termed as blue mozzarella, have been reported to the attention of public opinion. Causes of the alteration were bacteria belonging to the genus Pseudomonas. The strong media impact of such cases has created confusion, not only among consumers, but also among experts. In order to help improving the knowledge on microbial ecology of this microorganism a study has been set up with the collaboration of a medium-sized dairy plant producing fresh mozzarella cheese, with occasional blue discoloration, conducting surveys and sampling in the pre-operational, operational and post-operational process phase, milk before and after pasteurization, water (n=12), environmental surfaces (n=22) and the air (n=27). A shelf life test was conducted on finished products stored at different temperatures (4-8°C). Among the isolates obtained from the microbiological analysis of the samples, 60 were subjected to biomolecular tests in order to confirm the belonging to Pseudomonas genus and to get an identification at species level by the amplification and sequencing of the gyrB gene. The results of microbiological tests demonstrated the presence of microorganisms belonging to the genus Pseudomonas along the entire production lane; molecular tests showed 7 different species among the 40 isolates identified. One particular species (Pseudomonas koreensis) was isolated from blue discolored mozzarella cheese and was indicated as the most relevant for the production plant, both for the distribution along the processing chain and for the consequences on the finished product.

  12. Vertical Distribution and Seasonal Fluctuation of Nematode Trophic Groups as Affected by Land Use

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A field investigation was conducted at the Shenyang Experimental Station of Ecology, Chinese Academy of Sciences,in an aquic brown soil of Northeast China under three land use types (cropland, abandoned cropland, and woodland) in order to evaluate whether the vertical distribution and seasonal fluctuation for the number of total nematodes and trophic groups could reflect soil ecosystem differences and to determine the relationships between soil chemical properties and soil nematodes. The majority of soil nematodes were present in the 0-20 cm soil layers, and for these land use types plant parasites were the most abundant trophic group. In the abandoned cropland the numbers of plant parasites reached a peak on the August sampling date, whereas the cropland and woodland peaked on the October sampling date. Meanwhile,in all land use types the number of total nematodes, bacterivores, plant parasites, and omnivores-predators was negatively(P < 0.05, except for bacterivores in cropland, which was not significant) correlated with bulk density, and positively(P < 0.05, except for fungivores in abandoned cropland, which was not significant) correlated with total organic carbon and total nitrogen.

  13. Environmental stability affects phenotypic evolution in a globally distributed marine picoplankton

    Science.gov (United States)

    Schaum, C-Elisa; Rost, Björn; Collins, Sinéad

    2016-01-01

    Marine phytoplankton can evolve rapidly when confronted with aspects of climate change because of their large population sizes and fast generation times. Despite this, the importance of environment fluctuations, a key feature of climate change, has received little attention—selection experiments with marine phytoplankton are usually carried out in stable environments and use single or few representatives of a species, genus or functional group. Here we investigate whether and by how much environmental fluctuations contribute to changes in ecologically important phytoplankton traits such as C:N ratios and cell size, and test the variability of changes in these traits within the globally distributed species Ostreococcus. We have evolved 16 physiologically distinct lineages of Ostreococcus at stable high CO2 (1031±87 μatm CO2, SH) and fluctuating high CO2 (1012±244 μatm CO2, FH) for 400 generations. We find that although both fluctuation and high CO2 drive evolution, FH-evolved lineages are smaller, have reduced C:N ratios and respond more strongly to further increases in CO2 than do SH-evolved lineages. This indicates that environmental fluctuations are an important factor to consider when predicting how the characteristics of future phytoplankton populations will have an impact on biogeochemical cycles and higher trophic levels in marine food webs. PMID:26125683

  14. Patchy distributions of competitors affect the growth of a clonal plant when the competitor density is high.

    Directory of Open Access Journals (Sweden)

    Wei Xue

    Full Text Available Environments are patchy in not only abiotic factors but also biotic ones. Many studies have examined effects of spatial heterogeneity in abiotic factors such as light, water and nutrients on the growth of clonal plants, but few have tested those in biotic factors. We conducted a greenhouse experiment to examine how patchy distributions of competitors affect the growth of a rhizomatous wetland plant Bolboschoenus planiculmis and whether such effects depend on the density of the competitors. We grew one ramet of B. planiculmis in the center of each of the experimental boxes without competitors (Schoenoplectus triqueter, with a homogeneous distribution of the competitors of low or high density, and with a patchy distribution of the competitors of low or high density. The presence of competitors markedly decreased the growth (biomass, number of ramets, number of tubers and rhizome length of the B. planiculmis clones. When the density of the competitors was low, the growth of B. planiculmis did not differ significantly between the competitor patches and competitor-free patches. However, when the density of the competitors was high, the growth of B. planiculmis was significantly higher in the competitor-free patches than in the competitor patches. Therefore, B. planiculmis can respond to patchy distributions of competitors by placing more ramets in competition-free patches when the density of competitors is high, but cannot do so when the density of competitors is low.

  15. Patchy distributions of competitors affect the growth of a clonal plant when the competitor density is high.

    Science.gov (United States)

    Xue, Wei; Huang, Lin; Dong, Bi-Cheng; Zhang, Ming-Xiang; Yu, Fei-Hai

    2013-01-01

    Environments are patchy in not only abiotic factors but also biotic ones. Many studies have examined effects of spatial heterogeneity in abiotic factors such as light, water and nutrients on the growth of clonal plants, but few have tested those in biotic factors. We conducted a greenhouse experiment to examine how patchy distributions of competitors affect the growth of a rhizomatous wetland plant Bolboschoenus planiculmis and whether such effects depend on the density of the competitors. We grew one ramet of B. planiculmis in the center of each of the experimental boxes without competitors (Schoenoplectus triqueter), with a homogeneous distribution of the competitors of low or high density, and with a patchy distribution of the competitors of low or high density. The presence of competitors markedly decreased the growth (biomass, number of ramets, number of tubers and rhizome length) of the B. planiculmis clones. When the density of the competitors was low, the growth of B. planiculmis did not differ significantly between the competitor patches and competitor-free patches. However, when the density of the competitors was high, the growth of B. planiculmis was significantly higher in the competitor-free patches than in the competitor patches. Therefore, B. planiculmis can respond to patchy distributions of competitors by placing more ramets in competition-free patches when the density of competitors is high, but cannot do so when the density of competitors is low.

  16. Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

    Directory of Open Access Journals (Sweden)

    Yu-Yo Sun

    Full Text Available The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α through inhibition of prolyl hydrolase 2 (PHD2 and activation of the phosphatidylinositide-3 kinase (PI3K/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo and vascular endothelial growth factor (VEGF, two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.

  17. Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.

    Science.gov (United States)

    Sun, Yu-Yo; Lin, Shang-Hsuan; Lin, Hung-Cheng; Hung, Chia-Chi; Wang, Chen-Yu; Lin, Yen-Chu; Hung, Kuo-Sheng; Lien, Cheng-Chang; Kuan, Chia-Yi; Lee, Yi-Hsuan

    2013-01-01

    The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.

  18. VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Francois Labrousse; Yves Denizot

    2006-01-01

    @@ TO THE EDITOR We read with a great interest the recent work of Deli and colleagues.[1] in the World Journal of Gastroenterology reporting vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and cirrhotic liver tissues.

  19. Distribution of Pseudomonas species in a dairy plant affected by occasional blue discoloration

    Directory of Open Access Journals (Sweden)

    Francesco Chiesa

    2014-12-01

    Full Text Available During 2010 many cases of discoloration in mozzarella, popularly termed as blue mozzarella, have been reported to the attention of public opinion. Causes of the alteration were bacteria belonging to the genus Pseudomonas. The strong media impact of such cases has created confusion, not only among consumers, but also among experts. In order to help improving the knowledge on microbial ecology of this microorganism a study has been set up with the collaboration of a medium-sized dairy plant producing fresh mozzarella cheese, with occasional blue discoloration, conducting surveys and sampling in the pre-operational, operational and post-operational process phase, milk before and after pasteurization, water (n=12, environmental surfaces (n=22 and the air (n=27. A shelf life test was conducted on finished products stored at different temperatures (4-8°C. Among the isolates obtained from the microbiological analysis of the samples, 60 were subjected to biomolecular tests in order to confirm the belonging to Pseudomonas genus and to get an identification at species level by the amplification and sequencing of the gyrB gene. The results of microbiological tests demonstrated the presence of microorganisms belonging to the genus Pseudomonas along the entire production lane; molecular tests showed 7 different species among the 40 isolates identified. One particular species (Pseudomonas koreensis was isolated from blue discolored mozzarella cheese and was indicated as the most relevant for the production plant, both for the distribution along the processing chain and for the consequences on the finished product.

  20. Vascular endothelial growth factor (VEGF and prostate pathology

    Directory of Open Access Journals (Sweden)

    Francisco Botelho

    2010-08-01

    Full Text Available PURPOSE: Previous studies suggest that vascular endothelial growth factor (VEGF circulating levels might improve identification of patients with prostate cancer but results are conflicting. Our aim was to compare serum VEGF levels across different prostate pathologies (including benign prostatic hyperplasia, prostatitis, high grade prostate intraepithelial neoplasia and prostate cancer in patients at high risk of prostate cancer. MATERIALS AND METHODS: We consecutively enrolled 186 subjects with abnormal digital rectal examination and/or total PSA (tPSA = 2.5 ng/mL. Blood was collected before diagnostic ultrasound guided trans-rectal prostate biopsy, or any prostate oncology treatment, to measure PSA isoforms and VEGF. Unconditional logistic regression was used to compute age-, tPSA- and free/total PSA-adjusted odds ratios (OR and respective 95% confidence intervals (95% CI for the association between serum VEGF and different prostatic pathologies. RESULTS: Prostate biopsy main diagnoses were normal or benign prostatic hyperplasia (27.3%, prostatitis (16.6%, and prostatic cancer (55.0%. The median VEGF levels (ng/mL in these groups were 178.2, 261.3 and 266.4 (p = 0.029, respectively, but no significant differences were observed for benign vs. malignant pathologies (215.2 vs. 266.4, p = 0.551. No independent association was observed between VEGF (3rd vs. 1st third and prostate cancer, when compared to benign conditions (adjusted OR = 1.44; CI 95%: 0.64-3.26. CONCLUSIONS: In patients at high risk of prostate cancer, circulating VEGF levels have no clinical role in deciding which patients should be submitted to prostate biopsy. Prostatitis patients, often with higher PSA levels, also present high serum levels of VEGF, and their inclusion in control groups might explain the heterogeneous results in previous studies.

  1. Analysis of diabetic retinopathy biomarker VEGF gene by computational approaches

    OpenAIRE

    Jayashree Sadasivam; Ramesh, N.; K. Vijayalakshmi; Vinni Viridi; Shiva prasad

    2012-01-01

    Diabetic retinopathy, the most common diabetic eye disease, is caused by changes in the blood vessels of the retina which remains the major cause. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. One of the biomarker for Diabetic retinopathy has been identified as Vascular Endothelial Growth Factor ( VEGF )gene by computational analysis. VEGF is a sub-family of growth factors, the platelet-derived growth factor family of cystine-knot growth factors...

  2. Processes affecting the spatial distribution of seagrass meadow sedimentary material on Yao Yai Island, Thailand

    Science.gov (United States)

    Quak, Michelle S. Y.; Ziegler, Alan D.; Benner, Shawn G.; Evans, Sam; Todd, Peter A.; Gillis, Lucy G.; Vongtanaboon, Sukanya; Jachowski, Nick; Bouma, Tjeerd J.

    2016-12-01

    Many islands throughout SE Asia are experiencing rapid development and land-cover conversion that potentially threaten sensitive coastal ecosystems, such as seagrasses, through increased loading of sediment and nutrients originating from disturbed catchments draining to the sea. To evaluate this threat for one such island in Southern Thailand (Yao Yai), we perform sediment source tracing via end-member mixing analysis using stable isotopes δ13C and δ15N in organic matter to explore sediment loading in a seagrass meadow. The analysis indicates that sedimentary material in the meadow originates mostly from ocean-associated sources (∼62% from seagrass detritus, seston, and ocean sediments). Terrestrial material comprises ∼19% of the organic material found in the seagrass meadow, with another 20% originating from an adjacent mangrove forest. Approximately one-fourth of the seagrass meadow material (24%) is detritus that has been (re)deposited internally. The high contribution of terrestrial-derived organic matter deposited near the river mouth demonstrates that substantial quantities of sediment are being transferred from upslope erosion sources into the seagrass meadow. However, only a small amount of this material is deposited throughout the entire bay because much of the terrestrial- and mangrove-derived sediment is transferred to the open ocean via channels that are periodically dredged to allow boat access to two small inland harbours. This positive affect of dredging has not received very much attention in existing literature. River water flowing to the channels during falling tide delivers sediment to these efficient pathways, where much of it bypasses the seagrass meadow at periods of time when sediment deposition would normally be the greatest. There is growing concern that ongoing land-cover changes and planned urbanization related to tourism and agriculture on the island may boost sediment/nutrients above a critical threshold, beyond that revealed in

  3. Distribution of Exchangeable Calcium,Magnesium and Potassium as Affected by Fertilizer Application to Red Soil

    Institute of Scientific and Technical Information of China (English)

    SHENREN-FANG; ZHAOQI-GUO

    1995-01-01

    A leaching experiment was Carried out with repacked soil columns in laboratory to study the leaching process of a red soil derived from sandstone as affected by various fertilization practices.The treatments were CK(as a control),CaCO3,CaSO4,MgCO3,Ca(H2PO4)2,Urea,KCl,Multiple(a mixture of the above mentioned fertilizers) and KNO3,The fertilizers were added to the bare surface of the soil columns,and then the columns were leached with 120 mL deionized water daily through perstaltic pumps over a period of 92 days,At the end of leaching process,soils were sampled from different depths of the soil profiles ,i.o.,of 92 days,At the end of leaching process,soils were sampled from different depths of the soil profiles,I.e.0-5cm,5-10cm,10-20cm,20-40cm,and 40-60cm,The results showed when applying Ca,Mg,and K to the bare surface of the soil columns,exchangeable Ca2+,Mg2+,and K+ in the upper layer of the soil profile increased correspondingly,with an extent depending mainly on the application rates of Ca,Mg,and K and showing a downward trend,CaCO3,CaSO4,MgCO3,and Ca(H2PO4)2 treatments had scarcely and effect on movement of exchangeable K+,while CaCO3,and CaSO4 treatments singnificantly promoted the downward movement of exchangealble Mg2+ although these two treatments had no obvious effect on leaching losses of Mg,The fact that under Urea treatment,exchangeable Ca2+ and Mg2+,were higher as compared to CK treatment showed urea could prevent leaching of exchangeable Ca2+and Mg2+,the obvious downward movement of exchangeable Ca2+and Mg2+ was noticed in KCl treatment ,In Multiple treatment,the downward movement of exchangeable Ca2+ and Mg2+ was evident,while that of K+ was less evident,Application of KNO3 strongly promoted the downward movement of exchangeable Ca2+and Mg2+ in the soil profile.

  4. Study of distribution and factors affecting syphilis epidemic among inner-city minorities of Baltimore.

    Science.gov (United States)

    Williams, P B; Ekundayo, O

    2001-11-01

    Disparities in health and medical conditions among ethnic and racial groups have been repeatedly documented. These inequalities, which have been noted in the recent past, include health outcomes such as quality of life and mortality, process, accessibility and appropriateness of care, and the prevalence of certain degenerative conditions and infectious diseases. Syphilis, a sexually transmitted disease (STD) which seemed to have disappeared or had been controlled over the years, has now re-emerged as a major public health problem in many rural, urban and suburban communities. Progression of the current rate of syphilis, which erupted in Baltimore during the later part of 1994, has continued unabated, most especially among the ethnic minorities, despite efforts of the Baltimore City Health Department and Maryland Department of Health and Mental Hygiene to control the epidemic. With the current incidence rates of 270 per 100 000 live births for congenital syphilis and 99.3 per 100 000 population for primary, secondary and latent syphilis (96% of the cases being in the non-white population), Baltimore becomes the city with the highest number of syphilis cases in the nation, surpassing the national average of 2.6 cases per 100 000 population. This study, which utilizes a combination of retrospective and questionnaire-oriented approach, was designed to assess factors that influenced the high incidence of syphilis among Baltimore inner-city dwellers between 1994 and 1998. Data for the study included syphilis reports from private physicians, the Baltimore City Health Department, STD clinics, the Center for Disease Control (CDC), and ethnographic interviews. Factors favoring the distribution and infectivity of the disease among the inner-city dwellers include greater poverty, high level of communication gaps between providers and a cross-section of minority inner-city dwellers, exchange of sex for crack cocaine, lower educational background, and inadequate and

  5. Soil Tillage Management Affects Maize Grain Yield by Regulating Spatial Distribution Coordination of Roots, Soil Moisture and Nitrogen Status.

    Science.gov (United States)

    Wang, Xinbing; Zhou, Baoyuan; Sun, Xuefang; Yue, Yang; Ma, Wei; Zhao, Ming

    2015-01-01

    The spatial distribution of the root system through the soil profile has an impact on moisture and nutrient uptake by plants, affecting growth and productivity. The spatial distribution of the roots, soil moisture, and fertility are affected by tillage practices. The combination of high soil density and the presence of a soil plow pan typically impede the growth of maize (Zea mays L.).We investigated the spatial distribution coordination of the root system, soil moisture, and N status in response to different soil tillage treatments (NT: no-tillage, RT: rotary-tillage, SS: subsoiling) and the subsequent impact on maize yield, and identify yield-increasing mechanisms and optimal soil tillage management practices. Field experiments were conducted on the Huang-Huai-Hai plain in China during 2011 and 2012. The SS and RT treatments significantly reduced soil bulk density in the top 0-20 cm layer of the soil profile, while SS significantly decreased soil bulk density in the 20-30 cm layer. Soil moisture in the 20-50 cm profile layer was significantly higher for the SS treatment compared to the RT and NT treatment. In the 0-20 cm topsoil layer, the NT treatment had higher soil moisture than the SS and RT treatments. Root length density of the SS treatment was significantly greater than density of the RT and NT treatments, as soil depth increased. Soil moisture was reduced in the soil profile where root concentration was high. SS had greater soil moisture depletion and a more concentration root system than RT and NT in deep soil. Our results suggest that the SS treatment improved the spatial distribution of root density, soil moisture and N states, thereby promoting the absorption of soil moisture and reducing N leaching via the root system in the 20-50 cm layer of the profile. Within the context of the SS treatment, a root architecture densely distributed deep into the soil profile, played a pivotal role in plants' ability to access nutrients and water. An optimal

  6. Thrombospondin-1 and VEGF in inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Canan Alkim

    2012-01-01

    Full Text Available Angiogenesis is an important process in the pathogenesis of chronic inflammation. We aimed to study the angiogeneic balance in inflammatory bowel disease (IBD by evaluating the expression of vascular endothelial growth factor (VEGF and thrombospondin-1 (TSP-1 on colonic epithelial cells, together with the expression of inducible nitric oxide synthase (iNOS.Twenty-one ulcerative colitis (UC, 14 Crohn's disease (CD, 11 colorectal cancer patients, and 11 healthy controls colonic biopsy samples were evaluated immunohistochemically.The expressions of TSP-1, VEGF, and iNOS in UC and CD groups were higher than expression in healthy control group, all with statistical significance. However, in colorectal cancer group, VEGF and iNOS expressions were increased importantly, but TSP-1 expression was not statistically different from healthy control group's expression. Both TSP-1 and VEGF expressions were correlated with iNOS expression distinctly but did not correlate with each other.Both pro-angiogeneic VEGF and antiangiogeneic TSP-1 expressions were found increased in our IBD groups, but in colorectal cancer group, only VEGF expression was increased. TSP-1 increases in IBD patients as a response to inflammatory condition, but this increase was not enough to suppress pathologic angiogenesis and inflammation in IBD.

  7. Factors Affecting Distribution of Vegetation Types on Abandoned Cropland in the Hilly-Gullied Loess Plateau Region of China

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A study was conducted in the forest-steppe region of the Loess Plateau to provide insight into the factors affecting the process of vegetation establishment,and to provide recommendations for the selection of indigenous species in order to speed up the succession process and to allow the establishment of vegetation more resistant to soil erosion.Four distinctive vegetation types were identified,and their distribution was affected not only by the time since abandonment but also by other environmental factors,mainly soil water and total P in the upper soil layers.One of the vegetation types,dominated by Artemisia scoparia,formed the early successional stage after abandonment while the other three types formed later successional stages with their distribution determined by the soil water content and total P.It can be concluded that the selection of appropriate species for introduction to accelerate succession should be determined by the local conditions and especially the total P concentration and soil water content.

  8. The critical factors that affected the distribution of aboveground biomass in the alpine steppe and meadow, Tibetan Plateau

    Directory of Open Access Journals (Sweden)

    J. Sun

    2012-10-01

    Full Text Available Tibetan Plateau – the third pole of the world, with its extremly harsh and fragile ecological environment, is so sensitive to global change that it attracts many scientists' attention. Alpine grassland here is an important component of the global carbon cycle. Many studies have examined links between environmental factors and distribution of biomass, but little showed the critical environmental factors affecting the distribution of biomass. To document the general relationships between the habitat factors and aboveground biomass (AGB in Tibetan Plateau, and to identify the critical factors for the distribution of AGB in the alpine steppe and meadow, the data of AGB and habitat factors from 110 field sites across the widely distributed alpine steppe and meadow of the plateau were compiled and analyzed with the classification and regression tree (CART model, and the generalized additive model (GAM. The results showed that (1 the spatial pattern of AGB in alpine steppe was determined by six major environmental factors: soil organic carbon density of soil 0–30 cm depth (SOC1, longitude, mean annual precipitation (MAP, latitude, clay and soil moisture. As to the alpine meadow, the major factors were altitude, soil moisture, nitrogen, MAP and mean annual temperature (MAT. (2 As to the alpine steppe, increased SOC1, MAP and latitude were associated with increased AGB abundance, but increased longitude resulted in lower abundance of AGB. As to the alpine meadow, the distribution of AGB had strong negative relationships with altitude and soil moisture, but a positive correlation with soil nitrogen content across sites. The results suggested that the combined effects of meteorological factors, topographic factors, and soil factors were more significant for the spatial pattern of AGB in Tibetan Plateau. In addition, our work highlights the importance of further studies to seek effects of slope and aspect in alpine grassland.

  9. Electrochemical detection of vascular endothelial growth factors (VEGFs) using VEGF antibody fragments modified Au NPs/ITO electrode.

    Science.gov (United States)

    Kim, Gang-Il; Kim, Kyung-Woo; Oh, Min-Kyu; Sung, Yun-Mo

    2010-03-15

    A new electrochemical technique for the detection of vascular endothelial growth factors (VEGFs) as a cancer-related biomarker is presented in this paper. Gold nanoparticles (Au NPs) were self-assembled onto an indium tin oxide (ITO) electrode to prepare a modified sandwich type electrochemical immunoassay platform. VEGF antibodies were cleaved into two half-fragments by 2-mercaptoethylamine-HCl (2-MEA) and the fragments were immobilized onto the Au NP substrates by their thiol groups. Through this strategy, randomly oriented attachment of antibodies was prevented which frequently occurs in a general use of whole antibody and reduces the number of available sites for the attachment of target molecules. VEGF target molecules were applied to the immunoelectrodes and they combined with the antibody fragments covering the Au NP electrode, forming antigen-antibody complexes. Then, ferrocene-tagged antibodies, which release electrons under a proper applied potential, were added to the system and they combined with the VEGF molecules pre-attached to the antibody fragments. The redox current of ferrocene measured by the differential pulse voltammetry (DPV) increased almost linearly from 1.27 x 10(-4) to 4.17 x 10(-4)A according to the increase in the concentration of the VEGF target molecules from 100 to 600 pg/ml. The measured current values represent the concentration of the VEGF since they are proportional to the number of ferrocene molecules which is in turn proportional to the concentration of VEGF target molecules. Using this modified sandwich immunoassay with the Au NP/ITO electrode, VEGFs as low as 100 pg/ml were detected with high specificity.

  10. Accuracy of travel time distribution (TTD) models as affected by TTD complexity, observation errors, and model and tracer selection

    Science.gov (United States)

    Green, Christopher T.; Zhang, Yong; Jurgens, Bryant C.; Starn, J. Jeffrey; Landon, Matthew K.

    2014-01-01

    Analytical models of the travel time distribution (TTD) from a source area to a sample location are often used to estimate groundwater ages and solute concentration trends. The accuracies of these models are not well known for geologically complex aquifers. In this study, synthetic datasets were used to quantify the accuracy of four analytical TTD models as affected by TTD complexity, observation errors, model selection, and tracer selection. Synthetic TTDs and tracer data were generated from existing numerical models with complex hydrofacies distributions for one public-supply well and 14 monitoring wells in the Central Valley, California. Analytical TTD models were calibrated to synthetic tracer data, and prediction errors were determined for estimates of TTDs and conservative tracer (NO3−) concentrations. Analytical models included a new, scale-dependent dispersivity model (SDM) for two-dimensional transport from the watertable to a well, and three other established analytical models. The relative influence of the error sources (TTD complexity, observation error, model selection, and tracer selection) depended on the type of prediction. Geological complexity gave rise to complex TTDs in monitoring wells that strongly affected errors of the estimated TTDs. However, prediction errors for NO3− and median age depended more on tracer concentration errors. The SDM tended to give the most accurate estimates of the vertical velocity and other predictions, although TTD model selection had minor effects overall. Adding tracers improved predictions if the new tracers had different input histories. Studies using TTD models should focus on the factors that most strongly affect the desired predictions.

  11. Ghost of habitat past: historic habitat affects the contemporary distribution of giant garter snakes in a modified landscape.

    Science.gov (United States)

    Halstead, Brian J.; Wylie, Glenn D.; Casazza, Michael L.

    2014-01-01

    Historic habitat conditions can affect contemporary communities and populations, but most studies of historic habitat are based on the reduction in habitat extent or connectivity. Little is known about the effects of historic habitat on contemporary species distributions when historic habitat has been nearly completely removed, but species persist in a highly altered landscape. More than 93% of the historic wetlands in the Central Valley of California, USA, have been drained and converted to agricultural and other uses, but agricultural wetlands, such as rice and its supporting infrastructure of canals, allow some species to persist. Little is known about the distribution of giant garter snakes Thamnophis gigas, a rare aquatic snake species inhabiting this predominantly agricultural landscape, or the variables that affect where this species occurs. We used occupancy modeling to examine the distribution of giant garter snakes at the landscape scale in the Sacramento Valley (northern portion of the Central Valley) of California, with an emphasis on the relative strength of historic and contemporary variables (landscape-scale habitat, local microhabitat, vegetation composition and relative prey counts) for predicting giant garter snake occurrence. Proximity to historic marsh best explained variation in the probability of occurrence of giant garter snakes at the landscape scale, with greater probability of occurrence near historic marsh. We suspect that the importance of distance to historic marsh represents dispersal limitations of giant garter snakes. These results suggest that preserving and restoring areas near historic marsh, and minimizing activities that reduce the extent of marsh or marsh-like (e.g. rice agriculture, canal) habitats near historic marsh may be advantageous to giant garter snakes.

  12. Variations in Concentration and Distribution of Health-Related Elements Affected by Environmental and Genotypic Differences in Rice Grains

    Institute of Scientific and Technical Information of China (English)

    REN Xue-liang; LIU Qing-long; WU Dian-xing; SHU Qing-yao

    2006-01-01

    A research work was conducted to investigate the variations in concentration and distribution of health-related elements affected by environmental and genotypic differences in rice grains. The grain of Xieqingzao B (indica rice variety) and Xiushui 110 (japonica rice variety) were divided into: hull, bran and milled rice, based on the conventional rice consumption and process. Xieqingzao B was grown at four different locations, and at one location, it was planted in the same field and season as Xiushui 110. In addition, another four indica and four japonica varieties were cultivated in the same field and time to analyze the elements in milled rice. The average concentrations of total P and phytic acid P were the highest in the bran, followed by milled rice and hull; Zn, K, Mg, and As concentrations were the highest in bran, followed by hull and milled rice, while Fe, Ca, and Cu concentrations were the highest in the hull, but similar in bran and milled rice. The result indicated that genotype and environment significantly affected the concentrations of all the tested elements, while the distribution of the above elements in grains was not in the same order as concentration. Moreover, all the elements except 97.7% of Cu and 93.2% of Fe was deposited in the hull on average, were mostly distributed either in the bran (37.3% and 57.7% for K and phytic acid P) or in milled rice (41.7%, 42.6%, 40.3%, 49.8% for Zn, Mg, As, total P, respectively).

  13. The governance of natural resources: Issues affecting better management of revenues and distribution of benefits within Papua New Guinea

    Directory of Open Access Journals (Sweden)

    Hitelai Polume-Kiele

    2014-09-01

    Full Text Available Papua New Guinea is rich in natural resources, including minerals, oil, gas, timber and fish, and cash crops such as coffee, palm oil, cocoa, copra, rubber, tea and spices which contribute significantly to Papua New Guinea’s overall development. Several mining, oil and gas companies are currently operating in Porgera, Ok Tedi, Lihir, Hidden Valley, Sinivit, Simberi, Tolukuma, Kutubu and Gobe. The operations of these companies have generated an estimated K13.42 billion to Papua New Guinea’s economy. Landowners affected by these developments also receive royalties from those operations. However this wealth has not been translated into tangible human development across the country, as shown in persistently poorly performing social indicators. Instead income from the exploitation of natural resources is being used in unplanned projects and not focused on the delivery of core social functions, such as the provision of a stable and non-distorting policy aimed at building and sustaining the development of a modern market, and legislative and regulatory frameworks, social services, social security and social infrastructure which would lead to the improvement in the delivery of essential services to all Papua New Guineans. There is widespread evidence of benefits not being distributed to all landowners. Landowners are yet to fulfil their aspirations regarding these developments and to see improvements in their living standards. This paper discusses two case studies: the Porgera and Lihir mines, outlining the landowners associations’ experiences, which illustrate issues of governance and management of the distribution of benefit flows from the exploitation of Papua New Guinea’s natural resource wealth.The focus of the article’s discussion is on governance and management issues that affect the distribution of benefits, delivery of essential services to rural areas of PNG, stability within government, and the expectations of landowners.

  14. Porcine islet isolation outcome is not affected by the amount and distribution of collagen in the pancreas.

    Science.gov (United States)

    Hilling, Denise E; Rijkelijkhuizen, Josephine K R A; Töns, H Annemiek M; Terpstra, Onno T; Bouwman, Eelco

    2010-01-01

    Variable islet yields in porcine islet isolation may be caused by the collagen substrate within the pancreas. The aim of the present study was to determine the total amount and distribution of collagen within porcine pancreata and their relationship to islet isolation outcome. A total of 64 juvenile and 76 adult porcine pancreata of eight purebred breeds were histologically examined. The amount of collagen was quantitatively assessed in tissue samples stained with Sirius Red. Collagen distribution was semi-quantitatively determined by assessing the presence of collagen in the endocrine-exocrine interface and within the islet, in tissue samples stained with Sirius Red and anti-insulin. Islet isolation was performed in 58 pancreata of the adult group. Total collagen content and islet encapsulation ranged widely in both adult and juvenile pigs. However, the majority of islets in adult and juvenile pigs had no or only a limited collagen capsule. The difference in collagen content between adult and juvenile pigs could not be explained by age. Furthermore, no differences between adult and juvenile pigs were found in islet encapsulation or the amount of intra-islet collagen. In adult pigs, no significant relationships were found between obtained islet yield and total collagen content, islet encapsulation or amount of collagen within the islet. Considering the limitations in experimental design (staining method) and study material, isolation outcome does not seem to be affected by the total collagen content or collagen distribution. The influence of other matrix elements and collagen subtypes should be investigated.

  15. VEGF111b, a new member of VEGFxxxb isoforms and induced by mitomycin C, inhibits angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Fang; Li, Xiuli [Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing (China); Kong, Jian [Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing (China); Pan, Bing [The Institute of Cardiovascular Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing (China); Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing (China); Sun, Min [Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xian (China); Zheng, Lemin, E-mail: zhengl@bjmu.edu.cn [The Institute of Cardiovascular Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing (China); Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Key Laboratory of Molecular Cardiovascular Sciences of Education Ministry, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of Health Ministry, Beijing (China); Yao, Yuanqing, E-mail: yqyao@126.com [Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing (China)

    2013-11-08

    Highlights: •We discovered a new member of VEGFxxxb family-VEGF111b. •We found VEGF111b mRNA and protein can be induced by mitomycin C. •We confirmed VEGF111b over-expression inhibits angiogenesis. •VEGF111b inhibits angiogenesis through inhibiting VEGF-R2/PI3K/Akt and VEGF-R2/ERK1/2 phosphorylation. -- Abstract: Vascular endothelial growth factor (VEGF-A) stimulating angiogenesis is required for tumor growth and progression. The conventional VEGF-A isoforms have been considered as pro-angiogenic factors. Another family of VEGF-A isoforms generated by alternative splicing, termed VEGFxxxb isoforms, has anti-angiogenic property, exemplified by VEGF165b. Here, we identify a new number of VEGFxxx family-VEGF111b induced by mitomycin C, although not detected in mitomycin C-unexposed ovarian cancer cells. SKOV3 cells were transfected with pcDNA{sub 3.1} empty vector, pcDNA{sub 3.1}-VEGF111b or pcDNA{sub 3.1}-VEGF165b to collect conditioned mediums respectively. VEGF111b overexpression inhibits proliferation, migration and tube formation of endothelial cell by inhibiting VEGF-R2 phosphorylation and its downstream signaling, similar to VEGF165b but slightly lower than VEGF165b. The anti-angiogenic property depends on the six amino acids of exon 8b of the VEGFxxxb isoforms. Our results show that VEGF111b is a novel potent anti-angiogenic agent that can target the VEGF-R2 and its signaling pathway to inhibit ovarian tumor growth.

  16. Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA.

    Science.gov (United States)

    Hsu, Min-Yen; Hung, Yu-Chien; Hwang, De-Kuang; Lin, Shang-Chi; Lin, Keng-Hung; Wang, Chun-Yuan; Choi, Hin-Yeung; Wang, Yu-Ping; Cheng, Chao-Min

    2016-10-11

    Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies.

  17. CXCL7-Mediated Stimulation of Lymphangiogenic Factors VEGF-C, VEGF-D in Human Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Minghuan Yu

    2010-01-01

    Full Text Available Increased expression of lymphangiogenesis factors VEGF-C/D and heparanase has been correlated with the invasion of cancer. Furthermore, chemokines may modify matrix to facilitate metastasis, and they are associated with VEGF-C and heparanase. The chemokine CXCL7 binds heparin and the G-protein-linked receptor CXCR2. We investigated the effect of CXCR2 blockade on the expression of VEGF-C/D, heparanase, and on invasion. CXCL7 siRNA and a specific antagonist of CXCR2 (SB225002 were used to treat CXCL7 stably transfected MCF10AT cells. Matrigel invasion assays were performed. VEGF-C/D expression and secretion were determined by real-time PCR and ELISA assay, and heparanase activity was quantified by ELISA. SB225002 blocked VEGF-C/D expression and secretion (P<.01. CXCL7 siRNA knockdown decreased heparanase (P<.01. Both SB225002 and CXCL7 siRNA reduced the Matrigel invasion (P<.01. The MAP kinase signaling pathway was not involved. The CXCL7/CXCR2 axis is important for cell invasion and the expression of VEGF-C/D and heparanase, all linked to invasion.

  18. The expression of VEGF and its receptors in the human ductus arteriosus.

    Science.gov (United States)

    Weber, Sven C; Rheinlaender, Cornelia; Sarioglu, Nanette; Peiser, Christian; Rüdiger, Mario; Obladen, Michael; Koehne, Petra S

    2008-10-01

    Programmed proliferative degeneration of the human fetal ductus arteriosus (DA) preceding definite postnatal closure has a large developmental variability and is controlled by several signaling pathways. Among these vascular endothelial growth factor (VEGF) and its receptors (VEGF-Rs) play an important role. Until now, gestational age dependent expression of VEGF and its receptors has not been investigated in a large number of human DA tissue specimens. We examined protein expression of VEGF and the three VEGF-Rs immunohistochemically in 63 human fetal autopsy DA specimens of 11-38 wk gestation. Specimens were classified into different maturity stages according to their histologic appearance. VEGF and VEGF-Rs-staining was detected in all maturity stages. VEGF-staining was localized perinuclearly in all vascular layers and did not change during development. VEGF-R1 and VEGF-R3 expression was marked in the endothelium in early maturity stages and decreased during development. In contrast, -R2 predominated in the media in later developmental stages. Our results emphasize the importance of VEGF as a mediator during programmed proliferative degeneration of fetal DA and support the hypothesis that VEGF-R1 and VEGF-R3 are required for normal blood vessel development during embryogenesis. In contrast, VEGF-R2 is the predominant receptor in later angiogenic signaling.

  19. DNA methylation regulates expression of VEGF-C, and S-adenosylmethionine is effective for VEGF-C methylation and for inhibiting cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Da, M.X. [Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou (China); Zhang, Y.B. [Department of Surgery, Ningxia Medical University, Yinchuan (China); Yao, J.B. [Department of Surgical Oncology, Gansu Provincial Hospital, Lanzhou (China); Duan, Y.X. [Department of Surgery, Ningxia Medical University, Yinchuan (China)

    2014-09-30

    DNA hypomethylation may activate oncogene transcription, thus promoting carcinogenesis and tumor development. S-adenosylmethionine (SAM) is a methyl donor in numerous methylation reactions and acts as an inhibitor of intracellular demethylase activity, which results in hypermethylation of DNA. The main objectives of this study were to determine whether DNA hypomethylation correlated with vascular endothelial growth factor-C (VEGF-C) expression, and the effect of SAM on VEGF-C methylation and gastric cancer growth inhibition. VEGF-C expression was assayed by Western blotting and RT-qPCR in gastric cancer cells, and by immunohistochemistry in tumor xenografts. VEGF-C methylation was assayed by bisulfite DNA sequencing. The effect of SAM on cell apoptosis was assayed by flow cytometry analyses and its effect on cancer growth was assessed in nude mice. The VEGF-C promoters of MGC-803, BGC-823, and SGC-7901 gastric cancer cells, which normally express VEGF-C, were nearly unmethylated. After SAM treatment, the VEGF-C promoters in these cells were highly methylated and VEGF-C expression was downregulated. SAM also significantly inhibited tumor growth in vitro and in vivo. DNA methylation regulates expression of VEGF-C. SAM can effectively induce VEGF-C methylation, reduce the expression of VEGF-C, and inhibit tumor growth. SAM has potential as a drug therapy to silence oncogenes and block the progression of gastric cancer.

  20. Antiangiogenic VEGF-Ax: A New Participant in Tumor Angiogenesis.

    Science.gov (United States)

    Eswarappa, Sandeepa M; Fox, Paul L

    2015-07-15

    The transcript of the angiogenic factor vascular endothelial growth factor A (VEGF-A) is subject to a multitude of stimulus-dependent, posttranscriptional regulatory events, consistent with its unusually long 3' untranslated region. We have recently reported translational readthrough of VEGFA mRNA whereby translating ribosomes traverse the canonical stop codon to a conserved, downstream stop codon, generating VEGF-Ax ("x" for extended), a novel, extended isoform with an additional 22 amino acids appended at the C-terminus. This event is the first vertebrate example of protein-regulated, programmed translational readthrough that generates a protein with a known function. Remarkably, VEGF-Ax exhibits potent antiangiogenic activity, both in vitro and in vivo, thus raising profound clinical implications, particularly with respect to cancer treatment. In this review, we discuss the potential of VEGF-Ax as a therapeutic agent and drug target, as well as its possible role in the failure of, or resistance to, conventional anti-VEGF therapies in many types of cancers.

  1. Anti-VEGF Agents for Ocular Angiogenesis and Vascular Permeability

    Directory of Open Access Journals (Sweden)

    Kenichi Kimoto

    2012-01-01

    Full Text Available We review articles describing intravitreal injection of anti-VEGF drug trials, while discussing the mechanisms of the action of anti-VEGF antibodies, and also evaluating their outcomes. Intraocular injections of anti-VEGF drug are considered to be an effective treatment for macular edema after retinal vein occlusion, however, recurrent/persistent edema is common. The recent reports may lead to a shift in treatment paradigm for DME, from laser photocoagulation, to newer approaches using anti-VEGF drugs. There have been several well-publicized prospective, randomized studies that demonstrated the efficacy of intravitreal injection of anti-VEGF drugs for patients with AMD. Adjuvant bevacizumab for neovascular glaucoma may prevent further PAS formation, and it is likely to open up a therapeutic window for a panretinal photocoagulation and trabeculectomy. Intravitreal injection of bevacizumab (IVB results in a substantial decrease in bleeding from the retinal vessels or new vessels during a standard vitrectomy. IVB has also been reported to be effective for inducing the regression of new vessels in proliferative diabetic retinopathy. The use of bevacizumab in stage 4 or 5 retinopahty of permaturity (ROP is to reduce the plus sign to help reduce hemorrhage during the subsequent vitrectomy. Some authors reported cases of resolution of stage 4 A ROP after bevacizumab injection.

  2. SREBP inhibits VEGF expression in human smooth muscle cells.

    Science.gov (United States)

    Motoyama, Koka; Fukumoto, Shinya; Koyama, Hidenori; Emoto, Masanori; Shimano, Hitoshi; Maemura, Koji; Nishizawa, Yoshiki

    2006-03-31

    Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate expression of genes encoding enzymes for lipid biosynthesis. SREBPs are activated by HMG-CoA reductase inhibitors (statins). Statins have been also reported to suppress vascular endothelial growth factor (VEGF) expression in vascular smooth muscle cells (VSMCs). Therefore, we hypothesized that SREBPs are involved in statin-mediated regulation of VEGF production in VSMCs. SREBP1 was robustly expressed, and was activated by atorvastatin in VSMCs, as demonstrated by increased levels of the mature nuclear form of SREBP1, and increased promoter activities of a reporter containing sterol regulatory elements by atorvastatin. Moreover, overexpression of SREBP1a dose-dependently suppressed VEGF promoter activity. Site-specific mutation or deletion of the proximal Sp1 sites reduced the inhibitory effects of SREBP1a on VEGF promoter activity. These data demonstrated that SREBP1, activated by atorvastatin, suppressed VEGF expression through the indirect interaction with the proximal tandem Sp1 sites in VSMCs.

  3. VEGF Spliced Variants: Possible Role of Anti-Angiogenesis Therapy

    Directory of Open Access Journals (Sweden)

    Caroline Hilmi

    2012-01-01

    Full Text Available Angiogenesis has been targeted in retinopathies, psoriasis, and a variety of cancers (colon, breast, lung, and kidney. Among these tumour types, clear cell renal cell carcinomas (RCCs are the most vascularized tumours due to mutations of the von Hippel Lindau gene resulting in HIF-1 alpha stabilisation and overexpression of Vascular Endothelial Growth Factor (VEGF. Surgical nephrectomy remains the most efficient curative treatment for patients with noninvasive disease, while VEGF targeting has resulted in varying degrees of success for treating metastatic disease. VEGF pre-mRNA undergoes alternative splicing generating pro-angiogenic isoforms. However, the recent identification of novel splice variants of VEGF with anti-angiogenic properties has provided some insight for the lack of current treatment efficacy. Here we discuss an explanation for the relapse to anti-angiogenesis treatment as being due to either an initial or acquired resistance to the therapy. We also discuss targeting angiogenesis via SR (serine/arginine-rich proteins implicated in VEGF splicing.

  4. Trace metal distribution in pristine permafrost-affected soils of the Lena River Delta and its Hinterland, Northern Siberia, Russia

    Directory of Open Access Journals (Sweden)

    I. Antcibor

    2013-02-01

    Full Text Available Soils are an important compartment of ecosystems and have the ability to immobilize chemicals preventing their movement to other environment compartments. Predicted climatic changes together with other anthropogenic influences on Arctic terrestrial environments may affect biogeochemical processes enhancing leaching and migration of trace elements in permafrost-affected soils. This is especially important since the Arctic ecosystems are considered to be very sensitive to climatic changes as well as to chemical contamination. This study characterizes background levels of trace metals in permafrost-affected soils of the Lena River Delta and its hinterland in northern Siberia (73.5° N–69.5° N representing a remote region far from evident anthropogenic trace metal sources. Investigations on total element contents of iron (Fe, arsenic (As, manganese (Mn, zinc (Zn, nickel (Ni, copper (Cu, lead (Pb, cadmium (Cd, cobalt (Co and mercury (Hg in different soil types developed in different geological parent materials have been carried out. The highest concentrations of the majority of the measured elements were observed in soils belonging to ice-rich permafrost sediments formed during the Pleistocene (ice-complex in the Lena River Delta region. Correlation analyses of trace metal concentrations and soil chemical and physical properties at a Holocene estuarine terrace and two modern floodplain levels in the southern-central Lena River Delta (Samoylov Island showed that the main factors controlling the trace metal distribution in these soils are organic matter content, soil texture and contents of iron and manganese-oxides. Principal Component Analysis (PCA revealed that soil oxides play a significant role in trace metal distribution in both top and bottom horizons. Occurrence of organic matter contributes to Cd binding in top soils and Cu binding in bottom horizons. Observed ranges of the background concentrations of the majority of trace elements were

  5. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells.

    Science.gov (United States)

    Kimura, Hideki; Mikami, Daisuke; Kamiyama, Kazuko; Sugimoto, Hidehiro; Kasuno, Kenji; Takahashi, Naoki; Yoshida, Haruyoshi; Iwano, Masayuki

    2014-11-14

    Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  6. An experimental study of VEGF induced changes in vasoactivity in pig retinal arterioles and the influence of an anti-VEGF agent

    Directory of Open Access Journals (Sweden)

    Su Er-Ning

    2012-07-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF plays an important role in ocular physiology. Anti-VEGF agents are now used for treatment of common retinal diseases. This study characterises the vasoactive properties of VEGF in isolated perfused pig retinal arterioles under normal tone or endothelin-1 (ET-1 pre-contracted conditions and determines the influence of an anti VEGF agent on VEGF induced vasoactivity. Methods An isolated perfused retinal arteriole preparation was used. The outer diameter of retinal vessels was monitored at 2 second intervals in response to VEGF and the anti VEGF agent, bevacizumab. The effect of intraluminal delivery of VEGF was determined over a wide concentration range (10-16 to 10-7 M both with and without pre-contraction with ET-1 (3 x 10-9 M. Bevacizumab (0.35 mg mL-1 was applied extraluminally to determine the influence of bevacizumab on VEGF induced vasoactive changes on ET-1 pre-contracted vessels. Results In retinal arterioles with normal tone, VEGF induced a concentration dependent contraction at low concentrations, reaching 93.5% at 10-11 M and then contraction was reduced at higher concentrations, recovering to 98.1% at 10-7 M. VEGF produced a potent concentration dependent vasodilatation in arterioles pre-contracted with ET-1. VEGF induced vasodilatation in arterioles pre-contracted with ET-1 was significantly inhibited by bevacizumab. Conclusions VEGF induced vasoactive changes in pig retinal arterioles are dependent on concentration and vascular tone. Bevacizumab inhibits VEGF-induced vasodilatation in pre-contracted arterioles.

  7. Effect of antiprogesterone RU486 on VEGF expression and blood vessel remodeling on ovarian follicles before ovulation.

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    Annunziata Mauro

    Full Text Available BACKGROUND: The success of ovarian follicle growth and ovulation is strictly related to the development of an adequate blood vessel network required to sustain the proliferative and endocrine functions of the follicular cells. Even if the Vascular Endothelial Growth Factor (VEGF drives angiogenesis before ovulation, the local role exerted by Progesterone (P₄ remains to be clarified, in particular when its concentration rapidly increases before ovulation. AIM: This in vivo study was designed to clarify the effect promoted by a P₄ receptor antagonist, RU486, on VEGF expression and follicular angiogenesis before ovulation, in particular, during the transition from pre to periovulatory follicles induced by human Chorionic Gonadotropins (hCG administration. MATERIAL AND METHODS: Preovulatory follicle growth and ovulation were pharmacologically induced in prepubertal gilts by combining equine Chorionic Gonadotropins (eCG and hCG used in the presence or absence of RU486. The effects on VEGF expression were analyzed using biochemical and immunohistochemical studies, either on granulosa or on theca layers of follicles isolated few hours before ovulation. This angiogenic factor was also correlated to follicular morphology and to blood vessels architecture. RESULTS AND CONCLUSIONS: VEGF production, blood vessel network and follicle remodeling were impaired by RU486 treatment, even if the cause-effect correlation remains to be clarified. The P₄ antagonist strongly down-regulated theca VEGF expression, thus, preventing most of the angiogenic follicle response induced by hCG. RU486-treated follicles displayed a reduced vascular area, a lower rate of endothelial cell proliferation and a reduced recruitment of perivascular mural cells. These data provide important insights on the biological role of RU486 and, indirectly, on steroid hormones during periovulatory follicular phase. In addition, an in vivo model is proposed to evaluate how periovulatory

  8. Dynamics of aggregate stability and soil organic C distribution as affected by climatic aggressiveness: a mesocosm approach

    Science.gov (United States)

    Pellegrini, Sergio; Elio Agnelli, Alessandro; Costanza Andrenelli, Maria; Barbetti, Roberto; Castelli, Fabio; Costantini, Edoardo A. C.; Lagomarsino, Alessandra; Pasqui, Massimiliano; Tomozeiu, Rodica; Razzaghi, Somayyeh; Vignozzi, Nadia

    2014-05-01

    In the framework of a research project aimed at evaluating the adaptation scenarios of the Italian agriculture to the current climate change, a mesocosm experiment under controlled conditions was set up for studying the dynamics of soil aggregate stability and organic C in different size fractions. Three alluvial loamy soils (BOV - Typic Haplustalfs coarse-loamy; CAS - Typic Haplustalfs fine-loamy; MED - Typic Hapludalfs fine-loamy) along a climatic gradient (from dryer to moister pedoclimatic conditions) in the river Po valley (northern Italy), under crop rotation for animal husbandry from more than 40 years, were selected. The Ap horizons (0-30cm) were taken and placed in 9 climatic chambers under controlled temperature and rainfall. Each soil was subjected to three different climate scenarios in terms of erosivity index obtained by combining Modified Fournier and Bagnouls-Gaussen indexes: i) typical (TYP), the median year of each site related to the 1961-1990 reference period; ii) maximum aggressive year (MAX) observed in the same period, and iii) the simulated climate (SIM), obtained by projections of climate change precipitation and temperature for the period 2021-2050 as provided by the IPCC-A1B emission scenario. In the climatic chambers the year climate was reduced to six months. The soils were analyzed for particle size distribution, aggregate stability by wet and dry sieving, and organic C content at the beginning and at the end of the trial. The soils showed different behaviour in terms of aggregate stability and dynamics of organic C in the diverse size fractions. The soils significantly differed in terms of initial mean weight diameter (MWD) (CAS>MED>BOV). A general reduction of MWD in all sites was observed at the end of the experiment, with the increase of the smallest aggregate fractions (0.250-0.05 mm). In particular, BOV showed the maximum decrease of the aggregate stability and MED the lowest. C distribution in aggregate fractions significantly

  9. Subtle changes in bone mineralization density distribution in most severely affected patients with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Misof, B M; Roschger, P; Jorgetti, V; Klaushofer, K; Borba, V Z C; Boguszewski, C L; Cohen, A; Shane, E; Zhou, H; Dempster, D W; Moreira, C A

    2015-10-01

    Chronic obstructive pulmonary disease (COPD) is associated with low aBMD as measured by DXA and altered microstructure as assessed by bone histomorphometry and microcomputed tomography. Knowledge of bone matrix mineralization is lacking in COPD. Using quantitative backscatter electron imaging (qBEI), we assessed cancellous (Cn.) and cortical (Ct.) bone mineralization density distribution (BMDD) in 19 postmenopausal women (62.1 ± 7.3 years of age) with COPD. Eight had sustained fragility fractures, and 13 had received treatment with inhaled glucocorticoids. The BMDD outcomes from the patients were compared with healthy reference data and were correlated with previous clinical and histomorphometric findings. In general, the BMDD outcomes for the patients were not significantly different from the reference data. Neither the subgroups of with or without fragility fractures or of who did or did not receive inhaled glucocorticoid treatment, showed differences in BMDD. However, subgroup comparison according to severity revealed 10% decreased cancellous mineralization heterogeneity (Cn.CaWidth) for the most severely affected compared with less affected patients (p=0.042) and compared with healthy premenopausal controls (p=0.021). BMDD parameters were highly correlated with histomorphometric cancellous bone volume (BV/TV) and formation indices: mean degree of mineralization (Cn.CaMean) versus BV/TV (r=0.58, p=0.009), and Cn.CaMean and Ct.CaMean versus bone formation rate (BFR/BS) (r=-0.71, p50th percentile) BV/TV. The normality in most of the BMDD parameters and bone formation rates as well as the significant correlations between them suggests unaffected mineralization processes in COPD. Our findings also indicate no significant negative effect of treatment with inhaled glucocorticoids on the bone mineralization pattern. However, the observed concomitant occurrence of relatively lower bone volumes with lower bone matrix mineralization will both contribute to the reduced a

  10. Vertical distribution of radiocesium in soils of the area affected by the Fukushima Dai-ichi nuclear power plant accident

    Science.gov (United States)

    Konoplev, A. V.; Golosov, V. N.; Yoschenko, V. I.; Nanba, K.; Onda, Y.; Takase, T.; Wakiyama, Y.

    2016-05-01

    Presented are results of the study of radiocesium vertical distribution in the soils of the irrigation pond catchments in the near field 0.25 to 8 km from the Fukushima Dai-ichi NPP, on sections of the Niida River floodplain, and in a forest ecosystem typical of the territory contaminated after the accident. It is shown that the vertical migration of radiocesium in undisturbed forest and grassland soils in the zone affected by the Fukushima accident is faster than it was in the soils of the 30-km zone of the Chernobyl NPP for a similar time interval after the accident. The effective dispersion coefficients in the Fukushima soils are several times higher than those for the Chernobyl soils. This may be associated with higher annual precipitation (by about 2.5 times) in Fukushima as compared to the Chernobyl zone. In the forest soils the radiocesium dispersion is faster as compared to grassland soils, both in the Fukushima and Chernobyl zones. The study and analysis of the vertical distribution of the Fukushima origin radiocesium in the Niida gawa floodplain soils has made it possible to identify areas of contaminated sediment accumulation on the floodplain. The average accumulation rate for sediments at the study locations on the Niida gawa floodplain varied from 0.3 to 3.3 cm/year. Taking into account the sediments accumulation leading to an increase in the radiocesium inventory in alluvial soils is key for predicting redistribution of radioactive contamination after the Fukushima accident on the river catchments, as well as for decision-making on contaminated territories remediation and clean-up. Clean-up of alluvial soils does not seem to be worthwhile because of the following accumulation of contaminated sediments originating from more contaminated areas, including the exclusion zone.

  11. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Hideki, E-mail: hkimura@u-fukui.ac.jp [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Mikami, Daisuke; Kamiyama, Kazuko [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Sugimoto, Hidehiro [Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Kasuno, Kenji; Takahashi, Naoki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yoshida, Haruyoshi [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Division of Nephrology, Obama Municipal Hospital, Obama, Fukui (Japan); Iwano, Masayuki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)

    2014-11-14

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  12. Extracellular Matrix Stiffness Controls VEGF Signaling and Processing in Endothelial Cells.

    Science.gov (United States)

    Sack, Kelsey D; Teran, Madelane; Nugent, Matthew A

    2016-09-01

    Vascular endothelial growth factor A (VEGF) drives endothelial cell maintenance and angiogenesis. Endothelial cell behavior is altered by the stiffness of the substrate the cells are attached to suggesting that VEGF activity might be influenced by the mechanical cellular environment. We hypothesized that extracellular matrix (ECM) stiffness modifies VEGF-cell-matrix tethering leading to altered VEGF processing and signaling. We analyzed VEGF binding, internalization, and signaling as a function of substrate stiffness in endothelial cells cultured on fibronectin (Fn) linked polyacrylamide gels. Cell produced extracellular matrices on the softest substrates were least capable of binding VEGF, but the cells exhibited enhanced VEGF internalization and signaling compared to cells on all other substrates. Inhibiting VEGF-matrix binding with sucrose octasulfate decreased cell-internalization of VEGF and, inversely, heparin pre-treatment to enhance Fn-matrix binding of VEGF increased cell-internalization of VEGF regardless of matrix stiffness. β1 integrins, which connect cells to Fn, modulated VEGF uptake in a stiffness dependent fashion. Cells on hard surfaces showed decreased levels of activated β1 and inhibition of β1 integrin resulted in a greater proportional decrease in VEGF internalization than in cells on softer matrices. Extracellular matrix binding is necessary for VEGF internalization. Stiffness modifies the coordinated actions of VEGF-matrix binding and β1 integrin binding/activation, which together are critical for VEGF internalization. This study provides insight into how the microenvironment may influence tissue regeneration and response to injury and disease. J. Cell. Physiol. 231: 2026-2039, 2016. © 2016 Wiley Periodicals, Inc.

  13. Profile Distributions of Dissolved and Colloidal Phosphorus as Affected by Degree of Phosphorus Saturation in Paddy Soil

    Institute of Scientific and Technical Information of China (English)

    ZANG Ling; TIAN Guang-Ming; LIANG Xin-Qing; HE Miao-Miao; BAO Qi-Bei; YAO Jin-Hua

    2013-01-01

    Soil dissolved phosphorus (P) and colloidal P mobilization could be closely related to the degree of phosphorus saturation (DPS).Effects of a wide range of DPS on the distributions of dissolved P and colloidal P in a paddy soil profile were investigated in this study.Dissolved P and colloidal P in water-dispersible soil colloid suspension increased obviously with increasing DPS.The change point of DPS was at 0.12 by using a split-line model.Above the value,dissolved P (3.1 mg P kg-1) in soil profile would increase sharply and then transfer downward.Compared with dissolved P,colloidal P was the dominant fraction (78%-91%) of P in soil colloid suspension,and positively related to DPS without a significant change point.The high release of colloids in subsoils with low DPS was attributed to the low ionic strength and high pH value in subsoils.The DPS also had a significant and positive correlation with electrical conductivity (EC),but it showed a negative correlation with pH value.However,the concentration of colloidal P was not greatly correlated to the pH value,EC and optical density of the soil colloid suspension.The results indicated that DPS was an important factor that may affect the accumulation and mobilization of water-extractable colloidal P and dissolved P.

  14. Vertical Distribution of Cadmium and Lead on Soils Affected by Metropolitan Refuse Disposal in Owerri, Southeastern Nigeria

    Directory of Open Access Journals (Sweden)

    E.U. Onweremadu

    2011-01-01

    Full Text Available The authors investigated distribution of cadmium (Cd and lead (Pb in soil profile pits affected by municipal solid wastes in Avu dumpsite in Owerri, Southeastern Nigeria in 2010. Transect soil survey technique was used in aligning profile pits for field studies and sampling. Standard procedures were used in digging, describing and sampling from profile pits. Sieved soil samples were subjected to laboratory analyses and data were analyzed statistically using coefficient of variation measured in percentages. Results showed higher values of % CV in silt and clay contents. Variability of clay increased from dumpsite (CV=43.77 % to moderately dumped site (CV=62.73% decreased in slightly dumped side (20.98%. Highest mean values of organic matter (26.8 g/kg and pH water (5.7 were reported in heavily dumped site. Organic Matter showed very significant positive relationship with Cd (r = 0.92; p = 0.01 and Pb (r=0.97; P = 0.97. There is need to include more soil attributes; results of which should be subjected to multi-variate techniques for more reliability and confidence especially in field applications.

  15. The Hydrological Regimes Brought by the Three Gorges Project Affected Riparian Vegetation Distribution and Diversity in 2009 and 2010

    Science.gov (United States)

    Miao, Ling-Feng; Liu, Wei-Wei; Yang, Fan

    2017-01-01

    Post-dam riparian vegetations affected by the new hydrological regimes in the Three Gorges Reservoir (TGR) were investigated in 2009 and 2010, respectively. The investigation in 2009 showed that about 231 vascular plant species belonging to 169 genera of 61 families were distributed in the water-level-fluctuation zone (WLFZ) of the (TGR). Three vegetation types, including Chuanjiang, Gorge, and other vegetation types, were classified efficiently via cluster analysis. Alpha diversity analysis indicated that species richness gradually decreased with decreasing elevation. Beta diversity analysis indicated that high environment heterogeneity was existed between the lower section and the other two sections, and environment homogeneity was also existed between middle section and upper section. Using the analysis of the field growth in the 2009 and 2010 field surveys as bases, we proposed a list of perennial herb species and woody species that may potentially occurred in the WLFZ of the TGR. In addition, we predicted plant community structural changes in the different altitude sections of WLFZ in the future.

  16. Pharmacokinetics and tolerability of cediranib, a potent VEGF signalling inhibitor, in cancer patients with hepatic impairment

    DEFF Research Database (Denmark)

    van Herpen, Carla M L; Lassen, Ulrik; Desar, Ingrid M E

    2013-01-01

    Vascular endothelial growth factor (VEGF) signalling plays a key role in tumour angiogenesis. Cediranib (AZD2171) is a small-molecule VEGF signalling inhibitor with potent activity against all three VEGF receptors. In this phase I, open-label, parallel-group study, adults with advanced solid tumo...

  17. Pharmacokinetics and tolerability of cediranib, a potent VEGF signalling inhibitor, in cancer patients with hepatic impairment

    NARCIS (Netherlands)

    Herpen, C.M.L. van; Lassen, U.; Desar, I.M.E.; Brown, K.H.; Marotti, M.; Jonge, M.J. de

    2013-01-01

    Vascular endothelial growth factor (VEGF) signalling plays a key role in tumour angiogenesis. Cediranib (AZD2171) is a small-molecule VEGF signalling inhibitor with potent activity against all three VEGF receptors. In this phase I, open-label, parallel-group study, adults with advanced solid tumours

  18. Biological variations in plasma VEGF and VEGFR-1 may compromise their biomarker value in colorectal cancer

    DEFF Research Database (Denmark)

    Svendsen, Mads N.; Brunner, Nils; Christensen, Ib Jarle;

    2010-01-01

    Vascular Endothelial Growth Factor (VEGF) plays a prominent role in tumor angiogenesis and plasma VEGF concentration may carry prognostic information in colorectal cancer. The VEGF receptor 1 (VEGFR-1) is a regulatory receptor which is shredded into plasma of patients with colorectal cancer. For ...

  19. Opiate receptor blockade on human granulosa cells inhibits VEGF release.

    Science.gov (United States)

    Lunger, Fabian; Vehmas, Anni P; Fürnrohr, Barbara G; Sopper, Sieghart; Wildt, Ludwig; Seeber, Beata

    2016-03-01

    The objectives of this study were to determine whether the main opioid receptor (OPRM1) is present on human granulosa cells and if exogenous opiates and their antagonists can influence granulosa cell vascular endothelial growth factor (VEGF) production via OPRM1. Granulosa cells were isolated from women undergoing oocyte retrieval for IVF. Complementary to the primary cells, experiments were conducted using COV434, a well-characterized human granulosa cell line. Identification and localization of opiate receptor subtypes was carried out using Western blot and flow cytometry. The effect of opiate antagonist on granulosa cell VEGF secretion was assessed by enzyme-linked immunosorbent assay. For the first time, the presence of OPRM1 on human granulosa cells is reported. Blocking of opiate signalling using naloxone, a specific OPRM1 antagonist, significantly reduced granulosa cell-derived VEGF levels in both COV434 and granulosa-luteal cells (P opiate receptors and opiate signalling in granulosa cells suggest a possible role in VEGF production. Targeting this signalling pathway could prove promising as a new clinical option in the prevention and treatment of ovarian hyperstimulation syndrome.

  20. Programmed translational readthrough generates antiangiogenic VEGF-Ax.

    Science.gov (United States)

    Eswarappa, Sandeepa M; Potdar, Alka A; Koch, William J; Fan, Yi; Vasu, Kommireddy; Lindner, Daniel; Willard, Belinda; Graham, Linda M; DiCorleto, Paul E; Fox, Paul L

    2014-06-19

    Translational readthrough, observed primarily in less complex organisms from viruses to Drosophila, expands the proteome by translating select transcripts beyond the canonical stop codon. Here, we show that vascular endothelial growth factor A (VEGFA) mRNA in mammalian endothelial cells undergoes programmed translational readthrough (PTR) generating VEGF-Ax, an isoform containing a unique 22-amino-acid C terminus extension. A cis-acting element in the VEGFA 3' UTR serves a dual function, not only encoding the appended peptide but also directing the PTR by decoding the UGA stop codon as serine. Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 binds this element and promotes readthrough. Remarkably, VEGF-Ax exhibits antiangiogenic activity in contrast to the proangiogenic activity of VEGF-A. Pathophysiological significance of VEGF-Ax is indicated by robust expression in multiple human tissues but depletion in colon adenocarcinoma. Furthermore, genome-wide analysis revealed AGO1 and MTCH2 as authentic readthrough targets. Overall, our studies reveal a novel protein-regulated PTR event in a vertebrate system.

  1. Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA

    OpenAIRE

    Min-Yen Hsu; Yu-Chien Hung; De-Kuang Hwang; Shang-Chi Lin; Keng-Hung Lin; Chun-Yuan Wang; Hin-Yeung Choi; Yu-Ping Wang; Chao-Min Cheng

    2016-01-01

    Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with...

  2. ScVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA conjugates: comparison of easy-to-label recombinant proteins for [{sup 68}Ga]PET imaging of VEGF receptors in angiogenic vasculature

    Energy Technology Data Exchange (ETDEWEB)

    Eder, Matthias [German Cancer Research Center (DKFZ), 69120 Heidelberg (Germany)], E-mail: m.eder@dkfz.de; Krivoshein, Arcadius V.; Backer, Marina; Backer, Joseph M. [SibTech, Inc., Brookfield, CT 06804 (United States); Haberkorn, Uwe [Department of Nuclear Medicine, University of Heidelberg, 69120 Heidelberg (Germany); Eisenhut, Michael [German Cancer Research Center (DKFZ), 69120 Heidelberg (Germany)

    2010-05-15

    Introduction: VEGF receptors play a key role in angiogenesis and are important targets for several approved and many experimental drugs. Imaging of VEGF receptor expression in malignant tumors would provide important information, which can influence patient management. The aim of this study was the development of an easy-to-label positron-emitting tracer for imaging VEGF receptors. The tracer is based on engineered single-chain VEGF (scVEGF), expressed with cysteine-containing fusion tag (Cys-tag) for site-specific conjugation of PEGylated bifunctional chelating agents, HBED-CC or NOTA, suitable for labeling with {sup 68}Ga at ambient temperature. Methods: scVEGF-PEG-HBED-CC was synthesized by activating a single carboxyl group of the [Fe(HBED-CC)]{sup -} complex with N-hydroxysuccinimide. Reaction of the activated complex with NH{sub 2}-PEG-maleimide was followed by site-specific conjugation of PEGylated chelator to a thiol group in Cys-tag of scVEGF. The scVEGF-PEG-NOTA conjugate was synthesized using NHS-PEG-maleimide and p-NH{sub 2}-Bn-NOTA. {sup 68}Ga complexation was performed in HEPES buffer (pH 4.2) at room temperature. The functional activity after labeling was tested by radioligand cell binding assays. Biodistribution and PET studies in tumor-bearing mice were performed after 1, 2, 3 and 4 h postinjection. Results: The radiolabeling of scVEGF-PEG-HBED-CC proved more efficient than scVEGF-PEG-NOTA allowing to stop the reaction after 4 min (>97% radiochemical yield). Radioligand cell binding assays performed on HEK-293 cells overexpressing VEGFR-2 revealed no change in the binding properties of {sup 68}Ga-radiolabeled scVEGF relative to other scVEGF-based tracers. Both tracers showed comparable results in biodistribution, such as tumor accumulation and low liver uptake. The tracers were stable in 50% human serum for at least 72 h. Conclusions: The conjugates scVEGF-PEG-HBED-CC and scVEGF-PEG-NOTA revealed comparable in vivo characteristics and allowed easy

  3. The relationship of the angiogenesis regulators VEGF-A, VEGF-R1 and VEGF-R2 to p53 status and prognostic factors in epithelial ovarian carcinoma in FIGO-stages I-II.

    Science.gov (United States)

    Skirnisdottir, Ingiridur; Seidal, Tomas; Åkerud, Helena

    2016-03-01

    The aim of this study was to evaluate prognostic effect of the angiogenesis regulators VEGF-R1, VEGF-R2 and VEGF-A for recurrent disease and disease-free survival (DFS), and their relation to the apoptosis regulator p53, in 131 patients with FIGO-stages I-II with epithelial ovarian cancer. For the detection of positivity of the markers the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of positive staining for VEGF-R1 was 19%, for VEGF-R2 and VEGF-A, it was 77 and 70%, respectively. Positivity for p53 was detected in 25% of tumors. The total number of recurrences in the complete series was 34 out of 131 (26%) and 5-year disease-free survival (DFS) was 68%. Positive staining for VEGF-A (P=0.030), VEGF-R2 (P=0.011) and p53 (P=0.015) was found more frequently in type II tumors than in type I tumors. Patients with VEGF-R1 negative tumors had worse (P=0.021) DFS compared to patients with VEGF-R1 positive tumors. In two multivariate Cox analyzes with DFS as endpoint, FIGO-stage (HR=3.8), VEGF-R2 status (HR=0.4) and p53 status (HR=2.3), all were significant and independent prognostic factors. When the variables VEGF-R2 and p53 were replaced with the new variable VEGF-R2+p53-/other three combinations in one group, it was found that patients from that subgroup had 86% reduced risk of dying in disease (HR=0.24). Findings above, confirmed relationship between VEGF-R2 and VEGF-A and p53, respectively, with regard to recurrent disease and survival. Some findings from the present study are different from results from previous studies on the regulation of angiogenesis. Despite many trials with anti-angiogenic agents in the front line of ovarian cancer have shown to be positive for progression-free survival, no one has demonstrated an impact on overall survival. Therefore, one of the greatest challenges in ovarian cancer research, is to discover predictive and prognostic biomarkers.

  4. The prognosis was poorer in colorectal cancers that expressed both VEGF and PROK1 (No correlation coefficient between VEGF and PROK1).

    Science.gov (United States)

    Goi, Takanori; Nakazawa, Toshiyuki; Hirono, Yasuo; Yamaguchi, Akio

    2015-10-06

    The angiogenic proteins vascular endothelial growth factor (VEGF) and prokineticin1 (PROK1) proteins are considered important in colorectal cancer, the relationship between their simultaneous expression and prognosis was investigated in the present study. VEGF and PROK1 expression in 620 primary human colorectal cancer lesions was confirmed via immunohistochemical staining with anti-VEGF and anti-PROK1 antibodies, and the correlation between the expression of these 2 proteins and recurrence/prognosis were investigated. VEGF protein was expressed in 329 (53.1%) and PROK1 protein was expressed in 223 (36.0%). PROK1 and VEGF were simultaneously expressed in 116 (18.7%) of the 620 cases. The correlation coefficient between VEGF expression and PROK1 expression was r = 0.11, and therefore correlation was not observed. Clinical pathology revealed that substantially lymphnode matastasis, hematogenous metastasis, or TMN advanced-stage IV was significantly more prevalent in cases that expressed both VEGF and PROK1 than in the cases negative for both proteins or those positive for only 1 of the proteins. Also the cases positive for both proteins exhibited the worst recurrence and prognosis. In the Cox proportional hazards model, VEGF and PROK1 expression was an independent prognostic factor. The prognosis was poorer in colorectal cancers that expressed both PROK1 and VEGF relative to the cases that expressed only 1 protein, and the expression of both proteins was found to be an independent prognostic factor.

  5. VEGF regulates hippocampal neurogenesis and reverses cognitive deficits in immature rats after status epilepticus through the VEGF R2 signaling pathway.

    Science.gov (United States)

    Han, Wei; Song, Xiaojie; He, Rong; Li, Tianyi; Cheng, Li; Xie, Lingling; Chen, Hengsheng; Jiang, Li

    2017-02-10

    Epilepsy is the most common chronic disease in children, who exhibit a higher risk for status epilepticus (SE) than adults. Hippocampal neurogenesis is altered by epilepsy, particularly in the immature brain, which may influence cognitive development. Vascular endothelial growth factor (VEGF) represents an attractive target to modulate brain function at the neurovascular interface and is a double-edged sword in seizures. We used the lithium-pilocarpine-induced epilepsy model in immature Sprague-Dawley rats to study the effects of VEGF on hippocampal neurogenesis in the acute phase and on long-term cognitive behaviors in immature rats following status epilepticus (SE). VEGF correlates with cell proliferation in the immature brain after SE. By preprocessing VEGF in the lateral ventricles prior to the induction of the SE model, we found that VEGF increased the proliferation of neural stem cells (NSCs) and promoted the migration of newly generated cells via the VEGF receptor 2 (VEGFR2) signaling pathway. VEGF also inhibited cell loss and reversed the cognitive deficits that accompany SE. Based on our results, VEGF positively contributes to the initial stages of neurogenesis and alleviates cognitive deficits following seizures; moreover, the VEGF/VEGFR2 signaling pathway may provide a novel treatment strategy for epilepsy.

  6. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Science.gov (United States)

    Fearnley, Gareth W.; Smith, Gina A.; Abdul-Zani, Izma; Yuldasheva, Nadira; Mughal, Nadeem A.; Homer-Vanniasinkam, Shervanthi; Kearney, Mark T.; Zachary, Ian C.; Tomlinson, Darren C.; Harrison, Michael A.; Wheatcroft, Stephen B.; Ponnambalam, Sreenivasan

    2016-01-01

    ABSTRACT Vascular endothelial growth factor A (VEGF-A) binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145) promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes. PMID:27044325

  7. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2016-05-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A binding to the receptor tyrosine kinase VEGFR2 triggers multiple signal transduction pathways, which regulate endothelial cell responses that control vascular development. Multiple isoforms of VEGF-A can elicit differential signal transduction and endothelial responses. However, it is unclear how such cellular responses are controlled by isoform-specific VEGF-A–VEGFR2 complexes. Increasingly, there is the realization that the membrane trafficking of receptor–ligand complexes influences signal transduction and protein turnover. By building on these concepts, our study shows for the first time that three different VEGF-A isoforms (VEGF-A165, VEGF-A121 and VEGF-A145 promote distinct patterns of VEGFR2 endocytosis for delivery into early endosomes. This differential VEGFR2 endocytosis and trafficking is linked to VEGF-A isoform-specific signal transduction events. Disruption of clathrin-dependent endocytosis blocked VEGF-A isoform-specific VEGFR2 activation, signal transduction and caused substantial depletion in membrane-bound VEGFR1 and VEGFR2 levels. Furthermore, such VEGF-A isoforms promoted differential patterns of VEGFR2 ubiquitylation, proteolysis and terminal degradation. Our study now provides novel insights into how different VEGF-A isoforms can bind the same receptor tyrosine kinase and elicit diverse cellular outcomes.

  8. Manipulation of the HIF–Vegf pathway rescues methyl tert-butyl ether (MTBE)-induced vascular lesions

    Energy Technology Data Exchange (ETDEWEB)

    Bonventre, Josephine A., E-mail: josephine.bonventre@oregonstate.edu [Rutgers, The State University of New Jersey, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Rutgers, The State University of New Jersey, Department of Biochemistry and Microbiology, 76 Lipman Dr., New Brunswick, NJ 08901 (United States); Oregon State University, Department of Environmental and Molecular Toxicology, 1011 Agricultural and Life Sciences Bldg, Corvallis, OR 97331 (United States); Kung, Tiffany S., E-mail: tiffany.kung@rutgers.edu [Rutgers, The State University of New Jersey, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Rutgers, The State University of New Jersey, Department of Biochemistry and Microbiology, 76 Lipman Dr., New Brunswick, NJ 08901 (United States); White, Lori A., E-mail: lawhite@aesop.rutgers.edu [Rutgers, The State University of New Jersey, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Rutgers, The State University of New Jersey, Department of Biochemistry and Microbiology, 76 Lipman Dr., New Brunswick, NJ 08901 (United States); Cooper, Keith R., E-mail: cooper@aesop.rutgers.edu [Rutgers, The State University of New Jersey, Joint Graduate Program in Toxicology, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States); Rutgers, The State University of New Jersey, Department of Biochemistry and Microbiology, 76 Lipman Dr., New Brunswick, NJ 08901 (United States)

    2013-12-15

    Methyl tert-butyl ether (MTBE) has been shown to be specifically anti-angiogenic in piscine and mammalian model systems at concentrations that appear non-toxic in other organ systems. The mechanism by which MTBE targets developing vascular structures is unknown. A global transcriptome analysis of zebrafish embryos developmentally exposed to 0.00625–5 mM MTBE suggested that hypoxia inducible factor (HIF)-regulated pathways were affected. HIF-driven angiogenesis via vascular endothelial growth factor (vegf) is essential to the developing vasculature of an embryo. Three rescue studies were designed to rescue MTBE-induced vascular lesions: pooled blood in the common cardinal vein (CCV), cranial hemorrhages (CH), and abnormal intersegmental vessels (ISV), and test the hypothesis that MTBE toxicity was HIF–Vegf dependent. First, zebrafish vegf-a over-expression via plasmid injection, resulted in significantly fewer CH and ISV lesions, 46 and 35% respectively, in embryos exposed to 10 mM MTBE. Then HIF degradation was inhibited in two ways. Chemical rescue by N-oxaloylglycine significantly reduced CCV and CH lesions by 30 and 32% in 10 mM exposed embryos, and ISV lesions were reduced 24% in 5 mM exposed zebrafish. Finally, a morpholino designed to knock-down ubiquitin associated von Hippel–Lindau protein, significantly reduced CCV lesions by 35% in 10 mM exposed embryos. In addition, expression of some angiogenesis related genes altered by MTBE exposure were rescued. These studies demonstrated that MTBE vascular toxicity is mediated by a down regulation of HIF–Vegf driven angiogenesis. The selective toxicity of MTBE toward developing vasculature makes it a potentially useful chemical in the designing of new drugs or in elucidating roles for specific angiogenic proteins in future studies of vascular development. - Highlights: • Global gene expression of MTBE exposed zebrafish suggested altered HIF1 signaling. • Over expression of zebrafish vegf-a rescues MTBE

  9. PEA3 activates VEGF transcription in T47D and SKBR3 breast cancer cells

    Institute of Scientific and Technical Information of China (English)

    Dong Hua; Bobin Chen; Mei Bai; Hao Yu; Xiaohong Wu; Wei Jin

    2009-01-01

    Vascular endothelial growth factor(VEGF)is a potent stimulator of angiogenesis and a prognostic factor for many tumors,including those of endocrine-responsive tissues such as the breast and uterus.In this study,we found that overexpression of PEA3 could increase VEGF mRNA levels and VEGF promoter activity in human T47D and SKBR3 breast cancer cells.Chromatin immunoprecipitation assay demonstrated that PEA3 could bind to the VEGF promoter in the cells transfected with PEA3 expression vector.PEA3 small interfering RNA attenuated VEGF promoter activity and the binding of PEA3 to the VEGF promoter in T47D and SKBR3 cells.These results indicated that PEA3 could activate VEGF promoter transcription.

  10. The expression and function of VEGF at embryo implanta- tion "window" in the mouse

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that plays a critical role in angiogenesis. Recent reports indicated that VEGF was closely involved in embryo implantation and embryonic vasculogenesis. However, very little information is available about the detailed expression and function of VEGF at implantation "window". In this work, VEGFs were primarily present on uterine epithelial cell monolayer and blastocysts including the outgrew trophoblasts at implantation window. VEGF antibodies decreased the number of mice embryos implanted and the percentage of blastocysts with attachment and outgrowth in a co-culture model in a dose-dependant manner. These findings demonstrate that VEGF is one of the essential cytokines for embryo implantation in mouse. VEGF may act as a local mediator to regulate the maternal-fetal interaction, and facilitate blastocyst implantation.

  11. Defining response to anti-VEGF therapies in neovascular AMD.

    Science.gov (United States)

    Amoaku, W M; Chakravarthy, U; Gale, R; Gavin, M; Ghanchi, F; Gibson, J; Harding, S; Johnston, R L; Kelly, S P; Kelly, S; Lotery, A; Mahmood, S; Menon, G; Sivaprasad, S; Talks, J; Tufail, A; Yang, Y

    2015-06-01

    The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there

  12. Amyloid-β(25-35), an amyloid-β(1-42) surrogate, and proinflammatory cytokines stimulate VEGF-A secretion by cultured, early passage, normoxic adult human cerebral astrocytes.

    Science.gov (United States)

    Chiarini, Anna; Whitfield, James; Bonafini, Clara; Chakravarthy, Balu; Armato, Ubaldo; Dal Prà, Ilaria

    2010-01-01

    Cerebrovascular angiopathy affects late-onset Alzheimer's disease (LOAD) brains by possibly increasing vascular endothelial growth factor (VEGF). A expression, thereby stimulating endothelial cell proliferation and migration. Indeed, VEGF-A gene upregulation, with increased VEGF-A protein content of reactive astrocytes and microglia, occurs in LOAD brains, and neovascularization was observed one week after injecting amyloid-β (Aβ)(1-42) into rat hippocampus. We have now found, with cultured 'normoxic' normal adult human astrocytes (NAHAs), that fibrillar Aβ(25-35) (an active Aβ(1-42) fragment) or a cytokine mixture (the (CM)-trio (interleukin [IL]-1β+interferon [IFN]-γ+tumor necrosis factor [TNF]-α), or pair (IFN-γ+TNF-α) like those produced in LOAD brains) stimulates the nuclear translocation of stabilized hypoxia-inducible factor (HIF)-1α protein and its binding to VEGF-A hypoxia-response elements; the mRNA synthesis for three VEGF-A splice variants (121, 165, 189); and the secretion of VEGF-A165. The CM-trio was the most powerful stimulus, IFN-γ+TNF-α was less potent, and other cytokine pairs or single cytokines or Aβ(35-25) were ineffective. While Aβ(25-35) did not change HIF-1β protein levels, the CM-trio increased both HIF-1α and HIF-1β protein levels, thereby giving an earlier and stronger stimulus to VEGF-A secretion by NAHAs. Thus, increased VEGF-A secretion from astrocytes stimulated by Aβ(1-42) and by microglia-released cytokines might restore angiogenesis and Aβ(1-42) vascular clearance.

  13. Homocisteína e polimorfismos dos genes MTHFR e VEGF: impacto na doença arterial coronariana Homocisteína y polimorfismos de los genes MTHFR y VEGF: impacto en la enfermedad arterial coronaria Homocysteine and MTHFR and VEGF gene polymorphisms: impact on coronary artery disease

    Directory of Open Access Journals (Sweden)

    Alexandre Rodrigues Guerzoni

    2009-04-01

    íquida/espectrometría de masa secuencial (CL/EMS. RESULTADOS: No hubo diferencia significante en relación con la distribución de alelos y genotipos entre los grupos, para ambos polimorfismos. El análisis univariado reveló una frecuencia mayor del genotipo VEGF-2578AA en el grupo con enfermedad en tres vasos (P=0,044. Además de ello, se observó el genotipo VEGF-2578CA con más frecuencia entre individuos con BACKGROUND: Polymorphisms in genes involved in the atherosclerosis development, angiogenesis, and homocysteine (Hcy metabolism could be risk factors for coronary artery disease (CAD. OBJECTIVE: To evaluate the effect of the VEGF C-2578A and MTHFR C677T polymorphisms on CAD, and the association of these polymorphisms with the severity and extension of atherosclerotic lesions and Hcy concentrations. METHODS: Two hundred and forty-four subjects were evaluated by coronary angiography and included in the study (145 with CAD and 99 controls. The VEGF C-2578A and MTHFR C677T polymorphisms were investigated by the PCR-SSCP and PCR-RFLP techniques, respectively. Plasma Hcy was quantified by liquid chromatography/sequential mass spectrometry (LC-MS/MS. RESULTS: There was no significant difference in allele and genotype distribution between the groups, for both polymorphisms. The univariate analysis showed a higher frequency of the VEGF -2578AA genotype in the group with three-vessel disease (p=0.044. In addition, the VEGF -2578CA genotype was observed more frequently among individuals with <95% stenosis (p=0.010. After adjustment for other risk factors for CAD in a multivariate model, the VEGF C-2578A polymorphism was not found to be an independent correlate of CAD (p=0.688. The MTHFR polymorphism did not show any association with the extension and/or severity of the CAD. The MTHFR C677T polymorphism showed no direct association with hyperhomocysteinemia or increased mean plasma concentrations of Hcy. CONCLUSION: Although there is an apparent association between VEGF C-2578A and the

  14. VEGF-conjugated alginate hydrogel prompt angiogenesis and improve pancreatic islet engraftment and function in type 1 diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Nina; Han, Yongming [Department of Anatomy, Basic Medical College, Hubei University of Chinese Medicine, Wuhan, Hubei (China); Xu, Hanlin [Pharmacy Faculty, Hubei University of Chinese Medicine, Wuhan, Hubei (China); Gao, Yisen; Yi, Tao [Acupuncture and Moxibustion College, Hubei University of Chinese Medicine, Wuhan, Hubei (China); Yao, Jiale; Dong, Li; Cheng, Dejun [Basic Medical College, Hubei University of Chinese Medicine, Wuhan, Hubei (China); Chen, Zebin, E-mail: chenzebin-hbtcm@outlook.com [Acupuncture and Moxibustion College, Hubei University of Chinese Medicine/Hubei Provincial Collaborative Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan, Hubei (China)

    2016-02-01

    Type 1 diabetes was a life-long disease that affected numerous people around the world. Insulin therapy has its limitations that may involve hyperglycemia and heavy burden of patient by repeated dose. Islet transplantation emerged as a promising approach to reach periodical reverse of diabetes, however, transplanted islets suffer from foreign body reaction and lack of nutrition and oxygen supply, especially in the blood-vessel-shortage subcutaneous site which was preferred by patient and surgeon. In this study, we designed and synthesized a vascular endothelial growth factor (VEGF) conjugated alginate material to encapsulate the transplanted islets via 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction, and successful conjugation was confirmed by Nuclear Magnetic Resonance H1 spectrum. The best VEGF concentration (100 ng/ml) was determined by the combined studies of the mechanical property and endothelial cell growth assay. In vivo study, conjugated VEGF on alginate exhibited sustained promoting angiogenesis property after subcutaneous transplantation by histology study and islets encapsulated in this material achieved long term therapeutic effect (up to 50 days) in the diabetic mice model. In conclusion, this study establishes a simple biomaterial strategy for islet transplantation to enhance islet survival and function, which could be a feasible therapeutic alternative for type 1 diabetes. - Highlights: • We synthesized VEGF-conjugated alginate material to encapsulate the transplanted islets. • The biomaterials improve islet engraftment and function due to angiogenesis. • The biomaterials could be a strong support for cell therapy with islet transplantation in type 1 diabetes.

  15. Blocking αvβ3 integrin by a recombinant RGD disintegrin impairs VEGF signaling in endothelial cells.

    Science.gov (United States)

    Montenegro, Cyntia F; Salla-Pontes, Carmen L; Ribeiro, Juliana U; Machado, Aline Z; Ramos, Rafael F; Figueiredo, Camila C; Morandi, Verônica; Selistre-de-Araujo, Heloisa S

    2012-08-01

    Vascular endothelial growth factor (VEGF) and αvβ3 integrin are key molecules that actively participate in tumor angiogenesis and metastasis. Some integrin-blocking molecules are currently under clinical trials for cancer and metastasis treatment. However, the mechanism of action of such inhibitors is not completely understood. We have previously demonstrated the anti-angiogenic and anti-metastatic properties of DisBa-01, a recombinant His-tag RGD-disintegrin from Bothrops alternatus snake venom in some experimental models. DisBa-01 blocks αvβ3 integrin binding to vitronectin and inhibits integrin-mediated downstream signaling cascades and cell migration. Here we add some new information on the mechanism of action of DisBa-01 in the tumor microenvironment. DisBa-01 supports the adhesion of fibroblasts and MDA-MB-231 breast cancer cells but it inhibits the adhesion of these cells to type I collagen under flow in high shear conditions, as a simulation of the blood stream. DisBa-01 does not affect the release of VEGF by fibroblasts or breast cancer cells but it strongly decreases the expression of VEGF mRNA and of its receptors, vascular endothelial growth factor receptors 1 and 2 (VEGFR1 and VEGFR2) in endothelial cells. DisBa-01 at nanomolar concentrations also modulates metalloprotease 2 (MMP-2) and 9 (MMP-9) activity, the latter being decreased in fibroblasts and increased in MDA-MB-231 cells. In conclusion, these results demonstrate that αvβ3 integrin inhibitors may induce distinct effects in the cells of the tumor microenvironment, resulting in blockade of angiogenesis by impairing of VEGF signaling and in inhibition of tumor cell motility.

  16. Gene therapy for cardiovascular disease: the potential of VEGF.

    Science.gov (United States)

    Tiong, Alice; Freedman, Saul Benedict

    2004-04-01

    The quest for new therapeutic options and the recent exponential explosion in our knowledge of genetics have led to active interest and research into gene therapy. One area of gene therapy that has generated much debate and controversy is the use of vascular endothelial growth factor (VEGF) for therapeutic angiogenesis for palliative intent, and for the prevention of restenosis following percutaneous revascularization in coronary and peripheral arterial disease. This review highlights the development in VEGF gene therapy in the last 12 to 18 months, particularly the results from randomized, double-blind, placebo-controlled phase I and II studies that have evolved from encouraging results from animal models and early pilot studies in humans.

  17. Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond.

    Science.gov (United States)

    Di Lisi, Daniela; Madonna, Rosalinda; Zito, Concetta; Bronte, Enrico; Badalamenti, Giuseppe; Parrella, Paolo; Monte, Ines; Tocchetti, Carlo Gabriele; Russo, Antonio; Novo, Giuseppina

    2017-01-15

    Cardiotoxicity induced by chemotherapeutic agents and radiotherapy is a growing problem. In recent years, an increasing number of new drugs with targeted action have been designed. These molecules, such as monoclonal antibodies and tyrosine kinase inhibitors, can cause different type of toxicities compared to traditional chemotherapy. However, they can also cause cardiac complications such as heart failure, arterial hypertension, QT interval prolongation and arrhythmias. Currently, a field of intense research is the vascular toxicity induced by new biologic drugs, particularly those which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) and other tyrosine kinases. In this review, we aim at focusing on the problem of vascular toxicity induced by new targeted therapies, chemotherapy and radiotherapy, and describe the main mechanisms and emphasizing the importance of early diagnosis of vascular damage, in order to prevent clinical complications.

  18. The remote effects of intravitreal anti-VEGF therapy.

    Science.gov (United States)

    Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V

    2016-01-01

    Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.

  19. Functional and pharmacological characterization of a VEGF mimetic peptide on reparative angiogenesis.

    Science.gov (United States)

    Finetti, Federica; Basile, Anna; Capasso, Domenica; Di Gaetano, Sonia; Di Stasi, Rossella; Pascale, Maria; Turco, Caterina Maria; Ziche, Marina; Morbidelli, Lucia; D'Andrea, Luca Domenico

    2012-08-01

    Vascular endothelial growth factor (VEGF) is the main regulator of physiological and pathological angiogenesis. Low molecular weight molecules able to stimulate angiogenesis have interesting medical application for example in regenerative medicine, but at present none has reached the clinic. We reported that a VEGF mimetic helical peptide, QK, designed on the VEGF helix sequence 17-25, is able to bind and activate the VEGF receptors, producing angiogenesis. In this study we evaluate the pharmacological properties of peptide QK with the aim to propose it as a VEGF-mimetic drug to be employed in reparative angiogenesis. We show that the peptide QK is able to recapitulate all the biological activities of VEGF in vivo and on endothelial cells. In experiments evaluating sprouting from aortic ring and vessel formation in an in vivo angiogenesis model, the peptide QK showed biological effects comparable with VEGF. At endothelial level, the peptide up-regulates VEGF receptor expression, activates intracellular pathways depending on VEGFR2, and consistently it induces endothelial cell proliferation, survival and migration. When added to angiogenic factors (VEGF and/or FGF-2), QK produces an improved biological action, which resulted in reduced apoptosis and accelerated in vitro wound healing. The VEGF-like activity of the short peptide QK, characterized by lower cost of production and easier handling compared to the native glycoprotein, suggests that it is an attractive candidate to be further developed for application in therapeutic angiogenesis.

  20. Clinicopathological and prognostic significance of HER-2/neu and VEGF expression in colon carcinomas

    Directory of Open Access Journals (Sweden)

    Li Jing

    2011-06-01

    Full Text Available Abstract Background HER-2/neu and VEGF expression is correlated with disease behaviors in various cancers. However, evidence for their expression in colon cancer is rather contradictory both for the protein expression status and prognostic value. HER-2/neu is found to participate in VEGF regulation, and has known correlation with VEGF expression in some tumors. In this study, we investigated HER-2/neu and VEGF expression in Chinese colon patients and explored whether there was any correlation between their expression patterns. Methods HER-2/neu and VEGF were investigated immunohistochemically using tumor samples obtained from 317 colon cancer patients with all tumor stages. Correlation of the degree of staining with clinicopathological parameters and survival was investigated. Results Positive expression rates of HER-2/neu and VEGF in colon cancer were 15.5% and 55.5% respectively. HER-2/neu expression was significantly correlated with tumor size and distant metastases (P (P > 0.05. Expression of VEGF was significantly correlated with tumor size, tumor stage, lymph node metastases, and distant metastases (P (P = 0.146. No correlation between HER-2/neu and VEGF expression was detected (P = 0.151. Conclusions HER-2/neu and VEGF are not important prognostic markers of colon cancer. The present results do not support any association between HER2/neu and VEGF expression in this setting.

  1. Angiogenic functionalisation of titanium surfaces using nano-anchored VEGF – an in vitro study

    Directory of Open Access Journals (Sweden)

    H Schliephake

    2012-03-01

    Full Text Available The aim of the present study was to test the hypothesis that sandblasted and acid etched titanium surfaces can be functionalised with vascular endothelial growth factor (VEGF using oligonucleotides for anchorage and slow release. rhVEGF165 molecules were conjugated to strands of 30-mer non-coding DNA oligonucleotides (ODN and hybridised to complementary ODN anchor strands which had been immobilised to the surface of sandblasted/acid etched (SAE Ti specimens. Specimens with non-conjugated VEGF adsorbed to ODN anchor strands and to blank SAE surfaces served as controls. Specific binding of conjugated VEGF exhibited the highest percentage of immobilised VEGF (71.0 %, whereas non-conjugated VEGF only achieved 53.2 and 30.7 %, respectively. Cumulative release reached 54.0 % of the immobilised growth factor in the group of specifically bound VEGF after 4 weeks, whereas non-conjugated VEGF adsorbed to ODN strands released 78.9% and VEGF adsorbed to SAE Ti surfaces released 97.4 %. Proliferation of human umbilical vein endothelial cells (HUVECs was significantly increased on the surfaces with specifically bound VEGF compared to the control surfaces and SAE Ti surfaces without VEGF. Moreover, the released conjugated VEGF exhibited biological activity by induction of von Willebrand Factor (vWF in mesenchymal stem cells. It is concluded that the angiogenic functionalisation of SAE titanium surfaces can be achieved by conjugation of VEGF to ODN strands and hybridisation to complementary ODN strands that are anchored to the titanium surface. The angiogenic effect is exerted both through the immobilised and the released portion of the growth factor.

  2. VEGF incorporated into calcium phosphate ceramics promotes vascularisation and bone formation in vivo

    Directory of Open Access Journals (Sweden)

    E Wernike

    2010-02-01

    Full Text Available Bone formation and osseointegration of biomaterials are dependent on angiogenesis and vascularization. Angiogenic growth factors such as vascular endothelial growth factor (VEGF were shown to promote biomaterial vascularization and enhance bone formation. However, high local concentrations of VEGF induce the formation of malformed, nonfunctional vessels. We hypothesized that a continuous delivery of low concentrations of VEGF from calcium phosphate ceramics may increase the efficacy of VEGF administration.VEGF was co-precipitated onto biphasic calcium phosphate (BCP ceramics to achieve a sustained release of the growth factor. The co-precipitation efficacy and the release kinetics of the protein were investigated in vitro. For in vivo investigations BCP ceramics were implanted into critical size cranial defects in Balb/c mice. Angiogenesis and microvascularization were investigated over 28 days by means of intravital microscopy. The formation of new bone was determined histomorphometrically. Co-precipitation reduced the burst release of VEGF. Furthermore, a sustained, cell-mediated release of low concentrations of VEGF from BCP ceramics was mediated by resorbing osteoclasts. In vivo, sustained delivery of VEGF achieved by protein co-precipitation promoted biomaterial vascularization, osseointegration, and bone formation. Short-term release of VEGF following superficial adsorption resulted in a temporally restricted promotion of angiogenesis and did not enhance bone formation. The release kinetics of VEGF appears to be an important factor in the promotion of biomaterial vascularization and bone formation. Sustained release of VEGF increased the efficacy of VEGF delivery demonstrating that a prolonged bioavailability of low concentrations of VEGF is beneficial for bone regeneration.

  3. Designer Leptin Receptor Antagonist Allo-aca Inhibits VEGF Effects in Ophthalmic Neoangiogenesis Models

    Science.gov (United States)

    Coroniti, Roberta; Fario, Rafal; Nuno, Didier J.; Otvos, Laszlo; Scolaro, Laura; Surmacz, Eva

    2016-01-01

    Experimental and clinical data suggest that pro-angiogenic, pro-inflammatory and mitogenic cytokine leptin can be implicated in ocular neovascularization and other eye pathologies. At least in part, leptin action appears to be mediated through functional interplay with vascular endothelial growth factor (VEGF). VEGF is a potent regulator of neoangiogenesis and vascular leakage with a proven role in conditions such as proliferative diabetic retinopathy, age-related macular degeneration and diabetic macular edema. Accordingly, drugs targeting VEGF are becoming mainstream treatments for these diseases. The crosstalk between leptin and VEGF has been noted in different tissues, but its involvement in the development of eye pathologies is unclear. Leptin is coexpressed with VEGF during ocular neovascularization and can potentiate VEGF synthesis and angiogenic function. However, whether or not VEGF regulates leptin expression or signaling has never been studied. Consequently, we addressed this aspect of leptin/VEGF crosstalk in ocular models, focusing on therapeutic exploration of underlying mechanisms. Here we show, for the first time, that in retinal (RF/6A) and corneal (BCE) endothelial cells, VEGF (100 ng/mL, 24 h) stimulated leptin mRNA synthesis by 70 and 30%, respectively, and protein expression by 56 and 28%, respectively. In parallel, VEGF induced RF/6A and BCE cell growth by 33 and 20%, respectively. In addition, VEGF upregulated chemotaxis and chemokinesis in retinal cells by ~40%. VEGF-dependent proliferation and migration were significantly reduced in the presence of the leptin receptor antagonist, Allo-aca, at 100–250 nmol/L concentrations. Furthermore, Allo-aca suppressed VEGF-dependent long-term (24 h), but not acute (15 min) stimulation of the Akt and ERK1/2 signaling pathways. The efficacy of Allo-aca was validated in the rat laser-induced choroidal neovascularization model where the compound (5 μg/eye) significantly reduced pathological

  4. Up-regulation of VEGF-C secreted by cancer cells and not VEGF-A correlates with clinical evaluation of lymph node metastasis in esophageal squamous cell carcinoma (ESCC).

    Science.gov (United States)

    Krzystek-Korpacka, Malgorzata; Matusiewicz, Malgorzata; Diakowska, Dorota; Grabowski, Krzysztof; Blachut, Katarzyna; Banas, Teresa

    2007-05-01

    Tissue expression of VEGF-C correlates with lymph node involvement (LNI) in ESCC and serum VEGF-C (sVEGF-C) in a non-small cell lung cancer has been more accurate marker of LNI than chest CT. Despite LNI importance in ESCC, the usefulness of serum VEGF-C (sVEGF-C) as a disease and LNI marker in ESCC has not been investigated yet. We found elevated sVEGF-C in ESCC (17.40 vs. 10.57 ng/ml in controls, pmarker than described elsewhere: CEA, CA19-9 and SCC-Ag, with: sensitivity--70%, specificity--81%, accuracy--83.7%. Analysis of sVEGF-C correlation with clinico-pathological cancer features revealed relation to LNI (N0: 15.77 vs. N1: 21.78 ng/ml, p=0.02), especially in advanced cancers. Serum VEGF-C as a marker of LNI was characterized by: sensitivity--76%, specificity--58%, accuracy--64.4%. No relation was observed between LNI and sVEGF-A or sVEGF-A/platelets (PLT). Because sVEGF-C was higher in N0 cancers (ptumor presence also up-regulates sVEGF-C. We found sVEGF-C correlation with PLT and WBC: R=0.36 and R=0.32 (pcancer features implies that elevation of sVEGF-C in N1 cancers is not related to them.

  5. Breeding resource distribution affects selection gradients on male phenotypic traits: experimental study on lifetime reproductive success in the bitterling fish (Rhodeus amarus).

    Science.gov (United States)

    Reichard, Martin; Ondracková, Markéta; Bryjová, Anna; Smith, Carl; Bryja, Josef

    2009-02-01

    The spatial distribution of breeding resources can have pronounced demographic and evolutionary consequences. We used 20 experimental groups of the bitterling (Rhodeus amarus), an annual fish with a promiscuous, resource-based mating system, and extended breeding season to investigate how the spatial distribution (clumped or regular) of bitterling oviposition sites (live freshwater mussels) affected offspring production, variation in reproductive success, and directional selection on phenotypic traits over their entire reproductive lifetime. We did not detect any effect of resource distribution on offspring production or variation in reproductive success among individual fish, although variation between replicates was higher with a clumped distribution. This finding is discussed with regard to the incidence of alternative mating behaviors (sneaking) within the limitations imposed by our experimental design. Breeding resource distribution had a significant effect on selection on male phenotypic traits. Stronger directional selection on traits associated with intrasexual competition for fertilizations, gonad mass (an indicator of sperm competition), and the extent of red, carotenoid-based pigment in the iris (an index of dominance status), was detected with a clumped resource distribution. With a regular resource distribution, a stronger positive selection on male body size was detected. We discuss the implications of our results for natural populations.

  6. Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

    DEFF Research Database (Denmark)

    Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki

    2016-01-01

    The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes......, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the 'off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge...... of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte...

  7. Vascular endothelial growth factor (VEGF) gene polymorphisms may influence the efficacy of thalidomide in multiple myeloma

    DEFF Research Database (Denmark)

    Andersen, Niels Frost; Vogel, Ulla Birgitte; Klausen, Tobias W;

    2012-01-01

    Vascular endothelial growth factor (VEGF) is a potent proangiogenic factor. Several single nucleotide polymorphisms (SNPs) in the VEGF gene with influence on VEGF expression have been described. In multiple myeloma, VEGF stimulates angiogenesis which is correlated with disease progression...... and prognosis. In this study, we evaluated the association between genetic variations in the VEGF gene in patients with multiple myeloma and time to treatment failure (TTF) after high-dose melphalan and stem cell support (HDT), overall survival (OS) and efficacy of the anti-angiogenic drug thalidomide....... Retrospectively, the SNPs -2,578C>A (rs699947), -460C>T (rs833061), +405G>C (rs2010963) and +936C>T (rs3025039) in the VEGF gene were examined in 348 patients with newly diagnosed multiple myeloma initially treated with HDT, where 176 patients were treated with thalidomide at relapse. None of the examined geno...

  8. Contraction induced secretion of VEGF from skeletal muscle cells is mediated by adenosine

    DEFF Research Database (Denmark)

    Høier, Birgitte; Olsen, Karina; Nyberg, Michael Permin

    2010-01-01

    The role of adenosine and contraction for secretion of VEGF in skeletal muscle was investigated in human subjects and rat primary skeletal muscle cells. Microdialysis probes were inserted into the thigh muscle of seven male subjects and dialysate was collected at rest, during infusion of adenosine...... and contraction caused secretion of VEGF (pcontraction induced secretion of VEGF protein was abolished by the A(2B) antagonist enprofyllin and markedly reduced by inhibition of PKA or MAPK. The results demonstrate that adenosine causes secretion of VEGF from human skeletal muscle cells...... and that the contraction induced secretion of VEGF is partially mediated via adenosine acting on A(2B) adenosine receptors. Moreover, the contraction induced secretion of VEGF protein from muscle is dependent on both PKA and MAPK activation, but only the MAPK pathway appears to be adenosine dependent....

  9. How will climate change affect the potential distribution of Eurasian tree sparrows Passer montanus in North America?

    Directory of Open Access Journals (Sweden)

    Jim GRAHAM, Catherine JARNEVICH, Nick YOUNG, Greg NEWMAN, Thomas STOHLGREN

    2011-10-01

    Full Text Available Habitat suitability models have been used to predict the present and future potential distribution of a variety of species. Eurasian tree sparrows Passer montanus, native to Eurasia, have established populations in other parts of the world. In North America, their current distribution is limited to a relatively small region around its original introduction to St. Louis, Missouri. We combined data from the Global Biodiversity Information Facility with current and future climate data to create habitat suitability models using Maxent for this species. Under projected climate change scenarios, our models show that the distribution and range of the Eurasian tree sparrow could increase as far as the Pacific Northwest and Newfoundland. This is potentially important information for prioritizing the management and control of this non-native species [Current Zoology 57 (5: 648–654, 2011].

  10. How will climate change affect the potential distribution of Eurasian tree sparrows Passer montanus in North America?

    Institute of Scientific and Technical Information of China (English)

    Jim GRAHAM; Catherine JARNEVICH; Nick YOUNG; Greg NEWMAN; Thomas STOHLGREN

    2011-01-01

    Habitat suitability models have been used to predict the present and future potential distribution of a variety of species.Eurasian tree sparrows Passer montanus,native to Eurasia,have established populations in other parts of the world.In North America,their current distribution is limited to a relatively small region around its original introduction to St.Louis,Missouri.We combined data from the Global Biodiversity Information Facility with current and future climate data to create habitat suitability models using Maxent for this species.Under projected climate change scenarios,our models show that the distribution and range of the Eurasian tree sparrow could increase as far as the Pacific Northwest and Newfoundland.This is potentially important information for prioritizing the management and control of this non-native species [Current Zoology 57 (5):648-654,2011].

  11. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer

    OpenAIRE

    2004-01-01

    The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF block...

  12. VEGF secretion during hypoxia depends on free radicals-induced Fyn kinase activity in mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Roman, Jonathan; Ibarra-Sanchez, Alfredo; Lamas, Monica [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav, IPN) (Mexico); Gonzalez Espinosa, Claudia, E-mail: cgonzal@cinvestav.mx [Departamento de Farmacobiologia, Centro de Investigacion y de Estudios Avanzados del IPN (Cinvestav, IPN) (Mexico)

    2010-10-15

    Research highlights: {yields} Bone marrow-derived mast cells (BMMCs) secrete functional VEGF but do not degranulate after Cobalt chloride-induced hypoxia. {yields} CoCl{sub 2}-induced VEGF secretion in mast cells occurs by a Ca{sup 2+}-insensitive but brefeldin A and Tetanus toxin-sensitive mechanism. {yields} Trolox and N-acetylcysteine inhibit hypoxia-induced VEGF secretion but only Trolox inhibits Fc{epsilon}RI-dependent anaphylactic degranulation in mast cells. {yields} Src family kinase Fyn activation after free radical production is necessary for hypoxia-induced VEGF secretion in mast cells. -- Abstract: Mast cells (MC) have an important role in pathologic conditions such as asthma and chronic obstructive pulmonary disease (COPD), where hypoxia conduce to deleterious inflammatory response. MC contribute to hypoxia-induced angiogenesis producing factors such as vascular endothelial growth factor (VEGF), but the mechanisms behind the control of hypoxia-induced VEGF secretion in this cell type is poorly understood. We used the hypoxia-mimicking agent cobalt chloride (CoCl{sub 2}) to analyze VEGF secretion in murine bone marrow-derived mast cells (BMMCs). We found that CoCl{sub 2} promotes a sustained production of functional VEGF, able to induce proliferation of endothelial cells in vitro. CoCl{sub 2}-induced VEGF secretion was independent of calcium rise but dependent on tetanus toxin-sensitive vesicle-associated membrane proteins (VAMPs). VEGF exocytosis required free radicals formation and the activation of Src family kinases. Interestingly, an important deficiency on CoCl{sub 2}-induced VEGF secretion was observed in Fyn kinase-deficient BMMCs. Moreover, Fyn kinase was activated by CoCl{sub 2} in WT cells and this activation was prevented by treatment with antioxidants such as Trolox and N-acetylcysteine. Our results show that BMMCs are able to release VEGF under hypoxic conditions through a tetanus toxin-sensitive mechanism, promoted by free radicals

  13. 果糖及血管内皮生长因子引起仓鼠颊囊血浆外渗%Fructose diet and VEGF-induced plasma extravasation in hamster cheek pouch

    Institute of Scientific and Technical Information of China (English)

    Michel FELETOU; Michelle BOULANGER; Joanna STACZEK; Olivier BROUX; Jacques DUHAULT

    2003-01-01

    AIM: To determine in the hamster cheek pouch whether or not the changes in plasma extravasation induced byvascular endothelial growth factor (VEGF) could be affected by fructose diet. METHODS: Hamsters were sub-jected to control drinking water or to water containing fructose (10 %) for 18 weeks. RESULTS: The fructose dietinduced a small but significant increase in glycemia (0.80±0.11 and 1.09±0.15, n= 8 and 9 for control and fructose-treated animals, respectively, P<0.05). Bradykinin-induced plasma extravasation was not affected by the fructosediet while the effects of VEGF were markedly increased (maximal number of leakage sites: 76±20 and 126±55, n =8 and 9 for control and fructose-treated animals, respectively, P<0.01). CONCLUSION: Even moderate changesin glycemic levels can produce profound alteration in the VEGF response.

  14. EXPERIMENTAL STUDY ON THE GENE THERAPY OF MALIGNANT GLIOMA WITH ANTISENSE VEGF RNA

    Institute of Scientific and Technical Information of China (English)

    浦佩玉; 王建桢; 黄强; 张敬; 张云亭

    2003-01-01

    Objective: To study the effect of antisense VEGF RNA on rat C6 gliomas in vivo and find out the feasibility of antiangiogenesis therapy with antisense VEGF RNA for malignant gliomas. Methods: Parental rat C6 glioma cells and C6 cells transfected with antisense VEGF cDNA were implanted intracerebrally and subcutaneously into SD rats as control and transfected group. Rats bearing cerebral and subcutaneous C6 gliomas were treated with antisense VEGF cDNA as treated group and sense VEGF cDNA and empty vector as control of treated group. The general manifestation, survival time, MRI and histopathological changes of all rats were observed. The volume of subcutaneously implanted tumors was determined regularly. In situ hybridization and immunohistochemical staining were used for detection of VEGF gene expression of gliomas while PCNA immunostaining and TUNEL method for examination of proliferation activity and apoptosis of gliomas, respectively. Results: The survival of the rats in transfected and treated group was prolonged. There were two rats surviving over 90 d in the treated group and their tumors disappeared. The VEGF gene expression, the number of microvessels and the proliferation activity were decreased and a large amount of apoptotic cells could be found in cerebral and subcutaneous gliomas in treated and transfected groups. Conclusion: VEGF is one of the candidate genes for gene therapy of malignant gliomas. Antisense VEGF RNA combined with other therapies should be studied further for enhancing the therapeutic effect of malignant gliomas.

  15. A Biomimic Reconstituted High Density Lipoprotein Nanosystem for Enhanced VEGF Gene Therapy of Myocardial Ischemia

    Directory of Open Access Journals (Sweden)

    Xiaotian Sun

    2015-01-01

    Full Text Available A biomimic reconstituted high density lipoprotein (rHDL based system, rHDL/Stearic-PEI/VEGF complexes, was fabricated as an advanced nanovector for delivering VEGF plasmid. Here, Stearic-PEI was utilized to effectively condense VEGF plasmid and to incorporate the plasmid into rHDL. The rHDL/Stearic-PEI/VEGF complexes with diameter under 100 nm and neutral surface charge demonstrated enhanced stability under the presence of bovine serum albumin. Moreover, in vitro cytotoxicity and transfection assays on H9C2 cells further revealed their superiority, as they displayed lower cytotoxicity with much higher transfection efficiency when compared to PEI 10K/VEGF and Lipos/Stearic-PEI/VEGF complexes. In addition, in vivo investigation on ischemia/reperfusion rat model implied that rHDL/Stearic-PEI/VEGF complexes possessed high transgene capacity and strong therapeutic activity. These findings indicated that rHDL/Stearic-PEI/VEGF complexes could be an ideal gene delivery system for enhanced VEGF gene therapy of myocardial ischemia, which might be a new promising strategy for effective myocardial ischemia treatment.

  16. Finite element lumbar spine facet contact parameter predictions are affected by the cartilage thickness distribution and initial joint gap size.

    Science.gov (United States)

    Woldtvedt, Daniel J; Womack, Wesley; Gadomski, Benjamin C; Schuldt, Dieter; Puttlitz, Christian M

    2011-06-01

    Current finite element modeling techniques utilize geometrically inaccurate cartilage distribution representations in the lumbar spine. We hypothesize that this shortcoming severely limits the predictive fidelity of these simulations. Specifically, it is unclear how these anatomically inaccurate cartilage representations alter range of motion and facet contact predictions. In the current study, cadaveric vertebrae were serially sectioned, and images were taken of each slice in order to identify the osteochondral interface and the articulating surface. A series of custom-written algorithms were utilized in order to quantify each facet joint's three-dimensional cartilage distribution using a previously developed methodology. These vertebrae-dependent thickness cartilage distributions were implemented on an L1 through L5 lumbar spine finite element model. Moments were applied in three principal planes of motion, and range of motion and facet contact predictions from the variable thickness and constant thickness distribution models were determined. Initial facet gap thickness dimensions were also parameterized. The data indicate that the mean and maximum cartilage thickness increased inferiorly from L1 to L5, with an overall mean thickness value of 0.57 mm. Cartilage distribution and initial facet joint gap thickness had little influence on the lumbar range of motion in any direction, whereas the mean contact pressure, total contact force, and total contact area predictions were altered considerably. The data indicate that range of motion predictions alone are insufficient to establish model validation intended to predict mechanical contact parameters. These data also emphasize the need for the careful consideration of the initial facet joint gap thickness with respect to the spinal condition being studied.

  17. Erythropoietin attenuates renal and pulmonary injury in polymicrobial induced-sepsis through EPO-R, VEGF and VEGF-R2 modulation.

    Science.gov (United States)

    Heitrich, Mauro; García, Daiana Maria de Los Ángeles; Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Aguirre, María Victoria

    2016-08-01

    Sepsis remains the most important cause of acute kidney injury (AKI) and acute lung injury (ALI) in critically ill patients. The cecal ligation and puncture (CLP) model in experimental mice reproduces most of the clinical features of sepsis. Erythropoietin (EPO) is a well-known cytoprotective multifunctional hormone, which exerts anti-inflammatory, anti-oxidant, anti-apoptotic and pro-angiogenic effects in several tissues. The aim of this study was to evaluate the underlying mechanisms of EPO protection through the expression of the EPO/EPO receptor (EPO-R) and VEGF/VEF-R2 systems in kidneys and lungs of mice undergoing CLP-induced sepsis. Male inbred Balb/c mice were divided in three experimental groups: Sham, CLP, and CLP+EPO (3000IU/kg sc). Assessment of renal functional parameters, survival, histological examination, immunohistochemistry and/or Western blottings of EPO-R, VEGF and VEGF-R2 were performed at 18h post-surgery. Mice demonstrated AKI by elevation of serum creatinine and renal histologic damage. EPO treatment attenuates renal dysfunction and ameliorates kidney histopathologic changes. Additionally, EPO administration attenuates deleterious septic damage in renal cortex through the overexpression of EPO-R in tubular interstitial cells and the overexpression of the pair VEGF/VEGF-R2. Similarly CLP- induced ALI, as evidenced by parenchymal lung histopathologic alterations, was ameliorated through pulmonary EPO-R, VEGF and VEGF-R2 over expression suggesting and improvement in endothelial survival and functionality. This study demonstrates that EPO exerts protective effects in kidneys and lungs in mice with CLP-induced sepsis through the expression of EPO-R and the regulation of the VEGF/VEGF-R2 pair.

  18. A re-assessment of biochemical marker distributions in T21 affected and unaffected twin pregnancies in the first trimester

    DEFF Research Database (Denmark)

    Madsen, Helen Nordahl; Tørring, Niels

    unaffected and 47 trisomy 21 affected twin pregnancies were included in the study. Chorionicity specific medians were generated for PAPP-A and free β-hCG from gestational age 8 to 14 weeks. Multiple of the median for each of the markers were calculated. Detection rates (DR) and false-positive rates (FPR....... Allowing for gestation and chorionicity, twin pregnancies affected with trisomy 21 had higher levels of free β-hCG and lower levels of PAPP-A. Adding biochemistry into the risk assessment increased the DR for fetal trisomy 21 in dizygotic twin pregnancies from 78% to 90%, and decreased the FPR from 8......INTRODUCTION Serum biochemical marker concentrations in twin pregnancies reflect the presence of two fetuses rather than one. In general, the concentrations are approximately double those found in singleton pregnancies. The objective was to estimate the difference between levels of the two...

  19. The Statistical and Numerical Study of the Longitudinally Asymmetric Distribution of Solar Proton Events Affecting the Earth Environment of 1996-2011

    CERN Document Server

    He, Hongqing

    2015-01-01

    Large solar proton events (SPEs) affect the solar-terrestrial space environment and become a very important aspect in space weather research. In this work, we statistically investigate 78 solar proton events of 1996-2011 and find that there exists a longitudinally asymmetric distribution of flare sources of the solar proton events observed near 1 AU, namely, with the same longitude separation between magnetic field line footpoint of observer and flare sources, the number of the solar proton events originating from sources located at eastern side of the nominal magnetic footpoint of observer is much larger than that of the solar proton events originating from sources located at western side. A complete model calculation of solar energetic particle (SEP) propagation in the three-dimensional Parker interplanetary magnetic field is presented to give a numerical explanation for this longitudinally asymmetric distribution phenomenon. We find that the longitudinally asymmetric distribution of solar proton events res...

  20. THE CHARACTERISTICS OF TEMPORAL AND SPATIAL DISTRIBUTION OF TROPICAL CYCLONE FREQUENCIES OVER THE SOUTH CHINA SEA AND ITS AFFECTING OCEANIC FACTORS IN THE PAST 50 YEARS

    Institute of Scientific and Technical Information of China (English)

    LI Chun-hui; LIU Chun-xia; CHENG Zheng-quan

    2007-01-01

    The characteristics of temporal and spatial distribution of tropical cyclone frequencies over the South China Sea areas and its affecting factors in the past 50yrs are analyzed based on typhoon data that provided by CMA and Simple Ocean Data Assimilation (SODA). The results show that the tropical cyclone frequencies from June to October show concentrated geographic distribution, for they mainly distribute over the SCS area from 15 - 20 °N. The characteristics present significant interdecadal changes. The impact of oceanic factors on the tropical cyclone frequencies in the SCS area is mainly realized by La Ni(n)a and La Ni(n)a-like events before 1975 but mainly by El Ni(n)o and El Nifo-like events after 1975.

  1. Ecological and social factors affecting the local habitat distribution of western sandpipers wintering at Bah?Santa Mar? Northwest Mexico

    OpenAIRE

    2005-01-01

    The process of habitat selection often requires individuals to choose among habitats that differ in foraging profitability and predation danger. The local habitat distribution of Western Sandpipers (Calidris maur~] was studied at Bahia Santa Maria, northwest Mexico, for three non-breeding seasons (1 999-2002). Western Sandpipers are highly sexually dimorphic, males being lighter and smaller-billed than females, and thus males may use visual foraging more often, be more susceptible to interfer...

  2. Predicting probability of occurrence and factors affecting distribution and abundance of three Ozark endemic crayfish species at multiple spatial scales

    Science.gov (United States)

    Nolen, Matthew S.; Magoulick, Daniel D.; DiStefano, Robert J.; Imhoff, Emily M.; Wagner, Brian K.

    2014-01-01

    Crayfishes and other freshwater aquatic fauna are particularly at risk globally due to anthropogenic demand, manipulation and exploitation of freshwater resources and yet are often understudied. The Ozark faunal region of Missouri and Arkansas harbours a high level of aquatic biological diversity, especially in regard to endemic crayfishes. Three such endemics, Orconectes eupunctus,Orconectes marchandi and Cambarus hubbsi, are threatened by limited natural distribution and the invasions of Orconectes neglectus.

  3. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

    Science.gov (United States)

    Debrah, Alexander Yaw; Mand, Sabine; Specht, Sabine; Marfo-Debrekyei, Yeboah; Batsa, Linda; Pfarr, Kenneth; Larbi, John; Lawson, Bernard; Taylor, Mark; Adjei, Ohene; Hoerauf, Achim

    2006-09-01

    Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS), dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(s)VEGFR-3]). Lymphedema patients were additionally monitored for stage (grade) of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with the mean stage of

  4. Doxycycline reduces plasma VEGF-C/sVEGFR-3 and improves pathology in lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Alexander Yaw Debrah

    2006-09-01

    Full Text Available Lymphatic filariasis is a disease of considerable socioeconomic burden in the tropics. Presently used antifilarial drugs are able to strongly reduce transmission and will thus ultimately lower the burden of morbidity associated with the infection, however, a chemotherapeutic principle that directly induces a halt or improvement in the progression of the morbidity in already infected individuals would constitute a major lead. In search of such a more-effective drug to complement the existing ones, in an area endemic for bancroftian filariasis in Ghana, 33 microfilaremic and 18 lymphedema patients took part in a double-blind, placebo-controlled trial of a 6-wk regimen of 200 mg/day doxycycline. Four months after doxycycline treatment, all patients received 150-200 microg/kg ivermectin and 400 mg albendazole. Patients were monitored for Wolbachia and microfilaria loads, antigenemia, filarial dance sign (FDS, dilation of supratesticular lymphatic vessels, and plasma levels of lymphangiogenic factors (vascular endothelial growth factor-C [VEGF-C] and soluble vascular endothelial growth factor receptor-3 [(sVEGFR-3]. Lymphedema patients were additionally monitored for stage (grade of lymphedema and the circumferences of affected legs. Wolbachia load, microfilaremia, antigenemia, and frequency of FDS were significantly reduced in microfilaremic patients up to 24 mo in the doxycycline group compared to the placebo group. The mean dilation of supratesticular lymphatic vessels in doxycycline-treated patients was reduced significantly at 24 mo, whereas there was no improvement in the placebo group. Preceding clinical improvement, at 12 mo, the mean plasma levels of VEGF-C and sVEGFR-3 decreased significantly in the doxycycline-treated patients to a level close to that of endemic normal values, whereas there was no significant reduction in the placebo patients. The extent of disease in lymphedema patients significantly improved following doxycycline, with

  5. Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

    Institute of Scientific and Technical Information of China (English)

    Junichi Takino; Shoichi Yamagishi; Masayoshi Takeuchi

    2012-01-01

    AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs)on hepatocellular carcinoma (HCC) cells.METHODS:Two HCC cell lines (Hep3B and HepG2cells) and human umbilical vein endothelial cells (HUVEC) were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs (RAGE) protein was detected in Hep3B and HepG2 cells.HepG2 cells were not affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor (VEGF) mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin (BSA)treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00 ± 0.10 vs 1.92± 0.09 (P < 0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63 ± 0.04ng/mL vs 2.28 ± 0.17 ng/mL for the 24 h treatment and 3.36 ± 0.10 ng/mL vs 4.79 ± 0.31 ng/mL for the 48 h treatment,respectively (P < 0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4% ± 9.0% vs 144.5% ± 11.3% for cell viability,4.29 ± 1.53 vs 6.78 ± 1.84 for migration indices,and 71.0 ± 7.5 vs 112.4 ± 8.0 for the number of branching points,respectively (P < 0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

  6. Diversity and Distribution of Arsenic-Related Genes Along a Pollution Gradient in a River Affected by Acid Mine Drainage.

    Science.gov (United States)

    Desoeuvre, Angélique; Casiot, Corinne; Héry, Marina

    2016-04-01

    Some microorganisms have the capacity to interact with arsenic through resistance or metabolic processes. Their activities contribute to the fate of arsenic in contaminated ecosystems. To investigate the genetic potential involved in these interactions in a zone of confluence between a pristine river and an arsenic-rich acid mine drainage, we explored the diversity of marker genes for arsenic resistance (arsB, acr3.1, acr3.2), methylation (arsM), and respiration (arrA) in waters characterized by contrasted concentrations of metallic elements (including arsenic) and pH. While arsB-carrying bacteria were representative of pristine waters, Acr3 proteins may confer to generalist bacteria the capacity to cope with an increase of contamination. arsM showed an unexpected wide distribution, suggesting biomethylation may impact arsenic fate in contaminated aquatic ecosystems. arrA gene survey suggested that only specialist microorganisms (adapted to moderately or extremely contaminated environments) have the capacity to respire arsenate. Their distribution, modulated by water chemistry, attested the specialist nature of the arsenate respirers. This is the first report of the impact of an acid mine drainage on the diversity and distribution of arsenic (As)-related genes in river waters. The fate of arsenic in this ecosystem is probably under the influence of the abundance and activity of specific microbial populations involved in different As biotransformations.

  7. SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

    Science.gov (United States)

    Bertagnolli, Nicolas M; Drake, Justin A; Tennessen, Jason M; Alter, Orly

    2013-01-01

    To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD) to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM) or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

  8. Monitoring PAI-1 and VEGF Levels in 6 Human Squamous Cell Carcinoma Xenografts During Fractionated Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bayer, Christine, E-mail: christine.bayer@yahoo.com [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Kielow, Achim [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Schilling, Daniela [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany); Maftei, Constantin-Alin [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Zips, Daniel; Yaromina, Ala; Baumann, Michael [OncoRay Center for Radiation Research, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany); Molls, Michael [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); Multhoff, Gabriele [Department of Radiation Oncology, Klinikum rechts der Isar der Technischen Universitaet Muenchen, Munich (Germany); HelmholtzZentrum Muenchen, German Research Center for Environmental Health, Department of Radiation Oncology, University Hospital and Medical Faculty Carl Gustav Carus University of Technology, Dresden (Germany)

    2012-11-01

    Purpose: Previous studies have shown that the plasminogen activator inhibitor type-1 (PAI-1) and vascular endothelial growth factor (VEGF) are regulated by hypoxia and irradiation and are involved in neoangiogenesis. The aim of this study was to determine in vivo whether changes in PAI-1 and VEGF during fractionated irradiation could predict for radiation resistance. Methods and Materials: Six xenografted tumor lines from human squamous cell carcinomas (HSCC) of the head and neck were irradiated with 0, 3, 5, 10, and 15 daily fractions of 2 Gy. The PAI-1 and VEGF antigen levels in tumor lysates were determined by enzyme-linked immunosorbent assay kits. The amounts of PAI-1 and VEGF were compared with the dose to cure 50% of tumors (TCD{sub 50}). Colocalization of PAI-1, pimonidazole (hypoxia), CD31 (endothelium), and Hoechst 33342 (perfusion) was examined by immunofluorescence. Results: Human PAI-1 and VEGF (hVEGF) expression levels were induced by fractionated irradiation in UT-SCC-15, UT-SCC-14, and UT-SCC-5 tumors, and mouse VEGF (msVEGF) was induced only in UT-SCC-5 tumors. High hVEGF levels were significantly associated with radiation sensitivity after 5 fractions (P=.021), and high msVEGF levels were significantly associated with radiation resistance after 10 fractions (P=.007). PAI-1 staining was observed in the extracellular matrix, the cytoplasm of fibroblast-like stroma cells, and individual tumor cells at all doses of irradiation. Colocalization studies showed PAI-1 staining close to microvessels. Conclusions: These results indicate that the concentration of tumor-specific and host-specific VEGF during fractionated irradiation could provide considerably divergent information for the outcome of radiation therapy.

  9. Detection of VEGF-A(xxx)b isoforms in human tissues.

    Science.gov (United States)

    Bates, David O; Mavrou, Athina; Qiu, Yan; Carter, James G; Hamdollah-Zadeh, Maryam; Barratt, Shaney; Gammons, Melissa V; Millar, Ann B; Salmon, Andrew H J; Oltean, Sebastian; Harper, Steven J

    2013-01-01

    Vascular Endothelial Growth Factor-A (VEGF-A) can be generated as multiple isoforms by alternative splicing. Two families of isoforms have been described in humans, pro-angiogenic isoforms typified by VEGF-A165a, and anti-angiogenic isoforms typified by VEGF-A165b. The practical determination of expression levels of alternative isoforms of the same gene may be complicated by experimental protocols that favour one isoform over another, and the use of specific positive and negative controls is essential for the interpretation of findings on expression of the isoforms. Here we address some of the difficulties in experimental design when investigating alternative splicing of VEGF isoforms, and discuss the use of appropriate control paradigms. We demonstrate why use of specific control experiments can prevent assumptions that VEGF-A165b is not present, when in fact it is. We reiterate, and confirm previously published experimental design protocols that demonstrate the importance of using positive controls. These include using known target sequences to show that the experimental conditions are suitable for PCR amplification of VEGF-A165b mRNA for both q-PCR and RT-PCR and to ensure that mispriming does not occur. We also provide evidence that demonstrates that detection of VEGF-A165b protein in mice needs to be tightly controlled to prevent detection of mouse IgG by a secondary antibody. We also show that human VEGF165b protein can be immunoprecipitated from cultured human cells and that immunoprecipitating VEGF-A results in protein that is detected by VEGF-A165b antibody. These findings support the conclusion that more information on the biology of VEGF-A165b isoforms is required, and confirm the importance of the experimental design in such investigations, including the use of specific positive and negative controls.

  10. Neither folic acid supplementation nor pregnancy affects the distribution of folate forms in the red blood cells of women.

    Science.gov (United States)

    Hartman, Brenda A; Fazili, Zia; Pfeiffer, Christine M; O'Connor, Deborah L

    2014-09-01

    It is not known whether folate metabolism is altered during pregnancy to support increased DNA and RNA biosynthesis. By using a state-of-the-art LC tandem mass spectrometry technique, the aim of this study was to investigate differences in RBC folate forms between pregnant and nonpregnant women and between nonpregnant women consuming different concentrations of supplemental folic acid. Forms of folate in RBCs were used to explore potential shifts in folate metabolism during early erythropoiesis. Total RBC folate and folate forms [tetrahydrofolate; 5-methyltetrahydrofolate (5-methyl-THF); 4α-hydroxy-5-methyl-tetrahydrofolate (an oxidation product of 5-methyl-THF); 5-formyl-tetrahydrofolate; and 5,10-methenyl-tetrahydrofolate] were measured in 4 groups of women (n = 26): pregnant women (PW) (30-36 wk of gestation) consuming 1 mg/d of folic acid, and nonpregnant women consuming 0 mg/d (NPW-0), 1 mg/d (NPW-1), and 5 mg/d (NPW-5) folic acid. The mean ± SD RBC folate concentration of the NPW-0 group (890 ± 530 nmol/L) was lower than the NPW-1 (1660 ± 350 nmol/L) and NPW-5 (1980 ± 570 nmol/L) groups as assessed by microbiologic assay (n = 26, P folic acid supplements had detectable concentrations of 5,10-methenyl-tetrahydrofolate (LOD = 0.31 nmol/L). However, there was no difference in the relative distribution of 5-methyl-THF (83-84%), sum of non-methyl folates (0.6-3%), or individual non-methyl folate forms in RBCs across groups. We conclude that although folic acid supplementation in nonpregnant women increases RBC total folate and the concentration of individual folate forms, it does not alter the relative distribution of folate forms. Similarly, distribution of RBC folate forms did not differ between pregnant and nonpregnant women. This trial was registered at clinicaltrials.gov as NCT01741077.

  11. SVD identifies transcript length distribution functions from DNA microarray data and reveals evolutionary forces globally affecting GBM metabolism.

    Directory of Open Access Journals (Sweden)

    Nicolas M Bertagnolli

    Full Text Available To search for evolutionary forces that might act upon transcript length, we use the singular value decomposition (SVD to identify the length distribution functions of sets and subsets of human and yeast transcripts from profiles of mRNA abundance levels across gel electrophoresis migration distances that were previously measured by DNA microarrays. We show that the SVD identifies the transcript length distribution functions as "asymmetric generalized coherent states" from the DNA microarray data and with no a-priori assumptions. Comparing subsets of human and yeast transcripts of the same gene ontology annotations, we find that in both disparate eukaryotes, transcripts involved in protein synthesis or mitochondrial metabolism are significantly shorter than typical, and in particular, significantly shorter than those involved in glucose metabolism. Comparing the subsets of human transcripts that are overexpressed in glioblastoma multiforme (GBM or normal brain tissue samples from The Cancer Genome Atlas, we find that GBM maintains normal brain overexpression of significantly short transcripts, enriched in transcripts that are involved in protein synthesis or mitochondrial metabolism, but suppresses normal overexpression of significantly longer transcripts, enriched in transcripts that are involved in glucose metabolism and brain activity. These global relations among transcript length, cellular metabolism and tumor development suggest a previously unrecognized physical mode for tumor and normal cells to differentially regulate metabolism in a transcript length-dependent manner. The identified distribution functions support a previous hypothesis from mathematical modeling of evolutionary forces that act upon transcript length in the manner of the restoring force of the harmonic oscillator.

  12. Vascular endothelial growth factor (VEGF-2578А/С gene polymorphism in combination with cytokine gene polymorphisms among patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    V I Konenkov

    2013-01-01

    Full Text Available Objective: to study the distribution of the genotypes of the vascular endothelial growth factor (VEGF gene and their combinations with those of other cytokines among patients with rheumatoid arthritis (RA and healthy individuals. Subjects and methods. 509 Europeoid women from the eastern regions of Russia, including 374 healthy individuals aged 23-64 years and 135 RA patients aged 27-66 years, were examined. The single nucleotide polymorphism in the promoter region of the genes of VEGC -2578 C/A, tumor necrosis factor-а (TNF-а -863 C/A, TNF-а -308 G/A, TNF-а -238 G/A, and interleukin (IL 1β -31 С/T, IL4 -590 С/T, IL6-174 G/C, IL10-1082 G/A, and IL10-592А/С was studied by restriction fragment length polymorphism analysis. Results. Analysis of the frequency of the genotypes of VEGF in combination with other genotypes has revealed a number of highly significant genetic differences between the groups of healthy individuals and RA patients. Among the combined genetic signs (CGS, whose frequency is significantly increased in RA, there is a predominance of heterozygous CA genotypes at the polymorphic position of VEGF -2578 C/A. Among the CGS positively associated with RA, which include homozygous VEGF -2578 variants, there is a preponderance of AA genotypes whereas all 100% of the homozygous genotypes, whose frequency is significantly decreased in RA, correspond to the variant of СС. The CGS whose frequency is altered in RA along with VEGF genotypes most commonly include the genotypes of IL1ß, IL4, IL10, IL6, and TNF-а. Conclusion. The pathogenesis of RA calls for comprehensive investigation of the role of the angiogenesis and inflammation regulation genes.

  13. Expression of Semaphorins, Neuropilins, VEGF, and Tenascins in Rat and Human Primary Sensory Neurons after a Dorsal Root Injury

    Science.gov (United States)

    Lindholm, Tomas; Risling, Mårten; Carlstedt, Thomas; Hammarberg, Henrik; Wallquist, Wilhelm; Cullheim, Staffan; Sköld, Mattias K.

    2017-01-01

    Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used in situ hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT). The studied survival times were 1–365 days. The different forms of mRNAs were unevenly distributed between the different size classes of sensory nerve cells. The results show that mRNA for SEMA3A was diminished after trauma to the sensory nerve roots in rats. The SEMA3A receptor NP1, and SEMA3F receptor NP2, was significantly upregulated in the DRG neurons after DRT and SNT. SEMA4F was upregulated after a SNT. The expression of mRNA for VEGF in DRG neurons after DRT showed a significant upregulation that was high even a year after the injuries. These data suggest a role for the semaphorins, neuropilins, VEGF, and J1 in the reactions after dorsal root lesions. PMID:28270793

  14. Disturbance frequency and vertical distribution of seeds affect long-term population dynamics: a mechanistic seed bank model.

    Science.gov (United States)

    Eager, Eric Alan; Haridas, Chirakkal V; Pilson, Diana; Rebarber, Richard; Tenhumberg, Brigitte

    2013-08-01

    Seed banks are critically important for disturbance specialist plants because seeds of these species germinate only in disturbed soil. Disturbance and seed depth affect the survival and germination probability of seeds in the seed bank, which in turn affect population dynamics. We develop a density-dependent stochastic integral projection model to evaluate the effect of stochastic soil disturbances on plant population dynamics with an emphasis on mimicking how disturbances vertically redistribute seeds within the seed bank. We perform a simulation analysis of the effect of the frequency and mean depth of disturbances on the population's quasi-extinction probability, as well as the long-term mean and variance of the total density of seeds in the seed bank. We show that increasing the frequency of disturbances increases the long-term viability of the population, but the relationship between the mean depth of disturbance and the long-term viability of the population are not necessarily monotonic for all parameter combinations. Specifically, an increase in the probability of disturbance increases the long-term viability of the total seed bank population. However, if the probability of disturbance is too low, a shallower mean depth of disturbance can increase long-term viability, a relationship that switches as the probability of disturbance increases. However, a shallow disturbance depth is beneficial only in scenarios with low survival in the seed bank.

  15. Epigallocatechin-3-gallate affects the growth of LNCaP cells via membrane fluidity and distribution of cellular zinc

    Institute of Scientific and Technical Information of China (English)

    Jun-guo YANG; Hai-ning YU; Shi-li SUN; Lan-cui ZHANG; Guo-qing HE; Undurti N. DAS; Hui RUAN; Sheng-rong SHEN

    2009-01-01

    Objective: To evaluate effects of epigallocatechin-3-gallate (EGCG) on the viability, membrane properties, and zinc distribution, with and without the presence of Zn2+, in human prostate carcinoma LNCaP cells. Methods: We examined changes in cellular morphology and membrane fluidity of LNCaP cells, distribution of cellular zinc, and the incorporated portion of EGCG after treatments with EGCG, Zn2+, and EGCG+Zn2+. Results: We observed an alteration in cellular morphology and a decrease in membrane fluidity of LNCaP cells after treatment with EGCG or Zn2+. The proportion of EGCG incorporated into liposomes treated with the mixture of EGCG and Zn2+ at the ratio of 1:l was 90.57%, which was significantly higher than that treated with EGCG alone (30.33%). Electron spin resonance (ESR) studies and determination of fatty acids showed that the effects of EGCG on the membrane fluidity of LNCaP were decreased by Zn2+. EGCG accelerated the accumulation of zinc in the mitochondria and cytosol as observed by atomic absorption spectrometer. Conclusion: These results show that EGCG interacted with cell membrane,decreased the membrane fluidity of LNCaP cells, and accelerated zinc accumulation in the mitochondria and cytosol, which could be the mechanism by which EGCG inhibits proliferation of LNCaP cells. In addition, high concentrations of Zn2+ could attenuate the actions elicited by EGCG.

  16. Addition of pectin and soy soluble polysaccharide affects the particle size distribution of casein suspensions prepared from acidified skim milk.

    Science.gov (United States)

    Liu, JinRu; Nakamura, Akihiro; Corredig, Milena

    2006-08-23

    Pectins are negatively charged polysaccharides employed as stabilizers in acidified milk dispersions, where caseins aggregate because of the low pH and serum separation needs to be prevented. The objective of this research was to study the effect of charge on the stabilizing functionality of the polysaccharide in acid milk drinks. Unstandardized pectins with various charges (as degree of esterification, DE) as well as soybean soluble polysaccharide (SSPS) were tested for their stabilizing behavior as a function of pH and concentration. Skim milk was acidified by glucono-delta-lactone and then homogenized in the presence of polysaccharide at different pH values (in the range from 4.2 to 3.0). Measurements of particle size distribution demonstrated that pectins with a DE of 71.4, 68.6, and 67.4 stabilized milk at pH > 4.0. Pectins with a lower DE (63.9%) needed a higher concentration (0.4%) at the same pH to show a monomodal distribution of particle sizes. Pectins with lower DE (milk, at pH milk dispersion was pH-dependent, and results were similar to those for samples containing pectin alone. This suggested that in the mixture, pectin dominated the behavior over SSPS, even when an excess of SSPS was added to the dispersions before homogenization.

  17. A post-implementation evaluation of ceramic water filters distributed to tsunami-affected communities in Sri Lanka.

    Science.gov (United States)

    Casanova, Lisa M; Walters, Adam; Naghawatte, Ajith; Sobsey, Mark D

    2012-06-01

    Sri Lanka was devastated by the 2004 Indian Ocean tsunami. During recovery, the Red Cross distributed approximately 12,000 free ceramic water filters. This cross-sectional study was an independent post-implementation assessment of 452 households that received filters, to determine the proportion still using filters, household characteristics associated with use, and quality of household drinking water. The proportion of continued users was high (76%). The most common household water sources were taps or shallow wells. The majority (82%) of users used filtered water for drinking only. Mean filter flow rate was 1.12 L/hr (0.80 L/hr for households with taps and 0.71 for those with wells). Water quality varied by source; households using tap water had source water of high microbial quality. Filters improved water quality, reducing Escherichia coli for households (largely well users) with high levels in their source water. Households were satisfied with filters and are potentially long-term users. To promote sustained use, recovery filter distribution efforts should try to identify households at greatest long-term risk, particularly those who have not moved to safer water sources during recovery. They should be joined with long-term commitment to building supply chains and local production capacity to ensure safe water access.

  18. Distribution of rare earth elements in an alluvial aquifer affected by acid mine drainage: the Guadiamar aquifer (SW Spain)

    Energy Technology Data Exchange (ETDEWEB)

    Olias, M. [Departamento de Geodinamica y Paleontologia, Universidad de Huelva, Avda. de las Fuerza Armadas s/n, 21071 Huelva (Spain)]. E-mail: manuel.olias@dgyp.uhu.es; Ceron, J.C. [Departamento de Geodinamica y Paleontologia, Universidad de Huelva, Avda. de las Fuerza Armadas s/n, 21071 Huelva (Spain); Fernandez, I. [Departamento de Geodinamica y Paleontologia, Universidad de Huelva, Avda. de las Fuerza Armadas s/n, 21071 Huelva (Spain); Rosa, J. de la [Departamento de Geologia, Universidad de Huelva, Avda. de las Fuerza Armadas s/n, 21071 Huelva (Spain)

    2005-05-01

    This work analyses the spatial distribution, the origin, and the shale-normalised fractionation patterns of the rare earth elements (REE) in the alluvial aquifer of the Guadiamar River (south-western Spain). This river received notoriety in April 1998 for a spill that spread a great amount of slurry (mainly pyrites) and acid waters in a narrow strip along the river course. Groundwaters and surface waters were sampled to analyse, among other elements, the REEs. Their spatial distribution shows a peak close to the mining region, in an area with low values of pH and high concentrations of sulphates and other metals such as Zn, Cu, Co, Ni, Pb, and Cd. The patterns of shale-normalised fractionation at the most-contaminated points show an enrichment in the middle rare earth elements (MREE) with respect to the light (LREE) and heavy (HREE) ones, typical of acid waters. The Ce-anomaly becomes more negative as pH increases, due to the preferential fractionation of Ce in oxyhydroxides of Fe. - Pollution of the aquifer with rare earth elements is documented at a site of a major spill from a mining operation.

  19. Factors affecting distribution of microbiotic crusts in the grain-for-green land of the loess region,northern Shaanxi,China

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A field survey was conducted in the grain-for-green land of the loess region,northern Shaanxi,China,from July to August of 2005 to provide a scientific evaluation of the grain-for-green project,including its soil and water conservation and other ecological benefits for the region.The distribution of microbiotic crusts were studied,while human disturbance,aspect,topography,vegetation structure and other factors affecting it were obtained from the analysis of survey data from 78 sample plots.Results show that crust coverage is larger on lessdisturbed plots than on highly-disturbed ones,on northfacing plots than on south-facing ones and on gully-slopes than on ridge-slopes.Coverage increases with herbal coverage and trees can provide better conditions for distribution of crusts than shrubs.Therefore,crust coverage is larger in herb-dominated plots than in tree-dominated ones and crusts in shrub-dominated plots are smaller.However,we made no progress in our study on deciding how slope degrees and herb species affect the distribution of crusts.We believe that more studies are necessary for a further exploration of the relationship between them.

  20. Distribution and factors affecting adsorption of sterols in the surface sediments of Bosten Lake and Manas Lake, Xinjiang.

    Science.gov (United States)

    Liu, Jiang; Yao, Xiaorui; Lu, Jianjiang; Qiao, Xiuwen; Liu, Zilong; Li, Shanman

    2016-03-01

    This study investigated the concentrations and distribution of eight sterol compounds in the surface sediments of Bosten Lake and Manas Lake, Xinjiang, China. The ratios of sterols as diagnostic indices were used to identify pollution sources. The sediment of the two lakes was selected as an adsorbent to investigate the adsorption behaviour of sterols. Results showed that the sterols were widely distributed in the sediments of the lakes in the study areas. The total concentrations of the detected sterols in Bosten Lake and in Manas Lake were 1.584-27.897 and 2.048-18.373 μg g(-1)∙dw, respectively. In all of the sampling sites, the amount of faecal sterols was less than that of plant sterols. β-sitosterol was the dominant plant sterol with a mean concentration of 2.378 ± 2.234 μg g(-1)∙dw; cholesterol was the most abundant faecal sterol with a mean concentration of 1.060 ± 1.402 μg g(-1)∙dw. The pollution level was higher in Bosten Lake than in Manas Lake. Majority of the ratios clearly demonstrated that the contamination by human faecal sources was occurring at stations which are adjacent to residential areas and water inlets. The adsorption behaviour of sterols to sediment suggested that the sterol adsorption coefficients were reduced as temperature increased. As salinity increased, the adsorption quantity also increased. As pH increased, the sediment adsorption of sterol slightly increased because the strong alkaline solution is not conducive to the adsorption of sterols. The ratios between sterols did not change largely with the change in external factors.

  1. VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy

    DEFF Research Database (Denmark)

    Cao, Renhai; Xue, Yuan; Hedlund, Eva-Maria

    2010-01-01

    , and adenoviral vectors ablates pericytes from the mature retinal vasculature through the VEGF receptor 1 (VEGFR1)-mediated signaling pathway, leading to increased vascular leakage. In contrast, we demonstrate VEGF receptor 2 (VEGFR2) is primarily expressed in nonvascular photoreceptors and ganglion cells...

  2. Anti-VEGF agents in metastatic colorectal cancer (mCRC: are they all alike?

    Directory of Open Access Journals (Sweden)

    Saif MW

    2013-06-01

    Full Text Available Muhammad Wasif Saif GI Oncology Program, Tufts University School of Medicine, Boston, MA, USA Abstract: Bevacizumab is a monoclonal antibody that binds and neutralizes vascular endothelial growth factor (VEGF-A, a key player in the angiogenesis pathway. Despite benefits of bevacizumab in cancer therapy, it is clear that the VEGF pathway is complex, involving multiple isoforms, receptors, and alternative ligands such as VEGF-B, and placental growth factor, which could enable escape from VEGF-A-targeted angiogenesis inhibition. Recently developed therapies have targeted other ligands in the VEGF pathway (eg, aflibercept, known as ziv-aflibercept in the United States, VEGF receptors (eg, ramucirumab, and their tyrosine kinase signaling (ie, tyrosine kinase inhibitors. The goal of the current review was to identify comparative preclinical data for the currently available VEGF-targeted therapies. Sources were compiled using PubMed searches (2007 to 2012, using search terms including, but not limited to: “bevacizumab,” “aflibercept,” “ramucirumab,” and “IMC-18F1.” Two preclinical studies were identified that compared bevacizumab and the newer agent, aflibercept. These studies identified some important differences in binding and pharmacodynamic activity, although the potential clinical relevance of these findings is not known. Newer antiangiogenesis therapies should help further expand treatment options for colorectal and other cancers. Comparative preclinical data on these agents is currently lacking. Keywords: aflibercept, antiangiogenesis, metastatic colorectal cancer (mCRC, tyrosine kinase inhibitor (TKI, vascular endothelial growth factor (VEGF

  3. RNA interference inhibits expression of vascular endothelial growth factor (VEGF) in human retinal pigment epithelial cells

    Institute of Scientific and Technical Information of China (English)

    CAI Chun-mei; SUN Bao-chen; LIU Xu-yang; WANG Jin-jin; LI Jun-fa; HAN Song; WANG Ning-li; LU Qing-jun

    2005-01-01

    @@ Choroidal neovascularization (CNV), a major cause of vision loss, is the result of the increased vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. It is important to inhibit the expression of VEGF protein in RPE cells.

  4. [Measurement and correlation analysis of plasma VEGF level in the patients of hyperthyroidism].

    Science.gov (United States)

    Zhao, Xiaoni; Wang, Guangrong; You, Jinhui

    2013-04-01

    Vascular endothelial growth factor (VEGF) is a glycoprotein that promotes endothelial regeneration, stimulates formation of collateral blood vessels and increases vascular permeability. The purpose of this study was to measure the peripheral blood plasma level of VEGF and FT3, FT4, TSH and to analyze the correlation of the level of VEGF and TSH, FT3, FT4, age and gender in the patients of hyperthyroidism. The relationship between hyperthyroidism and VEGF was investigated as well. The plasma level of VEGF in 45 hyperthyroidism patients and 27 healthy persons were measured by enzyme-linked immunosorbent assay (ELISA), while plasma FT3, FT4, TSH were detected by chemiluminescence. The result showed that the plasma level of VEGF in hyperthyroidism patients [(92.53 +/- 62.38) pg/mL] was significantly lower than that in the control group [(158.28 +/- 77.15) pg/mL] (P hyperthyroidism patients (P > 0.05). These results suggested that the peripheral blood plasma level of VEGF in hyperthyroidism patients was significantly lower than that in the control group. Further experimental investigations are needed to estimate the relationship between VEGF and hyperthyroidism.

  5. Platelet Activation Determines Angiopoietin-1 and VEGF Levels in Malaria : Implications for Their Use as Biomarkers

    NARCIS (Netherlands)

    Brouwers, Judith; Noviyanti, Rintis; Fijnheer, Rob; de Groot, Philip G.; Trianty, Leily; Mudaliana, Siti; Roest, Mark; Syafruddin, Din; van der Ven, Andre; de Mast, Quirijn

    2013-01-01

    Introduction: The angiogenic proteins angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF) are regulators of endothelial inflammation and integrity. Since platelets store large amounts of Ang-1 and VEGF, measurement of circulation levels of these proteins is sensitive to platele

  6. Pulmonary Large Cell Carcinoma Displays High Expression of EMMPRIN and VEGF

    Institute of Scientific and Technical Information of China (English)

    Yushuang Zheng; Miao Yu; Huachuan Zheng; Yifu Guan; Yasuo Takano

    2008-01-01

    OBJECTIVE To investigate the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and vascular endothelial growth factor (VEGF) in lung carcinomas,and to clarify their roles in carcinoma progression.METHODS Expression of EMMPRIN and VEGF was examined with tissue microarrays (TMAs) of lung carcinomas (n = 181),and their suppression in adjacent normal lung samples (n = 40) were determined by immunohistochemistry.The results were compared with clinicopathological findings for the same tumors.RESULTS Both EMMPRIN and VEGF were occasionally expressed in pseudostratified columnar epithelium and frequently in lung carcinomas.Histologically,EMMPRIN and VEGF displayed higher levels in large (LCC) cell carcinomas than adenocarcinoma (AD),squamous (SQ) and small cell carcinomas (SCC) (P < 0.05).EMMPRIN was more highly expressed in SQ as compared with AD (P < 0.05),while the converse was true for VEGF (P < 0.05).Binding was generally more intense for EMMPRIN in samples from male compared to female patients (P < 0.05),whereas the latter tended to exhibit more VEGF expression (P < 0.05).Positive associations of VEGF expression with the TNM stage and amounts of EMMPRIN were noted in the lung carcinomas (P < 0.05).CONCLUSION EMMPRIN and VEGF possibly contribute to physiological repair of normal lung and histogenesis of lung carcinoma.Both proteins might be involved in the molecular basis for differences in the incidence of lung carcinoma between men and women.

  7. Correlation of VEGF and COX-2 Expression with VM in Malignant Melanomas

    Institute of Scientific and Technical Information of China (English)

    BaocunSun; ShiwuZhang; XiulanZhao; YanxueLiu; ChunshengNi; DanfangZhang; HongQi; ZhiyongLiu; XishanHao

    2004-01-01

    OBJECTIVE To investigate the relationship between vascular epithelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in melanomas and the expressive difference of VEGF and COX-2 between melanomas with and without vasculogenic mimicry(VM).METHODS Sixty cases of malignant melanomas emoeaaea In paraffin were studied. The tumors were divided into a high-grade malignant group and a low-grade malignant group based on their tumor type, atypia and survival time of the patient. Then tissue microarrays were produced from these paraffin-embedded tumor tissues which were stained for VEGF, COX-2 and PAS. The difference in expression between VEGF and COX-2 in the malignant melanomas was compared using a grid-count. In addition, the tumors were also divided into mimicry and non-mimicry groups based on their PAS staining. Then the differences between the PAS positive and negative areas of the 2 groups were compared.RESULTS In malignant melanomas with VM, VEGF and COX-2 expression was less in tumors in which VM was absent, but VEGF, COX-2 expression in high-grade malignant melanomas was higher than that in low-grade grade malignant melanomas. Expression of VEGF was correlated with COX-2 expression.CONCLUSION VM exists in some high-grade malignant melanomas. The differences and relations between VEGF and COX-2 showed that some high-grade malignant melanomas possess a unique molecular-mechanism of tumor metastasis and blood supply.

  8. Prolonged presence of VEGF promotes vascularization in 3D bioprinted scaffolds with defined architecture

    NARCIS (Netherlands)

    Poldervaart, Michelle T; Gremmels, Hendrik; van Deventer, Kelly; Fledderus, Joost O; Oner, F Cumhur; Verhaar, Marianne C; Dhert, Wouter J A; Alblas, Jacqueline

    2014-01-01

    Timely vascularization is essential for optimal performance of bone regenerative constructs. Vascularization is efficiently stimulated by vascular endothelial growth factor (VEGF), a substance with a short half-life time. This study investigates the controlled release of VEGF from gelatin microparti

  9. Tumor-associated fibroblasts as "Trojan Horse" mediators of resistance to anti-VEGF therapy.

    Science.gov (United States)

    Francia, Giulio; Emmenegger, Urban; Kerbel, Robert S

    2009-01-06

    While targeting VEGF has shown success against a number of human cancers, drug resistance has resulted in compromised clinical benefits. In this issue of Cancer Cell, Crawford et al. (2009) report that tumors resistant to anti-VEGF therapy stimulate tumor-associated fibroblasts to express proangiogenic PDGF-C, implicating it as a potential therapeutic target.

  10. Inhibition of VEGF signaling pathways in multiple myeloma and other malignancies.

    Science.gov (United States)

    Podar, Klaus; Anderson, Kenneth C

    2007-03-01

    Due to its direct effects on endothelial cells, circulatory endothelial progenitor cells, hematopoietic stem cells, immune cells, osteoclasts, osteoblasts and neurons, vascular endothelial growth factor (VEGF) is linked to tumor cell development, progression, metastatic osteolysis and drug resistance, as well as clinical features such as metastatic osteolysis. Importantly, recent advances in the understanding of mechanisms of action of antiangiogenic drugs/VEGF-inhibitors have fundamentally changed treatment regimens in cancer. VEGF plays a key role not only in solid tumors but also in hematologic malignancies, including multiple myeloma (MM). Despite recent advances in our understanding of MM pathogenesis and novel therapies (bortezomib and lenalidomide), it remains incurable. Our own and others' work suggest that VEGF-inhibitors e.g., the small molecule VEGF receptor inhibitor pazopanib, may also improve patient outcome in MM.

  11. Metformin inhibits development of diabetic retinopathy through inducing alternative splicing of VEGF-A

    Science.gov (United States)

    Yi, Quan-Yong; Deng, Gang; Chen, Nan; Bai, Zhi-Sha; Yuan, Jian-Shu; Wu, Guo-Hai; Wang, Yu-Wen; Wu, Shan-Jun

    2016-01-01

    Previous studies have shown that metformin, an AMP-activated protein kinase activator widely prescribed for type 2 diabetes, is especially beneficial in cases of diabetic retinopathy (DR) with undetermined mechanisms. Here, we used a streptozotocin-induced diabetes model in mice to study the effects of metformin on the development of DR. We found that 10 weeks after STZ treatment, DR was induced in STZ-treated mice, regardless treatment of metformin. However, metformin alleviated the DR, seemingly through attenuating the retina neovascularization. The total vascular endothelial cell growth factor A (VEGF-A) in eyes was not altered by metformin, but the phosphorylation of the VEGF receptor 2 (VEGFR2) was decreased, which inhibited VEGF signaling. Further analysis showed that metformin may induce VEGF-A mRNA splicing to VEGF120 isoform to reduce its activation of the VEGFR2. These findings are critical for generating novel medicine for DR treatment.

  12. Sowing Density: A Neglected Factor Fundamentally Affecting Root Distribution and Biomass Allocation of Field Grown Spring Barley (Hordeum Vulgare L.).

    Science.gov (United States)

    Hecht, Vera L; Temperton, Vicky M; Nagel, Kerstin A; Rascher, Uwe; Postma, Johannes A

    2016-01-01

    Studies on the function of root traits and the genetic variation in these traits are often conducted under controlled conditions using individual potted plants. Little is known about root growth under field conditions and how root traits are affected by agronomic practices in particular sowing density. We hypothesized that with increasing sowing density, root length density (root length per soil volume, cm cm(-3)) increases in the topsoil as well as specific root length (root length per root dry weight, cm g(-1)) due to greater investment in fine roots. Therefore, we studied two spring barley cultivars at ten different sowing densities (24-340 seeds m(-2)) in 2 consecutive years in a clay loam field in Germany and established sowing density dose-response curves for several root and shoot traits. We took soil cores for measuring roots up to a depth of 60 cm in and between plant rows (inter-row distance 21 cm). Root length density increased with increasing sowing density and was greatest in the plant row in the topsoil (0-10 cm). Greater sowing density increased specific root length partly through greater production of fine roots in the topsoil. Rooting depth (D50) of the major root axes (root diameter class 0.4-1.0 mm) was not affected. Root mass fraction decreased, while stem mass fraction increased with sowing density and over time. Leaf mass fraction was constant over sowing density but greater leaf area was realized through increased specific leaf area. Considering fertilization, we assume that light competition caused plants to grow more shoot mass at the cost of investment into roots, which is partly compensated by increased specific root length and shallow rooting. Increased biomass per area with greater densities suggest that density increases the efficiency of the cropping system, however, declines in harvest index at densities over 230 plants m(-2) suggest that this efficiency did not translate into greater yield. We conclude that plant density is a

  13. Availability and temporal heterogeneity of water supply affect the vertical distribution and mortality of a belowground herbivore and consequently plant growth.

    Directory of Open Access Journals (Sweden)

    Tomonori Tsunoda

    Full Text Available We examined how the volume and temporal heterogeneity of water supply changed the vertical distribution and mortality of a belowground herbivore, and consequently affected plant biomass. Plantago lanceolata (Plantaginaceae seedlings were grown at one per pot under different combinations of water volume (large or small volume and heterogeneity (homogeneous water conditions, watered every day; heterogeneous conditions, watered every 4 days in the presence or absence of a larva of the belowground herbivorous insect, Anomala cuprea (Coleoptera: Scarabaeidae. The larva was confined in different vertical distributions to top feeding zone (top treatment, middle feeding zone (middle treatment, or bottom feeding zone (bottom treatment; alternatively no larva was introduced (control treatment or larval movement was not confined (free treatment. Three-way interaction between water volume, heterogeneity, and the herbivore significantly affected plant biomass. With a large water volume, plant biomass was lower in free treatment than in control treatment regardless of heterogeneity. Plant biomass in free treatment was as low as in top treatment. With a small water volume and in free treatment, plant biomass was low (similar to that under top treatment under homogeneous water conditions but high under heterogeneous ones (similar to that under middle or bottom treatment. Therefore, there was little effect of belowground herbivory on plant growth under heterogeneous water conditions. In other watering regimes, herbivores would be distributed in the shallow soil and reduced root biomass. Herbivore mortality was high with homogeneous application of a large volume or heterogeneous application of a small water volume. Under the large water volume, plant biomass was high in pots in which the herbivore had died. Thus, the combinations of water volume and heterogeneity affected plant growth via the change of a belowground herbivore.

  14. Distribution of hydroxyanthracene derivatives in Cassia alata and the factors affecting the quality of the raw material

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    Niwan Intaraksa

    2003-07-01

    Full Text Available Analyses have been carried out on the content of hydroxyanthracene derivatives of the leaves, flowers and pods of Cassia alata, which had been collected at different harvesting times and different leaf-positions. It was found that when the leaves had been harvested in March, June or September, the hydroxyanthracene derivatives were accumulated more in the leaf-positions 1-3 (1.82, 1.25, 1.63 %w/w, respectively and 4-6 (1.39, 1.58, 1.09 %w/w, respectively. In December (the flowering and fruiting season, hydroxyanthracene derivatives were accumulated more in the flowers (2.21%w/w and the pods (1.82 %w/w, respectively. The method and temperature of drying markedly affected the hydroxyanthracene derivative content. Drying of the leaves in a hot air oven at 50ºC gave a higher hydroxyanthracene derivative content (1.43 %w/w than drying in a hot air oven at 80ºC (0.44 %w/w or drying in the sun (0.95 %w/w. Study on the stability of hydroxyanthracene derivatives in C. alata leaf powder, which was kept in tight container at room temperature, found that the hydroxyanthracene derivative content did not decrease within 9 months.

  15. Updated distribution of Osmoderma eremita in Abruzzo (Italy and agro-pastoral practices affecting its conservation (Coleoptera: Scarabaeidae

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    Patrizia Giangregorio

    2015-12-01

    Full Text Available New records of Osmoderma eremita (Scopoli, 1763 (Coleoptera: Scarabaeidae: Cetoniinae are reported for Abruzzo (Italy, together with a review of its distribution in this region. O. eremita is a saproxylic beetle dependent on the presence of hollow deciduous trees with abundant wood mould in their cavities. The major threats for the species are habitat loss and fragmentation. EU Habitats Directive requests to the member States its protection and the monitoring of its conservation status. Detection of its occurrence is the first step to protect the species. The surveys have been carried out in ten sites of Abruzzo by using black cross-windows traps baited with specific pheromone. The species has been recorded for the first time in the Sant’Antonio forest and its presence is confirmed in the Peligna Valley, after a decade. The populations seem to be confined to small patches of suitable habitats. At local level, the abandonment of the pollarding practice (willow and beech forests and the use of pollarded trees as biomass for fuel are the major threats for this species. Indeed some key actions, such as the protection of old hollow trees and the continuation of pollarding practice in rural landscape, could be key factors for the conservation strategies of the species in the study area.

  16. Coordinating Etk/Bmx activation and VEGF upregulation to promote cell survival and proliferation.

    Science.gov (United States)

    Chau, Cindy H; Chen, Kai-Yun; Deng, Hong-Tao; Kim, Kwang-Jin; Hosoya, Ken-ichi; Terasaki, Tetsuya; Shih, Hsiu-Ming; Ann, David K

    2002-12-12

    Etk/Bmx, a member of the Tec family of non-receptor tyrosine kinase, is characterized by an N-terminal PH domain and has recently been shown to be involved in the regulation of various cellular processes, including proliferation, differentiation, motility and apoptosis. Since VEGF and the activation of its signaling pathway have been implicated in modulating a variety of biological responses, we characterized the role of Etk-dependent signaling pathways involved in the upregulation of VEGF expression, and explored the functional implications of this enhancement in sustaining cell proliferation and survival. Using Northern and Western analyses, transient transfections, and pharmacological agents, we demonstrate that Etk activation alone is sufficient to transcriptionally induce VEGF expression, independent of the previously identified hypoxia response element (HRE), in both Pa-4 epithelial and TR-BBB endothelial cells under normoxia. In addition, Etk utilizes both MEK/ERK and PI3-K/Pak1 signaling pathways in concert to activate VEGF transcription. Functionally, Etk activation elicits a profound stimulatory effect on TR-BBB cell proliferation and formation of capillary-like networks in Matrigel containing reduced levels of growth factors. Finally, antisense oligonucleotides against either endogenous VEGF or Etk abrogate the proliferation of Etk-activated TR-BBB cells, and exogenous VEGF treatment stimulates endogenous Etk tyrosine phosphorylation in HUVECs. Taken together, these results indicate that VEGF is both an Etk downstream target gene and an Etk upstream activator, constituting a reciprocal Etk-VEGF autoregulatory loop. These findings, to our knowledge, are the first delineation of a network of positive feedforward signaling pathways that converge on the Etk-VEGF axis, causally associating Etk-mediation of VEGF induction with enhanced cellular processes in both epithelial and endothelial cells.

  17. Sustained delivery of VEGF from designer self-assembling peptides improves cardiac function after myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Hai-dong [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Cui, Guo-hong; Yang, Jia-jun [Department of Neurology, Shanghai No. 6 People' s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200233 (China); Wang, Cun [Institutes of Biomedical Sciences, Fudan University, Shanghai 200032 (China); Zhu, Jing; Zhang, Li-sheng; Jiang, Jun [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Shao, Shui-jin, E-mail: shaoshuijin@163.com [Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer The designer peptide LRKKLGKA could self-assemble into nanofibers. Black-Right-Pointing-Pointer Injection of LRKKLGKA peptides could promote the sustained delivery of VEGF. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides lead to sufficient angiogenesis. Black-Right-Pointing-Pointer Injection of VEGF with LRKKLGKA peptides improves heart function. -- Abstract: Poor vascularization and insufficient oxygen supply are detrimental to the survival of residual cardiomyocytes or transplanted stem cells after myocardial infarction. To prolong and slow the release of angiogenic factors, which stimulate both angiogenesis and vasculogenesis, we constructed a novel self-assembling peptide by attaching the heparin-binding domain sequence LRKKLGKA to the self-assembling peptide RADA16. This designer self-assembling peptide self-assembled into nanofiber scaffolds under physiological conditions, as observed by atomic force microscopy. The injection of designer self-assembling peptides can efficiently provide the sustained delivery of VEGF for at least 1 month. At 4 weeks after transplantation, cardiac function was improved, and scar size and collagen deposition were markedly reduced in the group receiving VEGF with the LRKKLGKA scaffolds compared with groups receiving VEGF alone, LRKKLGKA scaffolds alone or VEGF with RADA16 scaffolds. The microvessel density in the VEGF with LRKKLGKA group was higher than that in the VEGF with RADA16 group. TUNEL and cleaved caspase-3 expression assays showed that the transplantation of VEGF with LRKKLGKA enhanced cell survival in the infarcted heart. These results present the tailor-made peptide scaffolds as a new generation of sustained-release biomimetic biomaterials and suggest that the use of angiogenic factors along with designer self-assembling peptides can lead to myocardial protection, sufficient angiogenesis, and improvement in cardiac function.

  18. Impaired Pulmonary Defense Against Pseudomonas aeruginosa in VEGF Gene Inactivated Mouse Lung

    Science.gov (United States)

    Breen, Ellen C.; Malloy, Jaret L.; Tang, Kechun; Xia, Feng; Fu, Zhenxing; Hancock, Robert E. W.; Overhage, Joerg; Wagner, Peter D.; Spragg, Roger G.

    2012-01-01

    Repeated bacterial and viral infections are known to contribute to worsening lung function in several respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Previous studies have reported alveolar wall cell apoptosis and parenchymal damage in adult pulmonary VEGF gene ablated mice. We hypothesized that VEGF expressed by type II cells is also necessary to provide an effective host defense against bacteria in part by maintaining surfactant homeostasis. Therefore, Pseudomonas aeruginosa (PAO1) levels were evaluated in mice following lung-targeted VEGF gene inactivation, and alterations in VEGF-dependent type II cell function were evaluated by measuring surfactant homeostasis in mouse lungs and isolated type II cells. In VEGF-deficient lungs increased PAO1 levels and pro-inflammatory cytokines, TNFα and IL-6, were detected 24 hours after bacterial instillation compared to control lungs. In vivo lung-targeted VEGF gene deletion (57% decrease in total pulmonary VEGF) did not alter alveolar surfactant or tissue disaturated phosphatidylcholine (DSPC) levels. However, sphingomyelin content, choline phosphate cytidylyltransferase (CCT) mRNA and SP-D expression were decreased. In isolated type II cells an 80% reduction of VEGF protein resulted in decreases in total phospholipids (PL), DSPC, DSPC synthesis, surfactant associated proteins (SP)-B and -D, and the lipid transporters, ABCA1 and Rab3D. TPA-induced DSPC secretion and apoptosis were elevated in VEGF-deficient type II cells. These results suggest a potential protective role for type II cell-expressed VEGF against bacterial initiated infection. PMID:22718316

  19. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Science.gov (United States)

    Lindenberg, Jelle J; Oosterhoff, Dinja; Sombroek, Claudia C; Lougheed, Sinéad M; Hooijberg, Erik; Stam, Anita G M; Santegoets, Saskia J A M; Tijssen, Henk J; Buter, Jan; Pinedo, Herbert M; van den Eertwegh, Alfons J M; Scheper, Rik J; Koenen, Hans J P M; van de Ven, Rieneke; de Gruijl, Tanja D

    2013-01-01

    In cancer patients pervasive systemic suppression of Dendritic Cell (DC) differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC) and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+)CD141(+)DC-SIGN(+) DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+) subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+) T cells, migration of immature CD14(+) DDC was accompanied by increased release of IL-10, poor expansion of CD4(+) and CD8(+) T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  20. In Absence of the Cellular Prion Protein, Alterations in Copper Metabolism and Copper-Dependent Oxidase Activity Affect Iron Distribution.

    Science.gov (United States)

    Gasperini, Lisa; Meneghetti, Elisa; Legname, Giuseppe; Benetti, Federico

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors. In this work we focused on the effect of prion protein absence on copper and iron metabolism during development and adulthood. In particular, we investigated copper and iron functional values in serum and several organs such as liver, spleen, total brain and isolated hippocampus. Our results show that iron content is diminished in prion protein-null mouse serum, while it accumulates in liver and spleen. Our data suggest that these alterations can be due to impairments in copper-dependent cerulopalsmin activity which is known to affect iron mobilization. In prion protein-null mouse total brain and hippocampus, metal ion content shows a fluctuating trend, suggesting the presence of homeostatic compensatory mechanisms. However, copper and iron functional values are likely altered also in these two organs, as indicated by the modulation of metal-binding protein expression levels. Altogether, these results reveal that the absence of the cellular prion protein impairs copper metabolism and copper-dependent oxidase activity, with ensuing alteration of iron mobilization from cellular storage compartments.

  1. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Directory of Open Access Journals (Sweden)

    Jelle J Lindenberg

    Full Text Available In cancer patients pervasive systemic suppression of Dendritic Cell (DC differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+CD141(+DC-SIGN(+ DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+ subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+ T cells, migration of immature CD14(+ DDC was accompanied by increased release of IL-10, poor expansion of CD4(+ and CD8(+ T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  2. In Absence of the Cellular Prion Protein, Alterations in Copper Metabolism and Copper-Dependent Oxidase Activity Affect Iron Distribution

    Science.gov (United States)

    Gasperini, Lisa; Meneghetti, Elisa; Legname, Giuseppe; Benetti, Federico

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors. In this work we focused on the effect of prion protein absence on copper and iron metabolism during development and adulthood. In particular, we investigated copper and iron functional values in serum and several organs such as liver, spleen, total brain and isolated hippocampus. Our results show that iron content is diminished in prion protein-null mouse serum, while it accumulates in liver and spleen. Our data suggest that these alterations can be due to impairments in copper-dependent cerulopalsmin activity which is known to affect iron mobilization. In prion protein-null mouse total brain and hippocampus, metal ion content shows a fluctuating trend, suggesting the presence of homeostatic compensatory mechanisms. However, copper and iron functional values are likely altered also in these two organs, as indicated by the modulation of metal-binding protein expression levels. Altogether, these results reveal that the absence of the cellular prion protein impairs copper metabolism and copper-dependent oxidase activity, with ensuing alteration of iron mobilization from cellular storage compartments. PMID:27729845

  3. Investigation of factors affecting the accumulation of vinyl chloride in polyvinyl chloride piping used in drinking water distribution systems.

    Science.gov (United States)

    Walter, Ryan K; Lin, Po-Hsun; Edwards, Marc; Richardson, Ruth E

    2011-04-01

    Plastic piping made of polyvinyl chloride (PVC), and chlorinated PVC (CPVC), is being increasingly used for drinking water distribution lines. Given the formulation of the material from vinyl chloride (VC), there has been concern that the VC (a confirmed human carcinogen) can leach from the plastic piping into drinking water. PVC/CPVC pipe reactors in the laboratory and tap samples collected from consumers homes (n = 15) revealed vinyl chloride accumulation in the tens of ng/L range after a few days and hundreds of ng/L after two years. While these levels did not exceed the EPA's maximum contaminant level (MCL) of 2 μg/L, many readings that simulated stagnation times in homes (overnight) exceeded the MCL-Goal of 0 μg/L. Considerable differences in VC levels were seen across different manufacturers, while aging and biofilm effects were generally small. Preliminary evidence suggests that VC may accumulate not only via chemical leaching from the plastic piping, but also as a disinfection byproduct (DBP) via a chlorine-dependent reaction. This is supported from studies with CPVC pipe reactors where chlorinated reactors accumulated more VC than dechlorinated reactors, copper pipe reactors that accumulated VC in chlorinated reactors and not in dechlorinated reactors, and field samples where VC levels were the same before and after flushing the lines where PVC/CPVC fittings were contributing. Free chlorine residual tests suggest that VC may be formed as a secondary, rather than primary, DBP. Further research and additional studies need to be conducted in order to elucidate reaction mechanisms and tease apart relative contributions of VC accumulation from PVC/CPVC piping and chlorine-dependent reactions.

  4. Cuspy no more: how outflows affect the central dark matter and baryon distribution in Λ cold dark matter galaxies

    Science.gov (United States)

    Governato, F.; Zolotov, A.; Pontzen, A.; Christensen, C.; Oh, S. H.; Brooks, A. M.; Quinn, T.; Shen, S.; Wadsley, J.

    2012-05-01

    We examine the evolution of the inner dark matter (DM) and baryonic density profile of a new sample of simulated field galaxies using fully cosmological, Λ cold dark matter (ΛCDM), high-resolution SPH+N-Body simulations. These simulations include explicit H2 and metal cooling, star formation (SF) and supernovae-driven gas outflows. Starting at high redshift, rapid, repeated gas outflows following bursty SF transfer energy to the DM component and significantly flatten the originally 'cuspy' central DM mass profile of galaxies with present-day stellar masses in the 104.5-109.8 M⊙ range. At z= 0, the central slope of the DM density profile of our galaxies (measured between 0.3 and 0.7 kpc from their centre) is well fitted by ρDM ∝ rα with α≃-0.5 + 0.35 log10(M★/108 M⊙), where M★ is the stellar mass of the galaxy and 4 < log M★ < 9.4. These values imply DM profiles flatter than those obtained in DM-only simulations and in close agreement with those inferred in galaxies from the THINGS and LITTLE THINGS surveys. Only in very small haloes, where by z= 0 SF has converted less than ˜0.03 per cent of the original baryon abundance into stars, outflows do not flatten the original cuspy DM profile out to radii resolved by our simulations. The mass (DM and baryonic) measured within the inner 500 pc of each simulated galaxy remains nearly constant over 4 orders of magnitudes in stellar mass for M★ < 109 M⊙. This finding is consistent with estimates for faint Local Group dwarfs and field galaxies. These results address one of the outstanding problems faced by the CDM model, namely the strong discrepancy between the original predictions of cuspy DM profiles and the shallower central DM distribution observed in galaxies.

  5. Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: targeting VEGF-VEGFR signaling.

    Directory of Open Access Journals (Sweden)

    Gagan Deep

    Full Text Available The role of neo-angiogenesis in prostate cancer (PCA growth and metastasis is well established, but the development of effective and non-toxic pharmacological inhibitors of angiogenesis remains an unaccomplished goal. In this regard, targeting aberrant angiogenesis through non-toxic phytochemicals could be an attractive angiopreventive strategy against PCA. The rationale of the present study was to compare the anti-angiogenic potential of four pure diastereoisomeric flavonolignans, namely silybin A, silybin B, isosilybin A and isosilybin B, which we established previously as biologically active constituents in Milk Thistle extract. Results showed that oral feeding of these flavonolignans (50 and 100 mg/kg body weight effectively inhibit the growth of advanced human PCA DU145 xenografts. Immunohistochemical analyses revealed that these flavonolignans inhibit tumor angiogenesis biomarkers (CD31 and nestin and signaling molecules regulating angiogenesis (VEGF, VEGFR1, VEGFR2, phospho-Akt and HIF-1α without adversely affecting the vessel-count in normal tissues (liver, lung, and kidney of tumor bearing mice. These flavonolignans also inhibited the microvessel sprouting from mouse dorsal aortas ex vivo, and the VEGF-induced cell proliferation, capillary-like tube formation and invasiveness of human umbilical vein endothelial cells (HUVEC in vitro. Further studies in HUVEC showed that these diastereoisomers target cell cycle, apoptosis and VEGF-induced signaling cascade. Three dimensional growth assay as well as co-culture invasion and in vitro angiogenesis studies (with HUVEC and DU145 cells suggested the differential effectiveness of the diastereoisomers toward PCA and endothelial cells. Overall, these studies elucidated the comparative anti-angiogenic efficacy of pure flavonolignans from Milk Thistle and suggest their usefulness in PCA angioprevention.

  6. Role of VEGF receptors in normal and psoriatic human keratinocytes: evidence from irradiation with different UV sources.

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    Jian-Wei Zhu

    Full Text Available Vascular endothelial growth factor (VEGF promotes angiogenesis and plays important roles both in physiological and pathological conditions. VEGF receptors (VEGFRs are high-affinity receptors for VEGF and are originally considered specific to endothelial cells. We previously reported that VEGFRs were also constitutively expressed in normal human keratinocytes and overexpressed in psoriatic epidermis. In addition, UVB can activate VEGFRs in normal keratinocytes, and the activated VEGFR-2 signaling is involved in the pro-survival mechanism. Here, we show that VEGFRs were also upregulated and activated by UVA in normal human keratinocytes via PKC, and interestingly, both the activated VEGFR-1 and VEGFR-2 protected against UVA-induced cell death. As VEGFRs were over-expressed in psoriatic epidermis, we further investigated whether narrowband UVB (NB-UVB phototherapy or topical halomethasone monohydrate 0.05% cream could affect their expression. Surprisingly, the over-expressed VEGFRs in psoriatic epidermis were significantly attenuated by both treatments. During NB-UVB therapy, VEGFRs declined first in the basal, and then gradually in the upper psoriatic epidermis. VEGFRs were activated in psoriatic epidermis, their activation was enhanced by NB-UVB, but turned undetectable after whole therapy. This process was quite different from that by halomethasone, in which VEGFRs and phospho-VEGFRs decreased in a gradual, homogeneous manner. Our findings further suggest that UV-induced activation of VEGFRs serves as a pro-survival signal for keratinocytes. In addition, VEGFRs may be involved in the pathological process of psoriasis, and UV phototherapy is effective for psoriasis by directly modulating the expression of VEGFRs.

  7. Vascular endothelial growth factor B (VEGF-B is up-regulated and exogenous VEGF-B is neuroprotective in a culture model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Zhang Shiling

    2009-12-01

    Full Text Available Abstract Parkinson's disease (PD results from the degeneration of dopaminergic neurons in the substantia nigra and the consequent deficit of dopamine released in the striatum. Current oral dopamine replacement or surgical therapies do not address the underlying issue of neurodegeneration, they neither slow nor halt disease. Neurotrophic factors have shown preclinical promise, but the choice of an appropriate growth factor as well as the delivery has proven difficult. In this study, we used a rotenone rat midbrain culture model to identify genes that are changed after addition of the neurotoxin. (1 We challenged rat midbrain cultures with rotenone (20 nM, a pesticide that has been shown to be toxic for dopaminergic neurons and that has been a well-characterized model of PD. A gene chip array analysis demonstrated that several genes were up-regulated after the rotenone treatment. Interestingly transcriptional activation of vascular endothelial growth factor B (VEGF-B was evident, while vascular endothelial growth factor A (VEGF-A levels remained unaltered. The results from the gene chip array experiment were verified with real time PCR and semi-quantitative western analysis using β-actin as the internal standard. (2 We have also found evidence that exogenously applied VEGF-B performed as a neuroprotective agent facilitating neuron survival in an even more severe rotenone culture model of PD (40 nM rotenone. VEGF-B has very recently been added to the list of trophic factors that reduce effects of neurodegeneration, as was shown in an in vivo model of motor neuron degeneration, while lacking potential adverse angiogenic activity. The data of an in vivo protective effect on motor neurons taken together with the presented results demonstrate that VEGF-B is a new candidate trophic factor distinct from the GDNF family of trophic factors. VEGF-B is activated by neurodegenerative challenges to the midbrain, and exogenous application of VEGF-B has a

  8. (-)-Epigallocatechin-3-gallate inhibits VEGF expression induced by IL-6 via Stat3 in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Bao-He Zhu; Hua-Yun Chen; Wen-Hua Zhan; Cheng-You Wang; Shi-Rong Cai; Zhao Wang; Chang-Hua Zhang; Yu-Long He

    2011-01-01

    AIM: To demonstrate that (-)-Epigallocatechin-3-gallate (EGCG) inhibits vascular endothelial growth factor (VEGF) expression and angiogenesis induced by interleukin-6 (IL-6) via suppressing signal transducer and activator of transcription 3 (Stat3) activity in gastric cancer.METHODS: Human gastric cancer (AGS) cells were treated with IL-6 (50 ng/mL) and EGCG at different concentrations. VEGF, total Stat3 and activated Stat3 protein levels in the cell lyses were examined by Western blotting, VEGF protein level in the conditioned medium was measured by enzyme-linked immunosorbent assay, and the level of VEGF mRNA was evaluated by reverse transcription polymerase chain reaction (RTPCR).Stat3 nuclear translocation was determined by Western blotting with nuclear extract, and Stat3-DNA binding activity was examined with Chromatin immunoprecipitation (ChIP) assay. IL-6 induced endothelial cell proliferation was measured with 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazoliumbromide assay, in vitro angiogenesis was determined with endothelial cell tube formation assay in Matrigel, and IL-6-induced angiogenesis in vitro was measured with Matrigel plug assay.RESULTS: There was a basal expression and secretion of VEGF in AGS cells. After stimulation with IL-6, VEGF expression was apparently up-regulated and a 2.4-fold increase was observed. VEGF secretion in the conditioned medium was also increased by 2.8 folds. When treated with EGCG, VEGF expression and secretion were dose-dependently decreased. IL-6 also increased VEGF mRNA expression by 3.1 folds. EGCG treatment suppressed VEGF mRNA expression in a dose-dependent manner. EGCG dose-dependently inhibited Stat3 activation induced by IL-6, but did not change the total Stat3 expression. When treated with EGCG or AG490,VEGF expressions were reduced to the level or an even lower level in the tumor cells not stimulated with IL-6. However, PD98059 and LY294002 did not change VEGF expression induced by IL-6. EGCG inhibited

  9. Integrin-specific hydrogels functionalized with VEGF for vascularization and bone regeneration of critical-size bone defects.

    Science.gov (United States)

    García, José R; Clark, Amy Y; García, Andrés J

    2016-04-01

    Vascularization of bone defects is considered a crucial component to the successful regeneration of large bone defects. Although vascular endothelial growth factor (VEGF) has been delivered to critical-size bone defect models to augment blood vessel infiltration into the defect area, its potential to increase bone repair remains ambiguous. In this study, we investigated whether integrin-specific biomaterials modulate the effects of VEGF on bone regeneration. We engineered protease-degradable, VEGF-loaded poly(ethylene glycol) (PEG) hydrogels functionalized with either a triple-helical, α2 β1 integrin-specific peptide GGYGGGP(GPP)5 GFOGER(GPP)5 GPC (GFOGER) or an αv β3 integrin-targeting peptide GRGDSPC (RGD). Covalent incorporation of VEGF into the PEG hydrogel allowed for protease degradation-dependent release of the protein while maintaining VEGF bioactivity. When applied to critical-size segmental defects in the murine radius, GFOGER-functionalized VEGF-free hydrogels exhibited significantly increased vascular volume and density and resulted in a larger number of thicker blood vessels compared to RGD-functionalized VEGF-free hydrogels. VEGF-loaded RGD hydrogels increased vascularization compared to VEGF-free RGD hydrogels, but the levels of vascularization for these VEGF-containing RGD hydrogels were similar to those of VEGF-free GFOGER hydrogels. VEGF transiently increased bone regeneration in RGD hydrogels but had no effect at later time points. In GFOGER hydrogels, VEGF did not show an effect on bone regeneration. However, VEGF-free GFOGER hydrogels resulted in increased bone regeneration compared to VEGF-free RGD hydrogels. These findings demonstrate the importance of integrin-specificity in engineering constructs for vascularization and associated bone regeneration.

  10. Acute hypoxia up-regulates HIF-1α and VEGF mRNA levels in Amazon hypoxia-tolerant Oscar (Astronotus ocellatus).

    Science.gov (United States)

    Baptista, R B; Souza-Castro, N; Almeida-Val, V M F

    2016-10-01

    Amazon fish maintain oxygen uptake through a variety of strategies considered evolutionary and adaptive responses to the low water oxygen saturation, commonly found in Amazon waters. Oscar (Astronotus ocellatus) is among the most hypoxia-tolerant fish in Amazon, considering its intriguing anaerobic capacity and ability to depress oxidative metabolism. Previous studies in hypoxia-tolerant and non-tolerant fish have shown that hypoxia-inducible factor-1α (HIF-1α) gene expression is positively regulated during low oxygen exposure, affecting vascular endothelial growth factor (VEGF) transcription and fish development or tolerance in different manners. However, whether similar isoforms exists in tolerant Amazon fish and whether they are affected similarly to others physiological responses to improve hypoxia tolerance remain unknown. Here we evaluate the hepatic HIF-1α and VEGF mRNA levels after 3 h of acute hypoxia exposure (0.5 mgO2/l) and 3 h of post-hypoxia recovery. Additionally, hematological parameters and oxidative enzyme activities of citrate synthase (CS) and malate dehydrogenase (MDH) were analyzed in muscle and liver tissues. Overall, three sets of responses were detected: (1) as expected, hematocrit, hemoglobin concentration, red blood cells, and blood glucose increased, improving oxygen carrying capacity and glycolysis potential; (2) oxidative enzymes from liver decreased, corroborating the tendency to a widespread metabolic suppression; and (3) HIF-1α and VEGF increased mRNA levels in liver, revealing their role in the oxygen homeostasis through, respectively, activation of target genes and vascularization. This is the first study to investigate a hypoxia-related transcription factor in a representative Amazon hypoxia-tolerant fish and suggests that HIF-1α and VEGF mRNA regulation have an important role in enhancing hypoxia tolerance in extreme tolerant species.

  11. The Farmers Perception on Effectiveness of Private Forest Revolving Fund Distribution and Factors Affecting its Repayment: Case in South Lampung District, Lampung Province

    Directory of Open Access Journals (Sweden)

    Sanudin

    2016-04-01

    Full Text Available Commercial s are ed providing for forest plantation development bank not interest in fund community based . - Therefore, in this case, non bank institutions such Forest Development Funding Center (pusat pembiayaan pembangunan hutan, PPPH private forest are highly required. This paper is aimed to find out the effectiveness of revolving fund and factors affecting its repayment distribution . The research was conducted during September–December 2014 in Private Forest Farmer Groups in Katibung Sub-District South Lampung Dist 3 , , rict Lampung Province. The data was collected through household surveys and in-depth interviews. The household surveys were done using structured questionnaires that included questions related to: characteristics of the borrowers, characteristics of private forest, characteristics of loan, and household perceptions on private forest revolving fund Household perceptions on private forest revolving fund are loan . pre requirement, loan procedure, realization, interest rate, , and repayment procedure The effectiveness of private forest length of repayment periode . revolving fund d t and factors affecting repayment of loan was analyzed by istribution was analyzed by liker scale logistic regression. ult private forest revolving fund in The res showed that: 1 three private forest farmer groups in Katibung Sub-District, South Lampung effective District was 2 income from non-private forest and amount of loan , are factors affecting repayment of private forest revolving fund, 3 faced private forest revolving f the problem in und distribution PPPH private could be overcame by maximizing the role of field officers in assisting and facilitating forest revolving fund ors debit candidate.

  12. Association of Chemerin and Vascular Endothelial Growth Factor (VEGF) with Diabetic Nephropathy

    Science.gov (United States)

    Lin, Shuhua; Teng, Jian; Li, Jixia; Sun, Fang; Yuan, Dong; Chang, Jing

    2016-01-01

    Background Diabetic nephropathy (DN) is a common complication of diabetes, caused by diabetic microvascular lesions. The pathogenesis of DN is complicated, involving genetics, physics, chemistry, and environmental factors. Chemerin is a fat cell factor that participates in regulating inflammation. Vascular endothelial growth factor (VEGF) promotes vascular endothelial cell proliferation, differentiation, and angiogenesis. The relationship role of Chemerin and VEGF in DN is not fully understood. Material/Methods SD rats were randomly divided into 2 groups: the control group and the DN group. Streptozotocin was used to construct the DN model. Serum creatinine (Scr), blood urea nitrogen (BUN), and urine microalbumin (UAlb) were detected. Real-time PCR and Western blot were used to test Chemerin and VEGF mRNA and protein expression in kidney tissue. ELISA was performed to test TGF-β1, TNF-α, and INF-γ levels. The correlation of Chemerin and VEGF with renal function and inflammatory factors was analyzed. Results DN group rats showed obviously increased Scr and BUN levels, and elevated TGF-β1, TNF-α, and INF-γ secretion (P<0.05). Compared with controls, Chemerin and VEGF were clearly overexpressed in the DN group (P<0.05). Chemerin and VEGF expression were positively correlated with inflammatory factors and renal function. Conclusions Chemerin and VEGF play important roles in DN by regulating inflammatory factors and renal function. They may be treated as indicators of DN. PMID:27612613

  13. Relationsip between PTEN and VEGF Expression and Clinicopathological Characteristics in HCC

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To investigate the expressions and significance of the tumor suppressor gene phosphatase and tensin homlog deleted on chromosome ten protein (PTEN) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC), and to analyze the relationship between their expressions and the tumor's invasion and their pericarcinomatous tissues, the correlation of their expressions with the tumor's clinicopathological characteristics and invasion potential were studied. Our study showed that the expression level of PTEN in HCC was remarkably lower than that in pericarcinomatous liver tissues, while the expressions of both VEGF and MVD were higher than that in pericarcinomatous liver tissues. Correlation analysis revealed that the expression of PTEN was negatively related to the progression of the pathological differentiation and invasion of tumor, whereas the expressions of VEGF and MVD were positively related. Moreover, there was a negative relationship between the expression of PTEN and the expressions of VEGF and MVD, and a positive one between VEGF and MVD. The expressions of PTEN and VEGF may reveal the degree of differentiation and the invasive potential of HCC tissues. The mechanism by which the lack of PTEN expression probably induces abnormal hyperexpression of VEGF may play an important role in the invasion and metastasis of HCC.

  14. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson's disease.

    Science.gov (United States)

    Xiong, N; Zhang, Z; Huang, J; Chen, C; Zhang, Z; Jia, M; Xiong, J; Liu, X; Wang, F; Cao, X; Liang, Z; Sun, S; Lin, Z; Wang, T

    2011-04-01

    The umbilical cord provides a rich source of primitive mesenchymal stem cells (human umbilical cord mesenchymal stem cells (HUMSCs)), which have the potential for transplantation-based treatments of Parkinson's Disease (PD). Our pervious study indicated that adenovirus-associated virus-mediated intrastriatal delivery of human vascular endothelial growth factor 165 (VEGF 165) conferred molecular protection to the dopaminergic system. As both VEGF and HUMSCs displayed limited neuroprotection, in this study we investigated whether HUMSCs combined with VEGF expression could offer enhanced neuroprotection. HUMSCs were modified by adenovirus-mediated VEGF gene transfer, and subsequently transplanted into rotenone-lesioned striatum of hemiparkinsonian rats. As a result, HUMSCs differentiated into dopaminergic neuron-like cells on the basis of neuron-specific enolase (NSE) (neuronal marker), glial fibrillary acidic protein (GFAP) (astrocyte marker), nestin (neural stem cell marker) and tyrosine hydroxylase (TH) (dopaminergic marker) expression. Further, VEGF expression significantly enhanced the dopaminergic differentiation of HUMSCs in vivo. HUMSC transplantation ameliorated apomorphine-evoked rotations and reduced the loss of dopaminergic neurons in the lesioned substantia nigra (SNc), which was enhanced significantly by VEGF expression in HUMSCs. These findings present the suitability of HUMSC as a vector for gene therapy and suggest that stem cell engineering with VEGF may improve the transplantation strategy for the treatment of PD.

  15. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jinqiao, E-mail: jinqiao1977@163.com [Institute of Pediatrics, Children' s Hospital of Fudan University (China); Sha, Bin [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Zhou, Wenhao, E-mail: zhou_wenhao@yahoo.com.cn [Department of Neonatology, Children' s Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102 (China); Yang, Yi [Institute of Pediatrics, Children' s Hospital of Fudan University (China)

    2010-03-26

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  16. Expression and significance of HIF-1α and VEGF in rats with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Hong-Tao Yan; Guan-Fang Su

    2014-01-01

    Objective:To investigate the expression of hypoxia inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF) in diabetic retinopathy(DR) rats and its effect on theDR occurrence and development.Methods:A total of120SD rats were randomly divided into trial group and control group with60 in each.STZi.p. was used in the trial group to establish theDM model, citrate buffer salt of same amount was usedi.p. to the control group.1,3 and6 months after injection, respective20 rats were sacrificed in each group to observe expression ofHIF-1α andVEGF in the rat retina tissue at different time points.Results:Expression ofHIF-1α andVEGF were negative in the control group; expression ofHIF-1α andVEGF protein in retinal tissue were weak after1 month ofDR mold formation.It showed progressive enhancement along with the progression in different organizations, differences between groups were significant (P<0.05).Conclusions:Expressions ofHIF-1α andVEGF were correlated with disease progression in early diabetic retinopathy.Retinal oxygen can induce over-expression ofHIF-1α andVEGF.It shows thatHIF-1α andVEGF play an important role in the pathogenesis ofDR.

  17. Influence of anti-VEGF about cardiovascular biomarkers in age related macular degeneration.

    Science.gov (United States)

    Manresa, N; Mulero, J; Losada, M; Zafrilla, P

    2015-02-01

    Systemic VEGF inhibition disrupts endothelial homeostasis and accelerates the atherogenesis, suggesting that these events contribute to the clinical cardiovascular adverse events of VEGF-inhibiting therapies. The objective of the current study was to analyze the effect of anti-VEGF therapy on cardiovascular risk factors in patients with exudative age related macular degeneration. A total of 73 patients with exudative age related macular degeneration (without previous anti-VEGF therapy) were treated with two anti-VEGF: Ranibizumab and Pegaptanib sodium. The follow up was 6 months. The following parameters were determined before and after treatment: homocysteine, lipids (total cholesterol, triglycerides, HDL-c, LDL-c), C-Reactive Protein and fibrinogen. There were not statistically significant differences in parameters studied before and after treatment with both Pegaptanib sodium and Ranibizumab, except C-Reactive Protein. Of all patients analyzed, only 3 of them have initially C-Reactive Protein levels above normal levels and after antiangiogenic therapy, there was a significant increase in C-Reactive Protein. We have not found results in our study who to suspect that treatment with anti-VEGF in the patients with exudative age related macular degeneration increases cardiovascular risk predictors. However, after therapy was increased the CRP and fibrinogen may mean that anti-VEGF contribute an alteration of endothelial homeostasis in exudative AMD.

  18. PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells.

    Science.gov (United States)

    Haider, Dominik G; Bucek, Robert A; Giurgea, Aura G; Maurer, Gerald; Glogar, Helmut; Minar, Erich; Wolzt, Michael; Mehrabi, Mohammad R; Baghestanian, Mehrdad

    2005-11-01

    Endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor 1-alpha (HIF-1alpha) are important regulators of endothelial function, which plays a role in the pathophysiology of heart failure (HF). PGE1 analog treatment in patients with HF elicits beneficial hemodynamic effects, but the precise mechanisms have not been investigated. We have investigated the effects of the PGE1 analog alprostadil on eNOS, VEGF, and HIF-1alpha expression in human umbilical vein endothelial cells (HUVEC) using RT-PCR and immunoblotting under normoxic and hypoxic conditions. In addition, we studied protein expression by immunohistochemical staining in explanted hearts from patients with end-stage HF, treated or untreated with systemic alprostadil. Alprostadil causes an upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases HIF-1alpha. Hypoxia potently increased eNOS, VEGF, and HIF-1alpha synthesis. The alprostadil-induced upregulation of eNOS and VEGF was prevented by inhibition of MAPKs with PD-98056 or U-0126. Consistently, the expression of eNOS and VEGF was increased, and HIF-1alpha was reduced in failing hearts treated with alprostadil. The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be useful for patients with HF where endothelial dysfunction is involved in the disease process.

  19. Construction and characterization of replication-deficient adenoviral vector containing the cDNA for human VEGF165 in an antisense orientation%反义VEGF165腺病毒重组体的构建及鉴定

    Institute of Scientific and Technical Information of China (English)

    王家宁; 黄永章; 王俊峰; 王卫民; 李瑞明; 张群林

    2001-01-01

    objective To construct the recombinant adenovirus vectorcontaining the cDNA for hVEGF165 in an antisense orientation for future study of tumor treatment by antisense hVEGF165 RNA strategy.Methods The VEGF165 cDNA has been extracted from pUCCAGGS/hVEGF165 with EcoRI and then inserted in an antisense orientation into the E1-deleted expression plasmid pHCMVsp1A shuttle vector, called pAd-ahVEGF165. pAd-ahVEGF165 was cotransfected with the plasmid pJM17 into the transformed human embryonic kidney cell line 293 cells by liposome-mediated method. Homologous recombination of the pAd-ahVEGF165 and pJM17 in 293 cells replaced the E1 region with the expression cassette from pAd-ahVEGF165. Ad-ahVEGF165 was confirmed by PCR.Ad-ahVEGF165 was propagated in 293 cells and then underwent CsCl density purification. subsequently, the preparations were didalyzed in dialysis buffer. The titer of each viral stock was determined by measuring the absorbance at 260nm. Results VEGF165 cDNA was successfully inserted into the shuttle vector pHCMVSPIA. pAd-ahVEGF165 was confirmed by NcoI and XhoI digestion. Ad-ahVEGF165 was characterized by PCR coamplification. The virus titer was 5.6×1011pfu/ml. Conclusions Ad-ahVEGF165 containing the antisense VEGF165 sequence was successfully constructd.This investigation provides the basis for future study of tumor treatment based on antisense VEGF RNA strategy.%目的:构建含人反义血管内皮生长因子165(VEGF165)基因的重组腺病毒载体,为采用反义VEGF165RNA防治肿瘤的研究奠定基础。方法:将人VEGF165 cDNA反向插入到穿梭质粒pHCMVSP1A的CMV启动子之下,即pAd-ahVEGF165。后者与pJM17通过脂质体共转染293细胞,经同源重组获得含人反义VEGF165基因的重组腺病毒Ad-ahVEGF165。通过PCR共扩增法鉴别Ad-ahVEGF165的正确与否。根据260nm的紫外光吸收值计算病毒滴度。结果:VEGF165 cDNA成功地反向插入了pHCMVSP1A载体,以重组病毒基因组DNA

  20. Distribution of free radicals and intermediates during the photodegradation of polychlorinated biphenyls strongly affected by cosolvents and TiO₂ catalyst.

    Science.gov (United States)

    Zhu, Xiangdong; Wang, Yujun; Qin, Wenxiu; Zhang, Shicheng; Zhou, Dongmei

    2016-02-01

    Polychlorinated biphenyls (PCBs) pose potential ecological risk because of their high toxicity and carcinogenicity. Photodegradation, which is an important process for the removal of PCBs, is greatly influenced by the cosolvent and catalyst. Hence, it is important to explore their effects on the photodegradation behavior of PCBs. In this study, 2,4,4'-trichlorobiphenyl (PCB28) was selected as a model compound, and the effects of two typical cosolvents, namely acetone and ethanol, and TiO2 catalyst on the distributions of free radicals and intermediates were investigated. Interestingly, the TiO2 catalyst did not promote PCB28 photodegradation. Moreover, the free radical distribution was greatly influenced in the presence of the TiO2 catalyst, while was only slightly affected in its absence by the cosolvent kinds. The main photodegradation pathways are proposed on the basis of the distribution of detected intermediates, which were significantly regulated by both the cosolvent and TiO2 catalyst. The results provide novel insights into the photodegradation of PCBs and may have important implications for choosing cosolvent in desorbing soil PCBs and consequently enhancing PCBs degradation.

  1. Expression of Protein Slit2, VEGF and VEGF -C Correlates with Clinical Study of Colorectal Cancers%Slit2、VEGF和VEGF-C蛋白表达与大肠癌关系的临床研究

    Institute of Scientific and Technical Information of China (English)

    王琴伊; 卢雪峰; 季锐; 杨淑萍

    2010-01-01

    研究神经迁移因子(Slit2)、血管生成因子(VEGF、VEGF-C)在大肠癌中的表达及临床意义.检测60例大肠癌组织和36例癌旁组织中Slit2、VEGF和VEGF-C的表达水平.结果三者在大肠癌和癌旁组织中的表达水平均与肿瘤大小、浸润深度、TNM分期、淋巴结转移相关;VEGF和VEGF-C表达水平还与远处转移相关.结果提示Slit2是调节大肠癌血管生成的重要因子.

  2. A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Farajpour, Zahra [Department of Pharmaceutical Biotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Rahbarizadeh, Fatemeh, E-mail: rahbarif@modares.ac.ir [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran (Iran, Islamic Republic of); Kazemi, Bahram [Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ahmadvand, Davoud [School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2014-03-28

    Highlights: • A novel nanobody directed to antigenic regions on VEGF was identified. • Our nanobody was successfully purified. • Our nanobody significantly inhibited VEGF-induced proliferation of HUVECs in a dose dependent manner. - Abstract: Compelling evidence suggests that vascular endothelial growth factor (VEGF), due to its essential role in angiogenesis, is a critical target for cancer treatment. Neutralizing monoclonal antibodies against VEGF are important class of drugs used in cancer therapy. However, the cost of production, large size, and immunogenicity are main drawbacks of conventional monoclonal therapy. Nanobodies are the smallest antigen-binding antibody fragments, which occur naturally in camelidae. Because of their remarkable features, we decided to use an immune library of nanobody to direct phage display to recognition of novel functional epitopes on VEGF. Four rounds of selection were performed and six phage-displayed nanobodies were obtained from an immune phage library. The most reactive clone in whole-cell ELISA experiments, was purified and assessed in proliferation inhibition assay. Purified ZFR-5 not only blocked interaction of VEGF with its receptor in cell ELISA experiments, but also was able to significantly inhibit proliferation response of human umbilical vein endothelial cells to VEGF in a dose-dependent manner. Taken together, our study demonstrates that by using whole-cell ELISA experiments, nanobodies against antigenic regions included in interaction of VEGF with its receptors can be directed. Because of unique and intrinsic properties of a nanobody and the ability of selected nanobody for blocking the epitope that is important for biological function of VEGF, it represents novel potential drug candidate.

  3. The angio-fibrotic switch of VEGF and CTGF in proliferative diabetic retinopathy.

    Directory of Open Access Journals (Sweden)

    Esther J Kuiper

    Full Text Available BACKGROUND: In proliferative diabetic retinopathy (PDR, vascular endothelial growth factor (VEGF and connective tissue growth factor (CTGF cause blindness by neovascularization and subsequent fibrosis, but their relative contribution to both processes is unknown. We hypothesize that the balance between levels of pro-angiogenic VEGF and pro-fibrotic CTGF regulates angiogenesis, the angio-fibrotic switch, and the resulting fibrosis and scarring. METHODS/PRINCIPAL FINDINGS: VEGF and CTGF were measured by ELISA in 68 vitreous samples of patients with proliferative DR (PDR, N = 32, macular hole (N = 13 or macular pucker (N = 23 and were related to clinical data, including degree of intra-ocular neovascularization and fibrosis. In addition, clinical cases of PDR (n = 4 were studied before and after pan-retinal photocoagulation and intra-vitreal injections with bevacizumab, an antibody against VEGF. Neovascularization and fibrosis in various degrees occurred almost exclusively in PDR patients. In PDR patients, vitreous CTGF levels were significantly associated with degree of fibrosis and with VEGF levels, but not with neovascularization, whereas VEGF levels were associated only with neovascularization. The ratio of CTGF and VEGF was the strongest predictor of degree of fibrosis. As predicted by these findings, patients with PDR demonstrated a temporary increase in intra-ocular fibrosis after anti-VEGF treatment or laser treatment. CONCLUSIONS/SIGNIFICANCE: CTGF is primarily a pro-fibrotic factor in the eye, and a shift in the balance between CTGF and VEGF is associated with the switch from angiogenesis to fibrosis in proliferative retinopathy.

  4. Impaired VEGF Signaling in Lungs with Hypoplastic Esophageal Atresia and Effects on Branching Morphogenesis

    Directory of Open Access Journals (Sweden)

    Xiaomei Liu

    2016-07-01

    Full Text Available Background/Aims: Patients with esophageal atresia (EA and tracheoesophageal fistula (TEF often suffer chronic respiratory tract disease. We previously reported that primary lung maldevelopment caused by deficient branching of embryonal airways in experimental EA-TEF was induced by Adriamycin. In this study, we investigated the Vascular endothelial growth factor (VEGF pathway in the developing lung in an EA-TEF rat model. We further analyzed the effect of recombinant VEGF treatment in vitro on branching morphogenesis of embryo lungs in experimental EA-TEF. Methods: Pregnant rats received either Adriamycin or vehicle on E7, E8 and E9. Lungs were recovered at E15, E18 and E21. Expression of VEGF and receptors (Flk-1 and Flt-1 were assessed by quantitative PCR, immunohistochemistry and immunoblotting. E13 lungs were cultured for 72 hours with 50 ng/mL of recombinant rat VEGF in serum-free medium. The rates of increase in bud count and airway contour were evaluated. Results: Our results showed a significant downregulation of VEGF during pseudoglandular and canalicular stages. In contrast, there were significantly higher levels of the Flt-1 receptor in the canalicular stage, which may represent a compensatory response to decreased VEGF. However, both variables returned to normal levels at the saccular stage. Exogenous VEGF treatment enhanced hypoplastic lung growth, evidenced by the increase in bud count and airway contour. Conclusions: A VEGF signaling defect possibly plays an important role in defective embryonic airway branching. Additionally, VEGF treatment may accelerate lung growth in EA-TEF lungs.

  5. VEGF-expressing Bone Marrow Mesenchymal Stem Cells Transplantation Improved Heart Function of Myocardial Infarct Rabbits

    Institute of Scientific and Technical Information of China (English)

    Sheng Xiaogang; Song Hui; Feng Jianzhang; Chen Qiuxiong; Wu Shulin

    2006-01-01

    Objectives To treat myocardial infarction with MSCs transplantation combined with VEGF gene therapy in rabbits and to study its mechanisms. Methods Forty-eight rabbits were randomly divided into MI group (n=12), MSCs group (n=12), VEGF group (n=12), MSCs+VEGF group (M+V group, n=12). Rabbit myocardial infarction models were founded by the ligation of left anterior descending artery. 107 MSCs were injected into the infarct-zone in four sites 2 weeks later in MSCs and M+V group. phVEGF gene were injected in infarct-zone in VEGF group and MSCs transfected with phVEGF gene were injected in M+V group. Heart function including LVEDP, LVSP, LVDP, -dp/dtmax, +dp/dtmax, were measured in vivo. The hearts were harvested at 4 weeks after transplantation and sectioned for HE stain,immunohistochemical stain of BrdU and Ⅷ factor antigen. Results The left ventricular hemodynamics parameters showed that heart function were improved more in M+V group than MSCs group, MI group and VEGF group. The numbers of BrdU positive cells in M+V group(61±8)were more than in MSCs group (44±8,P<0.01). The numbers of vessels in infarcted zone were more in M+V group (49±8) than in MSCs group (33±6, P<0.01)、VEGF group(30±8,P<0.01)and MI group (18±4,P<0.01). Conclusions VEGF-expressing MSCs transplantation could improve heart function after myocardial infarction, and they were more effective than sole MSCs transplantation. Keeping more MSCs survival and ameliorating the blood supply of infarct-zone might be involved in the mechanisms.

  6. TFF3 mediated induction of VEGF via hypoxia in human gastric cancer SGC-7901 cells.

    Science.gov (United States)

    Guleng, Bayasi; Han, Jia; Yang, Jin-Qiu; Huang, Qing-Wen; Huang, Jian-Kun; Yang, Xiao-Ning; Liu, Jing-Jing; Ren, Jian-Lin

    2012-04-01

    Increasing evidence indicates that in gastric epithelial cells, induction of TFF3 by hypoxia is mediated by HIF-1. Since VEGF is one of the most important angiogenic factors on cancer progression, we have started to investigate the possible link among HIF-1α, VEGF, and TFF3 in gastric cancer cells. We induced the hypoxic condition in SGC-7901cells using hypoxia-mimetic agent of CoCI2. SGC7901 cells were transfected with pcPUR + U6 plasmid carrying RNAi targeted to human TFF3 and selected puromycin-resistant pools to establish the stable knockdown of TFF3 cells. Our results showed the induction of HIF-1a via hypoxia and consequences of increased expressions of the TFF3 and VEGF in gastric cancer SGC-7901 cells. Overexpression of TFF3 upregulated the mRNA expressions of VEGF and HIF-1a induced by hypoxia, and stable knockdown of TFF3 impaired the mRNA upregulations of VEGF and HIF-1a induced by hypoxia. Furthermore, knockdown of TFF3 reduced the VEGF protein secretion: as VEGF secretion was increased time dependent manner in response to the hypoxia induction in TFF3-WT cells; however, VEGF production was significantly decreased in TFF3-KD cells (621 ± 89 vs. 264 ± 73 at 6 h and 969 ± 97 vs. 508 ± 69 at 12 h, P TFF3 mediated regulation of VEGF expression induced by hypoxia, and implicated that TFF3 might be applied as a potential anti-angiogenic target for treatment of gastric cancer.

  7. Correlation between {sup 18}F-fluoromisonidazole PET and expression of HIF-1α and VEGF in newly diagnosed and recurrent malignant gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Kawai, Nobuyuki; Ogawa, Daisuke; Miyake, Keisuke; Tamiya, Takashi [Kagawa University, Department of Neurological Surgery, Faculty of Medicine, Kagawa (Japan); Lin, Wei [Kagawa University, Department of Neurological Surgery, Faculty of Medicine, Kagawa (Japan); Fourth Military Medical University, Department of Neurosurgery, Xijing Hospital, Xi' an (China); Cao, Wei-Dong [Fourth Military Medical University, Department of Neurosurgery, Xijing Hospital, Xi' an (China); Haba, Reiji [Kagawa University, Department of Diagnostic Pathology, Faculty of Medicine, Kagawa (Japan); Maeda, Yukito; Yamamoto, Yuka; Nishiyama, Yoshihiro [Kagawa University, Department of Radiology, Faculty of Medicine, Kagawa (Japan)

    2014-10-15

    Hypoxia and its consequences at the molecular level promote tumour progression and affect patient prognosis. One of the main early cellular events evoked by hypoxia is induction of hypoxia-inducible factor 1 (HIF-1) and subsequent upregulation of vascular endothelial growth factor (VEGF). In this study we sought to determine whether hypoxia detected by {sup 18}F-fluoromisonidazole (FMISO) PET accurately reflects the expression of HIF-1α and VEGF in the tumour and can be used as a biomarker of antiangiogenic treatment and as a prognostic factor in newly diagnosed and recurrent malignant gliomas. Enrolled in this study were 32 patients with newly diagnosed glioma and 16 with recurrent glioma of grade III or grade IV. All the patients had undergone FMISO PET preoperatively. The maximum tumour-to-blood FMISO activity ratio (T/B{sub max}) was used to evaluate the degree of tumour hypoxia and the hypoxic volume (HV) was calculated using a tumour-to-blood FMISO uptake ratio of ≥1.2. Immunohistochemical expressions of HIF-1α and VEGF were evaluated semiquantitatively using the immunoreactivity score (IRS, scores 0 to 12) and the correlation was examined between IRS of HIF-1α or VEGF and FMISO uptake of the tumour (SUV{sub tumour}) using navigation-based sampling. Survival was estimated using the Kaplan-Meier method in relation to the T/B{sub max} and the HV. The T/B{sub max} and the HV in grade IV gliomas were significantly higher than in grade III gliomas (P < 0.01 and P < 0.01, respectively). Moderate to strong HIF-1α and VEGF expression was observed in the majority of malignant gliomas. The IRS of HIF-1α and VEGF in the tumour were not significantly different between grade III and grade IV gliomas. The IRS of HIF-1α in the tumour did not correlate with the SUV{sub tumour} of FMISO in either newly diagnosed or recurrent glioma. There was a significant but weak correlation between the IRS of VEGF and the SUV{sub tumour} of FMISO in newly diagnosed glioma, but not

  8. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer

    Science.gov (United States)

    Willett, Christopher G; Boucher, Yves; di Tomaso, Emmanuelle; Duda, Dan G; Munn, Lance L; Tong, Ricky T; Chung, Daniel C; Sahani, Dushyant V; Kalva, Sanjeeva P; Kozin, Sergey V; Mino, Mari; Cohen, Kenneth S; Scadden, David T; Hartford, Alan C; Fischman, Alan J; Clark, Jeffrey W; Ryan, David P; Zhu, Andrew X; Blaszkowsky, Lawrence S; Chen, Helen X; Shellito, Paul C; Lauwers, Gregory Y; Jain, Rakesh K

    2009-01-01

    The effects of vascular endothelial growth factor (VEGF) blockade on the vascular biology of human tumors are not known. Here we show here that a single infusion of the VEGF-specific antibody bevacizumab decreases tumor perfusion, vascular volume, microvascular density, interstitial fluid pressure and the number of viable, circulating endothelial and progenitor cells, and increases the fraction of vessels with pericyte coverage in rectal carcinoma patients. These data indicate that VEGF blockade has a direct and rapid antivascular effect in human tumors. PMID:14745444

  9. The VEGF system and tie-2 are spatio-temporal expressed during tayassu placentation

    DEFF Research Database (Denmark)

    Miglino, M.A.; Santos, T.C.; Papa, P.C.

    for immunhistochemistry using polyclonal antibodies against VEGF, VEGFR-1, VEGFR-2 and Tie-2. Results: In the present study the VEGF-system exhibited intense staining in the uterine epithelium, uterine glandular epithelium and trophoblast. The endothelial cells and smooth muscle cells of the vessels in the maternal...... and fetal compartment were also immunoreactive. Placentae from initial phase of gestation showed weaker staining when compared to middle and late gestation. In late gestation of the tayassu the Tie-2 was co-localized with the VEGF-system in both maternal (intense staining in glandular and uterine epithelium...

  10. Relationship between the Expression of VEGF, FIk-1 and Fit-1 Proteins and Clinicopcrthology in Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    JihuiHao; HuikaiLi; YuQin; QiangLi; DianchangWang; XishanHao

    2004-01-01

    OBJECTIVE To study the relationship between the expression of VEGF, FIk-1 and Fit-1 proteins and clinical pathology in hepatocellular carcinoma.METHODS The expression of VEGF, FIk-1 and Fit-1 proteins in hepatocellular carcinomas from 60 patients was determined by immunohistochemistry (ABC method) and VEGF expression in relation to the clinicopathology evaluated.RESULTS The positive rates of VEGF, FIk-1 and Fit-1 protein expression were 81.3%, 88.3%, 80.0% in tumor tissues, respectively, rates which were significantly higher than those in normal liver tissue (P<0.05). The expression of VEGF protein was correlated with the histologic grade and metastases of the tumors.CONCLUSION The results showed that, in hepatocellular carcinoma, a higher expression of VEGF protein was associated with a higher degree of malignancy and a greater tendency for metastases. VEGF, FIk-1 and Fit-1 play an important role in tumourgenesis.

  11. VEGF-C与胃癌淋巴管新生临床病理因素的关系%Vascular endothelial growth factor-C and lymphangiogenesis in gastric carcinoma and its clinicopathological features

    Institute of Scientific and Technical Information of China (English)

    何小科; 李荣江; 冯宇鹏; 刘维藩; 陈小建

    2012-01-01

    .01). The size, type of VEGF-c expression and gastric cancer, Lauren, age, sex, diet no clear relevance of regional distribution. Expression of VEGF-c group-positive gastric cancer recurrence rate of 1 year, 2 year, 3 year, 40.1 %, 66.7%, 79.2%, respectively, Expression of VEGF-c-neg-ative gastric cancer group, 27.4%, 31.3%, 45.7%, respectively. TP positive HCC Group 2-year, 3-year relapse rate significantly higher than the TP-negative group (P<0.01). In 54 cases with follow-up, VEGF-C-positive Group overall survival rates significantly lower than the negative group (P<0.01). Conclusion; VEGF-C played an important role in the new biochemical lymphatic vessels in gastric cancer, Positive rate of expression can be used a new indicators of prognosis of gastric cancer after operation.

  12. Vascular Endothelial Growth Factor (VEGF) Bioavailability Regulates Angiogenesis and Intestinal Stem and Progenitor Cell Proliferation during Postnatal Small Intestinal Development

    Science.gov (United States)

    Holoyda, Kathleen A.; Hou, Xiaogang; Fowler, Kathryn L.; Grikscheit, Tracy C.

    2016-01-01

    Background Vascular endothelial growth factor (VEGF) is a highly conserved, master regulatory molecule required for endothelial cell proliferation, organization, migration and branching morphogenesis. Podocoryne carnea and drosophila, which lack endothelial cells and a vascular system, express VEGF homologs, indicating potential roles beyond angiogenesis and vasculogenesis. The role of VEGF in the development and homeostasis of the postnatal small intestine is unknown. We hypothesized regulating VEGF bioavailability in the postnatal small intestine would exhibit effects beyond the vasculature and influence epithelial cell stem/progenitor populations. Methods VEGF mutant mice were created that overexpressed VEGF in the brush border of epithelium via the villin promotor following doxycycline treatment. To decrease VEGF bioavailability, sFlt-1 mutant mice were generated that overexpressed the soluble VEGF receptor sFlt-1 upon doxycycline administration in the intestinal epithelium. Mice were analyzed after 21 days of doxycycline administration. Results Increased VEGF expression was confirmed by RT-qPCR and ELISA in the intestine of the VEGF mutants compared to littermates. The VEGF mutant duodenum demonstrated increased angiogenesis and vascular leak as compared to littermate controls. The VEGF mutant duodenum revealed taller villi and increased Ki-67-positive cells in the transit-amplifying zone with reduced Lgr5 expression. The duodenum of sFlt-1 mutants revealed shorter villi and longer crypts with reduced proliferation in the transit-amplifying zone, reduced expression of Dll1, Bmp4 and VE-cadherin, and increased expression of Sox9 and EphB2. Conclusions Manipulating VEGF bioavailability leads to profound effects on not only the intestinal vasculature, but epithelial stem and progenitor cells in the intestinal crypt. Elucidation of the crosstalk between VEGF signaling in the vasculature, mesenchyme and epithelial stem/progenitor cell populations may direct future

  13. Expression of VEGF and neural repair after alprostadil treatment in a rat model of sciatic nerve crush injury

    Directory of Open Access Journals (Sweden)

    Tang Jinrong

    2009-01-01

    Full Text Available Background: Vasoactive drug alprostadil improves microcirculation and can be effective in treating disorders of peripheral nerves. Vascular endothelial growth factor (VEGF has been shown to have protective action in cerebral ischemia, disorders of spinal cord, and also peripheral nerves. However, the mechanism of action of VEGF in peripheral nerve injuries is uncertain. Objectives: To study the effect of application of alprostadil on the pathological and functional repair of crush nerve injuries and also the expression of VEGF. Materials and Methods: Rat sciatic nerves were crushed by pincers to establish the model of crush injury. All of the 400 sprague dawley (SD rats were randomly divided into: Control; saline; saline + VEGF-antibody; alprostadil; and alprostadil + VEGF antibody groups. The SPSS 11.5 software was used for statistical analysis. The expression of VEGF in dorsal root ganglia (DRGs, following crush injury to sciatic nerves, was studied by reverse transcribed-polymerase chain reaction (RT-PCR, immunohistochemistry, electromicroscope, and electrophysiology. The effects of alprostadil on expression of VEGF, repair of neural pathology, and recovery of neural function were also evaluated. Results: We found that VEGF messenger ribonucleic acid (mRNA was significantly increased in alprostadil and alprostadil + VEGF-antibody groups, compared to the saline and saline + VEGF antibody groups. The number of VEGF-positive neurons was significantly increased in the alprostadil group, compared to the saline, saline + VEGF antibody, and alprostadil + VEGF antibody groups. Besides, addition of this drug also caused less pathological changes in DRGs, better improvement of nerve conduction velocities of sciatic nerves, and more increase of toe spaces of right hind limbs of rats. Conclusions: The vasoactive agent alprostadil may reduce the pathological lesion of peripheral nerves and improve the rehabilitation of the neural function, which may

  14. Structure of the Full-length VEGFR-1 Extracellular Domain in Complex with VEGF-A.

    Science.gov (United States)

    Markovic-Mueller, Sandra; Stuttfeld, Edward; Asthana, Mayanka; Weinert, Tobias; Bliven, Spencer; Goldie, Kenneth N; Kisko, Kaisa; Capitani, Guido; Ballmer-Hofer, Kurt

    2017-02-07

    Vascular endothelial growth factors (VEGFs) regulate blood and lymph vessel development upon activation of three receptor tyrosine kinases: VEGFR-1, -2, and -3. Partial structures of VEGFR/VEGF complexes based on single-particle electron microscopy, small-angle X-ray scattering, and X-ray crystallography revealed the location of VEGF binding and domain arrangement of individual receptor subdomains. Here, we describe the structure of the full-length VEGFR-1 extracellular domain in complex with VEGF-A at 4 Å resolution. We combined X-ray crystallography, single-particle electron microscopy, and molecular modeling for structure determination and validation. The structure reveals the molecular details of ligand-induced receptor dimerization, in particular of homotypic receptor interactions in immunoglobulin homology domains 4, 5, and 7. Functional analyses of ligand binding and receptor activation confirm the relevance of these homotypic contacts and identify them as potential therapeutic sites to allosterically inhibit VEGFR-1 activity.

  15. VEGF-dependent mechanism of anti-angiogenic action of diamond nanoparticles in Glioblastoma Multiforme tumor

    DEFF Research Database (Denmark)

    Grodzik, M.; Sawosz, E.; Wierzbicki, M.

    2012-01-01

    of diamond nanoparticles on the growth of brain tumor (cultured on CAM membrane) and the development of its blood vessels. We hypothesize that diamond nanoparticles can bind VEGF or their receptors and this way influence of signal transduction between cells. The aim of our study was to evaluate the influence...... of diamond nanoparticle on VEGF level and inhibition of the brain tumor angiogenesis. We evaluated interaction of VEGF-A and VEGF-receptor proteins with diamond nanoparticles (TEM), visualized lower the permeability of blood vessels after diamond nanoparticles treatment and determined localization......Malignant gliomas are highly lethal cancers dependent on angiogenesis. The concept of treating tumors by inhibiting tumor angiogenesis was first articulated almost 30 years ago. Inhibition of tumor angiogenesis suppresses both tumor growth and metastasis. We determined the inhibition effect...

  16. A structural model of the VEGF signalling pathway: emergence of robustness and redundancy properties.

    Science.gov (United States)

    Lignet, Floriane; Calvez, Vincent; Grenier, Emmanuel; Ribba, Benjamin

    2013-02-01

    The vascular endothelial growth factor (VEGF) is known as one of the main promoter of angiogenesis - the process of blood vessel formation. Angiogenesis has been recognized as a key stage for cancer development and metastasis. In this paper, we propose a structural model of the main molecular pathways involved in the endothelial cells response to VEGF stimuli. The model, built on qualitative information from knowledge databases, is composed of 38 ordinary differential equations with 78 parameters and focuses on the signalling driving endothelial cell proliferation, migration and resistance to apoptosis. Following a VEGF stimulus, the model predicts an increase of proliferation and migration capability, and a decrease in the apoptosis activity. Model simulations and sensitivity analysis highlight the emergence of robustness and redundancy properties of the pathway. If further calibrated and validated, this model could serve as tool to analyse and formulate new hypothesis on th e VEGF signalling cascade and its role in cancer development and treatment.

  17. Tnactivation of PTEN is associated with increased angiogenesis and VEGF overexpression in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ye-Jiang Zhou; Yu-Xia Xiong; Xiao-Ting Wu; De Shi; Wei Fan; Tong Zhou; Yue-Chun Li; Xiong Huang

    2004-01-01

    AIM: To investigate the expression of PTEN/MMAC1/TEP1and vascular endothelial growth factor (VEGF), their roles in biologic behavior and angiogenesis and their association in gastric cancer.METHODS: Immunohistochemical staining was used to evaluate the expression of PTEN, VEGF and microvascular density (MVD) on paraffin-embedded sections in 70 patients with primary gastric cancer and 24 patients with chronic superficial gastritis (CSG). Expression of PTEN, VEGF and MVD were compared with clinicopathological features of gastric cancer. The relationship between expression of PTEN, VEGF and MVD as well as the relationship between PTEN and VEGF expression in caner cells were investigated.RESULTS: PTEN expression significantly decreased (t= 3.98,P<0.01) whereas both VEGF expression and MVD significant increased (t = 4.29 and 4.41, respectively, both P<0.01)in gastric cancer group compared with CSG group. PTEN expression was significantly down-regulated (t = 1.95,P<0.05) whereas VEGF expression (t = 2.37, P<0.05) and MVD (t = 3.28, P<0.01) was significantly up-regulated in advanced gastric cancer compared with early-stage gastric cancer. PTEN expression in gastric cancer showed a negative association with lymph node metastasis (t= 3.91, P<0.01),invasion depth (t= 1.95, P<0.05) and age (t= 4.69, P<0.01).MVD in PTEN-negative gastric cancer was significantly higher than that in PTEN-positive gastric cancer (t = 3.69,P<0.01), and there was a negative correlation between PTEN expression and MVD (γ = -0.363, P<0.05). VEGF expression was positively associated with invasion depth (especially with serosa invasion, t = 4.69, P<0.01), lymph node metastasis (t= 2.31, P<0.05) and TNM stage (t= 3.04,P<0.01). MVD in VEGF-positive gastric cancer was significantly higher than that in VEGF-negative gastric cancer (t = 4.62,P<0.01), and there was a positive correlation between VEGF expression of and MVD (γ = 0.512, P<0.05). VEGF expression in PTEN

  18. VEGF concentrations in tumour arteries and veins from patients with rectal cancer

    DEFF Research Database (Denmark)

    Werther, Kim; Bülow, Steffen; Hesselfeldt, Peter;

    2002-01-01

    , automated complete white cell and platelet counts were performed. In serum and EDTA plasma, no significant differences in VEGF concentrations were observed (p = 0.1 and p = 0.5), respectively) between tumour arteries and tumour veins. However, in supernatants from lysed blood, VEGF concentrations were......This pilot study investigated the hypothesis that the tumour itself is the source of the elevated vascular endothelial growth factor (VEGF) concentrations which are often observed in peripheral blood from patients with rectal cancer. Twenty-four consecutive patients with primary rectal cancer were...... included. Blood samples were drawn preoperatively from peripheral veins (I) and intraoperatively from peripheral veins (II), tumour arteries (III), and tumour veins (IV). In the four compartments, VEGF concentrations were measured in serum, EDTA plasma, and supernatants from lysed whole blood. Additionally...

  19. Study on VEGF, bFGF and TGF-β1 in the Endometriumof Norplant Users

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate the relationship between abnormal uterus bleeding and en dometrium vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) as well as transforming growth factor-β1(TGF-β1) expressions among Nor plant users. Materials & Methods Thirty-six endometrium samples from Norplant users with nor mal and abnormal bleeding were studied morphologically and immunohistochemically for VEGF, bFGF and TGF-β1 expression. Six normal samples of proliferate endome tria were studied as control. Results In the Norplant users, the characteristics of endometrium changed and glands decreased in numbers. The VEGF expression in epithelium and vascular en dothelium was lower in those with abnormal uterine bleeding. However, no difference was detected on bFGF and TGF-β1 expression. Conclusion The decline of VEGF expression may relate to the abnormal uterine bleed ing in Norplant users.

  20. Urethral tissue regeneration using collagen scaffold modified with collagen binding VEGF in a beagle model.

    Science.gov (United States)

    Jia, Weisheng; Tang, He; Wu, Jianjian; Hou, Xianglin; Chen, Bing; Chen, Wei; Zhao, Yannan; Shi, Chunying; Zhou, Feng; Yu, Wei; Huang, Shengquan; Ye, Gang; Dai, Jianwu

    2015-11-01

    Extensive urethral defects have a serious impact on quality of life, and treatment is challenging. A shortage of material for reconstruction is a key limitation. Improving the properties of biomaterials and making them suitable for urethral reconstruction will be helpful. Previously, we constructed a fusion protein, collagen-binding VEGF (CBD-VEGF), which can bind to collagen scaffold, stimulate cell proliferation, and promote angiogenesis and tissue regeneration. We proposed that CBD-VEGF could improve the performance of collagen in reconstruction of extensive urethral defects. Our results showed that collagen scaffolds modified with CBD-VEGF could promote urethral tissue regeneration and improve the function of the neo-urethra in a beagle extensive urethral defect model. Thus, modifying biomaterials with bioactive factors provides an alternative strategy for the production of suitable biomaterials for urethral reconstruction.

  1. Enhancement of musculocutaneous nerve reinnervation after vascular endothelial growth factor (VEGF gene therapy

    Directory of Open Access Journals (Sweden)

    Haninec Pavel

    2012-06-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF is not only a potent angiogenic factor but it also promotes axonal outgrowth and proliferation of Schwann cells. The aim of the present study was to quantitatively assess reinnervation of musculocutaneous nerve (MCN stumps using motor and primary sensory neurons after plasmid phVEGF transfection and end-to-end (ETE or end-to-side (ETS neurorrhaphy. The distal stump of rat transected MCN, was transfected with plasmid phVEGF, plasmid alone or treated with vehiculum and reinnervated following ETE or ETS neurorrhaphy for 2 months. The number of motor and dorsal root ganglia neurons reinnervating the MCN stump was estimated following their retrograde labeling with Fluoro-Ruby and Fluoro-Emerald. Reinnervation of the MCN stumps was assessed based on density, diameter and myelin sheath thickness of regenerated axons, grooming test and the wet weight index of the biceps brachii muscles. Results Immunohistochemical detection under the same conditions revealed increased VEGF in the Schwann cells of the MCN stumps transfected with the plasmid phVEGF, as opposed to control stumps transfected with only the plasmid or treated with vehiculum. The MCN stumps transfected with the plasmid phVEGF were reinnervated by moderately higher numbers of motor and sensory neurons after ETE neurorrhaphy compared with control stumps. However, morphometric quality of myelinated axons, grooming test and the wet weight index were significantly better in the MCN plasmid phVEGF transfected stumps. The ETS neurorrhaphy of the MCN plasmid phVEGF transfected stumps in comparison with control stumps resulted in significant elevation of motor and sensory neurons that reinnervated the MCN. Especially noteworthy was the increased numbers of neurons that sent out collateral sprouts into the MCN stumps. Similarly to ETE neurorrhaphy, phVEGF transfection resulted in significantly higher morphometric quality of myelinated axons

  2. Establishment of a recombinant adeno-associated virus expressing hVEGF165

    Institute of Scientific and Technical Information of China (English)

    Xianghui Huang; Zhibin Shi; Xiaoqian Dang; Chen Zhang; Pengbo Yu; Kunzheng Wang

    2008-01-01

    BACKGROUND: Because certain gene vectors could have deleterious effects in the central nervous system, the choice of a safe and effective vector system has become more important for gene therapy of nerve regeneration. OBJECTIVE: To construct a non-pathogenic, recombinant adeno-associated virus (AAV) simultaneously expressing human vascular endothelial growth factor 165 (hVEGF165) and green fluorescent protein (GFP). DESIGN, TIME AND SETTING: A randomized controlled experiment was performed at the Virology Laboratory of Shaanxi Provincial Center for Disease Control and Prevention between March and September 2007. MATERIALS: AAV helper-free system, AAV-293 packaging cell line, and AAV HT-1080 cells were purchased from Stratagene, USA. E. Coli DH5α was a stocked strain from Centers for Disease Control and Prevention of Shaanxi, China. Plasmid pUC18-hHVEGF165 was a gift from Zhibin Shi. METHODS: The hVEGF165 gene was amplified by PCR from pUC18-hHVEGF165 and inserted into plasmid pAAV-IRES-hrGFP to construct recombinant plasmid pAAV-hVEGF165-IRES-hrGFP. Subsequently pAAV-hVEGF165-IRES-hrGFP, pAAV-RC (the rep/cap-gene containing plasmid), and pHelper were co-transfected into AAV-293 cells to complete rAAV-hVEGF165-IRES-hrGFP packaging through homologous recombination. The efficiency of AAV packaging was monitored under a fluorescent microscope, and the recombinant viral particles were harvested from infected AAV-293 cells, and further concentrated and purified. AAV HT-1080 cells were infected with the recombinant virus AAV-hVEGF165-IRES-hrGFP. MAIN OUTCOME MEASURES: Recombinant virus titer was measured by fluorescent cell counting, and infection efficiency was detected by Fluorescence Activated Cell Sorter (FACS) upon infecting AAV-HT1080 cells. The recombination with the exogenous gene was verified by PCR. RESULTS: The PCR amplified products were verified as hVEGF165 gene by DNA sequencing, and the recombinant pAAV-hVEGF165-IRES-GFP was confirmed by double digestion

  3. The movement and distribution of Helicoverpa armigera (Hübner) larvae on pea plants is affected by egg placement and flowering.

    Science.gov (United States)

    Perkins, L E; Cribb, B W; Hanan, J; Zalucki, M P

    2010-10-01

    The distribution and movement of 1st instar Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) larvae on whole garden pea (Pisum sativum L.) plants were determined in glasshouse trials. This economically-important herbivore attacks a wide variety of agricultural, horticultural and indigenous plants. To investigate the mechanisms underlying larval intra-plant movement, we used early-flowering and wild-type plant genotypes and placed eggs at different vertical heights within the plants, one egg per plant. Leaf water and nitrogen content and cuticle hardness were measured at the different plant heights. Of 92 individual larvae, 41% did not move from the node of eclosion, 49% moved upwards and 10% moved downwards with the distance moved being between zero and ten plant nodes. Larvae from eggs placed on the lower third of the plant left the natal leaf more often and moved further than larvae from eggs placed in the middle or upper thirds. The low nutritive value of leaves was the most likely explanation for more movement away from lower plant regions. Although larvae on flowering plants did not move further up or down than larvae on non-flowering plants, they more often departed the leaflet (within a leaf) where they eclosed. The final distribution of larvae was affected by plant genotype, with larvae on flowering plants found less often on leaflets and more often on stipules, tendrils and reproductive structures. Understanding intra-plant movement by herbivorous insects under natural conditions is important because such movement determines the value of economic loss to host crops. Knowing the behaviour underlying the spatial distribution of herbivores on plants will assist us to interpret field data and should lead to better informed pest management decisions.

  4. Analysis of the factors that affect the distribution and abundance of three Neobuxbaumia species (Cactaceae) that differ in their degree of rarity

    Science.gov (United States)

    Ruedas, Marcela; Valverde, Teresa; Zavala-Hurtado, José Alejandro

    2006-03-01

    We studied three species of columnar cacti in the genus Neobuxbaumia which differ in their degree of rarity: Neobuxbaumia macrocephala (the rarest), Neobuxbaumia tetetzo (intermediate), and Neobuxbaumia mezcalaensis (the most common). To investigate the ecological factors that limit their distribution and abundance, we surveyed 80 localities within the region of Tehuacan-Cuicatlán, in Central Mexico. At each locality we measured several environmental variables, and the density of the Neobuxbaumia populations present. We used a principal component analysis (PCA) to identify the factors that are associated to the presence/absence of each species. Additionally, we carried out multiple regressions between environmental variables and population density to test whether the variation in these variables was related to changes in abundance. The results show that factors significantly affecting the distribution of these species are mean annual temperature, altitude, rainfall, and soil properties such as texture and organic matter content. N. mezcalaensis reaches maximum population densities of 14,740 plants per ha (average density = 3943 plants per ha) and is associated with localities with relatively abundant rainfall. N. tetetzo shows maximum population densities of 14,060 plants per ha (average = 3070 plants per ha), and is associated with sites located at high latitudes and with high phosphorous content in the soil. The rarest species, N. macrocephala, shows maximum densities of 1180 plants per ha (average = 607 plants per ha) and is associated with localities with high soil calcium content. The distribution of this species is limited to sites with specific values of the environmental variables recorded, conferring it a high habitat specificity which accounts for its rarity.

  5. Rôle du VEGF dans la régulation de la synapse glutamatergique

    OpenAIRE

    Rossi, Pierre

    2013-01-01

    The vascular endothelial growth factor (VEGF) plays a critical role during vascular development but recent evidence indicates that it also regulates various neuronal processes in the nervous system, such as neurogenesis, hippocampal synaptic plasticity, learning and memory. Recently, we showed a novel interaction between the glutamate receptor NMDA (NMDAR) and the VEGF receptor VEGFR2 during neuronal migration in the developing cerebellum. As NMDAR have been widely implicated in synaptic tran...

  6. Covalent immobilisation of VEGF on plasma-coated electrospun scaffolds for tissue engineering applications.

    Science.gov (United States)

    Guex, A G; Hegemann, D; Giraud, M N; Tevaearai, H T; Popa, A M; Rossi, R M; Fortunato, G

    2014-11-01

    Recent findings in the field of biomaterials and tissue engineering provide evidence that surface immobilised growth factors display enhanced stability and induce prolonged function. Cell response can be regulated by material properties and at the site of interest. To this end, we developed scaffolds with covalently bound vascular endothelial growth factor (VEGF) and evaluated their mitogenic effect on endothelial cells in vitro. Nano- (254±133 nm) or micro-fibrous (4.0±0.4 μm) poly(ɛ-caprolactone) (PCL) non-wovens were produced by electrospinning and coated in a radio frequency (RF) plasma process to induce an oxygen functional hydrocarbon layer. Implemented carboxylic acid groups were converted into amine-reactive esters and covalently coupled to VEGF by forming stable amide bonds (standard EDC/NHS chemistry). Substrates were analysed by X-ray photoelectron spectroscopy (XPS), enzyme-linked immuno-assays (ELISA) and immunohistochemistry (anti-VEGF antibody and VEGF-R2 binding). Depending on the reaction conditions, immobilised VEGF was present at 127±47 ng to 941±199 ng per substrate (6mm diameter; concentrations of 4.5 ng mm(-2) or 33.3 ng mm(-2), respectively). Immunohistochemistry provided evidence for biological integrity of immobilised VEGF. Endothelial cell number of primary endothelial cells or immortalised endothelial cells were significantly enhanced on VEGF-functionalised scaffolds compared to native PCL scaffolds. This indicates a sustained activity of immobilised VEGF over a culture period of nine days. We present a versatile method for the fabrication of growth factor-loaded scaffolds at specific concentrations.

  7. Moderation of calpain activity promotes neovascular integration and lumen formation during VEGF-induced pathological angiogenesis.

    Directory of Open Access Journals (Sweden)

    Mien V Hoang

    Full Text Available BACKGROUND: Successful neovascularization requires that sprouting endothelial cells (ECs integrate to form new vascular networks. However, architecturally defective, poorly integrated vessels with blind ends are typical of pathological angiogenesis induced by vascular endothelial growth factor-A (VEGF, thereby limiting the utility of VEGF for therapeutic angiogenesis and aggravating ischemia-related pathologies. Here we investigated the possibility that over-exuberant calpain activity is responsible for aberrant VEGF neovessel architecture and integration. Calpains are a family of intracellular calcium-dependent, non-lysosomal cysteine proteases that regulate cellular functions through proteolysis of numerous substrates. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse skin model of VEGF-driven angiogenesis, retroviral transduction with dominant-negative (DN calpain-I promoted neovessel integration and lumen formation, reduced blind ends, and improved vascular perfusion. Moderate doses of calpain inhibitor-I improved VEGF-driven angiogenesis similarly to DN calpain-I. Conversely, retroviral transduction with wild-type (WT calpain-I abolished neovessel integration and lumen formation. In vitro, moderate suppression of calpain activity with DN calpain-I or calpain inhibitor-I increased the microtubule-stabilizing protein tau in endothelial cells (ECs, increased the average length of microtubules, increased actin cable length, and increased the interconnectivity of vascular cords. Conversely, WT calpain-I diminished tau, collapsed microtubules, disrupted actin cables, and inhibited integration of cord networks. Consistent with the critical importance of microtubules for vascular network integration, the microtubule-stabilizing agent taxol supported vascular cord integration whereas microtubule dissolution with nocodazole collapsed cord networks. CONCLUSIONS/SIGNIFICANCE: These findings implicate VEGF-induction of calpain activity and impairment of

  8. Prognostic importance of VEGF-A haplotype combinations in a stage II colon cancer population

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, Sanne; Fredslund, Rikke; Lindebjerg, Jan;

    2012-01-01

    To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients.......To investigate the prognostic effect of three VEGF-A SNPs, -2578, -460 and 405, as well as the corresponding haplotype combinations, in a unique population of stage II colon cancer patients....

  9. Association of serum VEGF levels with prefrontal cortex volume in schizophrenia.

    Science.gov (United States)

    Pillai, A; Howell, K R; Ahmed, A O; Weinberg, D; Allen, K M; Bruggemann, J; Lenroot, R; Liu, D; Galletly, C; Weickert, C S; Weickert, T W

    2016-05-01

    A large body of evidence indicates alterations in brain regional cellular energy metabolism and blood flow in schizophrenia. Among the different molecules regulating blood flow, vascular endothelial growth factor (VEGF) is generally accepted as the major factor involved in the process of angiogenesis. In the present study, we examined whether peripheral VEGF levels correlate with changes in the prefrontal cortex (PFC) volume in patients with schizophrenia and in healthy controls. Whole-blood samples were obtained from 96 people with schizophrenia or schizoaffective disorder and 83 healthy controls. Serum VEGF protein levels were analyzed by enzyme-linked immunosorbent assay, whereas quantitative PCR was performed to measure interleukin-6 (IL-6, a pro-inflammatory marker implicated in schizophrenia) mRNA levels in the blood samples. Structural magnetic resonance imaging scans were obtained using a 3T Achieva scanner on a subset of 59 people with schizophrenia or schizoaffective disorder and 65 healthy controls, and prefrontal volumes were obtained using FreeSurfer software. As compared with healthy controls, individuals with schizophrenia had a significant increase in log-transformed mean serum VEGF levels (t(177)=2.9, P=0.005). A significant inverse correlation (r=-0.40, P=0.002) between serum VEGF and total frontal pole volume was found in patients with schizophrenia/schizoaffective disorder. Moreover, we observed a significant positive association (r=0.24, P=0.03) between serum VEGF and IL-6 mRNA levels in patients with schizophrenia. These findings suggest an association between serum VEGF and inflammation, and that serum VEGF levels are related to structural abnormalities in the PFC of people with schizophrenia.

  10. Genetic variation in VEGF does not contribute significantly to the risk of congenital cardiovascular malformation.

    Directory of Open Access Journals (Sweden)

    Helen R Griffin

    Full Text Available Several previous studies have investigated the role of common promoter variants in the vascular endothelial growth factor (VEGF gene in causing congenital cardiovascular malformation (CVM. However, results have been discrepant between studies and no study to date has comprehensively characterised variation throughout the gene. We genotyped 771 CVM cases, of whom 595 had the outflow tract malformation Tetralogy of Fallot (TOF, and carried out TDT and case-control analyses using haplotype-tagging SNPs in VEGF. We carried out a meta-analysis of previous case-control or family-based studies that had typed VEGF promoter SNPs, which included an additional 570 CVM cases. To identify rare variants potentially causative of CVM, we carried out mutation screening in all VEGF exons and splice sites in 93 TOF cases. There was no significant effect of any VEGF haplotype-tagging SNP on the risk of CVM in our analyses of 771 probands. When the results of this and all previous studies were combined, there was no significant effect of the VEGF promoter SNPs rs699947 (OR 1.05 [95% CI 0.95-1.17]; rs1570360 (OR 1.17 [95% CI 0.99-1.26]; and rs2010963 (OR 1.04 [95% CI 0.93-1.16] on the risk of CVM in 1341 cases. Mutation screening of 93 TOF cases revealed no VEGF coding sequence variants and no changes at splice consensus sequences. Genetic variation in VEGF appears to play a small role, if any, in outflow tract CVM susceptibility.

  11. Synthesis and VEGF inhibitory activity of 16,17-pyrazo-annulated steroids

    Institute of Scientific and Technical Information of China (English)

    Hong Shan Liu; Hu Ling Zheng; Mei Ge; Peng Xia; Ying Chen

    2011-01-01

    Eight 16,17-pyrazo-annulated steroidal derivatives were synthesized and evaluated in vitro vascular endothelial growth factor (VEGF) inhibitory activity with 2-methoxyestradiol (2-ME) as the reference compound. Most of the compounds showed potent VEGF inhibitory activity with EC50 values of micromolar or submicromolar range. Among them, the compounds 3 and 8 exhibited similar EC50 values and obviously better TI values compared with 2-ME.

  12. Construction of adeno-associated virus coexpression system for human angiopoietin-1 and VEGF gene

    Institute of Scientific and Technical Information of China (English)

    陈德杰; 谭最; 谢友利; 刘芳

    2004-01-01

    Background Ischemic disease is one of the leading causes of death in the world. In order to further study gene therapy for ischemic disease, we constructed a recombinant plasmid for co-expression of human angiopoietin-1 and vascular endothelial growth factor 165 (VEGF165) gene in adeno-associated virus (AAV) gene delivery system.Methods Human angiopoietin 1 and VEGF165 gene were obtained using PCR. The upstream of angiopoietin 1 contained restriction enzyme site Hind Ⅲ, and the downstream of angiopoietin 1contained restriction enzyme site BamH Ⅰ. The upstream of VEGF165 contained restriction enzyme site Bgl Ⅱ, and the downstream of VEGF165 contained restriction enzyme site BamH Ⅰ . Using the multiple cloning sites (MCS) in plasmid pZero ++ such as BamH Ⅰ , Bgl Ⅱ, Hind Ⅲ, Not Ⅰ , XhoⅠ,Xba Ⅰ , Sal Ⅰ , BspH Ⅰ , Ksp Ⅰ and the corresponding MCS in plasmid pAAV-MCS, angiopoietin 1 and VEGF165 gene were subcloned into pAAV-MCS.Results DNA sequencing revealed that the PCR- amplified angiopoietin 1 and VEGF165 were consistent with NCBI Gene Bank. The recombinant plasmid was identified using PCR and digestion,which proved to be consistent with our hypothesis. In recombinant plasmid, angiopoietin1 and VEGF possessed a CMV promoter and polyA terminator system respectively, thus assuring co-expression of the two genes.Conclusion Successful construction of AAV co-expression system for human angiopoietin 1 and VEGF165 gene will provide the foundation for gene therapy to cure severe ischemic disease.

  13. VEGF165 Stimulates Vessel Density and Vessel Diameter Differently in Angiogenesis and Lymphangiogenesis

    Science.gov (United States)

    Parsons-Wingerter, Patricia; Radhakrishnan, Krishnan; DiCorleto, Paul E.; Leontiev, Dmitry; Anand-Apte, Bela; Albarran, Brian; Farr, Andrew G.

    2005-01-01

    Vascular endothelial growth factor-165 (VEGF(sub 165)) stimulated angiogenesis in the quail chorioallantoic membrane (CAM) by vessel expansion from the capillary network. However, lymphangiogenesis was stimulated by the filopodial guidance of tip cells located on blind-ended lymphatic sprouts. As quantified by fractal/generational branching analysis using the computer code VESGEN, vascular density increased maximally at low VEGF concentrations, and vascular diameter increased most at high VEGF concentrations. Increased vascular density and diameter were statistically independent events (r(sub s), -0.06). By fluorescence immunohistochemistry of VEGF receptors VEGFR-1 and VEGFR-2, alpha smooth muscle actin ((alpha) SMA) and a vascular/lymphatic marker, VEGF(sub 165) increased the density and diameter of sprouting lymphatic vessels guided by tip cells (accompanied by the dissociation of lymphatics from blood vessels). Isolated migratory cells expressing (alpha)SMA were recruited to blood vessels, whereas isolated cells expressing VEGFR-2 were recruited primarily to lymphatics. In conclusion, VEGF(sub 165) increased lymphatic vessel density by lymphatic sprouting, but increased blood vessel density by vascular expansion from the capillary network.

  14. Bmx is a downstream Rap1 effector in VEGF-induced endothelial cell activation.

    Science.gov (United States)

    Stoletov, Konstantin V; Terman, Bruce I

    2004-07-16

    We had previously shown that Rap1 mediates certain of the signaling pathways involved in VEGF-induced endothelial cell migration, although the downstream Rap1 effectors are not known. Towards the goal of identifying those effectors, we utilized a commercially available antibody array filter to identify proteins that either directly interact with Rap1 or interact indirectly through a multi-protein complex. The protocol identified 10 possible Rap1-interacting proteins, including the Bmx non-receptor tyrosine kinase. The conclusion that VEGF treatment leads to a Rap1/Bmx complex was confirmed by an experiment in which cell lysates from VEGF and control cells were immunoprecipitated with Bmx antibodies and Western blotting was done using anti-Rap1 antibodies. VEGF treatment led to the recruitment of Bmx to the CAS scaffolding protein, and inhibition of the Bmx kinase blocked VEGF-induced cell migration. Formation of a Rap1/Bmx complex was not observed in cells transfected with an expression vector for a dominant-negative Rap1, indicating that Bmx is a downstream Rap1 effector in VEGF-induced endothelial cell activation.

  15. Comparative VEGF receptor tyrosine kinase modeling for the development of highly specific inhibitors of tumor angiogenesis.

    Science.gov (United States)

    Schmidt, Ulrike; Ahmed, Jessica; Michalsky, Elke; Hoepfner, Michael; Preissner, Robert

    2008-01-01

    The Vascular Endothelial Growth Factor receptors (VEGF-Rs) play a significant role in tumor development and tumor angiogenesis and are therefore interesting targets in cancer therapy. Targeting the VEGF-R is of special importance as the feed of the tumor has to be reduced. In general, this can be carried out by inhibiting the tyrosine kinase function of the VEGF-R. Nevertheless, there arise some problems with the specificity of known kinase inhibitors: they bind to the ATP-binding site and inhibit a number of kinases, moreover the so far most specific inhibitors act at least on these three major types of VEGF-Rs: Flt-1, Flk-1/KDR, Flt-4. The goal is a selective VEGF-R-2 (Flk-1/KDR) inhibitor, because this receptor triggers rather unspecific signals from VEGF-A, -C, -D and -E. Here, we describe a protocol starting from an established inhibitor (Vatalanib) with 2D-/3D-searching and property filtering of the in silico screening hits and the "negative docking approach". With this approach we were able to identify a compound, which shows a fourfold higher reduction of the proliferation rate of endothelial cells compared to the reduction effect of the lead structure.

  16. The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel.

    Science.gov (United States)

    Aspelund, Aleksanteri; Tammela, Tuomas; Antila, Salli; Nurmi, Harri; Leppänen, Veli-Matti; Zarkada, Georgia; Stanczuk, Lukas; Francois, Mathias; Mäkinen, Taija; Saharinen, Pipsa; Immonen, Ilkka; Alitalo, Kari

    2014-09-01

    In glaucoma, aqueous outflow into the Schlemm's canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.

  17. Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Mishima Satoshi

    2009-11-01

    Full Text Available Abstract Background Vascular endothelial growth factor (VEGF is a key regulator of pathogenic angiogenesis in diseases such as cancer and diabetic retinopathy. Bee products [royal jelly (RJ, bee pollen, and Chinese red propolis] from the honeybee, Apis mellifera, have been used as traditional health foods for centuries. The aim of this study was to investigate the anti-angiogenic effects of bee products using human umbilical vein endothelial cells (HUVECs. Methods In an in vitro tube formation assay, HUVECs and fibroblast cells were incubated for 14 days with VEGF and various concentrations of bee products [RJ, ethanol extract of bee pollen, ethanol extract of Chinese red propolis and its constituent, caffeic acid phenethyl ester (CAPE]. To clarify the mechanism of in vitro angiogenesis, HUVEC proliferation and migration were induced by VEGF with or without various concentrations of RJ, bee pollen, Chinese red propolis, and CAPE. Results RJ, bee pollen, Chinese red propolis, and CAPE significantly suppressed VEGF-induced in vitro tube formation in the descending order: CAPE > Chinese red propolis >> bee pollen > RJ. RJ and Chinese red propolis suppressed both VEGF-induced HUVEC proliferation and migration. In contrast, bee pollen and CAPE suppressed only the proliferation. Conclusion Among the bee products, Chinese red propolis and CAPE in particular showed strong suppressive effects against VEGF-induced angiogenesis. These findings indicate that Chinese red propolis and CAPE may have potential as preventive and therapeutic agents against angiogenesis-related human diseases.

  18. Effects of VEGF and MSCs on vascular regeneration in a trauma model in rats.

    Science.gov (United States)

    Niyaz, Mehmet; Gürpınar, Özer Aylin; Oktar, Gürsel Levent; Günaydın, Serdar; Onur, Mehmet Ali; Özsin, Kadir Kaan; Yener, Ali

    2015-01-01

    In the human body, vascular injuries that are caused by trauma, vessel lumen stenosis, and occlusions are often irreversible and can lead to sequelae formation as the vessels cannot reproduce fast enough. To solve this problem, the blood flow must be returned to the region as fast as possible. The adipose tissue contains progenitor cells with angiogenic potential and can be used to resolve the issue. In the present study, mesenchymal stem cells (MSCs) derived from rat adipose tissue, vascular endothelial growth factor (VEGF), and their mixture were applied on the dorsum of a rat, which was traumatized and its contribution to vascular regeneration was reviewed. No application was made to the control group. The results showed that the percentage of necrotic area was significantly lower in the MSC group than that of all the other groups. When the VEGF group was compared to the VEGF + MSCs, the percentage of necrotic area was observed to be similiar. However, VEGF showed effects only when a large quantites of VEGF was applied to the flap area. VEGF could not fully respond to the needs, whereas MSCs can produce VEGF according to the needs of tissue. This makes them superior to stem cells.

  19. MET Suppresses Epithelial VEGFR2 via Intracrine VEGF-induced Endoplasmic Reticulum-associated Degradation

    Directory of Open Access Journals (Sweden)

    Tom T. Chen

    2015-05-01

    Full Text Available Hepatocyte growth factor (HGF and vascular endothelial growth factor (VEGF drive cancer through their respective receptors, MET and VEGF receptor 2 (VEGFR2. VEGFR2 inhibits MET by promoting MET dephosphorylation. However, whether MET conversely regulates VEGFR2 remains unknown. Here we show that MET suppresses VEGFR2 protein by inducing its endoplasmic-reticulum-associated degradation (ERAD, via intracrine VEGF action. HGF–MET signaling in epithelial cancer cells promoted VEGF biosynthesis through PI3-kinase. In turn, VEGF and VEGFR2 associated within the ER, activating inositol-requiring enzyme 1α, and thereby facilitating ERAD-mediated depletion of VEGFR2. MET disruption upregulated VEGFR2, inducing compensatory tumor growth via VEGFR2 and MEK. However, concurrent disruption of MET and either VEGF or MEK circumvented this, enabling more profound tumor inhibition. Our findings uncover unique cross-regulation between MET and VEGFR2—two RTKs that play significant roles in tumor malignancy. Furthermore, these results suggest rational combinatorial strategies for targeting RTK signaling pathways more effectively, which has potentially important implications for cancer therapy.

  20. VEGF-A and VEGFR1 SNPs associate with preeclampsia in a Philippine population.

    Science.gov (United States)

    Amosco, Melissa D; Villar, Van Anthony M; Naniong, Justin Michael A; David-Bustamante, Lara Marie G; Jose, Pedro A; Palmes-Saloma, Cynthia P

    The vascular endothelial growth factor (VEGF) family is important for establishing normal pregnancy, and related single nucleotide polymorphisms (SNPs) are implicated in abnormal placentation and preeclampsia. We evaluated the association between preeclampsia and several VEGF SNPs among Filipinos, an ethnically distinct group with high prevalence of preeclampsia. The genotypes and allelic variants were determined in a case-control study (191 controls and 165 preeclampsia patients) through SNP analysis of VEGF-A (rs2010963, rs3025039) and VEGF-C (rs7664413) and their corresponding receptors VEGFR1 (rs722503, rs12584067, rs7335588) and VEGFR3 (rs307826) from venous blood DNA. VEGF-A rs3025039 C allele has been shown to associate with preeclampsia (odds ratio of 1.648 (1.03-2.62)), while the T allele bestowed an additive effect for the maintenance of normal, uncomplicated pregnancy and against the development of preeclampsia (odds ratio of 0.62 (0.39-0.98)). VEGFR1 rs722503 is associated with preeclampsia occurring at or after the age of 40 years. The results showed that genetic variability of VEGF-A and VEGFR1 are important in the etiology of preeclampsia among Filipinos.

  1. Thymosin beta 10 Prompted the VEGF-C Expression in Lung Cancer Cell

    Directory of Open Access Journals (Sweden)

    Zixuan LI

    2014-05-01

    Full Text Available Background and objective Our previous study found that thymosin β10 overexpressed in lung cancer and positively correlated with differentiation, lymph node metastasis and stage of lung cancer. In this reasearch we aim to study the effects and mechanism of exogenous human recombinant Tβ10 on the expression of VEGF-C on non-small cell lung cancer. Methods After SPC, A549 and LK2 cells were treated with 100 ng/mL recombinant human Tβ10, the mRNA level of VEGF-C were detected by RT-PCR. The mean while the protein expression of VEGF-C, P-AKT and AKT were determined by Western blot assay. Results Exogenous recombinant human Tβ10 were significantly promote the expression levels of VEGF-C mRNA and protein while promoting the phosphorylation of AKT. Exogenous Tβ10 can promote the expression of VEGF-C mRNA and protein in lung cancer cell lines A549 and LK2 (P<0.05, and this effect can be inhibited by use AKT inhibitor LY294002 (P<0.05. Conclusion Tβ10 human recombinant proteins can promote the expression of VEGF-C by activating AKT phosphorylation in lung cancer cell lines.

  2. [VEGF in the cancer anorexia-cachexia syndrome in patients with lung cancer].

    Science.gov (United States)

    Weryńska, Bozena; Kosacka, Monika; Gołecki, Marcin; Jankowska, Renata

    2006-01-01

    Cancer anorexia-cachexia syndrome( CACS) occurs in 30-80% of patients with cancer. CACS is connected with poor prognosis and higher risk of treatment complications. CACS belongs to the common cause of death in cancer patients. Main role in the development of this syndrome play cytokines like TNF, interleukin 1 and 6 and interferon alpha and gamma. The importance of a lot of other substances is still unknown. VEGF promotes new vessels development,enhance vascular permeability and plays a role in inflammatory reaction. The aim of this study was comparison of VEGF levels in patients with lung cancer with and without CACS and in control group. The serum levels of VEGF were measured by ELISA method. The VEGF was significatly higher in patients with lung cancer then in control group (p = 0.004). There were no correlations between VEGF and weight lost, histological type and stage of disease. This suggest that VEGF doesnt play a role in development of CACS.

  3. NLRP3 Inflammasome Blockade Inhibits VEGF-A-Induced Age-Related Macular Degeneration

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    Alexander G. Marneros

    2013-09-01

    Full Text Available The NLRP3 inflammasome is activated in age-related macular degeneration (AMD, but it remains unknown whether its activation contributes to AMD pathologies. VEGF-A is increased in neovascular (“wet” AMD, but it is not known whether it plays a role in inflammasome activation, whether an increase of VEGF-A by itself is sufficient to cause neovascular AMD and whether it can contribute to nonexudative (“dry” AMD that often co-occurs with the neovascular form. Here, it is shown that an increase in VEGF-A results in NLRP3 inflammasome activation and is sufficient to cause both forms of AMD pathologies. Targeting NLRP3 or the inflammasome effector cytokine IL-1β inhibits but does not prevent VEGF-A-induced AMD pathologies, whereas targeting IL-18 promotes AMD. Thus, increased VEGF-A provides a unifying pathomechanism for both forms of AMD; combining therapeutic inhibition of both VEGF-A and IL-1β or the NLRP3 inflammasome is therefore likely to suppress both forms of AMD.

  4. Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A.

    Science.gov (United States)

    Carranza, Katherine; Veron, Dolores; Cercado, Alicia; Bautista, Noemi; Pozo, Wilson; Tufro, Alda; Veron, Delma

    2015-01-01

    The prevalence of diabetes mellitus increased during the last century and it is estimated that 45% of the patients are not diagnosed. In South America the prevalence of diabetes and chronic kidney disease (CKD) increased, with a great disparity among the countries with respect to access to dialysis. In Ecuador it is one of the main causes of mortality, principally in the provinces located on the coast of the Pacific Ocean. The greatest single cause of beginning dialysis is diabetic nephropathy (DN). Even using the best therapeutic options for DN, the residual risk of proteinuria and of terminal CKD remains high. In this review we indicate the importance of the problem globally and in our region. We analyse relevant cellular and molecular studies that illustrate the crucial significance of glomerular events in DN development and evolution and in insulin resistance. We include basic anatomical, pathophysiological and clinical concepts, with special attention to the role of angiogenic factors such as the vascular endothelial growth factor (VEGF-A) and their relationship to the insulin receptor, endothelial isoform of nitric oxide synthase (eNOS) and angiopoietins. We also propose various pathways that have therapeutic potential in our opinion. Greater in-depth study of VEGF-A and angiopoietins, the state of glomerular VEGF resistance, the relationship of VEGF receptor 2/nephrin, VEGF/insulin receptors/nephrin and the relationship of VEGF/eNOS-NO at glomerular level could provide solutions to the pressing world problem of DN and generate new treatment alternatives.

  5. Inhibition of VEGF- and NO-dependent angiogenesis does not impair liver regeneration

    Science.gov (United States)

    Shergill, U.; Das, A.; Langer, D.; Adluri, RS.; Maulik, N.

    2010-01-01

    Angiogenesis occurs through a convergence of diverse signaling mechanisms with prominent pathways that include autocrine effects of endothelial nitric oxide (NO) synthase (eNOS)-derived NO and vascular endothelial growth factor (VEGF). However, the redundant and distinct roles of NO and VEGF in angiogenesis remain incompletely defined. Here, we use the partial hepatectomy model in mice genetically deficient in eNOS to ascertain the influence of eNOS-derived NO on the angiogenesis that accompanies liver regeneration. While sinusoidal endothelial cell (SEC) eNOS promotes angiogenesis in vitro, surprisingly the absence of eNOS did not influence the angiogenesis that occurs after partial hepatectomy in vivo. While this observation could not be attributed to induction of alternate NOS isoforms, it was associated with induction of VEGF signaling as evidenced by enhanced levels of VEGF ligand in regenerating livers from mice genetically deficient in eNOS. However, surprisingly, mice that were genetically heterozygous for deficiency in the VEGF receptor, fetal liver kinase-1, also maintained unimpaired capacity for liver regeneration. In summary, inhibition of VEGF- and NO-dependent angiogenesis does not impair liver regeneration, indicating signaling redundancies that allow liver regeneration to continue in the absence of this canonical vascular pathway. PMID:20421635

  6. Effect of VEGF on the Regenerative Capacity of Muscle Stem Cells in Dystrophic Skeletal Muscle

    Science.gov (United States)

    Deasy, Bridget M; Feduska, Joseph M; Payne, Thomas R; Li, Yong; Ambrosio, Fabrisia; Huard, Johnny

    2009-01-01

    We have isolated a population of muscle-derived stem cells (MDSCs) that, when compared with myoblasts, display an improved regeneration capacity, exhibit better cell survival, and improve myogenesis and angiogenesis. In addition, we and others have observed that the origin of the MDSCs may reside within the blood vessel walls (endothelial cells and pericytes). Here, we investigated the role of vascular endothelial growth factor (VEGF)–mediated angiogenesis in MDSC transplantation–based skeletal muscle regeneration in mdx mice (an animal model of muscular dystrophy). We studied MDSC and MDSC transduced to overexpress VEGF; no differences were observed in vitro in terms of phenotype or myogenic differentiation. However, after in vivo transplantation, we observe an increase in angiogenesis and endogenous muscle regeneration as well as a reduction in muscle fibrosis in muscles transplanted with VEGF-expressing cells when compared to control cells. In contrast, we observe a significant decrease in vascularization and an increase in fibrosis in the muscles transplanted with MDSCs expressing soluble forms-like tyrosine kinase 1 (sFlt1) (VEGF-specific antagonist) when compared to control MDSCs. Our results indicate that VEGF-expressing cells do not increase the number of dystrophin-positive fibers in the injected mdx muscle, when compared to the control MDSCs. Together the results suggest that the transplantation of VEGF-expressing MDSCs improved skeletal muscle repair through modulation of angiogenesis, regeneration and fibrosis in the injected mdx skeletal muscle. PMID:19603004

  7. Hypertonic stress induces VEGF production in human colon cancer cell line Caco-2: inhibitory role of autocrine PGE₂.

    Directory of Open Access Journals (Sweden)

    Luciana B Gentile

    Full Text Available Vascular Endothelial Growth Factor (VEGF is a major regulator of angiogenesis. VEGF expression is up regulated in response to micro-environmental cues related to poor blood supply such as hypoxia. However, regulation of VEGF expression in cancer cells is not limited to the stress response due to increased volume of the tumor mass. Lipid mediators in particular arachidonic acid-derived prostaglandin (PGE₂ are regulators of VEGF expression and angiogenesis in colon cancer. In addition, increased osmolarity that is generated during colonic water absorption and feces consolidation seems to activate colon cancer cells and promote PGE₂ generation. Such physiological stimulation may provide signaling for cancer promotion. Here we investigated the effect of exposure to a hypertonic medium, to emulate colonic environment, on VEGF production by colon cancer cells. The role of concomitant PGE₂ generation and MAPK activation was addressed by specific pharmacological inhibition. Human colon cancer cell line Caco-2 exposed to a hypertonic environment responded with marked VEGF and PGE₂ production. VEGF production was inhibited by selective inhibitors of ERK 1/2 and p38 MAPK pathways. To address the regulatory role of PGE₂ on VEGF production, Caco-2 cells were treated with cPLA₂ (ATK and COX-2 (NS-398 inhibitors, that completely block PGE₂ generation. The Caco-2 cells were also treated with a non selective PGE₂ receptor antagonist. Each treatment significantly increased the hypertonic stress-induced VEGF production. Moreover, addition of PGE₂ or selective EP₂ receptor agonist to activated Caco-2 cells inhibited VEGF production. The autocrine inhibitory role for PGE₂ appears to be selective to hypertonic environment since VEGF production induced by exposure to CoCl₂ was decreased by inhibition of concomitant PGE₂ generation. Our results indicated that hypertonicity stimulates VEGF production in colon cancer cell lines. Also PGE

  8. A novel gene delivery system targeting cells expressing VEGF receptors

    Institute of Scientific and Technical Information of China (English)

    LIJUNMIN; JINGCHULUO; 等

    1999-01-01

    Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors.GV1,GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex.Using pSV2-β-galactosidase as a reporter gene,it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) and human malignant melanoma cell lines (A375) in vitro.In vivo experiments,exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO,human malignant melanoma A375 and human hepatoma graft in nude mice.This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice.These results are correlated with the relevant receptors(flt-1,flk-1/KDR) expression on the targeted cells and tissues.

  9. EXPRESSION OF VEGF RECEPTOR KDR IN DIFFERENT ORIGINATED CARCINOMAS

    Institute of Scientific and Technical Information of China (English)

    Song Shumei; Wujian; Shou Chengchao

    1998-01-01

    Objective: To detect the expression of KDR in different originated carcinomas and to explore its expressed ways and the relationship with tumor progression. Methods: KDR cDNA (Ⅴ-Ⅶ domains)fragment was cloned from human umbilical vein with RTPCR and was expressed in Ecoli.Jm109. The fusion protein of GST-KDR was used for immunizing Balb/c mice to prepare monoclonal antibodies against KDR.The different tumor tissues and related normal tissues were examined with KDR McAb by S-P immunohistochemistry. Results: the rate and intensification of KDR expression among different originated cancers are very different, bladder cancers from transmigrated epidermis are 100% positive and highest intensification.The expression of KDR in breast cancer and intestinal cancer lie in the second-rate, the weakest expression of KDR is in lung squamous carcinoma. Moreover,expression of KDR in tumor tissues lie both in endothelial cells (EC) of tumor blood vessels and tumor cells.Conclusion: VEGF may be not only the para-secretory factor making EC proliferation but also auto-secretory factor stimulating the proliferation of tumor cells to benefit the growth and metastasis of malignant tumors.The different expression of KDR in different originated carcinomas may relate with malignant degree of tumor.

  10. Lower values of VEGF in endometrial secretion are a possible cause of subfertility in non-atopic asthmatic patients

    DEFF Research Database (Denmark)

    Gade, Elisabeth Juul; Thomsen, Simon Francis; Lindenberg, Svend;

    2015-01-01

    Abstract Objective: Using endometrial secretion analysis, we assessed whether altered inflammatory cytokine levels can be detected in the uterine environment in asthma patients, thereby providing a possible cause of reduced fertility in asthmatics. Methods: Forty-four unexplained infertile women ...... endometrial secretions, which might affect the receptiveness of the endometrium and thereby increase time to pregnancy. The effect appears to be associated with non-atopic asthma with general increased systemic inflammation.......Abstract Objective: Using endometrial secretion analysis, we assessed whether altered inflammatory cytokine levels can be detected in the uterine environment in asthma patients, thereby providing a possible cause of reduced fertility in asthmatics. Methods: Forty-four unexplained infertile women...... (aged 28-44) underwent asthma and allergy testing, questionnaires, endometrial secretion and blood samples in the mid-secretory phase of the menstrual cycle (day 19-23) during assisted reproduction. Differences in cytokines and growth factors were analyzed. Results: Mean log-VEGF in uteri was lower...

  11. Low pH affects survival, growth, size distribution, and carapace quality of the postlarvae and early juveniles of the freshwater prawn Macrobrachium rosenbergii de Man

    Science.gov (United States)

    Kawamura, Gunzo; Bagarinao, Teodora; Yong, Annita Seok Kian; Chen, Chiau Yu; Noor, Siti Norasidah Mat; Lim, Leong Seng

    2015-06-01

    Acidification of rain water caused by air pollutants is now recognized as a serious threat to aquatic ecosystems. We examined the effects of low pH (control pH 7.5, pH 6, pH 5, pH 4) on the survival, growth, and shell quality of Macrobrachium rosenbergii postlarvae and early juveniles in the laboratory. Hatcheryproduced postlarvae (PL 5) were stocked at 250 PL per aquarium, acclimated over 7 d to experimental pH adjusted with hydrochloric acid, and reared for 30 d. Dead specimens were removed and counted twice a day. After 27 d rearing, all specimens were measured for total length and body weight. Carapace quality was assessed by spectrophotometry. Survival of juveniles was highest at pH 6 (binomial 95% confidence interval 79 - 89%) followed by control pH 7.5 (56 - 68%) and pH 5 (50 - 60%) and was lowest for unmetamorphosed postlarvae and juveniles at pH 4 (43 - 49%). The final median total length and body weight of juveniles were similar at control pH 7.5 (18.2 TL, 50.2 mg BW) and pH 6 (17.7 mm TL, 45.0 mg BW) but significantly less at pH 5 (16.7 mm TL, 38.2 mg BW); at pH 4, the postlarvae did not metamorphose and measured only 9.8 mm TL, 29.3 mg BW. Length frequency distribution showed homogeneous growth at pH 6, positive skew at control pH 7.5 and pH 5, and extreme heterogeneity at pH 4. The carapace showed different transmittance spectra and lower total transmittance (i.e. thicker carapace) in juveniles at pH 7.5, pH 6, and pH 5 than in unmetamorphosed postlarvae and juveniles with thinner carapace at pH 4. Thus, survival, growth, size distribution, and carapace quality of M. rosenbergii postlarvae and early juveniles were negatively affected by pH 5 and especially pH 4. The thinner carapace of the survivors at pH 4 was mostly due to their small size and failure to metamorphose. Natural waters affected by acid rain could decimate M. rosenbergii populations in the wild.

  12. Distribution of polychlorinated biphenyls in an urban riparian zone affected by wastewater treatment plant effluent and the transfer to terrestrial compartment by invertebrates

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Junchao [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 (China); Environment Research Institute, Shandong University, Jinan, 250100 (China); Wang, Thanh, E-mail: bswang@rcees.ac.cn [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 (China); Han, Shanlong [Environment Research Institute, Shandong University, Jinan, 250100 (China); Wang, Pu; Zhang, Qinghua; Jiang, Guibin [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085 (China)

    2013-10-01

    In this study, we investigated the distribution of polychlorinated biphenyls (PCBs) in a riparian zone affected by the effluent from a wastewater treatment plant (WWTP). River water, sediment, aquatic invertebrates and samples from the surrounding terrestrial compartment such as soil, reed plants and several land based invertebrates were collected. A relatively narrow range of δ{sup 13}C values was found among most invertebrates (except butterflies, grasshoppers), indicating a similar energy source. The highest concentration of total PCBs was observed in zooplankton (151.1 ng/g lipid weight), and soil dwelling invertebrates showed higher concentrations than phytophagous insects at the riparian zone. The endobenthic oligochaete Tubifex tubifex (54.28 ng/g lw) might be a useful bioindicator of WWTP derived PCBs contamination. High bioaccumulation factors (BAFs) were observed in collected aquatic invertebrates, although the biota-sediment/soil accumulation factors (BSAF) remained relatively low. Emerging aquatic insects such as chironomids could carry waterborne PCBs to the terrestrial compartment via their lifecycles. The estimated annual flux of PCBs for chironomids ranged from 0.66 to 265 ng⋅m{sup −2}⋅y{sup −1}. Although a high prevalence of PCB-11 and PCB-28 was found for most aquatic based samples in this riparian zone, the mid-chlorinated congeners (e.g. PCB-153 and PCB-138) became predominant among chironomids and dragonflies as well as soil dwelling invertebrates, which might suggest a selective biodriven transfer of different PCB congeners. Highlights: • The distribution of PCBs in an urban riparian zone around a wastewater effluent affected river was investigated. • Relatively high abundances of PCB-11 and PCB-28 were found for most samples. • Mid-chlorinated congeners (PCB-153 and PCB-138) were more accumulated in chironomids and dragonflies as well as soil dwelling invertebrates. • Emerging invertebrates can carry waterborne PCBs to the

  13. Placenta growth factor-1 antagonizes VEGF-induced angiogenesis and tumor growth by the formation of functionally inactive PIGF-1/VEGF heterodimers

    DEFF Research Database (Denmark)

    Eriksson, A.; Cao, R.; Pawliuk, R.;

    2002-01-01

    , the biological function of its related homolog, placenta growth factor (PlGF), is poorly understood. Here we demonstrate that PlGF-1, an alternatively spliced isoform of the PlGF gene, antagonizes VEGF-induced angiogenesis when both factors are coexpressed in murine fibrosarcoma cells. Overexpression of PlGF-1...

  14. Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF)

    Energy Technology Data Exchange (ETDEWEB)

    Dunst, J.; Becker, A.; Lautenschlaeger, C.; Markau, S.; Becker, H.; Fischer, K.; Haensgen, G. [Martin-Luther Univ. Halle-Wittenberg (Germany)

    2002-08-01

    Background: Tissue hypoxia is a major stimulus for the up-regulation of vascular endothelial growth factor (VEGF). Anemia might theoretically impact on angiogenesis via impairment of tissue oxygenation. We have investigated this hypothesis in patients with solid cancers and benign diseases. Patients and methods: 49 patients with untreated locoregionally confined solid cancers of the head and neck, cervix, rectum and lung and 59 additional patients with non-malignant diseases (36 normemic patients without serious diseases and 23 patients with renal anemia) were enrolled and the impact of anemia on plasma VEGF levels were determined. VEGF was measured with a commercially available sandwich enzyme immunoassay technique. Results: Plasma levels of VEGF were 16.2{+-}12.7 pg/ml in 36 normemic patients without malignant disease, 49,2{+-}34.5 pg/ml in 49 patients with cancers (p<0.001), and 89.9{+-}67.8 pg/ml in 23 patients with renal anemia (p=0.001). VEGF levels in cancer patients were significantly correlated with hemoglobin (hb) levels and platelet counts (each p=0.001), but not with type of tumor, stage, histology or age. Patients with cancers had higher plasma levels of VEGF than patients with non-malignant diseases in case of hb{>=}12 g/dl (33.1{+-}17.5 vs. 16.6{+-}13.0 pg/ml, p<0.001) and in case of hb between 11.0 and 11.9 g/dl (56.1{+-}26.4 vs 18.5{+-}14.5 pg/ml, p=0.038). In case of a hb<11 g/dl, plasma VEGF levels were significantly elevated in patients with and without cancers (67.0{+-}47.5 vs 88.9{+-}68.8 pg/ml, n.s.). In a multivariate model, a significant association between low hb levels and increased plasma levels of VEGF was confirmed. In 16 patients with renal anemia, changes in hb under erythropoietin treatment were inversely correlated with changes in plasma VEGF levels with decreasing VEGF after increase in hb (p=0.01). Conclusions: Anemic patients have elevated levels of VEGF. The data suggest that anemia might impact on the progression of

  15. Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

    Science.gov (United States)

    Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

    2014-08-01

    Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells.

  16. Prokaryotic Soluble Overexpression and Purification of Human VEGF165 by Fusion to a Maltose Binding Protein Tag.

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    Minh Tan Nguyen

    Full Text Available Human vascular endothelial growth factor (VEGF is a key regulator of angiogenesis and plays a central role in the process of tumor growth and metastatic dissemination. Escherichia coli is one of the most common expression systems used for the production of recombinant proteins; however, expression of human VEGF in E. coli has proven difficult because the E. coli-expressed VEGF tends to be misfolded and forms inclusion bodies, resulting in poor solubility. In this study, we successfully produced semi-preparative amounts of soluble bioactive human VEGF165 (hVEGF. We created seven N-terminal fusion tag constructs with hexahistidine (His6, thioredoxin (Trx, glutathione S-transferase (GST, maltose-binding protein (MBP, N-utilization substance protein A (NusA, human protein disulfide isomerase (PDI, and the b'a' domain of PDI (PDIb'a', and tested each construct for soluble overexpression in E. coli. We found that at 18°C, 92.8% of the MBP-tagged hVEGF to be soluble and that this tag significantly increased the protein's solubility. We successfully purified 0.8 mg of pure hVEGF per 500 mL cell culture. The purified hVEGF is stable after tag cleavage, contains very low levels of endotoxin, and is 97.6% pure. Using an Flk1+ mesodermal precursor cell (MPC differentiation assay, we show that the purified hVEGF is not only bioactive but has similar bioactivity to hVEGF produced in mammalian cells. Previous reports on producing hVEGF in E. coli have all been based on refolding of the protein from inclusion bodies. To our knowledge, this is the first report on successfully expressing and purifying soluble hVEGF in E. coli.

  17. The protective effect of the RAS inhibitor on diabetic patients with nephropathy in the context of VEGF suppression

    Institute of Scientific and Technical Information of China (English)

    Haibing CHEN; Junxi LU; Qing LI; Yuqian BAO; Junling TANG; Huijuan LU; Kunsan XIANG; Weiping JIA

    2009-01-01

    Aim:The aim of the present study was to explore whether renin angiotensin system (RAS) inhibitor can reduce the produc-tion of vascular endothelium growth factor (VEGF).Further,we sought to elucidate the correlation between VEGF level and certain clinical parameters,such as albumin excretion rate (AER),before and after treatment with angiotensin type 1 receptor blocker.Methods: We recruited 166 type 2 diabetic patients at various stages of diabetic nephropathy (DN) and 46 healthy control subjects for a cross-sectional study.We recruited another 42 hypertensive type 2 diabetic patients with microalbuminuria for a longitudinal study involving a 6-month irbesartan treatment protocol.Urinary VEGF (uVEGF) levels were determined using ELISA.Results: In the cross-sectional study,hypertensive type 2 diabetic patients who received RAS inhibitor presented lower uVEGF levels than those who did not receive the RAS inhibitor.Statistical analysis indicated that uVEGF level was independently correlated with the AER.In the longitudinal study involving the 6-month irbesartan treatment,we demonstrated that uVEGF levels decreased significantly in patients who achieved a 50% AER reduction (remission group,n=32).In contrast,uVEGF levels remained unchanged in patients who did not exhibit a 50% AER reduction (nonremission group,n=10).Furthermore,the change in uVEGF was significantly correlated with the change in AER (r=0.65,P<0.01) before and after 6 months of irbesartan treatment.This result held true even after we had adjusted for the decrease in average blood pressure.Conclusion: The protective effect of the RAS inhibitor in DN patients is associated with the suppression of VEGF.Accordingly,it may be possible to use uVEGF as a marker of DN progression.We suggest that uVEGF may be an important target for therapeutic intervention in the context of DN.

  18. Clinical significance of co-expression of VEGF-C and VEGFR-3 in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    李庆昌; 董昕; 顾伟; 邱雪杉; 王恩华

    2003-01-01

    Objective To investigate the relationship between vascular endothelial growth factor C (VEGF-C) expression, VEGFR-3 expression, lymphangiogenesis and angiogenesis in human non-small cell lung cancer (NSCLC).Methods Seventy-six NSCLC samples were stained for VEGF-C, VEGFR-3 and CD34 with immunohistochemical methods. Assessment of lymphatic vessel density (LVD) and microvessel density (MVD) was performed. The expressions of VEGF-C in 24 fresh NSCLC samples were determined with Western blot assay.Results Of the 76 NSCLC cases, 55 were VEGF-C positive and 40 were VEGFR-3 positive in cancer cells. A significant positive correlation was found between VEGF-C expression and VEGFR-3 expression in cancer cells (P<0.05). VEGF-C expression was negatively associated with differentiation of tumor cells (P<0.05). VEGF-C expression and VEGFR-3 expression were positively associated with lymph node metastasis and lymphatic invasion (P<0.05). LVD was positively related to VEGF-C expression, lymph node metastasis, lymphatic invasion and clinical stage (P<0.05). There was a significant correlation between LVD and MVD (R=0.732, P<0.05). Patients with positive VEGF-C expression had worse outcomes than those with negative VEGF-C expression (P<0.001).Conclusions In NSCLC, VEGF-C and VEGFR-3 are related to the lymphangiogenesis, angiogenesis, and occurrence and development of lung cancers. VEGF-C expression could be a useful predictor of poor prognosis in NSCLC.

  19. Inhibiting angiogenesis with human single-chain variable fragment antibody targeting VEGF.

    Science.gov (United States)

    Hosseini, Hossien; Rajabibazl, Masoumeh; Ebrahimizadeh, Walead; Dehbidi, Gholamreza Rafiei

    2015-01-01

    Vascular endothelial growth factor (VEGF) is a highly specific angiogenesis factor which has crucial roles in the angiogenesis of tumors. Anti-angiogenesis agents can inhibit growth and metastasis of tumor cells. Single-chain variable fragments (scFv) have the same affinity as whole antibodies and smaller size, thus result in more tissue permeability and higher production yield. In this research we aim to isolate a human scFv antibody against VEGF that inhibits angiogenesis. For that, we have used human scFv phage library to isolate a specific scFv antibody against binding site of VEGF. The human scFv phage library was amplified according to the manufacture protocol and panned against recombinant VEGF. ScFv antibody was isolated after five rounds of panning. Phage ELISA was used for detection of the highest affinity binder (HR6). Soluble HR6 scFv was expressed in non-suppressor strain of Escherichia coli HB2151 and purified using Ni-NTA chromatography. In vivo and in vitro function of the HR6 scFv was analyzed by chorioallantoic membrane assay and endothelial cell proliferation assay on VEGF stimulated HUVECs. Result of the cross reactivity showed that HR6 scFv specifically bounds to VEGF. The affinity was calculated to be 1.8×10(-7)M. HR6 could stop HUVEC proliferation in a dose dependent manner and anti-angiogenesis activity was observed using 10μg of HR6 in chorioallantoic membrane assay. In this work, we demonstrate that a HR6 scFv selected from human library phage display specifically blocks VEGF signaling, furthermore, this scFv has an anti-angiogenesis effect and because of its small size has more tissue diffusion. The HR6 antibody was isolated form a human library thus, it is not immunogenic for humans and could serve as a potential therapeutic agent in cancer.

  20. Treadmill Exercise Promotes Neurogenesis in Ischemic Rat Brains via Caveolin-1/VEGF Signaling Pathways.

    Science.gov (United States)

    Zhao, Yun; Pang, Qiongyi; Liu, Meixia; Pan, Jingzi; Xiang, Bingwu; Huang, Tingting; Tu, Fengxia; Liu, Chan; Chen, Xiang

    2017-02-01

    Using a model of middle cerebral artery occlusion (MCAO), we have previously demonstrated that treadmill exercise promotes angiogenesis in the ischemic penumbra through caveolin-1/VEGF signaling pathways. However, the function of caveolin-1/VEGF signaling in neurogenesis after MCAO has not been determined. In this study, we aimed to investigate the potential of treadmill exercise to promote neurogenesis after MCAO and whether caveolin-1/VEGF signaling pathways are involved. After MCAO, rats were subjected to a program of treadmill exercise. Daidzein (a specific inhibitor of caveolin-1 protein expression, 0.4 mg/kg) was used to confirm the effect of caveolin-1/VEGF signaling on exercise-mediated neurogenesis. We found that the total protein expression of both caveolin-1 and VEGF was increased by exercise and consistent with the improved neurological recovery, decreased infarct volumes and increased 5-bromo-2'-deoxyuridine (BrdU) in the ipsilateral Subventricular zone (SVZ), as well as increased numbers of BrdU/DCX and BrdU/Neun-positive cells in the peri-infarct region. Furthermore, we observed that the treadmill exercise-induced increased VEGF expression, improved neurological recovery, decreased infarct volumes, increased BrdU/DCX and BrdU/Neun-positive cells were significantly inhibited by the caveolin-1 inhibitor. Our results indicate that treadmill exercise improves neurological recovery in ischemic rats, possibly by enhancement of SVZ-derived neural stem cell (NSC) proliferation, migration and differentiation in the penumbra. Moreover, caveolin-1/VEGF signaling is involved in exercise-mediated NSC migration and neuronal differentiation.

  1. Expression of HIF-1A/VEGF/ING-4 Axis in Pulmonary Sarcoidosis.

    Science.gov (United States)

    Piotrowski, W J; Kiszałkiewicz, J; Pastuszak-Lewandoska, D; Górski, P; Antczak, A; Migdalska-Sęk, M; Górski, W; Czarnecka, K H; Domańska, D; Nawrot, E; Brzeziańska-Lasota, E

    2015-01-01

    Angiogenesis/angiostasis regulated by hypoxia inducible factor-1A (HIF-1A)/vascular endothelial growth factor (VEGF)/inhibitor of growth protein 4 (ING-4) axis may be crucial for the course and outcome of sarcoidosis. Overexpression of angiogenic factors (activation of VEGF through HIF-1A) may predispose to chronic course and lung fibrosis, whereas immunoangiostasis (related to an overexpression of inhibitory ING-4) may be involved in granuloma formation in early sarcoid inflammation, or sustained or recurrent formation of granulomas. In this work we investigated gene expression of HIF-1A, VEGF and ING-4 in bronchoalveolar fluid (BALF) cells and in peripheral blood (PB) lymphocytes of sarcoidosis patients (n=94), to better understand mechanisms of the disease and to search for its biomarkers. The relative gene expression level (RQ value) was analyzed by qPCR. The results were evaluated according to the presence of lung parenchymal involvement (radiological stage I vs. II-IV), acute vs. insidious onset, lung function tests, calcium metabolism parameters, percentage of lymphocytes (BALL%) and BAL CD4+/CD8+ in BALF, age, and gender. In BALF cells, the ING-4 and VEGF RQ values were increased, while HIF-1A expression was decreased. In PB lymphocytes all studied genes were overexpressed. Higher expression of HIF-1A in PB lymphocytes of patients with abnormal spirometry, and in BALF cells of patients with lung volume restriction was found. VEGF gene expression in BALF cells was also higher in patients with abnormal spirometry. These findings were in line with previous data on the role of HIF-1A/VEGF/ING-4 axis in the pathogenesis of sarcoidosis. Up-regulated HIF-1A and VEGF genes are linked to acknowledged negative prognostics.

  2. The UL24 protein of herpes simplex virus 1 affects the sub-cellular distribution of viral glycoproteins involved in fusion.

    Science.gov (United States)

    Ben Abdeljelil, Nawel; Rochette, Pierre-Alexandre; Pearson, Angela

    2013-09-01

    Mutations in UL24 of herpes simplex virus type 1 can lead to a syncytial phenotype. We hypothesized that UL24 affects the sub-cellular distribution of viral glycoproteins involved in fusion. In non-immortalized human foreskin fibroblasts (HFFs) we detected viral glycoproteins B (gB), gD, gH and gL present in extended blotches throughout the cytoplasm with limited nuclear membrane staining; however, in HFFs infected with a UL24-deficient virus (UL24X), staining for the viral glycoproteins appeared as long, thin streaks running across the cell. Interestingly, there was a decrease in co-localized staining of gB and gD with F-actin at late times in UL24X-infected HFFs. Treatment with chemical agents that perturbed the actin cytoskeleton hindered the formation of UL24X-induced syncytia in these cells. These data support a model whereby the UL24 syncytial phenotype results from a mislocalization of viral glycoproteins late in infection.

  3. VEGF-A isoform-specific regulation of calcium ion flux, transcriptional activation and endothelial cell migration

    Directory of Open Access Journals (Sweden)

    Gareth W. Fearnley

    2015-07-01

    Full Text Available Vascular endothelial growth factor A (VEGF-A regulates many aspects of vascular physiology such as cell migration, proliferation, tubulogenesis and cell-cell interactions. Numerous isoforms of VEGF-A exist but their physiological significance is unclear. Here we evaluated two different VEGF-A isoforms and discovered differential regulation of cytosolic calcium ion flux, transcription factor localisation and endothelial cell response. Analysis of VEGF-A isoform-specific stimulation of VEGFR2-dependent signal transduction revealed differential capabilities for isoform activation of multiple signal transduction pathways. VEGF-A165 treatment promoted increased phospholipase Cγ1 phosphorylation, which was proportional to the subsequent rise in cytosolic calcium ions, in comparison to cells treated with VEGF-A121. A major consequence of this VEGF-A isoform-specific calcium ion flux in endothelial cells is differential dephosphorylation and subsequent nuclear translocation of the transcription factor NFATc2. Using reverse genetics, we discovered that NFATc2 is functionally required for VEGF-A-stimulated endothelial cell migration but not tubulogenesis. This work presents a new mechanism for understanding how VEGF-A isoforms program complex cellular outputs by converting signal transduction pathways into transcription factor redistribution to the nucleus, as well as defining a novel role for NFATc2 in regulating the endothelial cell response.

  4. Sustained release of VEGF from PLGA nanoparticles embedded thermo-sensitive hydrogel in full-thickness porcine bladder acellular matrix

    Directory of Open Access Journals (Sweden)

    Song Hua

    2011-01-01

    Full Text Available Abstract We fabricated a novel vascular endothelial growth factor (VEGF-loaded poly(lactic-co-glycolic acid (PLGA-nanoparticles (NPs-embedded thermo-sensitive hydrogel in porcine bladder acellular matrix allograft (BAMA system, which is designed for achieving a sustained release of VEGF protein, and embedding the protein carrier into the BAMA. We identified and optimized various formulations and process parameters to get the preferred particle size, entrapment, and polydispersibility of the VEGF-NPs, and incorporated the VEGF-NPs into the (poly(ethylene oxide-poly(propylene oxide-poly(ethylene oxide (Pluronic® F127 to achieve the preferred VEGF-NPs thermo-sensitive gel system. Then the thermal behavior of the system was proven by in vitro and in vivo study, and the kinetic-sustained release profile of the system embedded in porcine bladder acellular matrix was investigated. Results indicated that the bioactivity of the encapsulated VEGF released from the NPs was reserved, and the VEGF-NPs thermo-sensitive gel system can achieve sol-gel transmission successfully at appropriate temperature. Furthermore, the system can create a satisfactory tissue-compatible environment and an effective VEGF-sustained release approach. In conclusion, a novel VEGF-loaded PLGA NPs-embedded thermo-sensitive hydrogel in porcine BAMA system is successfully prepared, to provide a promising way for deficient bladder reconstruction therapy.

  5. Mechanical Forces Induce Changes in VEGF and VEGFR-1/sFlt-1 Expression in Human Chondrocytes

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    Rainer Beckmann

    2014-09-01

    Full Text Available Expression of the pro-angiogenic vascular endothelial growth factor (VEGF stimulates angiogenesis and correlates with the progression of osteoarthritis. Mechanical joint loading seems to contribute to this cartilage pathology. Cyclic equibiaxial strains of 1% to 16% for 12 h, respectively, induced expression of VEGF in human chondrocytes dose- and frequency-dependently. Stretch-mediated VEGF induction was more prominent in the human chondrocyte cell line C-28/I2 than in primary articular chondrocytes. Twelve hours of 8% stretch induced VEGF expression to 175% of unstrained controls for at least 24 h post stretching, in promoter reporter and enzyme-linked immunosorbent assay (ELISA studies. High affinity soluble VEGF-receptor, sVEGFR-1/sFlt-1 was less stretch-inducible than its ligand, VEGF-A, in these cells. ELISA assays demonstrated, for the first time, a stretch-mediated suppression of sVEGFR-1 secretion 24 h after stretching. Overall, strained chondrocytes activate their VEGF expression, but in contrast, strain appears to suppress the secretion of the major VEGF decoy receptor (sVEGFR-1/sFlt-1. The latter may deplete a biologically relevant feedback regulation to inhibit destructive angiogenesis in articular cartilage. Our data suggest that mechanical stretch can induce morphological changes in human chondrocytes in vitro. More importantly, it induces disturbed VEGF signaling, providing a molecular mechanism for a stress-induced increase in angiogenesis in cartilage pathologies.

  6. Pre-Analytical Parameters Affecting Vascular Endothelial Growth Factor Measurement in Plasma: Identifying Confounders.

    Directory of Open Access Journals (Sweden)

    Johanna M Walz

    Full Text Available Vascular endothelial growth factor-A (VEGF-A is intensively investigated in various medical fields. However, comparing VEGF-A measurements is difficult because sample acquisition and pre-analytic procedures differ between studies. We therefore investigated which variables act as confounders of VEGF-A measurements.Following a standardized protocol, blood was taken at three clinical sites from six healthy participants (one male and one female participant at each center twice one week apart. The following pre-analytical parameters were varied in order to analyze their impact on VEGF-A measurements: analyzing center, anticoagulant (EDTA vs. PECT / CTAD, cannula (butterfly vs. neonatal, type of centrifuge (swing-out vs. fixed-angle, time before and after centrifugation, filling level (completely filled vs. half-filled tubes and analyzing method (ELISA vs. multiplex bead array. Additionally, intrapersonal variations over time and sex differences were explored. Statistical analysis was performed using a linear regression model.The following parameters were identified as statistically significant independent confounders of VEGF-A measurements: analyzing center, anticoagulant, centrifuge, analyzing method and sex of the proband. The following parameters were no significant confounders in our data set: intrapersonal variation over one week, cannula, time before and after centrifugation and filling level of collection tubes.VEGF-A measurement results can be affected significantly by the identified pre-analytical parameters. We recommend the use of CTAD anticoagulant, a standardized type of centrifuge and one central laboratory using the same analyzing method for all samples.

  7. Significance of VEGF and NF-κB Expression in Thyroid Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhenxian Du; Haiyan Zhang; Daxin Gao; Huaqin Wang; Yongjun Li; Guoliang Liu

    2006-01-01

    OBJECTIVE To investigate the significance of vascular endothelial growth factor (VEGF) and nuclear factor-kappaB (NF-κB) expression in thyroid carcinoma.METHODS The expression of NF-κB and VEGF was determined by immunohistochemistry in formalin-fixed and paraffin-embedded specimens obtained from 10 normal thyroid tissues (NT), 12 cases of thyroid adenoma (TA) and 68 cases of thyroid carcinoma (TC).Differences in expression between NT, TA and TC were statistically analyzed. In addition, in cases of TC, the relationship of NF-κB and VEGF expression with various clinicopathological factors, including histological typing, clinical staging and lymph node metastasis, as well as the correlation between NF-κB and VEGF expression was examined.RESULTS In contrast to the negative immunoreactivity for VEGF in NT,there was a significantly higher positive incidence (PI) in TA (41.7%, P=0.040) and TC (75.0%, P<0.001), and a significant difference between TA and TC (P=0.036). Immunoreactivity for NF-κB in NT was negative and significantly higher in TC (63.2%, P<0.001),but not in TA (16.7%, P=0.481). However the PI difference between TA and TC (P=0.003) was significant. Between the histological types of TC, a significantly higher PI was found in undifferentiated thyroid carcinoma (UTC),namely, 100% for VEGF and 90.0% for NF-κB. We also found significant positive relationships of VEGF and NF-κB expression with the clinical stage and lymph node metastasis. Furthermore, a significant positive correlation between VEGF and NF-κB expression in TC was observed.CONCLUSION Our data showed that the expression of VEGF and NFκB/P65 was greater in TC and UTC, and documented their significant positive correlations with the clinical stage and lymph node metastasis in TC. In addition there was a significant positive relationship between their expression, suggesting that they have important roles in TC and that they may be potential targets for gene therapy in TC patients.

  8. VEGF Mediates ApoE4-Induced Neovascularization and Synaptic Pathology in the Choroid and Retina.

    Science.gov (United States)

    Antes, Ran; Salomon-Zimri, Shiran; Beck, Susanne C; Garcia Garrido, Marina; Livnat, Tami; Maharshak, Idit; Kadar, Tamar; Seeliger, Mathias; Weinberger, Dov; Michaelson, Daniel M

    2015-01-01

    Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. Recent findings suggest that retina of apoE4 mice have synaptic and functional impairments. We presently investigated the effects of apoE4 on retinal and choroidal vasculature and the possible role of VEGF in these effects. There were no histological differences between the retinal and choroidal vasculatures of naïve apoE3 and apoE4 mice. In contrast, laserdriven choroidal injury induced higher levels of choroidal neovascularization (CNV) in apoE4 than in apoE3 mice. These effects were associated with an inflammatory response and with activation of the Muller cells and asrocytic markers gluthatione synthetase and GFAP, all of which were more pronounced in the apoE4 mice. CNV also induced a transient increase in the levels of the synaptic markers synaptophysin and PSD95 which were however similar in the apoE4 and apoE3 naive mice. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation and the associated surge in VEGF following injury. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation

  9. Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells

    Institute of Scientific and Technical Information of China (English)

    叶琇锦; 林茂芳

    2004-01-01

    Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. However, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry, The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner, Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.

  10. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

    Science.gov (United States)

    Fey, Theres; Schubert, Kai Michael; Schneider, Holger; Fein, Evelyn; Kleinert, Eike; Pohl, Ulrich; Dendorfer, Andreas

    2016-08-01

    Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity. Podosomes were characterized by immunohistochemistry, and their proteolytic activity was assessed as degradation imprints in fluorescent gelatin that was used as growth substrate. Compared with controls (10 dyn/cm(2)), the number of podosomes formed per time was doubled when cells were exposed to low shear stress (0.3 dyn/cm(2)) or even increased 5-fold under static conditions. This was a result of an enhanced expression of VEGF after reduction of shear stress. Consequently, enhanced podosome formation could be prevented by a VEGF receptor antagonist as well by interruption of VEGF signaling via inhibition of PI3K, Src, or p38. Increase of podosome assembly went along with significantly augmented cell motility. In vivo experiments in mouse arteries confirmed increased endothelial podosome numbers when shear stress was abolished by vessel occlusion. We conclude that shear stress, by reducing VEGF release, inhibits podosome assembly. Hence, endothelial cell-mediated matrix proteolysis and migratory activity are inhibited, thereby stabilizing the structure of the vessel wall.-Fey, T., Schubert, K. M., Schneider, H., Fein, E., Kleinert, E., Pohl, U., Dendorfer, A. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

  11. VEGF EXPRESSION IS INHIBITED BY APIGENIN IN HUMAN BREAST CANCER CELLS

    Institute of Scientific and Technical Information of China (English)

    JIN Xue-ying; REN Chang-shan

    2006-01-01

    Objective: To study the effects of apigenin on vascular endothelial growth factor (VEGF) in human breast cancer cells(MDA-MB-231. Methods: MTT assay was used to detect the cell proliferation inhibitory effect of apigenin on MDA-MB-231 cell. ELISA was used to determine the protein level of VEGF secreted by MDA-MB-231 cells. RT-PCR was used to detect mRNA levels of VEGF in MDA-MB-231 cells. The protein levels of HIF-1α,p-AKT,p-ERK1/2,and p53 were detected by Western Blotting. Results: Apigenin did not inhibit the cell viability of MDA-MB-231 cell. Apigenin reduced the secretion and mRNA levels of VEGF in MDA-MB-231 cells. Additionally, apigenin decreased the expressions of HIF-1α,p-AKT and p-ERK1/2, but induced the expression of p53. Conclusion: Apigenin can inhibit VEGF expression in human breast cancer cells, and this may be achieved through decreasing HIF-1α.

  12. Dietary compound isoliquiritigenin inhibits breast cancer neoangiogenesis via VEGF/VEGFR-2 signaling pathway.

    Science.gov (United States)

    Wang, Zhiyu; Wang, Neng; Han, Shouwei; Wang, Dongmei; Mo, Suilin; Yu, Linzhong; Huang, Hui; Tsui, Kamchuen; Shen, Jiangang; Chen, Jianping

    2013-01-01

    Angiogenesis is crucial for cancer initiation, development and metastasis. Identifying natural botanicals targeting angiogenesis has been paid much attention for drug discovery in recent years, with the advantage of increased safety. Isoliquiritigenin (ISL) is a dietary chalcone-type flavonoid with various anti-cancer activities. However, little is known about the anti-angiogenic activity of isoliquiritigenin and its underlying mechanisms. Herein, we found that ISL significantly inhibited the VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs) at non-toxic concentration. A series of angiogenesis processes including tube formation, invasion and migration abilities of HUVECs were also interrupted by ISL in vitro. Furthermore, ISL suppressed sprout formation from VEGF-treated aortic rings in an ex-vivo model. Molecular mechanisms study demonstrated that ISL could significantly inhibit VEGF expression in breast cancer cells via promoting HIF-1α (Hypoxia inducible factor-1α) proteasome degradation and directly interacted with VEGFR-2 to block its kinase activity. In vivo studies further showed that ISL administration could inhibit breast cancer growth and neoangiogenesis accompanying with suppressed VEGF/VEGFR-2 signaling, elevated apoptosis ratio and little toxicity effects. Molecular docking simulation indicated that ISL could stably form hydrogen bonds and aromatic interactions within the ATP-binding region of VEGFR-2. Taken together, our study shed light on the potential application of ISL as a novel natural inhibitor for cancer angiogenesis via the VEGF/VEGFR-2 pathway. Future studies of ISL for chemoprevention or chemosensitization against breast cancer are thus warranted.

  13. Relationship of PARG with PARP, VEGF and b-FGF in Colorectal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ling Lin; Jia Li; Ya-lan Wang; Xiao Lin

    2009-01-01

    Objective: To investigate the relationship of poly(ADP-ribose)glycohydrolase(PARG) with poly (ADP-ribose) polymerase(PARP), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor(b-FGF) in colorectal carcinoma(CRC).Methods: Immunohistochemical analysis was used to detect PARG, PARP, VEGF and b-FGF in human colorectal carcinoma. Flow cytometry was used to detect PARG and PARP in murine CT26 cell line. Gallotannin (GLTN) was served as PARG inhibitor. Results: The individual positive rates of PARG, PARP, VEGF and b-FGF were 55.81%(24/43), 97.67%(42/43), 79.07%(34/43) and 81.40%(35/43), respectively, which were significantly higher than those of control group. The positive PARG was correlated to PARP(r=0.3703, P<0.05) and b-FGF (r=0.4838, P<0.05). The positive PARP was correlated to VEGF (r=0.3968, P<0.05) and b-FGF (r=0.5610, P<0.05). Both PARG and PARP were expressed in CT26 cells. The positive staining rates of PARG and PARP in GLTN-treated group were 7.3% and 52.38%, respectively. They were markedly reduced than those of control group (55.41% and 95.28%, P<0.01, n=10000).Conclusion: The data suggest that PARG expression probably plays a role for VEGF and b-FGF expression in colorectal carcinoma.

  14. The Role of Anti-VEGF Therapy in the Treatment of Diabetic Macular Edema.

    Science.gov (United States)

    Moshfeghi, Darius M; Kaiser, Peter K; Michels, Stephan; Midena, Edoardo; Kitchens, John W; Prenner, Jonathan L; Regillo, Carl D; Reichel, Elias

    2016-06-01

    Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults. DR often leads to diabetic macular edema (DME), which often goes unnoticed until a patient presents with vision loss. However, treatment options and data for DME are continually improving. We know that vascular endothelial growth factor (VEGF) plays a key role in DME progression; therapies that act by inhibiting VEGF production seem to improve visual acuity in patients with DME. Of the anti-VEGF therapies available, two have been approved by the U.S. Food and Drug Administration to treat DME: ranibizumab (Lucentis; Genentech, South San Francisco, CA) and aflibercept (Eylea; Regeneron, Tarrytown, NY). Bevacizumab (Avastin; Genentech, South San Francisco, CA), which is approved for the treatment of certain types of cancer, is occasionally used off-label to treat DME. Anti-VEGF therapy can stop vision loss and even improve visual acuity. Other treatments remain effective, and these various treatment options fuel a need for new data and discussion. This roundtable discussion, which took place during the 2015 annual meeting of the American Academy of Ophthalmology, outlines the current protocols used to treat DME and provides clinical opinions about selecting and treating with an appropriate anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:S5-14.].

  15. Expression of VEGF and semaphorin genes define subgroups of triple negative breast cancer.

    Directory of Open Access Journals (Sweden)

    R Joseph Bender

    Full Text Available Triple negative breast cancers (TNBC are difficult to treat due to a lack of targets and heterogeneity. Inhibition of angiogenesis is a promising therapeutic strategy, but has had limited effectiveness so far in breast cancer. To quantify heterogeneity in angiogenesis-related gene expression in breast cancer, we focused on two families--VEGFs and semaphorins--that compete for neuropilin co-receptors on endothelial cells. We compiled microarray data for over 2,600 patient tumor samples and analyzed the expression of VEGF- and semaphorin-related ligands and receptors. We used principal component analysis to identify patterns of gene expression, and clustering to group samples according to these patterns. We used available survival data to determine whether these clusters had prognostic as well as therapeutic relevance. TNBC was highly associated with dysregulation of VEGF- and semaphorin-related genes; in particular, it appeared that expression of both VEGF and semaphorin genes were altered in a pro-angiogenesis direction. A pattern of high VEGFA expression with low expression of secreted semaphorins was associated with 60% of triple-negative breast tumors. While all TNBC groups demonstrated poor prognosis, this signature also correlated with lower 5-year survival rates in non-TNBC samples. A second TNBC pattern, including high VEGFC expression, was also identified. These pro-angiogenesis signatures may identify cancers that are more susceptible to VEGF inhibition.

  16. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Yang S

    2016-06-01

    Full Text Available Shiqi Yang,1 Jingke Zhao,1 Xiaodong Sun1–3 1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 2Eye Research Institute of Shanghai Jiao Tong University, 3Shanghai Key Laboratory of Fundus Disease, Shanghai, People’s Republic of China Abstract: As a progressive chronic disease, age-related macular degeneration (AMD is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. Keywords: age-related macular degeneration, vascular endothelial growth factor, choroidal neovascularization, resistance

  17. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review.

    Science.gov (United States)

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance.

  18. Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1/VEGF Signaling under Hypoxia

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Chen

    2015-07-01

    Full Text Available Activation of hypoxia-induced hypoxia-inducible factors-1 (HIF-1 plays a critical role in promoting tumor angiogenesis, growth and metastasis. Low molecular weight fucoidan (LMWF is prepared from brown algae, and exhibits anticancer activity. However, whether LMWF attenuates hypoxia-induced angiogenesis in bladder cancer cells and the molecular mechanisms involved remain unclear. This is the first study to demonstrate that LMWF can inhibit hypoxia-stimulated H2O2 formation, HIF-1 accumulation and transcriptional activity vascular endothelial growth factor (VEGF secretion, and the migration and invasion in hypoxic human bladder cancer cells (T24 cells. LMWF also downregulated hypoxia-activated phosphorylation of PI3K/AKT/mTOR/p70S6K/4EBP-1 signaling in T24 cells. Blocking PI3K/AKT or mTOR activity strongly diminished hypoxia-induced HIF-1α expression and VEGF secretion in T24 cells, supporting the involvement of PI3K/AKT/mTOR in the induction of HIF-1α and VEGF. Additionally, LMWF significantly attenuated angiogenesis in vitro and in vivo evidenced by reduction of tube formation of hypoxic human umbilical vascular endothelial cells and blood capillary generation in the tumor. Similarly, administration of LMWF also inhibited the HIF-1α and VEGF expression in vivo, accompanied by a reduction of tumor growth. In summary, under hypoxia conditions, the antiangiogenic activity of LMWF in bladder cancer may be associated with suppressing HIF-1/VEGF-regulated signaling pathway.

  19. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Yi-Yong; Lee, Dong-Keon [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); So, Ju-Hoon; Kim, Cheol-Hee [Department of Biology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Jeoung, Dooil [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Lee, Hansoo [Department of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Choe, Jongseon [Department of Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Won, Moo-Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Ha, Kwon-Soo [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Kwon, Young-Guen [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-752 (Korea, Republic of); Kim, Young-Myeong, E-mail: ymkim@kangwon.ac.kr [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of)

    2015-08-07

    Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC{sub 50} of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases.

  20. Excessive ammonia inhibited transcription of MsU2 gene and furthermore affected accumulation distribution of allantoin and amino acids in alfalfa Medicago sativa

    Institute of Scientific and Technical Information of China (English)

    WANG Li; JIANG Lin-lin; Nomura Mika; Tajima Shigeyuki; CHENG Xian-guo

    2015-01-01

    In legume plants, uricase gene (Nodulin-35) plays a positive role in metabolism of ureide and amide compounds in symbiotic nitrogen-ifxing in the nodules. In this study, a pot experiment was performed to examine the effects of ammonium application on the transcription of MsU2 gene and distribution of major nitrogen compounds in alfalfa Medicago sativa. Data showed that alfalfa plant has a signiifcant difference in contents of nitrogen compounds in xylem saps compared with soybean plant, and belongs to typical amide type legume plants with little ureide accumulation, and the accumulation of asparagines and ureide in the tissues of alfalfa is mainly gathered in the nodules. Northern blotting showed that excessive ammonium signiifcantly inhibited the transcription of MsU2 gene in the nodules and roots, and mRNA accumulation of MsU2 gene in the plants exposed to excessive ammonium decreased gradual y with culture time extension, indicating that application of ammonium signiifcantly inhibited the transcription of MsU2 gene in the alfalfa plants. Although the application of exces-sive ammonium increased the contents of amino acids in various tissues of alfalfa, the accumulation of al antoin relfecting the strength of uricase activity is remarkably reduced in the xylem saps, stems and nodules when alfalfa plants exposed to excessive ammonium, suggesting that application of excessive ammonium generated a negative effect on symbiosis ifxing-nitrogen system due to inhibition of ammonium ion on uricase activity in the nodules of alfalfa. This result seems to imply that application of excessive ammonium in legume plants should not be proposed to avoid affecting the ability of ifxing nitrogen in the nodules of legume plants, and reasonable dose of ammonium should be recommended to effectively utilize the ifxed N from atmosphere in legume plant production.

  1. 非小细胞肺癌VEGF-C、VEGF-D、VEGFR-3表达与淋巴管生成和淋巴转移关系的研究%Investigation on the relationship between VEGF-C,VEGF-D,VEGFR-3 and lymphangiogenesis and lymph node metastasis in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    常超; 王平; 李琳; 杨慧; 张利斌

    2009-01-01

    目的:探讨血管内皮生长因子(VEGF)-C、-D及其受体3(VEGFR-3)在非小细胞肺癌(NSCLC)中的表达规律、与微淋巴管密度(MLVD)、淋巴转移之间的关系及其在NSCLC发生发展、预后中的意义.方法:以40例经病理确诊的NSCLC组织为实验组.以11例肺良性病变组织为对照组,采用免疫组织化学染色法对上述组织中VEGF-C、VEGF-D、VEGFR-3、淋巴管内皮透明质酸受体-1(LYVE-1)、同源异型盒转录因子(Prox-1)蛋白的表达进行分析,并计数微淋巴管密度.结果:①NSCLC组织中VEGF-C、VEGF-D及VEGFR-3蛋白的阳性率分别为77.50%(31/40例)、67.50%(27/40例)、62.50%(25/40例),明显高于肿瘤周边组织(距肿瘤边缘100 μm区域内)及肺良性病变组织(P<0.01).②VEGF-C与VEGFR-3(r=0.409,P=0.005)、VEGF-D与VEGFR-3蛋白表达(r=492.P=0.000)均存在相关性;而VEGF-C与VEGF-D蛋白表达无相关性(r=256.P=0.093).③VEGF-C、VEGF-D及VEGFR-3蛋白的表达与NSCLC患者的性别、年龄、肿瘤的大小、组织学类型、分化程度无关,但与肿瘤的淋巴结转移(P<0.05)、PTNM分期(P<0.05)显著相关.④NSCLC肿瘤中心组织中LYVE-1及Prex-1标记的MLVD分别为4.22±1.25、1.99±1.49,明显低于肺良性病变组织(P=0.000),而NSCLC肿瘤周边部位的MLVD显著高于肿瘤中心部位及肺良性病变组织(P=0.000).VEGF-C、VEGF-D、VEGFR-3表达阳性的组织中,MLVD显著高于阴性组织(P<0.05).MLVD与肿瘤的淋巴结转移(P=0.000)、PTNM分期(P=0.000)显著相关.结论:淋巴管生成冈子VEGF-C、VEGF-D及其受体VEGFR-3蛋白在NSCLC中表达显著增高,并且通过VEGF-C、VEGF-D/VEGFR-3信号通路诱导淋巴管内皮细胞新生和淋巴管生成,从而促进淋巴结转移和肿瘤生长:VEGF-C、VEGF-D及其受体VEGFR-3可能成为检测NSCLC淋巴转移和评估预后的重要分子指标;淋巴管内皮细胞特异性标志物LYVE-1、Prox-1可以较严格地区分血管和淋巴管内皮,相对精确地评价肿瘤的脉管系统.

  2. High Ki-67 and Vascular Endothelial Growth Factor (VEGF Protein Expression as Negative Predictive Factor for Combined Neoadjuvant Chemotherapy in Young Age Stage III Breast Cancer

    Directory of Open Access Journals (Sweden)

    I Wayan Sudarsa

    2016-05-01

    Full Text Available Background: Breast cancer was, in general, a heterogeneous disease with diverse biological characteristics, types, subtypes and clinical behavior. Its treatment and management need to be personalized and individualized. Breast cancer in young ages, although rare, is usually a unique and more aggressive cancer associated with poorer prognosis. The combination of young age and advanced stages of breast cancer would make this particular breast cancer harder to treat and cure. Unfortunately, majority of Breast Cancer Patients in Bali were in younger ages, and at advanced stages, that the mainstay of treatment was neo-adjuvant chemotherapy followed by other treatment modalities. Improve prognosis only, those patients who had had a complete pathological response involving primary tumor and regional lymph nodes in the axilla. Several factors had been studied and contributed to breast cancer response to combined neo-adjuvant chemotherapy. Usually, younger patients, was associated with high proliferation rate represented by Ki-67 and early distant metastasis represented by VEGF, which also had role as prognostic markers. The purpose of this study was to determine whether high Ki-67 and VEGF expression correlate with response to NAC and hence, they would be important predictive factors for response to NAC. Method: This study was a cross-sectional and a nested case-control study of stage III breast cancers affecting patients 40 years of age or less, at Sanglah General Hospital and Prima Medika Hospital, conducted from September 1st, 2012 until March 31st, 2014. Clinical and pathology reports were traced and recorded from both hospitals; routine Immunohistochemistry (IHC examinations were performed by both pathology labs. Statistical analysis was performed using Chi-Square test, Odds Ratio (OR, and logistic regression analysis with p<0.05. Results: There were 66 Stage III young breast cancer patients, where 35 (53% showed no or negative response and 31 (47

  3. Plexin-A4 promotes tumor progression and tumor angiogenesis by enhancement of VEGF and bFGF signaling.

    Science.gov (United States)

    Kigel, Boaz; Rabinowicz, Noa; Varshavsky, Asya; Kessler, Ofra; Neufeld, Gera

    2011-10-13

    Plexin-A4 is a receptor for sema6A and sema6B and associates with neuropilins to transduce signals of class-3 semaphorins. We observed that plexin-A1 and plexin-A4 are required simultaneously for transduction of inhibitory sema3A signals and that they form complexes. Unexpectedly, inhibition of plexin-A1 or plexin-A4 expression in endothelial cells using specific shRNAs resulted in prominent plexin type specific rearrangements of the actin cytoskeleton that were accompanied by inhibition of bFGF and VEGF-induced cell proliferation. The two responses were not interdependent since silencing plexin-A4 in U87MG glioblastoma cells inhibited cell proliferation and strongly inhibited the formation of tumors from these cells without affecting cytoskeletal organization. Plexin-A4 formed stable complexes with the FGFR1 and VEGFR-2 tyrosine-kinase receptors and enhanced VEGF-induced VEGFR-2 phosphorylation in endothelial cells as well as bFGF-induced cell proliferation. We also obtained evidence suggesting that some of the pro-proliferative effects of plexin-A4 are due to transduction of autocrine sema6B-induced pro-proliferative signals, since silencing sema6B expression in endothelial cells and in U87MG cells mimicked the effects of plexin-A4 silencing and also inhibited tumor formation from the U87MG cells. Our results suggest that plexin-A4 may represent a target for the development of novel anti-angiogenic and anti-tumorigenic drugs.

  4. The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    M Franklin; E Navarro; Y Wang; S Patel; P Singh; Y Zhang; K Persaud; A Bari; H Griffith; et al.

    2011-12-31

    The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonoverlapping among the three contact patches.

  5. The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Franklin, Matthew C.; Navarro, Elizabeth C.; Wang, Yujie; Patel, Sheetal; Singh, Pinki; Zhang, Yi; Persaud, Kris; Bari, Amtul; Griffith, Heather; Shen, Leyi; Balderes, Paul; Kussie, Paul (ImClone)

    2011-10-28

    The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonoverlapping among the three contact patches.

  6. A nanobody directed to a functional epitope on VEGF, as a novel strategy for cancer treatment

    DEFF Research Database (Denmark)

    Farajpour, Zahra; Rahbarizadeh, Fatemeh; Kazemi, Bahram

    2014-01-01

    , large size, and immunogenicity are main drawbacks of conventional monoclonal therapy. Nanobodies are the smallest antigen-binding antibody fragments, which occur naturally in camelidae. Because of their remarkable features, we decided to use an immune library of nanobody to direct phage display......Compelling evidence suggests that vascular endothelial growth factor (VEGF), due to its essential role in angiogenesis, is a critical target for cancer treatment. Neutralizing monoclonal antibodies against VEGF are important class of drugs used in cancer therapy. However, the cost of production...... to recognition of novel functional epitopes on VEGF. Four rounds of selection were performed and six phage-displayed nanobodies were obtained from an immune phage library. The most reactive clone in whole-cell ELISA experiments, was purified and assessed in proliferation inhibition assay. Purified ZFR-5 not only...

  7. VEGF pathway inhibition by anticancer agent sunitinib and susceptibility to atherosclerosis plaque disruption.

    Science.gov (United States)

    Ropert, Stanislas; Vignaux, Olivier; Mir, Olivier; Goldwasser, François

    2011-12-01

    Patients treated with anti-VEGF agents are at increased risk for arterial thrombo-embolic events (ATEs). However, the pathophysiology of such acute vascular complications remains unclear. We report on a case of bowel infarction in a renal cancer patient treated with the anti-VEGF agent sunitinib. An abdominal CT-scan evidenced the rupture of an atherosclerotic plaque located at the emergence of the superior mesenteric artery. In view of this report, we suggest that evaluation of the risk of ATE in patients receiving anti-VEGF agents should include not only age and past history of ATE as suggested by previous studies, but also assessment of atherosclerotic lesions on CT-scan.

  8. Increased serum levels of sortilin are associated with depression and correlated with BDNF and VEGF

    DEFF Research Database (Denmark)

    Buttenschøn, Henriette Nørmølle; Demontis, Ditte; Ollendorff, Mathias Kaas;

    2015-01-01

    measured by immunoassay, and potential determinants of the serum sortilin level were assessed by generalized linear models. Serum levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were measured in previous studies. We identified a significant increase of serum...... sortilin levels in depressed individuals compared with controls (P = 0.0002) and significant positive correlation between serum sortilin levels and the corresponding levels of BDNF and VEGF. None of the genotyped SNPs were associated with depression. Additional analyses showed that the serum sortilin level...... was influenced by several other factors. Alcohol intake and body mass index, as well as depression, serum BDNF and serum VEGF were identified as predictors of serum sortilin levels in our final multivariate model. In conclusion, the results suggest a role of circulating sortilin in depression which may relate...

  9. Identification and in vitro characterization of phage-displayed VHHs targeting VEGF

    DEFF Research Database (Denmark)

    Farajpour, Zahra; Rahbarizadeh, Fatemeh; Kazemi, Bahram;

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a potential target for cancer treatment because of its role in angiogenesis and its overexpression in most human cancers. Currently, anti-VEGF antibodies have been shown to be promising tools for therapeutic applications. However, large size, poor tumor......-targeting purposes. The present study was undertaken to generate and characterize anti-VEGF VHHs from an immune VHH library using phage display. Four rounds of panning were performed, and selected VHHs were characterized using various immunological techniques. Assessment of the antigenic profile of VHHs was done......, significantly inhibited the endothelial cell growth in a dose-dependent manner. Taken together, our results indicate that ZFR-5 and other VHHs may be promising tools in cancer research and treatment....

  10. Changes in neurophysiologic markers of visual processing following beneficial anti-VEGF treatment in macular degeneration

    Directory of Open Access Journals (Sweden)

    Vottonen P

    2013-02-01

    Full Text Available Pasi Vottonen,1 Kai Kaarniranta,1,2 Ari Pääkkönen,3 Ina M Tarkka41Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland; 2Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; 3Department of Clinical Neurophysiology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; 4Department of Health Sciences, University of Jyväskylä, Jyväskylä, FinlandPurpose: Antivascular endothelial growth factor (VEGF agents have been shown to improve visual acuity and prevent vision loss in exudative age-related macular degeneration. As the vision improves relatively quickly in response to intravitreal injections, we wanted to know whether this improvement is reflected in electrophysiological markers of visual cortical processing.Patients and methods: Our interventional case series included six elderly patients who underwent injection treatment to the affected eye. Their visual acuity, tomographic images of retinal thickness, and visual evoked potentials (VEP were assessed before treatment and six weeks after the last injection.Results: All patients showed improved visual acuity and reduced retinal fluid after the treatment. All but one patient showed increased VEP P100 component amplitudes and/or shortened latencies in the treated eye. These VEP changes were consistent with improved vision while the untreated eyes showed no changes.Conclusions: Our results indicate that antivascular endothelial growth factor injections improved visual function of the treated eyes both in the level of the retina and in the level of visual cortical processing.Keywords: age-related eye diseases, exudative age-related macular degeneration, visual evoked potentials, scalp-recorded EEG, visual acuity

  11. Association of mast cell-derived VEGF and proteases in Dengue shock syndrome.

    Directory of Open Access Journals (Sweden)

    Takahisa Furuta

    Full Text Available BACKGROUND: Recent in-vitro studies have suggested that mast cells are involved in Dengue virus infection. To clarify the role of mast cells in the development of clinical Dengue fever, we compared the plasma levels of several mast cell-derived mediators (vascular endothelial cell growth factor [VEGF], soluble VEGF receptors [sVEGFRs], tryptase, and chymase and -related cytokines (IL-4, -9, and -17 between patients with differing severity of Dengue fever and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: The study was performed at Children's Hospital No. 2, Ho Chi Minh City, and Vinh Long Province Hospital, Vietnam from 2002 to 2005. Study patients included 103 with Dengue fever (DF, Dengue hemorrhagic fever (DHF, and Dengue shock syndrome (DSS, as diagnosed by the World Health Organization criteria. There were 189 healthy subjects, and 19 febrile illness patients of the same Kinh ethnicity. The levels of mast cell-derived mediators and -related cytokines in plasma were measured by ELISA. VEGF and sVEGFR-1 levels were significantly increased in DHF and DSS compared with those of DF and controls, whereas sVEGFR-2 levels were significantly decreased in DHF and DSS. Significant increases in tryptase and chymase levels, which were accompanied by high IL-9 and -17 concentrations, were detected in DHF and DSS patients. By day 4 of admission, VEGF, sVEGFRs, and proteases levels had returned to similar levels as DF and controls. In-vitro VEGF production by mast cells was examined in KU812 and HMC-1 cells, and was found to be highest when the cells were inoculated with Dengue virus and human Dengue virus-immune serum in the presence of IL-9. CONCLUSIONS: As mast cells are an important source of VEGF, tryptase, and chymase, our findings suggest that mast cell activation and mast cell-derived mediators participate in the development of DHF. The two proteases, particularly chymase, might serve as good predictive markers of Dengue disease severity.

  12. P70S6K 1 regulation of angiogenesis through VEGF and HIF-1{alpha} expression

    Energy Technology Data Exchange (ETDEWEB)

    Bian, Chuan-Xiu; Shi, Zhumei [Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing 210029 (China); Meng, Qiao; Jiang, Yue; Liu, Ling-Zhi [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jiang, Bing-Hua, E-mail: binghjiang@yahoo.com [Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing 210029 (China); Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States)

    2010-07-30

    Research highlights: {yields} P70S6K1 regulates VEGF expression; {yields} P70S6K1 induces transcriptional activation through HIF-1{alpha} binding site; {yields} P70S6K1 regulates HIF-1{alpha}, but not HIF-1{beta} protein expression; {yields} P70S6K1 mediates tumor growth and angiogenesis through HIF-1{alpha} and VEGF expression. -- Abstract: The 70 kDa ribosomal S6 kinase 1 (p70S6K1), a downstream target of phosphoinositide 3-kinase (PI3K) and ERK mitogen-activated protein kinase (MAPK), is an important regulator of cell cycle progression, and cell proliferation. Recent studies indicated an important role of p70S6K1 in PTEN-negative and AKT-overexpressing tumors. However, the mechanism of p70S6K1 in tumor angiogenesis remains to be elucidated. In this study, we specifically inhibited p70S6K1 activity in ovarian cancer cells using vector-based small interfering RNA (siRNA) against p70S6K1. We found that knockdown of p70S6K1 significantly decreased VEGF protein expression and VEGF transcriptional activation through the HIF-1{alpha} binding site at its enhancer region. The expression of p70S6K1 siRNA specifically inhibited HIF-1{alpha}, but not HIF-1{beta} protein expression. We also found that p70S6K1 down-regulation inhibited ovarian tumor growth and angiogenesis, and decreased cell proliferation and levels of VEGF and HIF-1{alpha} expression in tumor tissues. Our results suggest that p70S6K1 is required for tumor growth and angiogenesis through HIF-1{alpha} and VEGF expression, providing a molecular mechanism of human ovarian cancer mediated by p70S6K1 signaling.

  13. Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration.

    Science.gov (United States)

    Finger, Robert P; Wickremasinghe, Sanjeewa S; Baird, Paul N; Guymer, Robyn H

    2014-01-01

    Currently available evidence on predictors of anti-vascular endothelial growth factor (VEGF) treatment response in neovascular age-related macular degeneration was reviewed. No meta-analysis of results is possible because of a lack of controlled and randomized trials, varying treatment regimes and outcome measures used, as well as suboptimal reporting. For genetic factors, most evidence to date has been generated for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), and VEGF-A genes. Just under half of the SNPs assessed in the CFH gene and 15% of the SNPs assessed in the VEGF gene were found to be associated with visual outcomes or the number of injections required during follow-up. Some evidence suggests association of worse treatment outcomes as well as a younger age at treatment onset with an increasing number of risk alleles in known risk genes (CFH and ARMS2/HTRA1) and polymorphisms in the VEGF-A gene. Clinical factors such as higher age, a better visual acuity (VA), a larger choroidal neovascularization (CNV) lesion at baseline, and a delay between symptom onset and initiation of treatment of more than 3 weeks also impact outcomes. Conversely, a worse acuity at baseline predicted more gain in vision. Overall, patients presenting with good acuity at baseline were more likely to have good VA at follow up, but the gain afforded by treatment was impacted by a ceiling effect. Most available evidence suggests a strong association of clinical factors such as age, baseline VA, and CNV lesion size with anti-VEGF treatment outcomes. No behavioral factors such as smoking influence treatment outcomes. Based on the studies conducted so far, the evidence suggests that underlying genotype of known AMD risk associated genes or of the VEGF-A gene have a limited effect, whereas presenting clinical factors appear to be more important in determining treatment outcomes.

  14. Prognosis of invasive breast cancer after adjuvant therapy evaluated with VEGF microvessel density and microvascular imaging.

    Science.gov (United States)

    Li, Ying; Wei, Xi; Zhang, Sheng; Zhang, Jin

    2015-11-01

    The aim of this study was to investigate the role of ultrasonographic microvascular imaging in the evaluation of prognosis of patients with invasive breast cancer treated by adjuvant therapies. A total of 121 patients with invasive breast cancer underwent ultrasonographic contrast-enhanced imaging, vascular endothelial growth factor (VEGF) staining, and microvessel density (MVD) counts. The parameters of microvascular imaging and the expression of VEGF and MVD in primary breast cancer were calculated. The correlation between these factors and the overall and progression-free survival rate were analyzed using the Kaplan-Meier method. Among 121 cases, the positive VEGF cases were 75 and negative ones were 46. The cut point of 52.3 was calculated by the regressive curve for MVD counts. The data showed the mean intensity (MI) was positively associated with both the MVD counts (r = .51, p prognosis of patients, high VEGF expression and MVD counts were associated with reduced progressive and survival times (PFS, p = .032 and p = .034; OS, p = .041 and p = .038, respectively). The correlation between parameters of microvascular imaging, VEGF expressive status, and the MVD counts were established. The cut point of mean intensity (MI = 40) was used to investigate as an independent predictor for PFS (p = .021) and OS (p = .025), respectively, due to a strong correlation between MVD counts and VEGF expression in patients with invasive breast cancer. The microvascular imaging could be a visual and helpful tool to predict the prognosis of patients with invasive breast cancer treated by adjuvant therapies.

  15. Extracellular matrix stiffness modulates VEGF calcium signaling in endothelial cells: individual cell and population analysis.

    Science.gov (United States)

    Derricks, Kelsey E; Trinkaus-Randall, Vickery; Nugent, Matthew A

    2015-09-01

    Vascular disease and its associated complications are the number one cause of death in the Western world. Both extracellular matrix stiffening and dysfunctional endothelial cells contribute to vascular disease. We examined endothelial cell calcium signaling in response to VEGF as a function of extracellular matrix stiffness. We developed a new analytical tool to analyze both population based and individual cell responses. Endothelial cells on soft substrates, 4 kPa, were the most responsive to VEGF, whereas cells on the 125 kPa substrates exhibited an attenuated response. Magnitude of activation, not the quantity of cells responding or the number of local maximums each cell experienced distinguished the responses. Individual cell analysis, across all treatments, identified two unique cell clusters. One cluster, containing most of the cells, exhibited minimal or slow calcium release. The remaining cell cluster had a rapid, high magnitude VEGF activation that ultimately defined the population based average calcium response. Interestingly, at low doses of VEGF, the high responding cell cluster contained smaller cells on average, suggesting that cell shape and size may be indicative of VEGF-sensitive endothelial cells. This study provides a new analytical tool to quantitatively analyze individual cell signaling response kinetics, that we have used to help uncover outcomes that are hidden within the average. The ability to selectively identify highly VEGF responsive cells within a population may lead to a better understanding of the specific phenotypic characteristics that define cell responsiveness, which could provide new insight for the development of targeted anti- and pro-angiogenic therapies.

  16. Angiogenetic axis angiopoietins/Tie2 and VEGF in familial breast cancer.

    Science.gov (United States)

    Danza, K; Pilato, B; Lacalamita, R; Addati, T; Giotta, F; Bruno, A; Paradiso, A; Tommasi, S

    2013-08-01

    Angiogenesis leads to the formation of blood vessels from pre-existing ones, allowing tumor growth. Vascular endothelial growth factor (VEGF) and Angiopoietins (Ang-1, Ang-2) have a pivotal role in tumor angiogenesis but few data regarding their role in hereditary breast cancer are available. The aim of the present study was to analyze Ang-1, Ang-2, tyrosine-protein kinase receptor Tie2 and VEGF expression and their correlation in a cohort of familial and sporadic breast cancers in order to verify whether the presence of germline mutations in BRCA may have a role in tumor microenvironment regulation. Tumor samples from a cohort of 41 patients with a first diagnosis and a family history of breast cancer and 19 patients with sporadic breast cancers were enrolled. The expression of Tie2, Ang-1, Ang-2 and VEGF were analyzed by quantitative real-time PCR. Patients harboring BRCA mutations had higher levels of Ang-1 (P=0.05), Ang-2 (P=0.02) and VEGF (P=0.04) mRNA compared with those without BRCA mutations (BRCAX). The same was observed in triple-negative breast cancer (TNBC). Moreover, a positive correlation between Ang-2 and VEGF was found in both the familial breast cancer group (BRCA carriers: r=0.83; P<0.0001 and BRCAX: r=0.58; P=0.008) and in TNBC (r=0.62; P=0.007). The higher levels of Ang-1, Ang-2 and VEGF mRNA found in BRCA carriers and TNBCs suggest that they could be attractive angiogenic therapeutic targets in these breast cancers.

  17. mRNA EXPRESSION OF PTEN AND VEGF GENES IN EPITHELIAL OVARIAN CANCER

    Institute of Scientific and Technical Information of China (English)

    陈颖; 赵雨杰; 郑华川; 杨雪飞; 汪桂兰; 辛彦

    2003-01-01

    Objective: To investigate the mRNA expression of PTEN and vascular endothelial growth factor (VEGF) genes in ovarian cancer. Methods:We examined mRNA expression of PTEN and VEGF165 in normal ovary (n=5), ovarian cyst (n=5), ovarian borderline tumor (n=9), epithelial ovarian cancer (n=60) and ovarian cancer cell line (CAOV-3) by RT-PCR. Their expressions were compared with clinicopathological features of ovarian cancer. The relationship between their expressions was concerned in all ovarian samples as well. Results:mRNA expression level of PTEN gene was significantly lower in ovarian borderline tumor or ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was negatively correlated with clinicopathological staging(P<0.05),whereas positively with histological differentiation (P<0.05). mRNA expression level of PTEN gene was significantly lower in ovarian endometrioid cancer than ovarian serous or mucinous cancer(P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian cancer than that in normal ovary or ovarian cyst(P<0.05). It was positively correlated with clinicopathological staging(P<0.05), whereas negatively with histological differentiation (P<0.05). mRNA expression level of VEGF165 gene was significantly higher in ovarian serous cancer than in other ovarian epithelial cancers (P<0.05). mRNA expression of VEGF165 gene was inversely correlated with mRNA expression level of PTEN gene. Conclusion:Down-regulated expression of PTEN and up-regulated expression of VEGF were considered as two important events in tumorigenesis of ovarian cancer and could be used as molecular markers to indicate the pathobiological behaviors of ovarian cancer. Decreased PTEN expression and increased VEGF expression were closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid and serous cancer respectively. Reduced expression of PTEN gene might be involved in carcinogenesis and progression of ovarian cancer by

  18. Penduliflaworosin, a Diterpenoid from Croton crassifolius, Exerts Anti-Angiogenic Effect via VEGF Receptor-2 Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Yeyin Liang

    2017-01-01

    Full Text Available Anti-angiogenesis targeting vascular endothelial growth factor receptor-2 (VEGFR-2 has been considered as an important strategy for cancer therapy. Penduliflaworosin is a diterpenoid isolated from the plant Croton crassifolius. Our previous study showed that this diterpenoid possesses strong anti-angiogenic activity by inhibiting vessel formation in zebrafish. This study was conducted to further investigate the anti-angiogenic activity and mechanism of penduliflaworosin. Results revealed that penduliflaworosin significantly inhibited VEGF-induced angiogenesis processes including proliferation, invasion, migration, and tube formation of human umbilical vein endothelial cells (HUVECs. Moreover, it notably inhibited VEGF-induced sprout formation of aortic rings and blocked VEGF-induced vessel formation in mice. Western blotting studies showed that penduliflaworosin inhibited phosphorylation of the VEGF receptor-2 and its downstream signaling mediators in HUVECs, suggesting that the anti-angiogenic activity was due to an interference with the VEGF/VEGF receptor-2 pathway. In addition, molecular docking simulation indicated that penduliflaworosin could form hydrogen bonds within the ATP-binding region of the VEGF receptor-2 kinase unit. Finally, cytotoxicity assay showed that penduliflaworosin possessed little toxicity toward both cancer and normal cells. Taken together, our findings demonstrate that penduliflaworosin exerts its anti-angiogenic effect via the VEGF receptor-2 signaling pathway. The anti-angiogenic property and low cytotoxicity of penduliflaworosin suggest that it may be useful in cancer treatments.

  19. Cloning, large-scale production, and purification of active dimeric rat vascular endothelial growth factor (rrVEGF-164).

    NARCIS (Netherlands)

    Geutjes, P.J.; Nillesen, S.T.M.; Lammers, G.; Daamen, W.F.; Kuppevelt, A.H.M.S.M. van

    2010-01-01

    Large-scale production of recombinant rat vascular endothelial growth factor (rrVEGF-164) is desirable for angiogenic studies. In this study, biologically active recombinant rat vascular endothelial growth factor (rrVEGF-164) was cloned and expressed in the yeast Pichia pastoris, and large-scale pro

  20. A HUVEC line with a stable expression of the VEGF121 gene to achieve complete endothelialization of blood conduits.

    Science.gov (United States)

    Liu, L-S; Wei, D-H; Tang, C-K; Wang, G-X; Zhang, S-C; Yin, W-D; Yang, Y-Z; Legrand, A-P; Guidoin, R

    2007-01-01

    The purpose of this investigation was to establish monoclonal cell lines of HUVEC with the stable expression of the VEGF(121) gene. Such cells are likely to better adhere to the luminal surface of stents or grafts and to promote a complete endothelialization. The eukaryotic expression vector PCD(2)-VEGF(121) was transfected into cell lines of HUVEC mediated by lipofect AMINE. The positive clones were obtained by the screening of G(418). The transcription and expression of the VEGF gene were investigated by RT-PCR and immunocytochemistry, respectively. The experiment of Miles was applied for the assay of the biological activity of the protein of the VEGF produced by the HUVEC lines with transfected PCD(2)-VEGF(121). The growth curve was made for comparison with that of non-transfected HUVEC line cells. The positive clone cells from which transcripted the mRNA of VEGF(121) gene were obtained by RT-PCR. The positive results of the immunocytochemistry were found and the high biological activity of VEGF in the media was detected in the positive clone cells only. The time to achieve the multiplication of the positive clone cells by a factor of 2 was shorter than that of the non-transfected HUVEC line calculated from the growth curve. The HUVEC line of monoclonal cells with the stable expression of VEGF(121) gene has been established successfully and can be employed on the luminal surfaces of foreign blood conduits.

  1. Bone marrow stromal cells with a combined expression of BMP-2 and VEGF-165 enhanced bone regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Xiao Caiwen; Zhou Huifang; Fu Yao; Gu Ping; Fan Xianqun [Department of Ophthalmology, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Liu Guangpeng [Key Laboratory of Tissue Engineering, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China); Zhang Peng [Center for Translational Medicine Research and Development, Shenzhen Institute of Advanced Technology, Chinese Academy of Science (China); Hou Hongliang; Tang Tingting, E-mail: drfanxianqun@126.com [Department of Orthopedics, Shanghai Ninth People' s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200011 (China)

    2011-02-15

    Bone graft substitutes with osteogenic factors alone often exhibit poor bone regeneration due to inadequate vascularization. Combined delivery of osteogenic and angiogenic factors from biodegradable scaffolds may enhance bone regeneration. We evaluated the effects of bone morphogenetic protein 2 (BMP2) and vascular endothelial growth factor (VEGF), combined with natural coral scaffolds, on the repair of critical-sized bone defects in rabbit orbits. In vitro expanded rabbit bone marrow stromal cells (BMSCs) were transfected with human BMP2 and VEGF165 genes. Target protein expression and osteogenic differentiation were confirmed after gene transduction. Rabbit orbital defects were treated with a coral scaffold loaded with BMP2-transduced and VEGF-transduced BMSCs, BMP2-expressing BMSCs, VEGF-expressing BMSCs, or BMSCs without gene transduction. Volume and density of regenerated bone were determined by micro-computed tomography at 4, 8, and 16 weeks after implantation. Neovascularity, new bone deposition rate, and new bone formation were measured by immunostaining, tetracycline and calcein labelling, and histomorphometric analysis at different time points. The results showed that VEGF increased blood vessel formation relative to groups without VEGF. Combined delivery of BMP2 and VEGF increased new bone deposition and formation, compared with any single factor. These findings indicate that mimicking the natural bone development process by combined BMP2 and VEGF delivery improves healing of critical-sized orbital defects in rabbits.

  2. Proteasome inhibitor MG-132 regulates the expression of VEGF in human bronchial epithelial cell line, BEAS-2B

    Institute of Scientific and Technical Information of China (English)

    Xuefan Cui; Kaisheng Yin; Mao Huang; Linfu Zhou

    2005-01-01

    Objective: To explore the effects of MG-132 on the expression of VEGF in bronchial epithelial cell line, BEAS2B. Methods: Semi-quantitive RT-PCR for VEGF mRNA and enzyme-linked immunosorbent assay (ELISA) for VEGF protein were performed. Results: MG-132 increased the expression of VEGF mRNA and protein BEAS-2B cells in time-and concentration-dependent manners. After 24-h stimulation, 25 μmol/L MG-132 increased the maximal levels of VEGF protein in cell-conditioned medium. When the cells were stimulated with cycloheximide(CHX) before treatment with MG-132, the MG-132-induced production of VEGF protein was inhibited compared to the unstimulated cells. Supernatant of condition-medium treatment with MG-132 enhanced the growth of HUVEC.Conclusion: MG-132 induces VEGF gene expression in human bronchial epithelial cells line, BEAS-2B, and the MG-132-induced expression of VEGF may modulate lung tissue injury due to airway inflammation.

  3. Vascular endothelial growth factor C (VEGF-C in esophageal cancer correlates with lymph node metastasis and poor patient prognosis

    Directory of Open Access Journals (Sweden)

    Naganawa Yasuhiro

    2010-06-01

    Full Text Available Abstract Background The diagnosis of lymph node metastasis in esophageal cancer by the presence and number of metastatic lymph nodes is an extremely important prognostic factor. In addition, the indication of non-surgical therapy is gaining more attention. Vascular endothelial growth factor C (VEGF-C is potentially lymphangiogenic and selectively induces hyperplasia of the lymphatic vasculature. In this study, we investigated the expression of VEGF-C and whether it correlated with various clinico-pathologic findings. Methods KYSE series of esophageal cancer cell lines and 106 patients with primary esophageal squamous cell carcinomas who had undergone radical esophagectomy were analyzed. VEGF-C mRNA expression was determined by quantitative RT-PCR. Results High expression of VEGF-C was detected in most of the KYSE cell lines, especially KYSE410, yet, in an esophageal normal epithelium cell line, Het-1A, VEGF-C was not detected. In the clinical specimen, the expression of VEGF-C in the cancerous tissue was higher than in the corresponding noncancerous esophageal mucosa (p = 0.026. The expression of VEGF-C was found to be higher in Stage2B-4A tumors than in Stage0-2A tumors (p = 0.049. When the patients were divided into two groups according to their expression levels of VEGF-C (a group of 53 cases with high expression and a group of 53 cases with low expression, the patients with high VEGF-C expression had significantly shorter survival after surgery than the patients with low expression (p = 0.0065. Although univariate analysis showed that high expression of VEGF-C was a statistically significant prognostic factor, this was not shown in multivariate analysis. In the subgroup of patients with Tis and T1 tumors, the expression of VEGF-C was higher in N1 tumors than in N0 tumors (p = 0.029. The survival rate of patients from the high expression group (n = 10 was lower than that in the low expression group (n = 11, and all the patients in the low

  4. Inhibitory effect of extracts of Ginkgo biloba leaves on VEGF-induced hyperpermeability of bovine coronary endothelial cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Yan QIU; Yao-cheng RUI; Tie-jun LI; Li ZHANG; Peng-yuan YANG

    2004-01-01

    AIM: To study whether extract of Ginkgo biloba (EGb) can protect against atherosclerosis. METHODS: Confluent monolayers of bovine coronary endothelial cells (BCECs), bovine coronary smooth muscle cells (BCSMCs), and cocultures of the two were incubated with medium containing VEGF and/or EGb, and flux of 125Ⅰ-labeled oxidized low density lipoprotein (ox-LDL) across the monolayers was measured. RESULTS: Incubation with VEGF significantly increased the permeability of BCEC monolayers to 125Ⅰ-ox-LDL in a time- and concentration-dependent manner, but had no effect on permeability of BCSMCs or endothelial cells-smooth muscle cells cocultures. EGb significantly inhibited the VEGF-induced hyperpermeability of BCECs. CONCLUSION: VEGF was important in the formation and development of atherosclerosis. The inhibition of VEGF-induced permeability by EGb suggests that extracts of Ginkgo biloba leaves may have important clinical applications in the treatment of cardiovascular diseases.

  5. Quantitative assessment of first-pass perfusion using a low-dose method at multidetector CT in oesophageal squamous cell carcinoma: Correlation with VEGF expression

    Energy Technology Data Exchange (ETDEWEB)

    Chen, T.-W. [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China) and Sichuan Province Key Laboratory of Medical Imaging and Department of Radiology, Affiliated Hospital of North Sichuan Medical College, 63 Wen Hua Lu, Nanchong, Sichuan 637000 (China); Yang, Z.-G., E-mail: yangzg1117@yahoo.com.cn [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Chen, H.-J. [Department of Pathology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); Li, Y.; Tang, S.-S.; Yao, J.; Dong, Z.-H. [Department of Radiology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China); He, D. [Department of Pathology, West China Hospital of Sichuan University, 37 Guo Xue Xiang, Chengdu, Sichuan 610041 (China)

    2012-08-15

    Aim: To investigate the correlation between vascular endothelial cell growth factor (VEGF) expression and first-pass perfusion parameters at multidetector computed tomography (MDCT) using a low-dose technique, and to determine how to discriminate VEGF positivity from VEGF negativity by perfusion CT in oesophageal squamous cell carcinomas. Materials and methods: Thirty-two patients with oesophageal squamous cell carcinomas underwent first-pass perfusion with 64-section MDCT at 50 mAs. Perfusion parameters, including perfusion, peak enhanced density (PED), time to peak (TTP), and blood volume (BV), were measured. Postoperative specimens were assessed for VEGF expression. Correlation tests were performed to determine the associations between each CT perfusion parameter and VEGF expression. The cut-off values of perfusion parameters were obtained statistically to discriminate VEGF positivity from VEGF negativity. Results: Mean perfusion, PED, TTP, and BV were 38.47 {+-} 30.26 ml/min/ml, 24.68 {+-} 9.65 HU, 28.35 {+-} 9.03 s, and 11.82 {+-} 6.06 ml/100 g, respectively. PED or BV were significantly higher in the VEGF-positive group than in the VEGF-negative group (all p < 0.05), but no significant difference in perfusion or TTP was found between the VEGF-positive and VEGF-negative groups (all p > 0.05). In VEGF positivity, PED and BV were correlated with VEGF expression (r = 0.576 and 0.765, respectively; all p < 0.05), whereas perfusion and TTP were not (r = 0.361 and 0.239, respectively; all p > 0.05). A threshold of BV (10.23 ml/100 g) achieved a sensitivity of 94.4%, and a specificity of 92.9% for discriminating VEGF positivity from VEGF negativity. Conclusion: BV could reflect tumour VEGF expression, and could be an indicator for evaluating angiogenesis in oesophageal tumours.

  6. Experimental Study of Adenovirus Vector Mediated-hVEGF165 Gene on Prevention of Restenosis after Angioplasty

    Institute of Scientific and Technical Information of China (English)

    刘启功; 陆再英; 岳远坤; 林立; 张卫东; 颜进

    2004-01-01

    This study evaluated the effects of adenovirus vector mediated human vascular endothelial growth factor-165 (hVEGF165) gene on prevention of restenosis after angioplasty. Rabbit models of bilateral carotid artery injury were established by balloon denudation. The recombinant adenoviruses containing hVEGF165 cDNA was directly injected into left side of the injured carotid arteries.On day 3 and week 3 after transfection the expression of VEGF was observed by RT-PCR and immunohistochemistry. The thrombokinesis, reendothelialization (rET) and intimal hyperplasia in carotid arteries were evaluated by computerized image analysis system 3 weeks after gene transfer.The changes in the VEGF gene-treated side were compared with the control side. Our results showed that 3 days and 3 weeks after hVEGF165 gene transfer the VEGF mRNA and antigen expression were detected in vivo. 3 weeks after the transfer, the carotid artery rET was markedly better in the VEGF gene-treated group compared with the control. The thrombokinesis, intima area/media area (I/M), maximal intimal and medial thicknesses (ITmax and MTmax) demonstrated a statistically significant decrease in arteries treated with VEGF gene as compared with the control group. It is concluded that VEGF gene transfer could be achieved by intra-arterial injection of recombinant adenoviruses. It might accelerate the restoration of endothelial integrity, inhibit thrombokinesis and attenuate intimal hyperplasia in the injured arteries after VEGF gene transfer. This procedure could be useful in preventing restenosis after angioplasty.

  7. VEGF siRNA致中国仓鼠肺细胞染色体畸变的研究%Research of chromosome aberration in Chinese hamster lung fibroblast induced by VEGF siRNA

    Institute of Scientific and Technical Information of China (English)

    荆春霞; 张洹; 杨光; 吴赤蓬; 何林

    2011-01-01

    Objective To explore the effects of VECF siRNA on chromosome aberration in Chinese hamster lung fibroblasts (CHL). Methods The chromosome aberrations were observed after CHL were transfected with VECF siRNA for 24 hours and 48h. Results There were a questionable positive in 100nmol/L VEGF siRNA after VECF siRNA were transfected for 24h and the chromosome aberration rate was 6 percentages. Both 50nmol/L VEGF siRNA and 100nmol/L VECF siRNA caused the questionable positive after VEGF siRNAs were transfected for 48h, and the chromosome aberration rates was 6 percentages and 10 percentages separately. There were no the chromosome aberration in 25nmol/L VEGF siRNA. The types of chromosomal aberration induced by VEGF siRNAs included break, Dicentric grain, polyploid, gap, and three trajectories. Conclusion lOOnmol/L VEGF siRNA might cause CHL chromosome aberration.%目的 研究VEGF siRNA对中国仓鼠肺细胞(CHL)的染色体畸变作用.方法 采用25、50和100nmol/L的VEGF siRNA转染中国仓鼠的肺细胞,分别观察24h、48h后的染色体畸变情况.结果 在VEGFsiRNA转染24小时,仅100nmol/L VEGF siRNA产生可疑阳性反应,其染色体的畸变率为6%;在VEGFsiRNA转染48小时后,50nmol/L的VEGF siRNA和100nmol/L的VEGF siRNA均产生可疑阳性反应,染色体的畸变率分别为6%和10%.而25nmol/L的VEGF siRNA无论是在转染后24h还是48h,均未产生染色体的畸变作用.VEGF siRNA产生的染色体畸变类型有断裂、双着丝粒、多倍体、裂隙、三射体.结论 100nmol/L的VEGFsiRNA分子可引起CHL细胞产生染色体畸变.

  8. The VEGF pathway and the AKT/mTOR/p70S6K1 signalling pathway in human epithelial ovarian cancer

    NARCIS (Netherlands)

    X.B. Trinh; W.A.A. Tjalma; P.B. Vermeulen; G. van den Eynden; I. van der Auwera; S.J. van Laere (Steven); J. Helleman (Jozien); P.M.J.J. Berns (Els); L.Y. Dirix (Luc); P.A. van Dam

    2009-01-01

    textabstractVascular endothelial growth factor (VEGF)-A inhibitors exhibit unseen high responses and toxicity in recurrent epithelial ovarian cancer suggesting an important role for the VEGF/VEGFR pathway. We studied the correlation of VEGF signalling and AKT/mTOR signalling. Using a tissue microarr

  9. VEGF-A immunohistochemical and mRNA expression in tissues and its serum levels in potentially malignant oral lesions and oral squamous cell carcinomas.

    Science.gov (United States)

    Nayak, Seema; Goel, Madhu Mati; Chandra, Saumya; Bhatia, Vikram; Mehrotra, Divya; Kumar, Sandeep; Makker, Annu; Rath, S K; Agarwal, S P

    2012-03-01

    The aim of the study was to investigate whether the estimation of circulating Vascular endothelial growth factor-A (VEGF-A) levels by ELISA could be used as surrogate of VEGF-A expression in tissues of pre-malignant oral lesions (PMOLs) and oral squamous cell carcinoma (OSCC) as compared to that in healthy controls. The study samples comprised of tissue and blood samples from 60 PMOLs, 60 OSCC, and 20 healthy controls. Serum VEGF-A levels were determined by an ELISA based assay (Quantikine human VEGF; R & D System, Minneapolis USA). Tissue VEGF-A expression and microvessel density (MVD) were assessed by immunohistochemistry (IHC) using antibodies against VEGF-A and CD-34 on formalin fixed paraffin embedded (FFPE) tissue sections. VEGF-A mRNA expression was analyzed by real-time PCR in snap frozen tissues. Serum VEGF-A levels and immunohistochemical VEGF-A expression were significantly high in PMOLs and OSCC in comparison with controls. VEGF mRNA gene expression showed more than 50-fold increase in PMOLs and OSCC. VEGF-A levels in serum correlated in a linear fashion with the tissue expression in oral pre-malignant and malignant lesions, suggesting that the serum levels may serve as surrogate material for tissue expression of VEGF-A.

  10. K20E, an oxidative-coupling compound of methyl caffeate, exhibits anti-angiogenic activities through down-regulations of VEGF and VEGF receptor-2

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Chun-Hsu [Department of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan (China); Lin, Wen-Hsin; Chien, Yi-Chung; Liu, Fon-Chang; Sheu, Ming-Jyh [School of Pharmacy, China Medical University, Taichung 40402, Taiwan (China); Kuo, Yueh-Hsiung, E-mail: kuoyh@mail.cmu.edu.tw [Tsuzuki Institute for Traditional Medicine, China Medical University, Taichung 40402, Taiwan (China); Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan (China); Department of Biotechnology, Asia University, Taichung 41354, Taiwan (China); Wu, Chieh-Hsi, E-mail: chhswu@tmu.edu.tw [Department of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan (China); School of Pharmacy, China Medical University, Taichung 40402, Taiwan (China); Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan (China)

    2015-01-15

    Anti-angiogenesis is one of the most popular clinical interventions for cancer chemotherapy. A series of synthesized derivative of methyl caffeate were used to evaluate the anti-angiogenic activity and to investigate possible pharmacological mechanisms in the present study. The most potent anti-angiogenic compound was evaluated in the experiments of murine allograft tumor model and Matrigel plug assay as well as cell models in the human umbilical vascular endothelial cells (HUVECs) and the LLC1 lung cancer cells. Our results suggested that K20E suppressed the tumor growth in the allograft tumor model and exhibited anti-angiogenic activity in Matrigel plug assay. Besides, HUVEC viability was found to be significantly reduced by arresting cell cycle at G{sub 2}/M phase and apoptosis. Cell migration, invasion, and tube formation of the HUVECs were also markedly suppressed by K20E treatment. K20E largely down-regulated the intracellular and secreted vascular endothelial growth factor (VEGF) in the LLC1 cancer cells. Besides, VEGF receptor-2 (VEGFR-2) and its downstream signaling cascades (AKT-mTOR and MEK1/2-ERK1/2) as well as gelatinases were all evidently reduced in the HUVECs treated with K20E. Inversely, K20E can up-regulate the expression levels of p53 and p21 proteins in the HUVECs. Based on these results, our study suggested that K20E possessed inhibiting angiogenesis through regulation of VEGF/VEGFR-2 and its downstream signaling cascades in the vascular endothelial cells (VECs). - Highlights: • K20E is an oxidative-coupling compound of methyl caffeate. • K20E exhibits anti-tumor and anti-angiogenesis effects. • K20E suppresses the expressions of VEGF and VEGF receptor-2 (VEGFR-2) proteins. • K20E deactivates VEGFR-2-mediated downstream signaling pathways to inhibit angiogenesis. • K20E up-regulates p53-p21 pathway to induce apoptosis and cell arrest at G2/M phase.

  11. Three-dimensional growth as multicellular spheroid activates the proangiogenic phenotype of colorectal carcinoma cells via LFA-1-dependent VEGF: implications on hepatic micrometastasis

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    Muruzabal Francisco J

    2008-10-01

    Full Text Available Abstract Background The recruitment of vascular stromal and endothelial cells is an early event occurring during cancer cell growth at premetastatic niches, but how the microenvironment created by the initial three-dimensional (3D growth of cancer cells affects their angiogenesis-stimulating potential is unclear. Methods The proangiogenic profile of CT26 murine colorectal carcinoma cells was studied in seven-day cultured 3D-spheroids of Results Spheroid-derived CT26 cells increased vascular endothelial growth factor (VEGF secretion by 70%, which in turn increased the in vitro migration of primary cultured hepatic sinusoidal endothelium (HSE cells by 2-fold. More importantly, spheroid-derived CT26 cells increased lymphocyte function associated antigen (LFA-1-expressing cell fraction by 3-fold; and soluble intercellular adhesion molecule (ICAM-1, given to spheroid-cultured CT26 cells, further increased VEGF secretion by 90%, via cyclooxygenase (COX-2-dependent mechanism. Consistent with these findings, CT26 cancer cells significantly increased LFA-1 expression in non-hypoxic avascular micrometastases at their earliest inception within hepatic lobules in vivo; and angiogenesis also markedly increased in both subcutaneous tumors and hepatic metastases produced by spheroid-derived CT26 cells. Conclusion 3D-growth per se enriched the proangiogenic phenotype of cancer cells growing as multicellular spheroids or as subclinical hepatic micrometastases. The contribution of integrin LFA-1 to VEGF secretion via COX-2 was a micro environmental-related mechanism leading to the pro-angiogenic activation of soluble ICAM-1-activated colorectal carcinoma cells. This mechanism may represent a new target for specific therapeutic strategies designed to block colorectal cancer cell growth at a subclinical micrometastatic stage within the liver.

  12. High Expression of HIF1a Is a Predictor of Clinical Outcome in Patients with Pancreatic Ductal Adenocarcinomas and Correlated to PDGFA, VEGF, and bFGF

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    Andreas-Claudius Hoffmann

    2008-07-01

    Full Text Available PURPOSE: Pancreatic cancer still has one of the worst prognoses in gastrointestinal cancers with a 5-year survival rate of 5%, making it necessary to find markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens. In this study, we investigated the prognostic values of HIF1a, bFGF, VEGF, and PDGFA gene expressions as well as their interrelationships. EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tissue samples were obtained from 41 patients with pancreatic adenocarcinoma (age, 65; range, 34–85 years. After laser capture microdissection, direct quantitative real-time reverse transcription-polymerase chain reaction assays were performed in triplicates to determine HIF1a, PDGFA, VEGF, and bFGF gene expression levels. Multivariate Cox proportional hazards regression analysis was used to assess the impact of HIF1a gene expression on prognosis. RESULTS:HIF1a was significantly correlated to every gene we tested: bFGF (P = .04, VEGF (P = .02, and PDGFA (P = .03. Tumor size, P = .04, and high HIF1a mRNA expression (cutoff, 75th percentile had a significant impact on survival, P = .009 (overall model fit, P = .02. High HIF1a expression had a sensitivity of 87.1% and a specificity of 55.6% for the diagnosis short (<6 months versus long (6–60 months survival. CONCLUSIONS: Measuring PDGFA, bFGF, and HIF1a expression may contribute to a better understanding of the prognosis of patients with pancreatic cancer and may even play a crucial role for the distribution of patients to multimodal therapeutic regimens. Larger studies including patients treated with actual chemotherapeutics seem to be warranted.

  13. Soluble forms of VEGF receptor-1 and -2 promote vascular maturation via mural cell recruitment.

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    Lorquet, Sophie; Berndt, Sarah; Blacher, Silvia; Gengoux, Emily; Peulen, Olivier; Maquoi, Erik; Noël, Agnès; Foidart, Jean-Michel; Munaut, Carine; Péqueux, Christel

    2010-10-01

    Two soluble forms of vascular endothelial growth factor (VEGF) receptors, sVEGFR-1 and sVEGFR-2, are physiologically released and overproduced in some pathologies. They are known to act as anti-VEGF agents. Here we report that these soluble receptors contribute to vessel maturation by mediating a dialogue between endothelial cells (ECs) and mural cells that leads to blood vessel stabilization. Through a multidisciplinary approach, we provide evidence that these soluble VEGF receptors promote mural cell migration through a paracrine mechanism involving interplay in ECs between VEGF/VEGFR-2 and sphingosine-1-phosphate type-1 (S1P)/S1P1 pathways that leads to endothelial nitric oxyde synthase (eNOS) activation. This new paradigm is supported by the finding that sVEGFR-1 and -2 perform the following actions: 1) induce an eNOS-dependent outgrowth of a mural cell network in an ex vivo model of angiogenesis, 2) increase the mural cell coverage of neovessels in vitro and in vivo, 3) promote mural cell migration toward ECs, and 4) stimulate endothelial S1P1 overproduction and eNOS activation that promote the migration and the recruitment of neighboring mural cells. These findings provide new insights into mechanisms regulating physiological and pathological angiogenesis and vessel stabilization.

  14. Immunolocalization of FGF-2 and VEGF in rat periodontal ligament during experimental tooth movement

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    Milene Freitas Lima Salomão

    2014-06-01

    Full Text Available OBJECTIVE: This article aimed at identifying the expression of fibroblast growth factor-2 (FGF-2 and vascular endothelial growth factor (VEGF in the tension and pressure areas of rat periodontal ligament, in different periods of experimental orthodontic tooth movement. METHODS: An orthodontic force of 0.5 N was applied to the upper right first molar of 18 male Wistar rats for periods of 3 (group I, 7 (group II and 14 days (group III. The counter-side first molar was used as a control. The animals were euthanized at the aforementioned time periods, and their maxillary bone was removed and fixed. After demineralization, the specimens were histologically processed and embedded in paraffin. FGF-2 and VEGF expressions were studied through immunohistochemistry and morphological analysis. RESULTS: The experimental side showed a higher expression of both FGF-2 and VEGF in all groups, when compared with the control side (P < 0.05. Statistically significant differences were also found between the tension and pressure areas in the experimental side. CONCLUSION: Both FGF-2 and VEGF are expressed in rat periodontal tissue. Additionally, these growth factors are upregulated when orthodontic forces are applied, thereby suggesting that they play an important role in changes that occur in periodontal tissue during orthodontic movement.

  15. The Increased Expression of Connexin and VEGF in Mouse Ovarian Tissue Vitrification by Follicle Stimulating Hormone

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    Yanzhou Yang

    2015-01-01

    Full Text Available Ovarian follicular damages were caused by cryoinjury during the process of ovarian vitrification and ischemia/reperfusion during the process of ovarian transplantation. And appropriate FSH plays an important role in antiapoptosis during ovarian follicle development. Therefore, in this study, 0.3 IU/mL FSH was administered into medium during mouse ovarian cryopreservation by vitrification to ascertain the function of FSH on ovarian vitrification and avascular transplantation. The results suggested that the expressions of Cx37, Cx43, apoptotic molecular caspase-3, and angiogenesis molecular VEGF were confirmed using immunohistochemistry, western blotting, and real-time PCR, and the results suggested that the treatment with FSH remarkably increased the number of morphologically normal follicles in vitrified/warmed ovaries by upregulating the expression of Cx37, Cx43, VEGF, and VEGF receptor 2, but downregulating the expression of caspase-3. In addition, the vitrified/warmed ovaries were transplanted, and the related fertility was analyzed, and the results suggested that the fertility, neoangiogenesis, and follicle reserve were remarkably increased in the FSH administrated group. Taken together, administration of 0.3 IU/mL FSH during ovarian cryopreservation by vitrification can maintain ovarian survival during ovarian vitrification and increases the blood supply with avascular transplantation via upregulation of Cx43, Cx37, and VEGF/VEGFR2, as well as through its antiapoptotic effects.

  16. Caveolin-1, caveolin-3 and VEGF expression in the masticatory muscles of mdx mice

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    Alexander Spassov

    2011-07-01

    Full Text Available Duchenne muscular dystrophy (DMD and murine X-linked muscular dystrophy (mdx, its murine model, are characterized by muscle damage and muscle weakness associated with inflammation and new vessel formation. Caveolins, dystrophin-associated proteins, are involved in the pathogenesis of DMD, because increased numbers of caveolae are found in DMD and mdx hindlimb muscles. Caveolae influence angiogenesis due to their content of vascular endothelial growth factor (VEGF receptors. Orofacial muscles in mdx mice undergo muscle necrosis followed by muscle regeneration. To ascertain the role of caveolins and VEGF in the pathogenesis of dystrophic masticatory muscles, we examined the expression of caveolin-1 (cav-1, caveolin-3 (cav-3 and VEGF in control and mdx mice. In mdx masticatory muscles, no changes in transcript and protein levels of VEGF were found, whereas cav-1 and cav-3 expression was increased. Using immunohistochemistry, a strong sarcolemmal staining of caveolin-3 in regenerated muscle fibers was found. Furthermore, immunohistochemistry with the caveolin-1 antibody showed an increase in the amount of blood vessels in areas with regenerating muscle fibers. Dystrophic masticatory muscles showed changes comparable to those of hindlimb muscles in the expression of cav-1 and cav-3. The angiogenesis seems to be unaffected in the jaw muscles of mdx mice. We speculate that the increased caveolin expression could cause extensive and efficient muscle regeneration. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 2, pp. 291–298

  17. Anthrax lethal toxin suppresses high glucose induced VEGF over secretion through a post-translational mechanism

    Institute of Scientific and Technical Information of China (English)

    Wei-Wei; Zhang; Xin; Wang; Ping; Xie; Song-Tao; Yuan; Qing-Huai; Liu

    2015-01-01

    AIM: To prove anthrax lethal toxin(Le Tx) blocks the mitogen activated protein kinases(MAPKs) activation by degrading the MAPK/ERK kinases(MEKs) to suppress vascular endothelial growth factor(VEGF) secretion.METHODS: Human adult retinal pigmented epithelium(ARPE) cells were cultured and treated with normal glucose, high glucose or high glucose with Le Tx for additional 24, 48 or 72 h for viable cell count. Total RNA from the ARPE was isolated for reverse transcription polymerase chain reaction(RT-PCR). The conditioned medium of ARPE cells treated in different group for 48 h was filtered and diluted to detect the concentration of VEGF by enzyme-linked immunosorbant assays.Evaluate the role of MEK/MAPK pathway in the secretion of VEGF by immunoblotting. RESULTS: In this study, we proved high glucose induced activation of the MAPK extracellular signal-regulated kinase(ERK1/2) and p38 in the ARPE cell line was blocked by anthrax Le Tx. Le Tx also inhibited high glucose induced ARPE cell over proliferation.CONCLUSION: Le Tx suppressed high glucose induced VEGF over secretion in the ARPE cells, mainly through a post-translational mechanism.

  18. Mapping of Fab-1:VEGF Interface Using Carboxyl Group Footprinting Mass Spectrometry

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    Wecksler, Aaron T.; Kalo, Matt S.; Deperalta, Galahad

    2015-12-01

    A proof-of-concept study was performed to demonstrate that carboxyl group footprinting, a relatively simple, bench-top method, has utility for first-pass analysis to determine epitope regions of therapeutic mAb:antigen complexes. The binding interface of vascular endothelial growth factor (VEGF) and the Fab portion of a neutralizing antibody (Fab-1) was analyzed using carboxyl group footprinting with glycine ethyl ester (GEE) labeling. Tryptic peptides involved in the binding interface between VEGF and Fab-1 were identified by determining the specific GEE-labeled residues that exhibited a reduction in the rate of labeling after complex formation. A significant reduction in the rate of GEE labeling was observed for E93 in the VEGF tryptic peptide V5, and D28 and E57 in the Fab-1 tryptic peptides HC2 and HC4, respectively. Results from the carboxyl group footprinting were compared with the binding interface identified from a previously characterized crystal structure (PDB: 1BJ1). All of these residues are located at the Fab-1:VEGF interface according to the crystal structure, demonstrating the potential utility of carboxyl group footprinting with GEE labeling for mapping epitopes.

  19. Effect of VEGF on Neural Differentiation of Human Embryonic Stem Cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Shujie JIAO; Huifang XU; Jie XU; Yanqiang ZHAN; Suming ZHANG

    2009-01-01

    The effects of vascular endothelial growth factor (VEGF) on neural differentiation of human embryonic stem cells (hESCs) in vitro and the possible mechanism were observed. The hESCs lines,TJMU1 and TJMU2, were established and stored by our laboratory, hESCs differentiated into neuronal cells through embryonic body formation. In this induction process, hESCs were divided into three groups: group A, routine induction; group B, routine induction+10 ng/mL VEGF; group C, routine in-duction+10 ng/mL VEGF+10 ng/mL VEGFR2/Fc. OCT4, Nestin and GFAP in each group were de-tected by RT-PCR, and the cells expressing Nestin and GFAP were counted by immunofluorescence.The percentage of Nestin positive cells in group B was significantly higher than in groups A and C,while the percentage of GFAP positive cells in group B was significantly lower than in groups A and C (P0.05). It was concluded that VEGF, via VEGFR2, stimulated the neural differentiation of hESCs in vitro.

  20. [VEGF--targeted therapy for the treatment of cervical cancer --literature review].

    Science.gov (United States)

    Salomon-Perzyńska, Magdalena; Perzyński, Aleksander; Rembielak-Stawecka, Beata; Michalski, Bogdan; Skrzypulec-Plinta, Violetta

    2014-06-01

    Cervical cancer is the third most common malignancy and the fourth leading cause of cancer-related death among women worldwide. Advances in the knowledge about molecular mechanisms of carcinogenesis have created opportunities for greater use of targeted therapies in contemporary oncology In view of the unsatisfactory results of advanced cervical cancer treatment and a well-documented role of the vascular endothelial growth factor (VEGF) family members in pathogenesis and progression of cervical cancer, the use of VEGF-targeted therapy in the treatment of cervical cancer offers interesting possibilities. The efficacy of bevacizumab, a monoclonal antibody neutralizing VEGF-A in the treatment of cervical cancer was first suggested in 2006 by a small retrospective analysis and confirmed in several Phase II clinical trials. Preliminary results of the randomized phase III studies presented at this year's ASCO (American Society of Clinical Oncology) conference shed new light on the role of VEGF-targeted therapy in the treatment of cervical cancer as they demonstrated that addition of bevacizumab to chemotherapy is associated with significantly improved overall survival in the group of patients with persistent, recurrent or metastatic cervical cancer.