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Sample records for acid promotes neural

  1. All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways

    Fang Bo

    2009-07-01

    Full Text Available Abstract Background All-trans retinoic acid (RA is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs, we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture. Results Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal-regulated kinase (ERK pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA-treated cultures at the early stage of differentiation. Conclusion RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways.

  2. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

    Heidi Wichmann

    2016-05-01

    Full Text Available The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP, produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA, a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2. Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells.

  3. Dimethylsulfoniopropionate Promotes Process Outgrowth in Neural Cells and Exerts Protective Effects against Tropodithietic Acid

    Wichmann, Heidi; Brinkhoff, Thorsten; Simon, Meinhard; Richter-Landsberg, Christiane

    2016-01-01

    The marine environment harbors a plethora of bioactive substances, including drug candidates of potential value in the field of neuroscience. The present study was undertaken to investigate the effects of dimethylsulfoniopropionate (DMSP), produced by several algae, corals and higher plants, on cells of the mammalian nervous system, i.e., neuronal N2a and OLN-93 cells as model system for nerve cells and glia, respectively. Additionally, the protective capabilities of DMSP were assessed in cells treated with tropodithietic acid (TDA), a marine metabolite produced by several Roseobacter clade bacteria. Both cell lines, N2a and OLN-93, have previously been shown to be a sensitive target for the action of TDA, and cytotoxic effects of TDA have been connected to the induction of oxidative stress. Our data shows that DMSP promotes process outgrowth and microtubule reorganization and bundling, accompanied by an increase in alpha-tubulin acetylation. Furthermore, DMSP was able to prevent the cytotoxic effects exerted by TDA, including the breakdown of the mitochondrial membrane potential, upregulation of heat shock protein Hsp32 and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2). Our study points to the conclusion that DMSP provides an antioxidant defense, not only in algae but also in mammalian neural cells. PMID:27164116

  4. REN: a novel, developmentally regulated gene that promotes neural cell differentiation.

    Gallo, Rita; Zazzeroni, Francesca; Alesse, Edoardo; Mincione, Claudia; Borello, Ugo; Buanne, Pasquale; D'Eugenio, Roberta; Mackay, Andrew R; Argenti, Beatrice; Gradini, Roberto; Russo, Matteo A; Maroder, Marella; Cossu, Giulio; Frati, Luigi; Screpanti, Isabella; Gulino, Alberto

    2002-08-19

    Expansion and fate choice of pluripotent stem cells along the neuroectodermal lineage is regulated by a number of signals, including EGF, retinoic acid, and NGF, which also control the proliferation and differentiation of central nervous system (CNS) and peripheral nervous system (PNS) neural progenitor cells. We report here the identification of a novel gene, REN, upregulated by neurogenic signals (retinoic acid, EGF, and NGF) in pluripotent embryonal stem (ES) cells and neural progenitor cell lines in association with neurotypic differentiation. Consistent with a role in neural promotion, REN overexpression induced neuronal differentiation as well as growth arrest and p27Kip1 expression in CNS and PNS neural progenitor cell lines, and its inhibition impaired retinoic acid induction of neurogenin-1 and NeuroD expression. REN expression is developmentally regulated, initially detected in the neural fold epithelium of the mouse embryo during gastrulation, and subsequently throughout the ventral neural tube, the outer layer of the ventricular encephalic neuroepithelium and in neural crest derivatives including dorsal root ganglia. We propose that REN represents a novel component of the neurogenic signaling cascade induced by retinoic acid, EGF, and NGF, and is both a marker and a regulator of neuronal differentiation. PMID:12186855

  5. Neonatal Maternal Separation Alters the Capacity of Adult Neural Precursor Cells to Differentiate into Neurons Via Methylation of Retinoic Acid Receptor Gene Promoter

    Boku, Shuken; Toda, Hiroyuki; Nakagawa, Shin; Kato, Akiko; Inoue, Takeshi; Koyama, Tsukasa; Hiroi, Noboru; Kusumi, Ichiro

    2015-01-01

    BACKGROUND: Early life stress is thought to contribute to psychiatric disorders, but the precise mechanisms underlying this link are poorly understood. As neonatal stress decreases adult hippocampal neurogenesis, which, in turn, functionally contributes to many behavioral phenotypes relevant to psychiatric disorders, we examined how in vivo neonatal maternal separation (NMS) impacts the capacity of adult hippocampal neural precursor cells via epigenetic alterations in vitro. METHODS: Rat pups...

  6. Neural Tube Defects, Folic Acid and Methylation

    Henk J. Blom

    2013-09-01

    Full Text Available Neural tube defects (NTDs are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.

  7. Senegenin promotes in vitro proliferation of human neural progenitor cells

    Fang Shi; Zhigang Liang; Zixuan Guo; Ran Li; Fen Yu; Zhanjun Zhang; Xuan Wang; Xiaomin Wang

    2011-01-01

    Senegenin, an effective component of Polygala tenuifolia root extract, promotes proliferation and differentiation of neural progenitor cells in the hippocampus.However, the effects of senegenin on mesencephalon-derived neural progenitor cells remain poorly understood.Cells from a ventral mesencephalon neural progenitor cell line (ReNcell VM) were utilized as models for pharmaceutical screening.The effects of various senegenin concentrations on cell proliferation were analyzed,demonstrating that high senegenin concentrations (5, 10, 50, and 100 pmo/L), particularly 50 pmol/L, significantly promoted proliferation of ReNcell VM cells.In the mitogen-activated protein kinase signal transduction pathway, senegenin significantly increased phosphorylation levels of extracellular signal-regulated kinases.Moreover, cell proliferation was suppressed by extracellular signal-regulated kinase inhibitors.Results suggested that senegenin contributed to in vitro proliferation of human neural progenitor cells by upregulating phosphorylation of extracellular signal-regulated kinase.

  8. Eukaryotic Promoter Recognition Using Back propagation Neural Network

    XIONGQing; WANGYuan-Qiang; LIZhi-Liang

    2004-01-01

    A new system is developed to recognize promoter sequences from non-promoter sequences based on position weight matrix and backpropagation neural network in this paper. The system performs significantly better on the training set and the test set, the mean recognition rate is as high as 99% on the training set and 97% on the testing set. Experimental results demonstrate the effectiveness of the system to recognize the promoter sequences that have been trained and the promoter sequences that have not been seen previously.

  9. CPAP promotes timely cilium disassembly to maintain neural progenitor pool.

    Gabriel, Elke; Wason, Arpit; Ramani, Anand; Gooi, Li Ming; Keller, Patrick; Pozniakovsky, Andrei; Poser, Ina; Noack, Florian; Telugu, Narasimha Swamy; Calegari, Federico; Šarić, Tomo; Hescheler, Jürgen; Hyman, Anthony A; Gottardo, Marco; Callaini, Giuliano; Alkuraya, Fowzan Sami; Gopalakrishnan, Jay

    2016-04-15

    A mutation in the centrosomal-P4.1-associated protein (CPAP) causes Seckel syndrome with microcephaly, which is suggested to arise from a decline in neural progenitor cells (NPCs) during development. However, mechanisms ofNPCs maintenance remain unclear. Here, we report an unexpected role for the cilium inNPCs maintenance and identifyCPAPas a negative regulator of ciliary length independent of its role in centrosome biogenesis. At the onset of cilium disassembly,CPAPprovides a scaffold for the cilium disassembly complex (CDC), which includes Nde1, Aurora A, andOFD1, recruited to the ciliary base for timely cilium disassembly. In contrast, mutatedCPAPfails to localize at the ciliary base associated with inefficientCDCrecruitment, long cilia, retarded cilium disassembly, and delayed cell cycle re-entry leading to premature differentiation of patientiPS-derivedNPCs. AberrantCDCfunction also promotes premature differentiation ofNPCs in SeckeliPS-derived organoids. Thus, our results suggest a role for cilia in microcephaly and its involvement during neurogenesis and brain size control. PMID:26929011

  10. Nerve growth factor promotes in vitro proliferation of neural stem cells from tree shrews

    Liu-lin Xiong; Zhi-wei Chen; Ting-hua Wang

    2016-01-01

    Neural stem cells promote neuronal regeneration and repair of brain tissue after injury, but have limited resources and proliferative ability in vivo. We hypothesized that nerve growth factor would promotein vitro proliferation of neural stem cells derived from the tree shrews, a primate-like mammal that has been proposed as an alternative to primates in biomedical translational research. We cultured neural stem cells from the hippocampus of tree shrews at embryonic day 38, and added nerve growth factor (100 μg/L) to the culture medium. Neural stem cells from the hippocampus of tree shrews cultured without nerve growth factor were used as controls. After 3 days, lfuorescence mi-croscopy after DAPI and nestin staining revealed that the number of neurospheres and DAPI/nestin-positive cells was markedly greater in the nerve growth factor-treated cells than in control cells. These ifndings demonstrate that nerve growth factor promotes the proliferation of neural stem cells derived from tree shrews.

  11. Environmental enrichment promotes neural plasticity and cognitive ability in fish

    Salvanes, Anne Gro Vea; Moberg, Olav; Ebbesson, Lars O.E.; Nilsen, Tom Ole; Jensen, Knut Helge; Braithwaite, Victoria A.

    2013-01-01

    Different kinds of experience during early life can play a significant role in the development of an animal's behavioural phenotype. In natural contexts, this influences behaviours from anti-predator responses to navigation abilities. By contrast, for animals reared in captive environments, the homogeneous nature of their experience tends to reduce behavioural flexibility. Studies with cage-reared rodents indicate that captivity often compromises neural development and neural plasticity. Such...

  12. Folic acid supplement use in the prevention of neural tube defects.

    Delany, C

    2011-01-01

    In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284\\/297 (96%), had heard of folic acid, and 178\\/297 (60%) knew that it could prevent NTD. Most, 270\\/297 (91%) had taken it during their pregnancy, but only 107\\/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.

  13. Shaping Early Reorganization of Neural Networks Promotes Motor Function after Stroke.

    Volz, L. J.; Rehme, A K; Michely, J.; Nettekoven, C.; Eickhoff, Simon; Fink, G R; Grefkes, Christian

    2016-01-01

    Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1-16 days) with hand motor deficits were e...

  14. Folic acid supplements to prevent neural tube defects: trends in East of Ireland 1996-2002.

    Ward, M

    2004-10-01

    Promotion of folic acid to prevent neural Tube Defects (NTD) has been ongoing for ten years in Ireland, without a concomitant reduction in the total birth prevalence of NTD. The effectiveness of folic acid promotion as the sole means of primary prevention of NTD is therefore questionable. We examined trends in folic acid knowledge and peri-conceptional use from 1996-2002 with the aim of assessing the value of this approach. From 1996-2002, 300 women attending ante-natal clinics in Dublin hospitals annually were surveyed regarding their knowledge and use of folic acid. During the period the proportion who had heard of folic acid rose from 54% to 94% between 1996 and 2002 (c2 test for trend: p<0.001). Knowledge that folic acid can prevent NTD also rose from 21% to 66% (c2 test for trend: p<0.001). Although the proportion who took folic acid during pregnancy increased from 14% to 83% from 1996 to 2002 (c2 test for trend: p<0.001), peri-conceptional intake did not rise above 24% in any year. There is a high awareness of folic acid and its relation to NTD, which is not matched by peri-conceptional uptake. The main barrier to peri-conceptional uptake is the lack of pregnancy planning. To date promotional campaigns appear to have been ineffective in reducing the prevalence of NTD in Ireland. Consequently, fortification of staple foodstuffs is the only practical and reliable means of primary prevention of NTD.

  15. Neural regeneration protein is a novel chemoattractive and neuronal survival-promoting factor

    Neurogenesis and neuronal migration are the prerequisites for the development of the central nervous system. We have identified a novel rodent gene encoding for a neural regeneration protein (NRP) with an activity spectrum similar to the chemokine stromal-derived factor (SDF)-1, but with much greater potency. The Nrp gene is encoded as a forward frameshift to the hypothetical alkylated DNA repair protein AlkB. The predicted protein sequence of NRP contains domains with homology to survival-promoting peptide (SPP) and the trefoil protein TFF-1. The Nrp gene is first expressed in neural stem cells and expression continues in glial lineages. Recombinant NRP and NRP-derived peptides possess biological activities including induction of neural migration and proliferation, promotion of neuronal survival, enhancement of neurite outgrowth and promotion of neuronal differentiation from neural stem cells. NRP exerts its effect on neuronal survival by phosphorylation of the ERK1/2 and Akt kinases, whereas NRP stimulation of neural migration depends solely on p44/42 MAP kinase activity. Taken together, the expression profile of Nrp, the existence in its predicted protein structure of domains with similarities to known neuroprotective and migration-inducing factors and the high potency of NRP-derived synthetic peptides acting in femtomolar concentrations suggest it to be a novel gene of relevance in cellular and developmental neurobiology

  16. Acid-functionalized polyolefin materials and their use in acid-promoted chemical reactions

    Oyola, Yatsandra; Tian, Chengcheng; Bauer, John Christopher; Dai, Sheng

    2016-06-07

    An acid-functionalized polyolefin material that can be used as an acid catalyst in a wide range of acid-promoted chemical reactions, wherein the acid-functionalized polyolefin material includes a polyolefin backbone on which acid groups are appended. Also described is a method for the preparation of the acid catalyst in which a precursor polyolefin is subjected to ionizing radiation (e.g., electron beam irradiation) of sufficient power and the irradiated precursor polyolefin reacted with at least one vinyl monomer having an acid group thereon. Further described is a method for conducting an acid-promoted chemical reaction, wherein an acid-reactive organic precursor is contacted in liquid form with a solid heterogeneous acid catalyst comprising a polyolefin backbone of at least 1 micron in one dimension and having carboxylic acid groups and either sulfonic acid or phosphoric acid groups appended thereto.

  17. MYC Expression Promotes the Proliferation of Neural Progenitor Cells in Culture and In Vivo

    Dan Fults

    2002-01-01

    Full Text Available Primitive neuroectodermal tumors. (20PNETs are pediatric brain tumors that result from defects in signaling molecules governing the growth and differentiation of neural progenitor cells. We used the RCAS-TVA system to study the growth effects of three genetic alterations implicated in human PNETs on a subset of neural progenitor cells that express the intermediate filament protein, nestin. The genetic alterations tested were: 1 overexpression of the cellular oncoprotein, MYC; 2 activation of transcription factor, β-catenin; and 3 haploinsufficiency of Ptc, the hedgehog receptor gene. The RCAS-TVA system uses an avian retroviral vector, RCAS, to target gene expression to specific cell types in transgenic mice. To express exogenous genes in neural progenitor cells, we used Ntv-a mice. In these mice, the Nestin gene promoter drives expression of TVA, the cell surface receptor for the virus. Ectopic expression of MYC, but not activated β-catenin, promoted the proliferation of neural progenitor cells in culture and in the cerebral leptomeninges in vivo. These effects were equally penetrant in mice with Ptc+/− and Ptc+/+ genetic backgrounds. Although overexpression of MYC is not sufficient to cause intraparenchymal tumors, it may facilitate PNET formation by sustaining the growth of undifferentiated progenitor cells.

  18. A ginkgo biloba extract promotes proliferation of endogenous neural stem cells in vascular dementia rats

    Jiwei Wang; Wen Chen; Yuliang Wang

    2013-01-01

    The ginkgo biloba extract EGb761 improves memory loss and cognitive impairments in patients with senile dementia. It also promotes proliferation of neural stem cells in the subventricular zone in Parkinson's disease model mice and in the hippocampal zone of young epileptic rats. However, it remains unclear whether EGb761 enhances proliferation of endogenous neural stem cells in the brain of rats with vascular dementia. In this study, a vascular dementia model was established by repeatedly clipping and reperfusing the bilateral common carotid arteries of rats in combination with an intraperitoneal injection of a sodium nitroprusside solution. Seven days after establishing the model, rats were intragastrically given EGb761 at 50 mg/kg per day. Learning and memory abilities were assessed using the Morris water maze and proliferation of endogenous neural stem cells in the subventricular zone and dentate gyrus were labeled by 5-bromo-2-deoxyuridine immunofluorescence in all rats at 15 days, and 1, 2, and 4 months after model establishment. The escape latencies in Morris water maze tests of rats with vascular dementia after EGb761 treatment were significantly shorter than the model group. Immunofluorescence staining showed that the number and proliferation of 5-bromo-2-deoxyuridine-positive cells in the subventricular zone and dentate gyrus of the EGb761-treated group were significantly higher than in the model group. These experimental findings suggest that EGb761 enhances proliferation of neural stem cells in the subventricular zone and dentate gyrus, and significantly improves learning and memory in rats with vascular dementia.

  19. The prevention of neural tube defects by folic acid supplementation

    H. W. Hitzeroth

    1993-05-01

    Full Text Available Neural tube defects, in particular spina bifida and anencephaly, are serious and relatively common congenital abnormalities worldwide. They also occur in South Africa and affect all population groups to varying degrees. The overall incidence in South Africa is approximately 1-2 per 1000 newborns. Higher incidences, up to 6 per 1000 newborns have been recorded in certain parts, especially in some rural areas of the country. In total as many as 1500 newborns could be affected by a neural tube defect each year. The precise aetiology of neural tube defects is still unknown.

  20. Microbes Promote Amino Acid Harvest to Rescue Undernutrition in Drosophila

    Ryuichi Yamada

    2015-02-01

    Full Text Available Microbes play an important role in the pathogenesis of nutritional disorders such as protein-specific malnutrition. However, the precise contribution of microbes to host energy balance during undernutrition is unclear. Here, we show that Issatchenkia orientalis, a fungal microbe isolated from field-caught Drosophila melanogaster, promotes amino acid harvest to rescue the lifespan of undernourished flies. Using radioisotope-labeled dietary components (amino acids, nucleotides, and sucrose to quantify nutrient transfer from food to microbe to fly, we demonstrate that I. orientalis extracts amino acids directly from nutrient-poor diets and increases protein flux to the fly. This microbial association restores body mass, protein, glycerol, and ATP levels and phenocopies the metabolic profile of adequately fed flies. Our study uncovers amino acid harvest as a fundamental mechanism linking microbial and host metabolism, and highlights Drosophila as a platform for quantitative studies of host-microbe relationships.

  1. Combined MSC-Secreted Factors and Neural Stem Cell Transplantation Promote Functional Recovery of PD Rats.

    Yao, Yuan; Huang, Chen; Gu, Ping; Wen, Tieqiao

    2016-01-01

    Stem cell transplantation has enormous potential for the treatment of neurodegenerative disorders like Parkinson's disease (PD). Mesenchymal stem cells (MSCs) have attracted much attention because they can secrete a wide variety of cellular factors that promote cell growth. In this study, we prepared a conditioned medium (CM) using lyophilized MSC culture medium that contained the secretome of MSCs and applied this CM to the culture of neural stem cells (CM-NSCs) for the transplantation of PD model rats. Quantitative real-time PCR, Western blot, and immunocytochemistry were used to identify cell differentiation and expression of dopaminergic neuron-specific genes in vitro. Behavioral tests including rotational behavior and MWM training tests were also performed to assess the recovery. Our results indicated that combined treatment of CM and neural stem cell transplantation can significantly reduce apomorphine-induced rotational asymmetry and improve spatial learning ability. The CM-NSCs were able to differentiate into dopaminergic neurons in the ventral tegmental area (VTA) and medial forebrain bundle (MFB), and migrated around the lesion site. They showed a higher activity than untreated NSCs in cell survival, migration, and behavior improvement in the dopa-deficit rat model. These findings suggest that the neural stem cells treated with conditioned medium possess a great potential as a graft candidate for the treatment of Parkinson's disease. PMID:26607204

  2. Acid-Base Pairs in Lewis Acidic Zeolites Promote Direct Aldol Reactions by Soft Enolization.

    Lewis, Jennifer D; Van de Vyver, Stijn; Román-Leshkov, Yuriy

    2015-08-17

    Hf-, Sn-, and Zr-Beta zeolites catalyze the cross-aldol condensation of aromatic aldehydes with acetone under mild reaction conditions with near quantitative yields. NMR studies with isotopically labeled molecules confirm that acid-base pairs in the Si-O-M framework ensemble promote soft enolization through α-proton abstraction. The Lewis acidic zeolites maintain activity in the presence of water and, unlike traditional base catalysts, in acidic solutions. PMID:26138135

  3. Organic cation transporter-mediated ergothioneine uptake in mouse neural progenitor cells suppresses proliferation and promotes differentiation into neurons.

    Takahiro Ishimoto

    Full Text Available The aim of the present study is to clarify the functional expression and physiological role in neural progenitor cells (NPCs of carnitine/organic cation transporter OCTN1/SLC22A4, which accepts the naturally occurring food-derived antioxidant ergothioneine (ERGO as a substrate in vivo. Real-time PCR analysis revealed that mRNA expression of OCTN1 was much higher than that of other organic cation transporters in mouse cultured cortical NPCs. Immunocytochemical analysis showed colocalization of OCTN1 with the NPC marker nestin in cultured NPCs and mouse embryonic carcinoma P19 cells differentiated into neural progenitor-like cells (P19-NPCs. These cells exhibited time-dependent [(3H]ERGO uptake. These results demonstrate that OCTN1 is functionally expressed in murine NPCs. Cultured NPCs and P19-NPCs formed neurospheres from clusters of proliferating cells in a culture time-dependent manner. Exposure of cultured NPCs to ERGO or other antioxidants (edaravone and ascorbic acid led to a significant decrease in the area of neurospheres with concomitant elimination of intracellular reactive oxygen species. Transfection of P19-NPCs with small interfering RNA for OCTN1 markedly promoted formation of neurospheres with a concomitant decrease of [(3H]ERGO uptake. On the other hand, exposure of cultured NPCs to ERGO markedly increased the number of cells immunoreactive for the neuronal marker βIII-tubulin, but decreased the number immunoreactive for the astroglial marker glial fibrillary acidic protein (GFAP, with concomitant up-regulation of neuronal differentiation activator gene Math1. Interestingly, edaravone and ascorbic acid did not affect such differentiation of NPCs, in contrast to the case of proliferation. Knockdown of OCTN1 increased the number of cells immunoreactive for GFAP, but decreased the number immunoreactive for βIII-tubulin, with concomitant down-regulation of Math1 in P19-NPCs. Thus, OCTN1-mediated uptake of ERGO in NPCs inhibits

  4. Hyaluronic acid-based scaffold for central neural tissue engineering

    Wang, Xiumei; He, Jin; Wang, Ying; CUI, FU-ZHAI

    2012-01-01

    Central nervous system (CNS) regeneration with central neuronal connections and restoration of synaptic connections has been a long-standing worldwide problem and, to date, no effective clinical therapies are widely accepted for CNS injuries. The limited regenerative capacity of the CNS results from the growth-inhibitory environment that impedes the regrowth of axons. Central neural tissue engineering has attracted extensive attention from multi-disciplinary scientists in recent years, and ma...

  5. The use of artificial neural networks to study fatty acids in neuropsychiatric disorders

    Tonello Lucio

    2008-04-01

    Full Text Available Abstract Background The range of the fatty acids has been largely investigated in the plasma and erythrocytes of patients suffering from neuropsychiatric disorders. In this paper we investigate, for the first time, whether the study of the platelet fatty acids from such patients may be facilitated by means of artificial neural networks. Methods Venous blood samples were taken from 84 patients with a DSM-IV-TR diagnosis of major depressive disorder and from 60 normal control subjects without a history of clinical depression. Platelet levels of the following 11 fatty acids were analyzed using one-way analysis of variance: C14:0, C16:0, C16:1, C18:0, C18:1 n-9, C18:1 n-7, C18:2 n-6, C18:3 n-3, C20:3 n-3, C20:4 n-6 and C22:6 n-3. The results were then entered into a wide variety of different artificial neural networks. Results All the artificial neural networks tested gave essentially the same result. However, one type of artificial neural network, the self-organizing map, gave superior information by allowing the results to be described in a two-dimensional plane with potentially informative border areas. A series of repeated and independent self-organizing map simulations, with the input parameters being changed each time, led to the finding that the best discriminant map was that obtained by inclusion of just three fatty acids. Conclusion Our results confirm that artificial neural networks may be used to analyze platelet fatty acids in neuropsychiatric disorder. Furthermore, they show that the self-organizing map, an unsupervised competitive-learning network algorithm which forms a nonlinear projection of a high-dimensional data manifold on a regular, low-dimensional grid, is an optimal type of artificial neural network to use for this task.

  6. Induction of cranial and posterior trunk neural crest by exogenous retinoic acid in zebrafish

    2002-01-01

    Retinoic acid (RA) plays an important role in development of vertebrate embryos. We demonstrate impacts of exogenous RA on the formation of neural crest cells in zebrafish using specific neural crest markers sox9b and crestin. Treatment with all-trans RA at 10?7 mmol/L at 50% epiboly induces sox9b expression in the forebrain and crestin expression in the forebrain and midbrain, resulting in significant increase of pigment cells in the head derived from the cranial neural crest. In addition, RA treatment induces expression of sox9b and crestin in the caudal marginal cells of the neuroectoderm during early segmentation. Earlier commitment of these cells to the neural crest fate in the posterior margins leads to abnormal development of the posterior body, probably by preventing mingling of ventral derived and dorsal-derived cells during the formation of the tailbud.

  7. Shaping Early Reorganization of Neural Networks Promotes Motor Function after Stroke.

    Volz, L J; Rehme, A K; Michely, J; Nettekoven, C; Eickhoff, S B; Fink, G R; Grefkes, C

    2016-06-01

    Neural plasticity is a major factor driving cortical reorganization after stroke. We here tested whether repetitively enhancing motor cortex plasticity by means of intermittent theta-burst stimulation (iTBS) prior to physiotherapy might promote recovery of function early after stroke. Functional magnetic resonance imaging (fMRI) was used to elucidate underlying neural mechanisms. Twenty-six hospitalized, first-ever stroke patients (time since stroke: 1-16 days) with hand motor deficits were enrolled in a sham-controlled design and pseudo-randomized into 2 groups. iTBS was administered prior to physiotherapy on 5 consecutive days either over ipsilesional primary motor cortex (M1-stimulation group) or parieto-occipital vertex (control-stimulation group). Hand motor function, cortical excitability, and resting-state fMRI were assessed 1 day prior to the first stimulation and 1 day after the last stimulation. Recovery of grip strength was significantly stronger in the M1-stimulation compared to the control-stimulation group. Higher levels of motor network connectivity were associated with better motor outcome. Consistently, control-stimulated patients featured a decrease in intra- and interhemispheric connectivity of the motor network, which was absent in the M1-stimulation group. Hence, adding iTBS to prime physiotherapy in recovering stroke patients seems to interfere with motor network degradation, possibly reflecting alleviation of post-stroke diaschisis. PMID:26980614

  8. miR-21 promotes the differentiation of hair follicle-derived neural crest stem cells into Schwann cells

    Yuxin Ni; Kaizhi Zhang; Xuejuan Liu; Tingting Yang; Baixiang Wang; Li Fu; Lan A; Yanmin Zhou

    2014-01-01

    Hair follicle-derived neural crest stem cells can be induced to differentiate into Schwann cells in vivo and in vitro. However, the underlying regulatory mechanism during cell differentiation remains poorly understood. This study isolated neural crest stem cells from human hair folli-cles and induced them to differentiate into Schwann cells. Quantitative RT-PCR showed that microRNA (miR)-21 expression was gradually increased during the differentiation of neural crest stem cells into Schwann cells. After transfection with the miR-21 agonist (agomir-21), the differentiation capacity of neural crest stem cells was enhanced. By contrast, after transfection with the miR-21 antagonist (antagomir-21), the differentiation capacity was attenuated. Further study results showed that SOX-2 was an effective target of miR-21. Without compromising SOX2 mRNA expression, miR-21 can down-regulate SOX protein expression by binding to the 3′-UTR of miR-21 mRNA. Knocking out the SOX2 gene from the neural crest stem cells significantly reversed the antagomir-21 inhibition of neural crest stem cells differentiating into Schwann cells. The results suggest that miR-21 expression was increased during the differentiation of neural crest stem cells into Schwann cells and miR-21 promoted the differentiation through down-regu-lating SOX protein expression by binding to the 3′-UTR of SOX2 mRNA.

  9. Investigations of Escherichia coli promoter sequences with artificial neural networks: new signals discovered upstream of the transcriptional startpoint

    Pedersen, Anders Gorm; Engelbrecht, Jacob

    We present a novel method for using the learning ability of a neural network as a measure of information in local regions of input data. Using the method to analyze Escherichia coli promoters, we discover all previously described signals, and furthermore find new signals that are regularly spaced...

  10. Heteropoly acid promoted Cu and Fe catalysts for the selective catalytic reduction of NO with ammonia

    Putluru, Siva Sankar Reddy; Mossin, Susanne L.; Riisager, Anders; Fehrmann, Rasmus

    2011-01-01

    were studied and compared with the catalytic activity for the selective catalytic reduction (SCR) of NO with ammonia. The SCR activities and acidity values of heteropoly acid promoted catalysts were found to be much higher than unpromoted catalysts. The influence of potassium poisons on the SCR...... activity and acidity was lower for promoted catalysts than for unpromoted catalysts. In the heteropoly acid promoted catalysts the SCR active Cu and Fe metals were protected from potassium poisons by bonding of the potassium to the Brønsted acid centres. Thus heteropoly acid promoted catalysts might be...... suitable for biomass fired power plant SCR applications....

  11. Co-culture with microglia promotes neural stem cells differentiation into astrocytes

    GU Feng; WANG Juan; FU Li; MA Yong-jie

    2011-01-01

    Background Neural stem cells (NSCs) are a self-renewing and multipotent population of the central nervous system (CNS),which are active during development and maintain homeostasis and tissue integrity throughout life.Microglias are an immune cell population resident in the CNS,which have crucial physiological functions in the developing and adult CNS.This study aimed to investigate that whether microglia co-cultured with NSCs could promote astrogliogenesis from NSCs.Methods Microglia and NSCs were co-cultured in 24-well insert plates.NSCs were plated in the bottom of the well and microglia in the insert.Fluorescent staining,Western blotting and RT-PCR were used to determine the effect of microglia on NSCs differentiation.Results Co-culture of microglia and NSCs promoted astrogliogenesis from NSCs.Several key genes,such as Notch 1,Notch 2,Notch 3,Hes 5,and NRSFwera downregulated,while the critical genes Id1 and Id2 were upregulated.BMP2 and FGF2 were upregulated.Conclusion Microglias act as a regulator of NSCs astrogliogenesis.

  12. Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential

    The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effect was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells

  13. Biphasic electrical currents stimulation promotes both proliferation and differentiation of fetal neural stem cells.

    Keun-A Chang

    Full Text Available The use of non-chemical methods to differentiate stem cells has attracted researchers from multiple disciplines, including the engineering and the biomedical fields. No doubt, growth factor based methods are still the most dominant of achieving some level of proliferation and differentiation control--however, chemical based methods are still limited by the quality, source, and amount of the utilized reagents. Well-defined non-chemical methods to differentiate stem cells allow stem cell scientists to control stem cell biology by precisely administering the pre-defined parameters, whether they are structural cues, substrate stiffness, or in the form of current flow. We have developed a culture system that allows normal stem cell growth and the option of applying continuous and defined levels of electric current to alter the cell biology of growing cells. This biphasic current stimulator chip employing ITO electrodes generates both positive and negative currents in the same culture chamber without affecting surface chemistry. We found that biphasic electrical currents (BECs significantly increased the proliferation of fetal neural stem cells (NSCs. Furthermore, BECs also promoted the differentiation of fetal NSCs into neuronal cells, as assessed using immunocytochemistry. Our results clearly show that BECs promote both the proliferation and neuronal differentiation of fetal NSCs. It may apply to the development of strategies that employ NSCs in the treatment of various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases.

  14. Synergistic Effect of Schwann Cells and Retinoic Acid on Differentiation and Synaptogenesis of Hippocampal Neural Stem Cells in vitro

    XUE-BAO ZHANG; YUAN-SHAN ZENG; WEI ZHANG; YA-YUN CHEN; WEI ZHANG; YI XIONG; SUI-JUN CHEN

    2006-01-01

    Objective To investigate the synergistic effect of Schwann cells (YCs) and retinoic acid (RA) on differentiation and synaptogenesis of neural stem cells (NSCs) derived from hippocampus of neonatal rats. Methods The classical method for 2×2 factorial analysis experiment was used to assess synergistic action of SCs and RA. NSCs were treated with RA, SCs,and SCs + RA in DMEM/F12 with 0.5% fetal bovine serum for six days, respectively. Double immunofluorescent staining was used to detect the differentiation of NSCs including nestin, glial fibrillary acidic protein (GFAP) and Map2. The expression of PSD95 was used to demonstrate synaptogenesis. Results After NSCs were treated with RA or SCs, the expression of nestin and GFAP was significantly decreased while the expression of Map2 and PSD95 was significantly increased in comparison with the control. Factorial ANOVA showed that interactions between SCs and RA could induce the expression of Map2 and PSD95. Conclusion SCs and RA could promote synergistically the neuronal differentiation and synaptogenesis of hippocampal neural stem cells in vitro while they decreased the astrocytes and nestin positive NSCs.

  15. Retinoic acid induction of genes associated with neural tube developmental defects

    Xinjun Li; Zhong Yang; Yi Zeng; Hong Xu; Hongli Li; Yangyun Han; Xiaodong Long; Chao You

    2010-01-01

    To date, little information has been available regarding genes involved in the regulation of embryonic cell development, which participate in retinoic acid-induced neural tube defects in mice.Previous studies have revealed seven differentially expressed genes involved in neural tube developmental defects. However, gene expression and regulation is a complex process. Therefore,gene expression differences between normal and defective neural tubes at 9.5 and 10.5 days were compared. A total of eight differentially expressed genes exhibited coincident alterations at embryonic 9.5 and 10.5 days. In mice with retinoic acid-induced neural tube defects, NeK7, IGFBP5,ZW10, Csf3r, PSMC6, Cdk5, and Rb1 expressions were downregulated, but Apoa-4 expression was upregulated. These results were confirmed by Northern blot hybridization. Results suggested that NeK7, IGFBP5, ZW10, Csf3r, PSMC6, Cdk5, Rb1, and Apoa-4 are important regulatory factors involved in neural tube defects.

  16. Spirulina promotes stem cell genesis and protects against LPS induced declines in neural stem cell proliferation.

    Adam D Bachstetter

    Full Text Available Adult stem cells are present in many tissues including, skin, muscle, adipose, bone marrow, and in the brain. Neuroinflammation has been shown to be a potent negative regulator of stem cell and progenitor cell proliferation in the neurogenic regions of the brain. Recently we demonstrated that decreasing a key neuroinflammatory cytokine IL-1beta in the hippocampus of aged rats reversed the age-related cognitive decline and increased neurogenesis in the age rats. We also have found that nutraceuticals have the potential to reduce neuroinflammation, and decrease oxidative stress. The objectives of this study were to determine if spirulina could protect the proliferative potential of hippocampal neural progenitor cells from an acute systemic inflammatory insult of lipopolysaccharide (LPS. To this end, young rats were fed for 30 days a control diet or a diet supplemented with 0.1% spirulina. On day 28 the rats were given a single i.p. injection of LPS (1 mg/kg. The following day the rats were injected with BrdU (50 mg/kg b.i.d. i.p. and were sacrificed 24 hours after the first injection of BrdU. Quantification of the BrdU positive cells in the subgranular zone of the dentate gyrus demonstrated a decrease in proliferation of the stem/progenitor cells in the hippocampus as a result of the LPS insult. Furthermore, the diet supplemented with spirulina was able to negate the LPS induced decrease in stem/progenitor cell proliferation. In a second set of studies we examined the effects of spirulina either alone or in combination with a proprietary formulation (NT-020 of blueberry, green tea, vitamin D3 and carnosine on the function of bone marrow and CD34+ cells in vitro. Spirulina had small effects on its own and more than additive effects in combination with NT-020 to promote mitochondrial respiration and/or proliferation of these cells in culture. When examined on neural stem cells in culture spirulina increased proliferation at baseline and protected

  17. Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus

    Gao, Xiang; Enikolopov, Grigori; Chen, Jinhui

    2009-01-01

    Recent evidence shows that traumatic brain injury (TBI) regulates proliferation of neural stem/progenitor cells in the dentate gyrus (DG) of adult hippocampus. There are distinct classes of neural stem/progenitor cells in the adult DG, including quiescent neural progenitors (QNPs), which carry stem cell properties, and their progeny, amplifying neural progenitors (ANPs). The response of each class of progenitors to TBI is not clear. We here used a transgenic reporter Nestin-GFP mouse line, in...

  18. Prevention of neural tube defects with folic acid: The Chinese experience.

    Ren, Ai-Guo

    2015-08-01

    Neural tube defects (NTDs) are a group of congenital malformations of the central nervous system that are caused by the closure failure of the embryonic neural tube by the 28(th) day of conception. Anencephaly and spina bifida are the two major subtypes. Fetuses with anencephaly are often stillborn or electively aborted due to prenatal diagnosis, or they die shortly after birth. Most infants with spina bifida are live-born and, with proper surgical treatment, can survive into adulthood. However, these children often have life-long physical disabilities. China has one of the highest prevalence of NTDs in the world. Inadequate dietary folate intake is believed to be the main cause of the cluster. Unlike many other countries that use staple fortification with folic acid as the public health strategy to prevent NTDs, the Chinese government provides all women who have a rural household registration and who plan to become pregnant with folic acid supplements, free of charge, through a nation-wide program started in 2009. Two to three years after the initiation of the program, the folic acid supplementation rate increased to 85% in the areas of the highest NTD prevalence. The mean plasma folate level of women during early and mid-pregnancy doubled the level before the program was introduced. However, most women began taking folic acid supplements when they knew that they were pregnant. This is too late for the protection of the embryonic neural tube. In a post-program survey of the women who reported folic acid supplementation, less than a quarter of the women began taking supplements prior to pregnancy, indicating that the remaining three quarters of the fetuses remained unprotected during the time of neural tube formation. Therefore, staple food fortification with folic acid should be considered as a priority in the prevention of NTDs. PMID:26261765

  19. Impact of Lactic Acid on Cell Proliferation and Free Radical Induced Cell Death in Monolayer Cultures of Neural Precursor Cells

    Lampe, Kyle J.; Namba, Rachael M.; Silverman, Tyler R.; Bjugstad, Kimberly B.; Mahoney, Melissa J.

    2009-01-01

    Biomaterials prepared from polyesters of lactic acid and glycolic acid, or a mixture of the two, degrade in the presence of water into the naturally occurring metabolites, lactic acid and glycolic acid. While the lactic acid degradation product that is released from biomaterials is well-tolerated by the body, lactic acid can influence the metabolic function of cells; it can serve as an energy substrate for cells, and has been shown to have antioxidant properties. Neural precursor cells, a cel...

  20. Inhibition of Sirt1 promotes neural progenitors toward motoneuron differentiation from human embryonic stem cells

    Zhang, Yun; Wang, Jing [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Chen, Guian [Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Reproductive Medical Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Fan, Dongsheng, E-mail: dsfan@yahoo.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Deng, Min, E-mail: dengmin1706@yahoo.com.cn [Department of Neurology, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China); Clinical Stem Cell Center, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191 (China)

    2011-01-14

    Research highlights: {yields} Nicotinamide inhibit Sirt1. {yields} MASH1 and Ngn2 activation. {yields} Increase the expression of HB9. {yields} Motoneurons formation increases significantly. -- Abstract: Several protocols direct human embryonic stem cells (hESCs) toward differentiation into functional motoneurons, but the efficiency of motoneuron generation varies based on the human ESC line used. We aimed to develop a novel protocol to increase the formation of motoneurons from human ESCs. In this study, we tested a nuclear histone deacetylase protein, Sirt1, to promote neural precursor cell (NPC) development during differentiation of human ESCs into motoneurons. A specific inhibitor of Sirt1, nicotinamide, dramatically increased motoneuron formation. We found that about 60% of the cells from the total NPCs expressed HB9 and {beta}III-tubulin, commonly used motoneuronal markers found in neurons derived from ESCs following nicotinamide treatment. Motoneurons derived from ESC expressed choline acetyltransferase (ChAT), a positive marker of mature motoneuron. Moreover, we also examined the transcript levels of Mash1, Ngn2, and HB9 mRNA in the differentiated NPCs treated with the Sirt1 activator resveratrol (50 {mu}M) or inhibitor nicotinamide (100 {mu}M). The levels of Mash1, Ngn2, and HB9 mRNA were significantly increased after nicotinamide treatment compared with control groups, which used the traditional protocol. These results suggested that increasing Mash1 and Ngn2 levels by inhibiting Sirt1 could elevate HB9 expression, which promotes motoneuron differentiation. This study provides an alternative method for the production of transplantable motoneurons, a key requirement in the development of hESC-based cell therapy in motoneuron disease.

  1. [Macrophages promote the migration of neural stem cells into mouse spinal cord injury site].

    Cheng, Zhijian; Zhu, Wen; Li, Haopeng; He, Xijing

    2016-09-01

    Objective To explore the role of macrophages in the migration of neural stem cells (NSCs) in vivo and in vitro . Methods NSCs with green fluorescent protein (GFP) were isolated from GFP transgenic mice and the immunofluorescence cytochemical staining of nestin was used to identify NSCs. After spinal cord injury was induced, the tissue level of macrophage chemotactic protein-1 (MCP-1) mRNA was detected using quantitative real time PCR. The migration of GFP-NSCs was investigated 1 week after GFP-NSCs were injected into both sides of the damaged area. The effect of macrophage on the migration of NSCs in vitro was tested by Transwell(TM) system and the content of MCP-1 was detected by ELISA. Results NSCs highly expressed nestin. Compared with the control group, the level of MCP-1 mRNA significantly increased in the spinal cord injury group. The NSCs which were injected into the spinal cord migrated into the center of the injured site where F4/80 was highly expressed. Macrophages significantly increased the number of migrating NSCs in vitro and the secretion of MCP-1. Conclusion Macrophages induce NSC migrating into the spinal cord injury site possibly through promoting the secretion of MCP-1. PMID:27609570

  2. ZEB1 Promotes Invasion in Human Fetal Neural Stem Cells and Hypoxic Glioma Neurospheres.

    Kahlert, Ulf D; Suwala, Abigail K; Raabe, Eric H; Siebzehnrubl, Florian A; Suarez, Maria J; Orr, Brent A; Bar, Eli E; Maciaczyk, Jaroslaw; Eberhart, Charles G

    2015-11-01

    Diffuse spread through brain parenchyma and the presence of hypoxic foci rimmed by neoplastic cells are two cardinal features of glioblastoma, and low oxygen is thought to drive movement of malignant gliomas in the core of the lesions. Transcription factors associated with epithelial-to-mesenchymal transition (EMT) have been linked to this invasion, and we found that hypoxia increased in vitro invasion up to fourfold in glioblastoma neurosphere lines and induced the expression of ZEB1. Immunohistochemical assessment of 295 surgical specimens consisting of various types of pediatric and adult brain cancers showed that ZEB1 expression was significantly higher in infiltrative lesions than less invasive tumors such as pilocytic astrocytoma and ependymoma. ZEB1 protein was also present in human fetal periventricular stem and progenitor cells and ZEB1 inhibition impaired migration of in vitro propagated human neural stem cells. The induction of ZEB1 protein in hypoxic glioblastoma neurospheres could be partially blocked by the HIF1alpha inhibitor digoxin. Targeting ZEB1 blocked hypoxia-augmented invasion of glioblastoma cells in addition to slowing them in normoxia. These data support the role for ZEB1 in invasive and high-grade brain tumors and suggest its key role in promoting invasion in the hypoxic tumor core as well as in the periphery. PMID:25521330

  3. International retrospective cohort study of neural tube defects in relation to folic acid recommendations : are the recommendations working?

    Botto, LD; Lisi, A; Robert-Gnansia, E; Erickson, JD; Vollset, SE; Mastroiacovo, P; Botting, B; Cocchi, G; de Vigan, C; de Walle, H; Feijoo, M; Irgens, LM; McDonnell, B; Merlob, P; Ritvanen, A; Scarano, G; Siffel, C; Metneki, J; Stoll, C; Smithells, R; Goujard, J

    2005-01-01

    Objective To evaluate the effectiveness of policies and recommendations on folic acid aimed at reducing the occurrence of neural tube defects. Design Retrospective cohort study of births monitored by birth defect registries. Setting 13 birth defects registries monitoring rates of neural tube defects

  4. Use of Ferritin Expression, Regulated by Neural Cell-Specific Promoters in Human Adipose Tissue-Derived Mesenchymal Stem Cells, to Monitor Differentiation with Magnetic Resonance Imaging In Vitro.

    Chengang Song

    Full Text Available The purpose of this study was to establish a method for monitoring the neural differentiation of stem cells using ferritin transgene expression, under the control of a neural-differentiation-inducible promoter, and magnetic resonance imaging (MRI. Human adipose tissue-derived mesenchymal stem cells (hADMSCs were transduced with a lentivirus containing the human ferritin heavy chain 1 (FTH1 gene coupled to one of three neural cell-specific promoters: human synapsin 1 promoter (SYN1p, for neurons, human glial fibrillary acidic protein promoter (GFAPp, for astrocytes, and human myelin basic protein promoter (MBPp, for oligodendrocytes. Three groups of neural-differentiation-inducible ferritin-expressing (NDIFE hADMSCs were established: SYN1p-FTH1, GFAPp-FTH1, and MBPp-FTH1. The proliferation rate of the NDIFE hADMSCs was evaluated using a Cell Counting Kit-8 assay. Ferritin expression was assessed with western blotting and immunofluorescent staining before and after the induction of differentiation in NDIFE hADMSCs. The intracellular iron content was measured with Prussian blue iron staining and inductively coupled plasma mass spectrometry. R2 relaxation rates were measured with MRI in vitro. The proliferation rates of control and NDIFE hADMSCs did not differ significantly (P > 0.05. SYN1p-FTH1, GFAPp-FTH1, and MBPp-FTH1 hADMSCs expressed specific markers of neurons, astrocytes, and oligodendrocytes, respectively, after neural differentiation. Neural differentiation increased ferritin expression twofold, the intracellular iron content threefold, and the R2 relaxation rate two- to threefold in NDIFE hADMSCs, resulting in notable hypointensity in T2-weighted images (P < 0.05. These results were cross-validated. Thus, a link between neural differentiation and MRI signals (R2 relaxation rate was established in hADMSCs. The use of MRI and neural-differentiation-inducible ferritin expression is a viable method for monitoring the neural differentiation of

  5. Phosphate limitation promotes unsaturated fatty acids and arachidonic acid biosynthesis by microalgae Porphyridium purpureum.

    Su, Gaomin; Jiao, Kailin; Li, Zheng; Guo, Xiaoyi; Chang, Jingyu; Ndikubwimana, Theoneste; Sun, Yong; Zeng, Xianhai; Lu, Yinghua; Lin, Lu

    2016-07-01

    Polyunsaturated fatty acids (PUFAs) are highly appreciated on their nutritive value for human health and aquaculture. P. purpureum, one of the red microalgae acknowledged as a promising accumulator of ARA, was chosen as the target algae in the present research. Effects of sodium bicarbonate (0.04-1.2 g/L), temperature (25, 30 and 33 °C) and phosphate (0.00-0.14 g/L) on biomass yield, total fatty acids (TFA) and arachidonic acid (ARA) accumulation were investigated systemically. NaHCO3 dose of 0.8 g/L and moderate temperature of 30 °C were preferred. In addition, TFA and ARA production were significantly enhanced by an appropriate concentration of phosphate, and the highest TFA yield of 666.38 mg/L and ARA yield of 159.74 mg/L were obtained at a phosphate concentration of 0.035 g/L. Interestingly, with phosphate concentration continuing to fall, UFA/TFA and ARA/EPA ratios were increased accordingly, suggesting that phosphate limitation promoted unsaturated fatty acids and arachidonic acid biosynthesis. Low concentration of phosphate may be favored to increase the enzymatic activities of ∆6-desaturase, which played a key role in catalyzing the conversion of C16:0 to C18:2, and thus the selectivity of UFA increased. Meanwhile, the increase of ARA selectivity could be attributed to ω6 pathway promotion and ∆17-desaturase activity inhibition with phosphate limitation. Phosphate limitation strategy enhanced unsaturated fatty acids and ARA biosynthesis in P. purpureum, and can be applied in commercial scale manufacturing and commercialization of ARA. PMID:27004948

  6. Trifluoromethanesulfonic acid promoted Dakin-West reaction: An efficient and convenient synthesis of -acetamido ketones

    Ravindra M Kumbhare; Madabhushi Sridhar

    2012-03-01

    Trifluoromethanesulfonic acid promoted efficient condensation of an aromatic aldehyde with an acetophenone and acetonitrile in the presence of acetylchloride as an activator producing -acetamido carbonyl compounds is described.

  7. Wnt signaling pathway participates in valproic acid-induced neuronal differentiation of neural stem cells

    Wang, Li; Liu, Yuan; Li, Sen; Zai-yun LONG; Wu, Ya-min

    2015-01-01

    Neural stem cells (NSCs) are multipotent cells that have the capacity for differentiation into the major cell types of the nervous system, i.e. neurons, astrocytes and oligodendrocytes. Valproic acid (VPA) is a widely prescribed drug for seizures and bipolar disorder in clinic. Previously, a number of researches have been shown that VPA has differential effects on growth, proliferation and differentiation in many types of cells. However, whether VPA can induce NSCs from embryonic cerebral cor...

  8. p63 promotes cell survival through fatty acid synthase.

    Venkata Sabbisetti

    Full Text Available There is increasing evidence that p63, and specifically DeltaNp63, plays a central role in both development and tumorigenesis by promoting epithelial cell survival. However, few studies have addressed the molecular mechanisms through which such important function is exerted. Fatty acid synthase (FASN, a key enzyme that synthesizes long-chain fatty acids and is involved in both embryogenesis and cancer, has been recently proposed as a direct target of p53 family members, including p63 and p73. Here we show that knockdown of either total or DeltaN-specific p63 isoforms in squamous cell carcinoma (SCC9 or immortalized prostate epithelial (iPrEC cells caused a decrease in cell viability by inducing apoptosis without affecting the cell cycle. p63 silencing significantly reduced both the expression and the activity of FASN. Importantly, stable overexpression of either FASN or myristoylated AKT (myr-AKT was able to partially rescue cells from cell death induced by p63 silencing. FASN induced AKT phosphorylation and a significant reduction in cell viability was observed when FASN-overexpressing SCC9 cells were treated with an AKT inhibitor after p63 knockdown, indicating that AKT plays a major role in FASN-mediated survival. Activated AKT did not cause any alteration in the FASN protein levels but induced its activity, suggesting that the rescue from apoptosis documented in the p63-silenced cells expressing myr-AKT cells may be partially mediated by FASN. Finally, we demonstrated that p63 and FASN expression are positively associated in clinical squamous cell carcinoma samples as well as in the developing prostate. Taken together, our findings demonstrate that FASN is a functionally relevant target of p63 and is required for mediating its pro-survival effects.

  9. Dysregulated hepatic bile acids collaboratively promote liver carcinogenesis.

    Xie, Guoxiang; Wang, Xiaoning; Huang, Fengjie; Zhao, Aihua; Chen, Wenlian; Yan, Jingyu; Zhang, Yunjing; Lei, Sha; Ge, Kun; Zheng, Xiaojiao; Liu, Jiajian; Su, Mingming; Liu, Ping; Jia, Wei

    2016-10-15

    Dysregulated bile acids (BAs) are closely associated with liver diseases and attributed to altered gut microbiota. Here, we show that the intrahepatic retention of hydrophobic BAs including deoxycholate (DCA), taurocholate (TCA), taurochenodeoxycholate (TCDCA), and taurolithocholate (TLCA) were substantially increased in a streptozotocin and high fat diet (HFD) induced nonalcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mouse model. Additionally chronic HFD-fed mice spontaneously developed liver tumors with significantly increased hepatic BA levels. Enhancing intestinal excretion of hydrophobic BAs in the NASH-HCC model mice by a 2% cholestyramine feeding significantly prevented HCC development. The gut microbiota alterations were closely correlated with altered BA levels in liver and feces. HFD-induced inflammation inhibited key BA transporters, resulting in sustained increases in intrahepatic BA concentrations. Our study also showed a significantly increased cell proliferation in BA treated normal human hepatic cell lines and a down-regulated expression of tumor suppressor gene CEBPα in TCDCA treated HepG2 cell line, suggesting that several hydrophobic BAs may collaboratively promote liver carcinogenesis. PMID:27273788

  10. Near-infrared Spectral Detection of the Content of Soybean Fat Acids Based on Genetic Multilayer Feed forward Neural Network

    CHAI Yu-hua; PAN Wei; NING Hai-long

    2005-01-01

    In the paper, a method of building mathematic model employing genetic multilayer feed forward neural network is presented, and the quantitative relationship of chemical measured values and near-infrared spectral data is established. In the paper, quantitative mathematic model related chemical assayed values and near-infrared spectral data is established by means of genetic multilayer feed forward neural network, acquired near-infrared spectral data are taken as input of network with the content of five kinds of fat acids tested from chemical method as output,weight values of multilayer feed forward neural network are trained by genetic algorithms and detection model of neural network of soybean is built. A kind of multilayer feed forward neural network trained by genetic algorithms is designed in the paper. Through experiments, all the related coefficients of five fat acids can approach 0.9 which satisfies the preliminary test of soybean breeding.

  11. Dennexin peptides modeled after the homophilic binding sites of the neural cell adhesion molecule (NCAM) promote neuronal survival, modify cell adhesion and impair spatial learning

    Køhler, Lene B; Christensen, Claus; Rossetti, Clara; Fantin, Martina; Sandi, Carmen; Bock, Elisabeth; Berezin, Vladimir

    2010-01-01

    Neural cell adhesion molecule (NCAM)-mediated cell adhesion results in activation of intracellular signaling cascades that lead to cellular responses such as neurite outgrowth, neuronal survival, and modulation of synaptic activity associated with cognitive processes. The crystal structure of the...... between Ig1 and Ig3 and between Ig2 and Ig2, respectively, observed in the crystal structure. Although the two dennexin peptides differed in amino acid sequence, they both modulated cell adhesion, reflected by inhibition of NCAM-mediated neurite outgrowth. Both dennexins also promoted neuronal survival...... immunoglobulin (Ig) 1-2-3 fragment of the NCAM ectodomain has revealed novel mechanisms for NCAM homophilic adhesion. The present study addressed the biological significance of the so called dense zipper formation of NCAM. Two peptides, termed dennexinA and dennexinB, were modeled after the contact interfaces...

  12. Tungsten carbide promoted Pd and Pd–Co electrocatalysts for formic acid electrooxidation

    Yin, Min; Li, Qingfeng; Jensen, Jens Oluf; Huang, Yunjie; Cleemann, Lars Nilausen; Bjerrum, Niels; Xing, Wei

    2012-01-01

    Tungsten carbide (WC) promoted palladium (Pd) and palladium–cobalt (Pd–Co) nanocatalysts are prepared and characterized for formic acid electrooxidation. The WC as the dopant to carbon supports is found to enhance the CO tolerance and promote the activity of the Pd-based catalysts for formic acid...

  13. SEM ANALYSIS OF THE ACID-ETCHED ENAMEL PATTERNS PROMOTED BY ACIDIC MONOMERS AND PHOSPHORIC ACIDS

    Mirela Sanae Shinohara; Marcelo Tavares de Oliveira; Vinícius Di Hipólito; Marcelo Giannini; Mario Fernando de Goes

    2006-01-01

    ABSTRACT OBJECTIVE: Although self-etching bonding systems (SES) are indicated to prepare dental enamel for bonding, concerns have been expressed regarding their effectiveness. The aim of this study was to analyze the etching pattern (EP) of nine SES in comparison with 35% and 34% phosphoric acid etchants (FA) on intact (IN) and ground (GR) enamel surface. MATERIALS AND METHODS: Twenty-two human third molars were sectioned in mesial-distal and buccal-lingual directions, and four dental fragmen...

  14. Gene expression in retinoic acid-induced neural tube defects A cDNA mieroarray analysis

    Xiaodong Long; Zhong Yang; Yi Zeng; Hongli Li; Yangyun Han; Chao You

    2009-01-01

    BACKGROUND: Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regulation are still unknown.OBJECTIVE: To compare the differences in gene expression between normal embryos and those with neural tube defects.DESIGN, TIME AND SETTING: A neural development study was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA between January 2006 and October 2007.MATERIALS: Among 120 adult Kunming mice, 60 pregnant mice were randomly and evenly divided into a retinoic acid group (n = 30) and a normal control group (n =30). The retinoic acid was produced by Sigma, USA, the gene microarray by the Amersham Pharmacia Company, Hong Kong, and the gene sequence was provided by the Incyte database, USA.METHODS: Retinoic acid was administered to prepare models of neural tube defects, and corn oil was similady administered to the normal control group. Total RNA was extracted from embryonic tissue of the two groups using a Trizol kit, and a cDNA microarray containing 1 100 known genes was used to compare differences in gene expression between the normal control group and the retinoic acid group on embryonic (E) clay 10.5 and 11.5. Several differentially expressed genes were randomly selected from the two groups for Northern blotting, to verify the results of the cDNA microarray.MAIN OUTCOME MEASURES: Morphological changes and differential gene expression between the normal control group and the retinoic acid group.RESULTS: Anatomical microscopy demonstrated that an intact closure of the brain was formed in the normal mouse embryos by days E10.5 and E11.5. The cerebral appearance was full and smooth, and the surface of the spine was intact. However, in the retinoic acid group on days E10.5 and E11.5, there were more dead embryos. Morphological malformations typically included non-closure at the top of

  15. Acid adaptation promotes survival of Salmonella spp. in cheese.

    Leyer, G J; Johnson, E A

    1992-01-01

    Salmonella typhimurium was adapted to acid by exposure to hydrochloric acid at pH 5.8 for one to two doublings. Acid-adapted cells had increased resistance to inactivation by organic acids commonly present in cheese, including lactic, propionic, and acetic acids. Recovery of cells during the treatment with organic acids was increased 1,000-fold by inclusion of 0.1% sodium pyruvate in the recovery medium. Acid-adapted S. typhimurium cells survived better than nonadapted cells during a milk fer...

  16. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    Khalifa, Shaden A.M., E-mail: shaden.khalifa@ki.se [Department of Neuroscience, Karolinska Institute, Stockholm (Sweden); Medina, Philippe de [Affichem, Toulouse (France); INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); Erlandsson, Anna [Department of Public Health and Caring Sciences, Uppsala University, Uppsala (Sweden); El-Seedi, Hesham R. [Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala (Sweden); Silvente-Poirot, Sandrine [INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); University of Toulouse III, Toulouse (France); Institut Claudius Regaud, Toulouse (France); Poirot, Marc, E-mail: marc.poirot@inserm.fr [INSERM UMR 1037, Team “Sterol Metabolism and Therapeutic Innovations in Oncology”, Cancer Research Center of Toulouse, F-31052 Toulouse (France); University of Toulouse III, Toulouse (France); Institut Claudius Regaud, Toulouse (France)

    2014-04-11

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain.

  17. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells

    Highlights: • Dendrogenin A and B are new aminoalkyl oxysterols. • Dendrogenins stimulated neural stem cells proliferation. • Dendrogenins induce neuronal outgrowth from neurospheres. • Dendrogenins provide new therapeutic options for neurodegenerative disorders. - Abstract: Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. Taken together, our results demonstrate a novel role for dendrogenins A and B in neural stem cell proliferation and differentiation which further increases their likely importance to compensate for neuronal cell loss in the brain

  18. The novel steroidal alkaloids dendrogenin A and B promote proliferation of adult neural stem cells.

    Khalifa, Shaden,; de Medina, Philippe; Erlandsson, Anna; El-Seedi, Hesham; Silvente-Poirot, Sandrine; Poirot, Marc

    2014-01-01

    International audience Dendrogenin A (DDA) and dendrogenin B (DDB) are new aminoalkyl oxysterols which display re-differentiation of tumor cells of neuronal origin at nanomolar concentrations. We analyzed the influence of dendrogenins on adult mice neural stem cell proliferation, sphere formation and differentiation. DDA and DDB were found to have potent proliferative effects in neural stem cells. Additionally, they induce neuronal outgrowth from neurospheres during in vitro cultivation. T...

  19. A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2.

    Daniela Annibali

    Full Text Available The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9 and miR-103--restrain ID2 expression by directly targeting the coding sequence and 3' untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development.

  20. Optimal time point for the transplantation of neural stem cells induced to differentiate with retinoic acid

    Shuxin Wang; Dengji Pan; Na Liu; Yongming Liu; Juan Chen; Houjie Ni; Zhouping Tang

    2011-01-01

    Previous studies have demonstrated that differentiated neural stem cells (NSCs) are more suitable for transplantation than non-differentiated NSCs. In this study, NSCs were expanded in vitro for two passages, induced with retinoic acid to differentiate, and harvested between 1-6 days later. They were subsequently cultured in artificial cerebrospinal fluid for an additional 3 days, during which their growth and morphology was monitored. NSCs induced for 4 days exhibited a peak rate of cells differentiating into neurons and robust growth. Our results indicate that the optimal time point for transplanting NSCs is following a 4-day period of induced differentiation.

  1. MetaProm: a neural network based meta-predictor for alternative human promoter prediction

    Wang Junwen; Ungar Lyle H; Tseng Hung; Hannenhalli Sridhar

    2007-01-01

    Abstract Background De novo eukaryotic promoter prediction is important for discovering novel genes and understanding gene regulation. In spite of the great advances made in the past decade, recent studies revealed that the overall performances of the current promoter prediction programs (PPPs) are still poor, and predictions made by individual PPPs do not overlap each other. Furthermore, most PPPs are trained and tested on the most-upstream promoters; their performances on alternative promot...

  2. Modeling and prediction of retardance in citric acid coated ferrofluid using artificial neural network

    Lin, Jing-Fung; Sheu, Jer-Jia

    2016-06-01

    Citric acid coated (citrate-stabilized) magnetite (Fe3O4) magnetic nanoparticles have been conducted and applied in the biomedical fields. Using Taguchi-based measured retardances as the training data, an artificial neural network (ANN) model was developed for the prediction of retardance in citric acid (CA) coated ferrofluid (FF). According to the ANN simulation results in the training stage, the correlation coefficient between predicted retardances and measured retardances was found to be as high as 0.9999998. Based on the well-trained ANN model, the predicted retardance at excellent program from Taguchi method showed less error of 2.17% compared with a multiple regression (MR) analysis of statistical significance. Meanwhile, the parameter analysis at excellent program by the ANN model had the guiding significance to find out a possible program for the maximum retardance. It was concluded that the proposed ANN model had high ability for the prediction of retardance in CA coated FF.

  3. Omega-3 Polyunsaturated Fatty Acids Protect Neural Progenitor Cells against Oxidative Injury

    Qiang Liu

    2014-04-01

    Full Text Available The omega-3 polyunsaturated fatty acids (ω-3 PUFAs, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, derived mainly from fish oil, play important roles in brain development and neuroplasticity. Here, we reported that application of ω-3 PUFAs significantly protected mouse neural progenitor cells (NPCs against H2O2-induced oxidative injury. We also isolated NPCs from transgenic mice expressing the Caenorhabditis elegans fat-1 gene. The fat-1 gene, which is absent in mammals, can add a double bond into an unsaturated fatty acid hydrocarbon chain and convert ω-6 to ω-3 fatty acids. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining showed that a marked decrease in apoptotic cells was found in fat-1 NPCs after oxidative injury with H2O2 as compared with wild-type NPCs. Quantitative RT-PCR and Western blot analysis demonstrated a much higher expression of nuclear factor erythroid 2-related factor 2 (Nrf2, a master transcriptional factor for antioxidant genes, in fat-1 NPCs. The results of the study provide evidence that ω-3 PUFAs resist oxidative injury to NPCs.

  4. Lipoic acid enhances survival of transplanted neural stem cells by reducing transplantation-associated injury

    Gao J

    2013-07-01

    Full Text Available Junling Gao,1,* Jason R Thonhoff,1,2,* Tiffany J Dunn,1 Ping Wu1 1Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX, USA; 2Department of Neurology, The Methodist Hospital, Houston, TX, USA *These authors contributed equally to this work Abstract: The efficacy of stem cell-based therapy for neurological diseases depends highly on cell survival post-transplantation. One of the key factors affecting cell survival is the grafting procedure. The current study aims to determine whether needle insertion into intact rat spinal cords creates a hypoxic environment that is prone to lipid peroxidation damage upon reperfusion, and whether an antioxidant protects human neural stem cells (hNSCs both in vitro and post-transplantation into rat spinal cords. We show here that a single needle injection creates a hypoxic environment within the rat spinal cord that peaks at approximately 12 hours before reperfusion occurs. Lipid peroxidation damage at the transplantation site is evident by 48 hours post-needle insertion. In an in vitro model, hypoxia-reperfusion results in apoptotic death of hNSCs. Pretreatment with the antioxidant, α-lipoic acid, protects hNSCs against hypoxia-reperfusion injury and oxidative stress–mediated cell death. Increasing glutathione, but not Akt signaling, contributes to the protective effect of lipoic acid. Pretreating hNSCs with lipoic acid also increases the cell survival rate 1 month post-transplantation. Further investigation is warranted to develop improved techniques to maximize the survival of transplanted stem cells. Keywords: neural stem cell, transplantation, hypoxia-reperfusion, antioxidant, cell survival, lipoic acid

  5. Mechanisms of action of okadaic acid class tumor promoters on mouse skin

    Fujiki, Hirota; Suganuma, Masami; Yoshizawa, Seiji; Nishiwaki, Shinji; Winyar, Boonsong (National Cancer Center Research Inst., Tokyo (Japan)); Sugimura, Takashi (National Cancer Center, Tokyo (Japan))

    1991-06-01

    Okadaic acid, dinophysistoxin-1 (35-methylokadaic acid), and calyculin A are the okadaic acid class of non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoters, which do not bind to the phorbol ester receptors in cell membranes or activate protein kinase C in vitro. They have potent tumor-promoting activities on mouse skin, as strong as TPA-type tumor promoters, such as TPA, teleocidin, and aplysiatoxin. DNA samples isolated from tumors induced by dimethylbenz(a)anthracene and each of the okadaic acid class tumor promoters had the same mutation at the second nucleotide of codon 61 (CAA to CTA) in the c-H-ras gene. Okadaic acid receptors, protein phosphatases 1 and 2A, are present in the particulate as well as cytosolic fractions of various mouse tissues. The apparent activation of protein kinases by the okadaic acid class tumor promoters, after their incubation with {sup 32}P-ATP, protein kinases, and protein phosphatases, was observed. This activation was caused by inhibition of protein phosphatases 1 and 2A by the okadaic acid class tumor promoters. Treatment of primary human fibroblasts and human keratinocytes with the okadaic acid class tumor promoters induced the hyperphosphorylation of a 60-k-Da protein in nuclear and cytosolic fractions, due to the inhibition of protein phosphatases. The 60-kDa protein is a proteolytic fragment of nucleolin, a major nonhistone protein and is designated as N-60. The mechanisms of action of the okadaic acid class tumor promoters are discussed with emphasis on the inhibition of protein phosphatase activity.

  6. Disruption of retinoic acid receptor alpha reveals the growth promoter face of retinoic acid.

    Giulia Somenzi

    Full Text Available BACKGROUND: Retinoic acid (RA, the bioactive derivative of Vitamin A, by epigenetically controlling transcription through the RA-receptors (RARs, exerts a potent antiproliferative effect on human cells. However, a number of studies show that RA can also promote cell survival and growth. In the course of one of our studies we observed that disruption of RA-receptor alpha, RARalpha, abrogates the RA-mediated growth-inhibitory effects and unmasks the growth-promoting face of RA (Ren et al., Mol. Cell. Biol., 2005, 25:10591. The objective of this study was to investigate whether RA can differentially govern cell growth, in the presence and absence of RARalpha, through differential regulation of the "rheostat" comprising ceramide (CER, the sphingolipid with growth-inhibitory activity, and sphingosine-1-phosphate (S1P, the sphingolipid with prosurvival activity. METHODOLOGY/PRINCIPAL FINDINGS: We found that functional inhibition of endogenous RARalpha in breast cancer cells by using either RARalpha specific antagonists or a dominant negative RARalpha mutant hampers on one hand the RA-induced upregulation of neutral sphingomyelinase (nSMase-mediated CER synthesis, and on the other hand the RA-induced downregulation of sphingosine kinase 1, SK1, pivotal for S1P synthesis. In association with RA inability to regulate the sphingolipid rheostat, cells not only survive, but also grow more in response to RA both in vitro and in vivo. By combining genetic, pharmacological and biochemical approaches, we mechanistically demonstrated that RA-induced growth is, at least in part, due to non-RAR-mediated activation of the SK1-S1P signaling. CONCLUSIONS/SIGNIFICANCE: In the presence of functional RARalpha, RA inhibits cell growth by concertedly, and inversely, modulating the CER and S1P synthetic pathways. In the absence of a functional RARalpha, RA-in a non-RAR-mediated fashion-promotes cell growth by activating the prosurvival S1P signaling. These two distinct

  7. DISP3 promotes proliferation and delays differentiation of neural progenitor cells

    Zíková, Martina; Konířová, Jana; Ditrychová, Karolína; Corlett, Alicia; Kolář, Michal; Bartůněk, Petr

    2014-01-01

    Roč. 588, č. 21 (2014), s. 4071-4077. ISSN 0014-5793 R&D Projects: GA ČR GAP301/12/1478; GA MŠk LO1220 Keywords : Cancer * Proliferation * Neural cells * Differentiation * Lipids Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.169, year: 2014

  8. Retinoic acid enhances expression of neural specific genes in Sca-1+ cells of mouse fetal liver through activating protein kinase C

    Gexiu Liu; Yuan Zhang; Dongmei He

    2006-01-01

    BACKGROUND: Interstitial stem cell is characterized by multiple differentiations,and retinoic acid (RA) can induce differentiation of stromal cells into nerve tissue cells in fetal liver of mice, so, its signal transduction pathway should be discussed to trigger differentiation.OBJECTIVE: To study the effect of RA on expression of neural specific gene and its signal transduction in fetal liver of mice.DESIGN: Paired controlled study on the basis of cell.SETTING: Institute of Hematology, Medical College of Jinan University.MATERIALS: The experiment was completed in the Institute of Hematology, Medical College of Jinan University from April to December 2005. C57BL/6 mice, of clean grade, aged 8-10 weeks, weighting 20-35 g,10 females and 4 males, were selected in this study.METHODS: Sca-1+ cells in fetal liver were prepared with MACS kit and cultured with DMEM + 10% fetal bovine serum (FBS). On the fourth day, it was added with or without protein kinase C (PKC) inhibitor chelerythrine chloride (3 μmol/L) and 5×10-7 mol/L RA for 24 hours, and then incubated in serum-free medium for 5 days. Expressions of genes were assayed by Western blotting and semi-quantitative RT-PCR.MAIN OUTCOME MEASURES: Expression of neural specific gene NF-L, NF-H, BF-1 and TH.RESULTS: Expression of neural specific gene NF-L, NF-H, BF-1 and TH was significantly increased after treatment with RA and they were increased 5.06, 5.15, 4.63 and 3.33 times, respectively. However, chelerythrine chloride could inhibit expression of neural specific gene NF-L, NF-H, BF-1 and TH induced by RA.CONCLUSION: RA can promote the expression of neural specific genes in Sca-1+ cells of fetal liver, and its pathway may be related to PKC.

  9. Role of Arachidonic Acid in Promoting Hair Growth

    Munkhbayar, Semchin; Jang, Sunhyae; Cho, A-Ri; Choi, Soon-Jin; Shin, Chang Yup; Eun, Hee Chul; Kim, Kyu Han; Kwon, Ohsang

    2016-01-01

    Background Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid present in all mammalian cell membranes, and involved in the regulation of many cellular processes, including cell survival, angiogenesis, and mitogenesis. The dermal papilla, composed of specialized fibroblasts located in the bulb of the hair follicle, contributes to the control of hair growth and the hair cycle. Objective This study investigated the effect of AA on hair growth by using in vivo and in vitro models. Met...

  10. Omega-3 Polyunsaturated Fatty Acids Enhance Neuronal Differentiation in Cultured Rat Neural Stem Cells

    Masanori Katakura

    2013-01-01

    Full Text Available Polyunsaturated fatty acids (PUFAs can induce neurogenesis and recovery from brain diseases. However, the exact mechanisms of the beneficial effects of PUFAs have not been conclusively described. We recently reported that docosahexaenoic acid (DHA induced neuronal differentiation by decreasing Hes1 expression and increasing p27kip1 expression, which causes cell cycle arrest in neural stem cells (NSCs. In the present study, we examined the effect of eicosapentaenoic acid (EPA and arachidonic acid (AA on differentiation, expression of basic helix-loop-helix transcription factors (Hes1, Hes6, and NeuroD, and the cell cycle of cultured NSCs. EPA also increased mRNA levels of Hes1, an inhibitor of neuronal differentiation, Hes6, an inhibitor of Hes1, NeuroD, and Map2 mRNA and Tuj-1-positive cells (a neuronal marker, indicating that EPA induced neuronal differentiation. EPA increased the mRNA levels of p21cip1 and p27kip1, a cyclin-dependent kinase inhibitor, which indicated that EPA induced cell cycle arrest. Treatment with AA decreased Hes1 mRNA but did not affect NeuroD and Map2 mRNA levels. Furthermore, AA did not affect the number of Tuj-1-positive cells or cell cycle progression. These results indicated that EPA could be involved in neuronal differentiation by mechanisms alternative to those of DHA, whereas AA did not affect neuronal differentiation in NSCs.

  11. Effect of Ultrasonic Frequency on Lactic Acid Fermentation Promotion by Ultrasonic Irradiation

    Shimada, Tadayuki; Ohdaira, Etsuzo; Masuzawa, Nobuyoshi

    2004-05-01

    The authors have been researching the promotion of lactic acid fermentation by ultrasonic irradiation. In the past research, it was proven that ultrasonic irradiation is effective in the process of fermentation, and the production of yoghurt and kefir was promoted. In this study, the effect of the ultrasonic frequency in this fermentation process was examined. In the frequency range of this study, it was found that the action of fermentation promotion was exponentially proportionate to the irradiated ultrasonic frequency.

  12. Neural-Induced Human Mesenchymal Stem Cells Promote Cochlear Cell Regeneration in Deaf Guinea Pigs

    Jang, Sujeong; Cho, Hyong-Ho; Kim, Song-Hee; Lee, Kyung-Hwa; Jun, Jae Yeoul; Park, Jong-Seong; Jeong, Han-Seong; Cho, Yong-Beom

    2015-01-01

    Objectives In mammals, cochlear hair cell loss is irreversible and may result in a permanent sensorineural hearing loss. Secondary to this hair cell loss, a progressive loss of spiral ganglion neurons (SGNs) is presented. In this study, we have investigated the effects of neural-induced human mesenchymal stem cells (NI-hMSCs) from human bone marrow on sensory neuronal regeneration from neomycin treated deafened guinea pig cochleae. Methods HMSCs were isolated from the bone marrow which was ob...

  13. Endogenous Expression of Matriptase in Neural Progenitor Cells Promotes Cell Migration and Neuron Differentiation*

    Fang, Jung-Da; Chou, Hsiao-Chin; Tung, Hsiu-Hui; Huang, Pao-Yi; Lee, Sheau-Ling

    2010-01-01

    Recent studies show that type II transmembrane serine proteases play important roles in diverse cellular activities and pathological processes. Their expression and functions in the central nervous system, however, are largely unexplored. In this study, we show that the expression of one such member, matriptase (MTP), was cell type-restricted and primarily expressed in neural progenitor (NP) cells and neurons. Blocking MTP expression or MTP activity prevented NP cell traverse of reconstituted...

  14. Fatty acid extracts from Lucilia sericata larvae promote murine cutaneous wound healing by angiogenic activity

    Zhang Jianing

    2010-03-01

    Full Text Available Abstract Background fatty acids are considered to be effective components to promote wound healing and Lucilia sericata larvae are applied clinically to treat intractable wounds. We aimed to investigat the effect of fatty acid extracts from dried Lucilia sericata larvae on murine cutaneuous wound healing as well as angiogenesis. Results On day 7 and 10 after murine acute excision wounds creation, the percent wound contraction of fatty acid extracts group was higher than that of vaseline group. On day 3, 7 and 10 after wounds creation, the wound healing quality of fatty acid extracts group was better than that of vaseline group on terms of granulation formation and collagen organization. On day 3 after wounds creation, the micro vessel density and vascular endothelial growth factor expression of fatty acid extracts group were higher than that of vaseline group. Component analysis of the fatty acid extracts by gas chromatography-mass spectrometry showed there were 10 kinds of fatty acids in total and the ratio of saturated fatty acid, monounsaturated fatty acid and polyunsaturated fatty acid (PUFA was: 20.57%:60.32%:19.11%. Conclusions Fatty acid extracts from dried Lucilia sericata larvae, four fifths of which are unsaturated fatty acids, can promote murine cutaneous wound healing probably resulting from the powerful angiogenic activity of the extracts.

  15. p-Nitrobenzoic acid promoted synthesis of 1,5-benzodiazepine derivatives

    Varala, Ravi; Enugala, Ramu; Adapa, Srinivas R. [Indian Institute of Chemical Technology, Hyderabad (India)]. E-mail: rvarala_iict@yahoo.co.in

    2007-03-15

    p-Nitrobenzoic acid was found to be the versatile Bronsted organic acid promoter among the carboxylic acids tested for the preparation of 1,5-benzodiazepine derivatives from a wide range of substituted o-phenylenediamines and ketones. The corresponding products were obtained in good isolated yields (62-92%) under mild conditions using acetonitrile as solvent at ambient temperature. Further, the reagent could be easily recovered and reused. (author00.

  16. Distinctive effects of eicosapentaenoic and docosahexaenoic acids in regulating neural stem cell fate are mediated via endocannabinoid signalling pathways.

    Dyall, S C; Mandhair, H K; Fincham, R E A; Kerr, D M; Roche, M; Molina-Holgado, F

    2016-08-01

    Emerging evidence suggests a complex interplay between the endocannabinoid system, omega-3 fatty acids and the immune system in the promotion of brain self-repair. However, it is unknown if all omega-3 fatty acids elicit similar effects on adult neurogenesis and if such effects are mediated or regulated by interactions with the endocannabinoid system. This study investigated the effects of DHA and EPA on neural stem cell (NSC) fate and the role of the endocannabinoid signalling pathways in these effects. EPA, but not DHA, significantly increased proliferation of NSCs compared to controls, an effect associated with enhanced levels of the endocannabinoid 2-arachidonylglycerol (2-AG) and p-p38 MAPK, effects attenuated by pre-treatment with CB1 (AM251) or CB2 (AM630) receptor antagonists. Furthermore, in NSCs derived from IL-1β deficient mice, EPA significantly decreased proliferation and p-p38 MAPK levels compared to controls, suggesting a key role for IL-1β signalling in the effects observed. Although DHA similarly increased 2-AG levels in wild-type NSCs, there was no concomitant increase in proliferation or p-p38 MAPK activity. In addition, in NSCs from IL-1β deficient mice, DHA significantly increased proliferation without effects on p-P38 MAPK, suggesting effects of DHA are mediated via alternative signalling pathways. These results provide crucial new insights into the divergent effects of EPA and DHA in regulating NSC proliferation and the pathways involved, and highlight the therapeutic potential of their interplay with endocannabinoid signalling in brain repair. PMID:27044662

  17. A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution.

    Crawford, Michael A; Broadhurst, C Leigh; Guest, Martin; Nagar, Atulya; Wang, Yiqun; Ghebremeskel, Kebreab; Schmidt, Walter F

    2013-01-01

    Six hundred million years ago, the fossil record displays the sudden appearance of intracellular detail and the 32 phyla. The "Cambrian Explosion" marks the onset of dominant aerobic life. Fossil intracellular structures are so similar to extant organisms that they were likely made with similar membrane lipids and proteins, which together provided for organisation and specialisation. While amino acids could be synthesised over 4 billion years ago, only oxidative metabolism allows for the synthesis of highly unsaturated fatty acids, thus producing novel lipid molecular species for specialised cell membranes. Docosahexaenoic acid (DHA) provided the core for the development of the photoreceptor, and conversion of photons into electricity stimulated the evolution of the nervous system and brain. Since then, DHA has been conserved as the principle acyl component of photoreceptor synaptic and neuronal signalling membranes in the cephalopods, fish, amphibian, reptiles, birds, mammals and humans. This extreme conservation in electrical signalling membranes despite great genomic change suggests it was DHA dictating to DNA rather than the generally accepted other way around. We offer a theoretical explanation based on the quantum mechanical properties of DHA for such extreme conservation. The unique molecular structure of DHA allows for quantum transfer and communication of π-electrons, which explains the precise depolarisation of retinal membranes and the cohesive, organised neural signalling which characterises higher intelligence. PMID:23206328

  18. Neural networks applied to determine the thermophysical properties of amino acid based ionic liquids.

    Cancilla, John C; Perez, Ana; Wierzchoś, Kacper; Torrecilla, José S

    2016-03-01

    A series of models based on artificial neural networks (ANNs) have been designed to estimate the thermophysical properties of different amino acid-based ionic liquids (AAILs). Three different databases of AAILs were modeled using these algorithms with the goal set to estimate the density, viscosity, refractive index, ionic conductivity, and thermal expansion coefficient, and requiring only data regarding temperature and electronic polarizability of the chemicals. Additionally, a global model was designed combining all of the databases to determine the robustness of the method. In general, the results were successful, reaching mean prediction errors below 1% in many cases, as well as a statistically reliable and accurate global model. Attaining these successful models is a relevant fact as AAILs are novel biodegradable and biocompatible compounds which may soon make their way into the health sector forming a part of useful biomedical applications. Therefore, understanding the behavior and being able to estimate their thermophysical properties becomes crucial. PMID:26899458

  19. Microwave Irradiation Promoted Synthesis of Aryloxy Acetic Acids

    LIN Min; ZHOU Jin-mei; XIA Hai-ping; YANG Rui-feng; LIN Chen

    2004-01-01

    Several aryloxy acetic acids were synthesized under microwave irradiation. The factors, which affect the reaction, were investigated and optimized. It was revealed that the best yields(92.7%-97.4%) were obtained when the molar ratio of the reactants was n(ArOH) : n(NaOH): n(ClCH2CO2H) =1: 2.5: 1.2 with microwave irradiation power of 640 W for 65-85 s.

  20. Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

    Kim, Joo Yeon; Choi, Kyuhyun; Shaker, Mohammed R; Lee, Ju-Hyun; Lee, Boram; Lee, Eunsoo; Park, Jae-Yong; Lim, Mi-Sun; Park, Chang-Hwan; Shin, Ki Soon; Kim, Hyun; Geum, Dongho; Sun, Woong

    2016-04-01

    Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy. Stem Cells 2016;34:888-901. PMID:26701067

  1. Regulation of endogenous neural stem/progenitor cells for neural repair - factors that promote neurogenesis and gliogenesis in the normal and damaged brain

    Kimberly eChristie

    2013-01-01

    Full Text Available Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ of the lateral ventricles and the subgranular zone (SGZ of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioural outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem /precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation.

  2. T cells promote the regeneration of neural precursor cells in the hippocampus of Alzheimer’s disease mice

    Jing Liu; Yuxin Ma; Sumin Tian; Li Zhang; Mengmeng Zhao; Yaqiong Zhang; Dachuan Xu

    2014-01-01

    Alzheimer’s disease is closely associated with disorders of neurogenesis in the brain, and growing evidence supports the involvement of immunological mechanisms in the development of the disease. However, at present, the role of T cells in neuronal regeneration in the brain is unknown. We injected amyloid-beta 1-42 peptide into the hippocampus of six BALB/c wild-type mice and six BALB/c-nude mice with T-cell immunodeifciency to establish an animal model of Alzhei-mer’s disease. A further six mice of each genotype were injected with same volume of normal saline. Immunohistochemistry revealed that the number of regenerated neural progenitor cells in the hippocampus of BALB/c wild-type mice was signiifcantly higher than that in BALB/c-nude mice. Quantitative fluorescence PCR assay showed that the expression levels of peripheral T cell-associated cytokines (interleukin-2, interferon-γ) and hippocampal microglia-related cyto-kines (interleukin-1β, tumor necrosis factor-α) correlated with the number of regenerated neural progenitor cells in the hippocampus. hTese results indicate that T cells promote hippocampal neurogenesis in Alzheimer’s disease and T-cell immunodeifciency restricts neuronal regeneration in the hippocampus. The mechanism underlying the promotion of neuronal regeneration by T cells is mediated by an increased expression of peripheral T cells and central microglial cytokines in Alzheimer’s disease mice. Our ifndings provide an experimental basis for understanding the role of T cells in Alzheimer’s disease.

  3. Hydroxycitric acid does not promote inflammation or liver toxicity

    Clouatre, Dallas L.; Preuss, Harry G.

    2013-01-01

    Garcinia cambogia extract (GC) with its active component consisting of hydroxycitric acid (HCA) is widely utilized for weight loss. Various HCA salts are available, including calcium, magnesium, potassium and mixtures of these. Experimentally, these salts exhibit different properties with some, but not all, improving glucose tolerance and blood pressure. Recently, obesity-prone C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without GC (1%, w/w) for 16 wk. The active arm re...

  4. Polypyrrole-coated electrospun poly(lactic acid) fibrous scaffold: effects of coating on electrical conductivity and neural cell growth.

    Sudwilai, Thitima; Ng, Jun Jye; Boonkrai, Chatikorn; Israsena, Nipan; Chuangchote, Surawut; Supaphol, Pitt

    2014-01-01

    Neuronal activities play critical roles in both neurogenesis and neural regeneration. In that sense, electrically conductive and biocompatible biomaterial scaffolds can be applied in various applications of neural tissue engineering. In this study, we fabricated a novel biomaterial for neural tissue engineering applications by coating electrospun poly(lactic acid) (PLA) nanofibers with a conducting polymer, polypyrole (PPy), via admicellar polymerization. Optimal conditions for polymerization and preparation of PPy-coated electrospun PLA nanofibers were obtained by comparing results from scanning electron microscopy, X-ray photoelectron spectrometer, and surface conductivity tests. In vitro cell culture experiments showed that PPy-coated electrospun PLA fibrous scaffold is not toxic. The scaffold could support attachment and migration of neural progenitor cells. Neurons derived from progenitor exhibited long neurite outgrowth under electrical stimulation. Our study concluded that PPy-coated electrospun PLA fibers had a good biocompatibility with neural progenitor cells and may serve as a promising material for controlling progenitor cell behaviors and enhancing neural repair. PMID:24933469

  5. Gallic Acid Promotes Wound Healing in Normal and Hyperglucidic Conditions.

    Yang, Dong Joo; Moh, Sang Hyun; Son, Dong Hwee; You, Seunghoon; Kinyua, Ann W; Ko, Chang Mann; Song, Miyoung; Yeo, Jinhee; Choi, Yun-Hee; Kim, Ki Woo

    2016-01-01

    Skin is the outermost layer of the human body that is constantly exposed to environmental stressors, such as UV radiation and toxic chemicals, and is susceptible to mechanical wounding and injury. The ability of the skin to repair injuries is paramount for survival and it is disrupted in a spectrum of disorders leading to skin pathologies. Diabetic patients often suffer from chronic, impaired wound healing, which facilitate bacterial infections and necessitate amputation. Here, we studied the effects of gallic acid (GA, 3,4,5-trihydroxybenzoic acid; a plant-derived polyphenolic compound) on would healing in normal and hyperglucidic conditions, to mimic diabetes, in human keratinocytes and fibroblasts. Our study reveals that GA is a potential antioxidant that directly upregulates the expression of antioxidant genes. In addition, GA accelerated cell migration of keratinocytes and fibroblasts in both normal and hyperglucidic conditions. Further, GA treatment activated factors known to be hallmarks of wound healing, such as focal adhesion kinases (FAK), c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinases (Erk), underpinning the beneficial role of GA in wound repair. Therefore, our results demonstrate that GA might be a viable wound healing agent and a potential intervention to treat wounds resulting from metabolic complications. PMID:27399667

  6. Promotion of neural sprouting using low-level green light-emitting diode phototherapy

    Alon, Noa; Duadi, Hamootal; Cohen, Ortal; Samet, Tamar; Zilony, Neta; Schori, Hadas; Shefi, Orit; Zalevsky, Zeev

    2015-02-01

    We irradiated neuroblastoma SH-SY5Y cell line with low-level light-emitting diode (LED) illumination at a visible wavelength of 520 nm (green) and intensity of 100 mW/cm2. We captured and analyzed the cell morphology before LED treatment, immediately after, and 12 and 24 h after treatment. Our study demonstrated that LED illumination increases the amount of sprouting dendrites in comparison to the control untreated cells. This treatment also resulted in more elongated cells after treatment in comparison to the control cells and higher levels of expression of a differentiation related gene. This result is a good indication that the proposed method could serve in phototherapy treatment for increasing sprouting and enhancing neural network formation.

  7. Familiarity promotes the blurring of self and other in the neural representation of threat.

    Beckes, Lane; Coan, James A; Hasselmo, Karen

    2013-08-01

    Neurobiological investigations of empathy often support an embodied simulation account. Using functional magnetic resonance imaging (fMRI), we monitored statistical associations between brain activations indicating self-focused threat to those indicating threats to a familiar friend or an unfamiliar stranger. Results in regions such as the anterior insula, putamen and supramarginal gyrus indicate that self-focused threat activations are robustly correlated with friend-focused threat activations but not stranger-focused threat activations. These results suggest that one of the defining features of human social bonding may be increasing levels of overlap between neural representations of self and other. This article presents a novel and important methodological approach to fMRI empathy studies, which informs how differences in brain activation can be detected in such studies and how covariate approaches can provide novel and important information regarding the brain and empathy. PMID:22563005

  8. 8-hydroxy-dipropylaminotetralin promotes neural plasticity in epileptic rats with depression

    Ping Yang; Meizhen Sun; Liang Li; Yihua Shen

    2012-01-01

    Rats with chronic pilocarpine-induced temporal lobe epilepsy complicated with depression were studied. Anti-5-bromodeoxyuridine immunofluorescence staining and Timms staining showed that neurogenesis within the hippocampal dentate gyrus and mossy fiber sprouting were increased in model rats. Neurogenesis within the hippocampal dentate gyrus was further enhanced, while mossy fiber sprouting was decreased in model rats administered carbamazepine alone or in combination with the 5-hydroxytryptamine 1A receptor agonist, 8-hydroxy-dipropylaminotetralin (0.1 and 1 mg/kg). Among the groups, the effect was the most significant in rats receiving carbamazepine in conjunction with 1 mg/kg 8-hydroxy-dipropylaminotetralin. Thus, high dose 8-hydroxy-dipropylaminotetralin can improve neural plasticity in epileptic rats with depression.

  9. State of available capacity estimation for lead-acid batteries in electric vehicles using neural network

    This paper reviews recent definitions of the state of charge (SOC) that are often used to estimate the battery residual available capacity (BRAC) for lead-acid batteries in electric vehicles (EVs) and identifies their shortcomings. Then, the state of available capacity (SOAC), instead of the SOC, is defined to denote the BRAC in EVs, which refers to the percentage of the battery available capacity (BAC) of the discharge current profile for the EV battery at the fully charged state. Based on the experimentation of different discharge current profiles, including theoretical current profiles and practical current profiles under EV driving cycles, the discharged and regenerative capacity distribution is proposed to describe discharge current profiles for the SOAC estimation. Because of the complexity and nonlinearity of the relationship between the SOAC and the capacity distribution at different temperatures, a neural network (NN) is applied to this SOAC estimation. Comparisons between the estimated SOACs by the NN and the calculated SOACs from the experimental data are used for verification. The results confirm that the proposed approach can provide an accurate and effective estimation of the BRAC for lead-acid batteries in EVs

  10. Dehydroepiandroesteron Accompanied Retinoic Acid Enhances Differentiation of P19 Embryonal Stem Cells into Neural Cells

    Hossein Azizi

    2009-01-01

    Full Text Available Objective: Dehydroepiandroesteron (DHEA is a neurosteroid with potential effect on neurogenesis,neuronal survival and proliferation of neural progenitor cells. However there is nodirect evidence for its biological effect during the differentiation of stem cell-derived neurons.The p19 line of embryonal carcinoma cells develops into neurons, astroglia and fibroblastsafter exposure to retinoic acid (RA. This study was initiated to assess the effect of DHEA onneural cells derived from p19 embryonal carcinoma stem cells.Materials and Methods: P19 cells were suspended in dulbecco’s modified eagle’s medium(DMED containing fetal bovine serum (FBS in bacterial-grade petri dishes in the presenceof RA, DHEA and RA+DHEA for 6 days. Then cells were trypsinized for dispersion and replacedin poly L- lysine (10μg/ml coated tissue culture dishes without RA and DHEA for 4days. The expression of neural markers Map-2, Tau, beta-tubulin III- clone Juj (Tuj1, astrocytemarker GFAP and the percent of neurotransmitters tyrosin hydroxylase, glutamate, serotoninand actyl cholin transferase were evaluated by flowcytometry, immunocytochemistryand RT-PCR analysis.Results: Flowcytometry analysis showed that about 63 ± 3% of the cells express neuronalmarker Tuj1 and about 5 ± 1% of the cells express tyrosine hydroxylase neurotransmittersin RA treated groups. However when RA and DHEA were added to the culture medium, Tuj1expression increased to about 74 ± 1% and tyrosine hydroxylase expression increased to23 ± 2%.Conclusion: Results showed that DHEA accompanied RA increased the number of Tuj1 anddopaminergic neurons that were derived from p19 embryonal carcinoma stem cells.

  11. scratch, a pan-neural gene encoding a zinc finger protein related to snail, promotes neuronal development.

    Roark, M; Sturtevant, M A; Emery, J; Vaessin, H; Grell, E; Bier, E

    1995-10-01

    The Drosophila scratch (scrt) gene is expressed in most or all neuronal precursor cells and encodes a predicted zinc finger transcription factor closely related to the product of the mesoderm determination gene snail (sna). Adult flies homozygous for scrt null alleles have a reduced number of photoreceptors in the eye, and embryos lacking the function of both scrt and the pan-neural gene deadpan (dpn), which encodes a basic helix-loop-helix (bHLH) protein, exhibit a significant loss of neurons. Conversely, ectopic expression of a scrt transgene during embryonic and adult development leads to the production of supernumerary neurons. Consistent with scrt functioning as a transcription factor, various genes are more broadly expressed than normal in scrt null mutants. Reciprocally, these same genes are expressed at reduced levels in response to ectopic scrt expression. We propose that scrt promotes neuronal cell fates by suppressing expression of genes promoting non-neuronal cell fates. We discuss the similarities between the roles of the ancestrally related scrt, sna, and escargot (esc) genes in regulating cell fate choices. PMID:7557390

  12. Environmental enrichment promotes neural remodeling in newborn rats with hypoxic-ischemic brain damage

    Chuanjun Liu; Yankui Guo; Yalu Li; Zhenying Yang

    2011-01-01

    We evaluated the effect of hypoxic-ischemic brain damage and treatment with early environmental enrichment intervention on development of newborn rats, as evaluated by light and electron microscopy and morphometry. Early intervention with environmental enrichment intelligence training attenuated brain edema and neuronal injury, promoted neuronal repair, and increased neuronal plasticity in the frontal lobe cortex of the newborn rats with hypoxic-ischemic brain damage.

  13. Lithocholic acid induction of the FGF19 promoter in intestinal cells is mediated by PXR

    Wolfgang Wistuba; Carsten Gnewuch; Gerhard Liebisch; Gerd Schmitz; Thomas Langmann

    2007-01-01

    AIM: To study the effect of the toxic secondary bile acid lithocholic acid (LCA) on the expression of fibroblast growth factor 19 (FGF19) in intestinal cells and to characterize the pregnane-X-receptor (PXR) response of the FGF19 promoter region.METHODS: The intestinal cell line LS174T was stimulated with various concentrations of chenodeoxycholic acid and lithocholic acid for several time points.FGF19 mRNA levels were determined with quantitative realtime RT-PCR. FGF19 deletion promoter constructs were generated and the LCA response was analzyed in reporter assays. Co-transfections with PXR and RXR were carried out to study FGF19 regulation by these factors.RESULTS: LCA and CDCA strongly up-regulate FGF19 mRNA expression in LS174T cells in a time and dose dependent manner. Using reporter gene assays with several deletion constructs we found that the LCA responsive element in the human FGF19 promoter maps to the proximal regulatory region containing two potential binding sites for PXR. Overexpression of PXR and its dimerization partner retinoid X receptor (RXR) and stimulation with LCA or the potent PXR ligand rifampicin leads to a significant induction of FGF19 promoter activity in intestinal cells.CONCLUSION: LCA induced feedback inhibition of bile acid synthesis in the liver is likely to be regulated by PXR inducing intestinal FGF19 expression.

  14. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia

    Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.

    2016-04-01

    Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

  15. Conjugated bile acids promote cholangiocarcinoma cell invasive growth through activation of sphingosine 1-phosphate receptor 2

    Liu, Runping; Zhao, Renping; Zhou, Xiqiao; Liang, Xiuyin; Campbell, Deanna JW; Zhang, Xiaoxuan; ZHANG, LUYONG; Shi, Ruihua; Wang, Guangji; Pandak, William M.; Sirica, Alphonse E.; Hylemon, Phillip B.; Zhou, Huiping

    2014-01-01

    Cholangiocarcinoma (CCA) is an often fatal primary malignancy of the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantly elevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, ...

  16. Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

    Lu Chen

    2014-06-01

    Full Text Available Using a viral model of the demyelinating disease multiple sclerosis (MS, we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4+CD25+FOXP3+ regulatory T cells (Tregs within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.

  17. Periostin Promotes Neural Stem Cell Proliferation and Differentiation following Hypoxic-Ischemic Injury.

    Si-Min Ma

    Full Text Available Neural stem cell (NSC proliferation and differentiation are required to replace neurons damaged or lost after hypoxic-ischemic events and recover brain function. Periostin (POSTN, a novel matricellular protein, plays pivotal roles in the survival, migration, and regeneration of various cell types, but its function in NSCs of neonatal rodent brain is still unknown. The purpose of this study was to investigate the role of POSTN in NSCs following hypoxia-ischemia (HI. We found that POSTN mRNA levels significantly increased in differentiating NSCs. The proliferation and differentiation of NSCs in the hippocampus is compromised in POSTN knockout mice. Moreover, NSC proliferation and differentiation into neurons and astrocytes significantly increased in cultured NSCs treated with recombinant POSTN. Consistently, injection of POSTN into neonatal hypoxic-ischemic rat brains stimulated NSC proliferation and differentiation in the subventricular and subgranular zones after 7 and 14 days of brain injury. Lastly, POSTN treatment significantly improved the spatial learning deficits of rats subjected to HI. These results suggest that POSTN significantly enhances NSC proliferation and differentiation after HI, and provides new insights into therapeutic strategies for the treatment of hypoxic-ischemic encephalopathy.

  18. Human neural precursor cells promote neurologic recovery in a viral model of multiple sclerosis.

    Chen, Lu; Coleman, Ronald; Leang, Ronika; Tran, Ha; Kopf, Alexandra; Walsh, Craig M; Sears-Kraxberger, Ilse; Steward, Oswald; Macklin, Wendy B; Loring, Jeanne F; Lane, Thomas E

    2014-06-01

    Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments. PMID:24936469

  19. Relative efficacy of organic acids and antibiotics as growth promoters in broiler chicken

    Vikrant Laxman Bagal

    2016-04-01

    Full Text Available Aim: The objective of this study was to evaluate the effect of organic acids as replacer to antibiotics in their various combinations on feed consumption, body weight gain, and feed conversion ratio (FCR in broiler chicks during different phases of growth. Materials and Methods: Antibiotics and organic acids were incorporated into boiler feed in different combinations to form 10 maize based test diets (T1 to T10. Each test diet was offered to four replicates of 10 birds each constituting a total of 400 birds kept for 45 days. Results: Significantly better effect in terms of body weight gain from supplementation of 1% citric acid and 1% citric acid along with antibiotic was observed throughout the entire study, whereas the effect of tartaric acid supplementation was similar to control group. Citric acid (1% along with antibiotic supplementation showed highest feed intake during the experimental period. Significantly better FCR was observed in groups supplemented with 1% citric acid and 1% citric acid along with antibiotic followed by antibiotic along with organic acids supplemented group. Conclusion: Growth performance of birds in terms of body weight, body weight gain, and FCR improved significantly in 1% citric acid which was significantly higher than antibiotic supplemented group. 1% citric acid can effectively replace antibiotic growth promoter (chlortetracycline without affecting growth performance of birds.

  20. Uric acid promotes neuronal differentiation of human placenta-derived mesenchymal stem cells in a time- and concentration-dependent manner

    Nailong Yang; Lili Xu; Peng Lin; Jing Cui

    2012-01-01

    Uric acid is an important, naturally occurring serum antioxidant. The present study investigates the use of uric acid for promoting proliferation and neuronal differentiation of mesenchymal stem cells derived from human placenta tissue. Human placenta-derived mesenchymal stem cells were pre-induced in the presence of either 0, 0.2, 0.4 or 0.8 mM uric acid in combination with 1 mM β-mercaptoethanol for 24 hours, followed by exposure to identical uric acid concentrations and 5 mM β-mercaptoethanol for 6 and 10 hours. Cells developed a neuronal-like morphology, with formation of interconnected process extensions, typical of neural cells. Immunocytochemistry and immunofluorescence staining showed neuron specific enolase positive cells were present in each group except the control group. A greater number of neuron specific enolase positive cells were observed in 0.8 mM uric acid in combination with 5 mM β-mercaptoethanol at 10 hours. After 24 hours of induction, Nissl bodies were detected in the cytoplasm of all differentiated cell groups except the control group and Nissl body numbers were greatest in human placenta-derived mesenchymal stem cells grown in the presence of 0.8 mM uric acid and 5 mM β-mercaptoethanol. These results suggest uric acid accelerates differentiation of human placenta-derived mesenchymal stem cells into neuronal-like cells in a time- and concentration-dependent manner.

  1. Signalling through the type 1 insulin-like growth factor receptor (IGF1R interacts with canonical Wnt signalling to promote neural proliferation in developing brain

    Qichen Hu

    2012-07-01

    Full Text Available Signalling through the IGF1R [type 1 IGF (insulin-like growth factor receptor] and canonical Wnt signalling are two signalling pathways that play critical roles in regulating neural cell generation and growth. To determine whether the signalling through the IGF1R can interact with the canonical Wnt signalling pathway in neural cells in vivo, we studied mutant mice with altered IGF signalling. We found that in mice with blunted IGF1R expression specifically in nestin-expressing neural cells (IGF1RNestin−KO mice the abundance of neural β-catenin was significantly reduced. Blunting IGF1R expression also markedly decreased: (i the activity of a LacZ (β-galactosidase reporter transgene that responds to Wnt nuclear signalling (LacZTCF reporter transgene and (ii the number of proliferating neural precursors. In contrast, overexpressing IGF-I (insulin-like growth factor I in brain markedly increased the activity of the LacZTCF reporter transgene. Consistently, IGF-I treatment also markedly increased the activity of the LacZTCF reporter transgene in embryonic neuron cultures that are derived from LacZTCF Tg (transgenic mice. Importantly, increasing the abundance of β-catenin in IGF1RNestin−KO embryonic brains by suppressing the activity of GSK3β (glycogen synthase kinase-3β significantly alleviated the phenotypic changes induced by IGF1R deficiency. These phenotypic changes includes: (i retarded brain growth, (ii reduced precursor proliferation and (iii decreased neuronal number. Our current data, consistent with our previous study of cultured oligodendrocytes, strongly support the concept that IGF signalling interacts with canonical Wnt signalling in the developing brain to promote neural proliferation. The interaction of IGF and canonical Wnt signalling plays an important role in normal brain development by promoting neural precursor proliferation.

  2. Treadmill step training promotes spinal cord neural plasticity after incomplete spinal cord injury**

    Tiansheng Sun; Chaoqun Ye; Jun Wu; Zhicheng Zhang; Yanhua Cai; Feng Yue

    2013-01-01

    A large body of evidence shows that spinal circuits are significantly affected by training, and that intrinsic circuits that drive locomotor tasks are located in lumbosacral spinal segments in rats with complete spinal cord transection. However, after incomplete lesions, the effect of treadmil training has been debated, which is likely because of the difficulty of separating spontaneous stepping from specific training-induced effects. In this study, rats with moderate spinal cord contusion were sub-jected to either step training on a treadmil or used in the model (control) group. The treadmil training began at day 7 post-injury and lasted 20 ± 10 minutes per day, 5 days per week for 10 weeks. The speed of the treadmil was set to 3 m/min and was increased on a daily basis according to the tolerance of each rat. After 3 weeks of step training, the step training group exhibited a sig-nificantly greater improvement in the Basso, Beattie and Bresnahan score than the model group. The expression of growth-associated protein-43 in the spinal cord lesion site and the number of tyrosine hydroxylase-positive ventral neurons in the second lumbar spinal segment were greater in the step training group than in the model group at 11 weeks post-injury, while the levels of brain-derived neurotrophic factor protein in the spinal cord lesion site showed no difference between the two groups. These results suggest that treadmil training significantly improves functional re-covery and neural plasticity after incomplete spinal cord injury.

  3. GM1485, a nonimmunosuppressive immunophilin ligand, promotes neurofunctional improvement and neural regeneration following stroke.

    Ducruet, Andrew F; DeRosa, Peter A; Zacharia, Brad E; Sosunov, Sergey A; Connolly, E Sander; Weinstein, David E

    2012-07-01

    Stroke is the leading cause of disability in the industrialized world, and the development of pharmacologic strategies to promote poststroke recovery is of paramount importance. GM1485, a nonimmunosuppressive immunophilin ligand, promotes regeneration of multiple cell types following injury. In the present study, we evaluated the effect of GM1485 treatment on functional recovery and neurogenesis following rat stroke. Transient cerebral ischemia was induced in rats receiving daily GM1485 (5 mg/kg) beginning 24 hr postischemia and continuing for a total of 6 weeks. Neurological function was evaluated over this period using a battery of neurobehavioral tests, and immunostaining for stem-cell markers was performed following animal sacrifice. An in vitro model of oxidative stress was also employed to evaluate the ability of GM1485 to mediate stem-cell-like induction and plasticity. GM1485-treated rats demonstrated improved neurological function as well as increased Sox2(+) cells in the ipsilateral SVZ and striatum relative to vehicle-treated rats. Additionally, GM1485-treated fibroblasts subjected to oxidative stress were reprogrammed to a stem-cell-like phenotype and were able to differentiate down a neuronal lineage. These data demonstrate that GM1485 administration improves neurological function and is consistent with an upregulation of endogenous neurogenesis following stroke in rats. Further experiments are necessary to characterize the molecular pathways involved in these processes. PMID:22431363

  4. Mfge8 promotes obesity by mediating the uptake of dietary fats and serum fatty acids

    Khalifeh-Soltani, Amin; McKleroy, William; Sakuma, Stephen; Cheung, Yuk Yin; Tharp, Kevin; Qiu, Yifu; Turner, Scott M; Chawla, Ajay; Stahl, Andreas; Atabai, Kamran

    2014-01-01

    Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8−/−) mice are protected from diet-induce...

  5. p-Toluenesulphonic acid-promoted, I2-catalysed sulphenylation of pyrazolones with aryl sulphonyl hydrazides.

    Zhao, Xia; Zhang, Lipeng; Li, Tianjiao; Liu, Guiyan; Wang, Haomeng; Lu, Kui

    2014-11-01

    Aryl pyrazolone thioethers were synthesized via the I2-catalysed cross-coupling of pyrazolones with aryl sulphonyl hydrazides in the presence of p-toluenesulphonic acid, which has been proposed to promote the reaction by facilitating the decomposition of sulphonyl hydrazides. PMID:25225659

  6. Human neural stem cells promote corticospinal axons regeneration and synapse reformation in injured spinal cord of rats

    LIANG Peng; JIN Lian-hong; LIANG Tao; LIU En-zhong; ZHAO Shi-guang

    2006-01-01

    Background Axonal regeneration in lesioned mammalian central nervous system is abortive, and this causes permanent disabilities in individuals with spinal cord injuries. This paper studied the action of neural stem cell (NSC) in promoting corticospinal axons regeneration and synapse reformation in rats with injured spinal cord.Methods NSCs were isolated from the cortical tissue of spontaneous aborted human fetuses in accordance with the ethical request. The cells were discarded from the NSC culture to acquire NSC-conditioned medium. Sixty adult Wistar rats were randomly divided into four groups (n=15 in each): NSC graft, NSC medium, graft control and medium control groups. Microsurgical transection of the spinal cord was performed in all the rats at the T11. The NSC graft group received stereotaxic injections of NSCs suspension into both the spinal cord stumps immediately after transection; graft control group received DMEM injection. In NSC medium group,NSC-conditioned medium was administered into the spinal cord every week; NSC culture medium was administered to the medium control group. Hindlimb motor function was assessed using the BBB Locomotor Rating Scale. Regeneration of biotin dextran amine (BDA) labeled corticospinal tract was assessed. Differentiation of NSCs and the expression of synaptophysin at the distal end of the injured spinal cord were observed under a confocal microscope. Group comparisons of behavioral data were analyzed with ANOVA.Results NSCs transplantation resulted in extensive growth of corticospinal axons and locomotor recovery in adult rats after complete spinal cord transection, the mean BBB scores reached 12.5 in NSC graft group and 2.5 in graft control group (P< 0.05). There was also significant difference in BBB score between the NSC medium (11.7) and medium control groups (3.7, P< 0.05). BDA traces regenerated fibers sprouted across the lesion site and entered the caudal part of the spinal cord. Synaptophysin expression

  7. Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

    Andrew E. Czeizel

    2013-11-01

    Full Text Available Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled trials indicated that periconceptional folic acid (FA-containing multivitamin supplementation prevented the major proportion (about 90% of neural-tube defects (NTD as well as a certain proportion (about 40% of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i dietary intake; (ii periconceptional supplementation; and (iii flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”.

  8. Functional analysis of a Lemna gibba rbcS promoter regulated by abscisic acid and sugar

    Youru Wang

    2013-04-01

    Photosynthesis-associated nuclear genes (PhANGs) are able to respond to multiple environmental and developmental signals, including light, sugar and abscisic acid (ABA). PhANGs have been extensively studied at the level of transcriptional regulation, and several cis-acting elements important for light responsiveness have been identified in their promoter sequences. However, the regulatory elements involved in sugar and ABA regulation of PhANGs have not been completely characterized. A ribulose-1,5-bisphosphate carboxylase small subunit gene (rbcS) promoter (SSU5C promoter) was isolated from duckweed (Lemna gibba). A series of SSU5C promoter 5′ deletion fragments were fused to an intron–gus gene, and transgenic tobacco suspension cell lines were generated. Assay of tobacco suspension cell line harbouring the complete promoter in the fusion construct indicated that SSU5C promoter was negatively regulated by sugar and ABA under the condition of regular photoperiod. 5′ deletion analysis of SSU5C promoter in transgenic tobacco suspension cell lines confirmed that a region between positions $-310$ and $-152$ included the ABA-response region, and that sugar-response cis-acting elements might be located in the region between $-152$ and $-117$. Taken together, our results confirmed that the cis-regulatory region responsible for repression by ABA and sugar in the SSU5C promoter was located between $-310$ and $-117$.

  9. Principal component articial neural network calibration models for the simultaneous spectrophotometric estimation of mefenamic acid and paracetamol in tablets

    RAJAPPAN MANAVALAN; KAMARAJAN KANNAN; DONDETI SATYANARAYANA

    2006-01-01

    Simultaneous estimation of all drug components in a multicomponent analgesic dosage form with artificial neural networks calibration models using UV spectrophotometry is reported as a simple alternative to using separate models for each component. Anovel approach for calibration using a compund spectral dataset derived from three spectra of each component is described. The spectra of mefenamic acid and paracetamol were recorded as several concentrations within their linear range and used to c...

  10. Salt-inducible promoter derivable from a lactic acid bacterium, and its use in a lactic acid bacterium for production of a desired protein

    Sanders, Jan Willem; Kok, Jan; Venema, Gerard; Ledeboer, Adrianus Marinus

    1998-01-01

    The invention provides a salt-inducible promoter present in SEQ ID NO: 10 and derivable from a lactic acid bacterium in isolation from the coding sequence normally controlled by said promoter in a wild-type lactic acid bacterium, with modifications and important parts thereof. Also provided are a re

  11. Fat transforms ascorbic acid from inhibiting to promoting acid-catalysed N-nitrosation

    Combet, E; Paterson, S; Iijima, K; Winter, J; Mullen, W.; Crozier, A.; Preston, T; McColl, K E L

    2007-01-01

    Background: The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be converted to nitrosating species and N-nitroso compounds by acidification at low gastric pH in the presence of thiocyanate. Aims: To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating the human proximal stomach. M...

  12. Promotion

    Alam, Hasan B.

    2013-01-01

    This article gives an overview of the promotion process in an academic medical center. A description of different promotional tracks, tenure and endowed chairs, and the process of submitting an application is provided. Finally, some practical advice about developing skills and attributes that can help with academic growth and promotion is dispensed.

  13. The available capacity computation model based on artificial neural network for lead-acid batteries in electric vehicles

    Chan, C. C.; Lo, E. W. C.; Weixiang, Shen

    The available capacity computation model based on the artificial neural network (ANN) for lead-acid batteries in an electric vehicle (EV) is presented. Comparing with the methods based on the Peukert equation, which is often used for the calculation of the available capacity for lead-acid batteries in EVs, this model is more accurate. The results of the experiment have proven the accuracy of the proposed model; the computation values are in good agreement with experimental data, the associated error has been considered acceptable from an engineering point of view.

  14. Neural tube defects in Costa Rica, 1987-2012: origins and development of birth defect surveillance and folic acid fortification.

    Barboza-Argüello, María de la Paz; Umaña-Solís, Lila M; Azofeifa, Alejandro; Valencia, Diana; Flores, Alina L; Rodríguez-Aguilar, Sara; Alfaro-Calvo, Thelma; Mulinare, Joseph

    2015-03-01

    Our aim was to provide a descriptive overview of how the birth defects surveillance and folic acid fortification programs were implemented in Costa Rica-through the establishment of the Registry Center for Congenital Anomalies (Centro de Registro de Enfermedades Congénitas-CREC), and fortification legislation mandates. We estimated the overall prevalence of neural tube defects (i.e., spina bifida, anencephaly and encephalocele) before and after fortification captured by CREC. Prevalence was calculated by dividing the total number of infants born with neural tube defects by the total number of live births in the country (1987-2012).A total of 1,170 newborns with neural tube defects were identified from 1987 to 2012 (1992-1995 data excluded); 628 were identified during the baseline pre-fortification period (1987-1991; 1996-1998); 191 during the fortification period (1999-2002); and 351 during the post-fortification time period (2003-2012). The overall prevalence of neural tube defects decreased from 9.8 per 10,000 live-births (95 % CI 9.1-10.5) for the pre-fortification period to 4.8 per 10,000 live births (95 % CI 4.3-5.3) for the post-fortification period. Results indicate a statistically significant (P < 0.05) decrease of 51 % in the prevalence of neural tube defects from the pre-fortification period to the post-fortification period. Folic acid fortification via several basic food sources has shown to be a successful public health intervention for Costa Rica. Costa Rica's experience can serve as an example for other countries seeking to develop and strengthen both their birth defects surveillance and fortification programs. PMID:24952876

  15. A Nanoscale Interface Promoting Molecular and Functional Differentiation of Neural Cells.

    Posati, Tamara; Pistone, Assunta; Saracino, Emanuela; Formaggio, Francesco; Mola, Maria Grazia; Troni, Elisabetta; Sagnella, Anna; Nocchetti, Morena; Barbalinardo, Marianna; Valle, Francesco; Bonetti, Simone; Caprini, Marco; Nicchia, Grazia Paola; Zamboni, Roberto; Muccini, Michele; Benfenati, Valentina

    2016-01-01

    Potassium channels and aquaporins expressed by astrocytes are key players in the maintenance of cerebral homeostasis and in brain pathophysiologies. One major challenge in the study of astrocyte membrane channels in vitro, is that their expression pattern does not resemble the one observed in vivo. Nanostructured interfaces represent a significant resource to control the cellular behaviour and functionalities at micro and nanoscale as well as to generate novel and more reliable models to study astrocytes in vitro. However, the potential of nanotechnologies in the manipulation of astrocytes ion channels and aquaporins has never been previously reported. Hydrotalcite-like compounds (HTlc) are layered materials with increasing potential as biocompatible nanoscale interface. Here, we evaluate the effect of the interaction of HTlc nanoparticles films with primary rat neocortical astrocytes. We show that HTlc films are biocompatible and do not promote gliotic reaction, while favouring astrocytes differentiation by induction of F-actin fibre alignment and vinculin polarization. Western Blot, Immunofluorescence and patch-clamp revealed that differentiation was accompanied by molecular and functional up-regulation of both inward rectifying potassium channel Kir 4.1 and aquaporin 4, AQP4. The reported results pave the way to engineering novel in vitro models to study astrocytes in a in vivo like condition. PMID:27503424

  16. Cell-permeable p38 MAP kinase promotes migration of adult neural stem/progenitor cells

    Hamanoue, Makoto; Morioka, Kazuhito; Ohsawa, Ikuroh; Ohsawa, Keiko; Kobayashi, Masaaki; Tsuburaya, Kayo; Akasaka, Yoshikiyo; Mikami, Tetsuo; Ogata, Toru; Takamatsu, Ken

    2016-01-01

    Endogenous neural stem/progenitor cells (NPCs) can migrate toward sites of injury, but the migration activity of NPCs is insufficient to regenerate damaged brain tissue. In this study, we showed that p38 MAP kinase (p38) is expressed in doublecortin-positive adult NPCs. Experiments using the p38 inhibitor SB203580 revealed that endogenous p38 participates in NPC migration. To enhance NPC migration, we generated a cell-permeable wild-type p38 protein (PTD-p38WT) in which the HIV protein transduction domain (PTD) was fused to the N-terminus of p38. Treatment with PTD-p38WT significantly promoted the random migration of adult NPCs without affecting cell survival or differentiation; this effect depended on the cell permeability and kinase activity of the fusion protein. These findings indicate that PTD-p38WT is a novel and useful tool for unraveling the roles of p38, and that this protein provides a reasonable approach for regenerating the injured brain by enhancing NPC migration. PMID:27067799

  17. Updated estimates of neural tube defects prevented by mandatory folic Acid fortification - United States, 1995-2011.

    Williams, Jennifer; Mai, Cara T; Mulinare, Joe; Isenburg, Jennifer; Flood, Timothy J; Ethen, Mary; Frohnert, Barbara; Kirby, Russell S

    2015-01-16

    In 1992, the U.S. Public Health Service recommended that all women capable of becoming pregnant consume 400 µg of folic acid daily to prevent neural tube defects (NTDs). NTDs are major birth defects of the brain and spine that occur early in pregnancy as a result of improper closure of the embryonic neural tube, which can lead to death or varying degrees of disability. The two most common NTDs are anencephaly and spina bifida. Beginning in 1998, the United States mandated fortification of enriched cereal grain products with 140 µg of folic acid per 100 g. Immediately after mandatory fortification, the birth prevalence of NTD cases declined. Fortification was estimated to avert approximately 1,000 NTD-affected pregnancies annually. To provide updated estimates of the birth prevalence of NTDs in the period after introduction of mandatory folic acid fortification (i.e., the post-fortification period), data from 19 population-based birth defects surveillance programs in the United States, covering the years 1999-2011, were examined. After the initial decrease, NTD birth prevalence during the post-fortification period has remained relatively stable. The number of births occurring annually without NTDs that would otherwise have been affected is approximately 1,326 (95% confidence interval = 1,122-1,531). Mandatory folic acid fortification remains an effective public health intervention. There remain opportunities for prevention among women with lower folic acid intakes, especially among Hispanic women, to further reduce the prevalence of NTDs in the United States. PMID:25590678

  18. Neuritogenic and survival-promoting effects of the P2 peptide derived from a homophilic binding site in the neural cell adhesion molecule

    Pedersen, Martin V; Køhler, Lene B; Ditlevsen, Dorte K;

    2004-01-01

    The neural cell adhesion molecule (NCAM) plays a pivotal role in neural development, regeneration, and plasticity. NCAM mediates adhesion and subsequent signal transduction through NCAM-NCAM binding. Recently, a peptide ligand termed P2 corresponding to a 12-amino-acid sequence in the FG loop of...... fragmentation were lowered by P2. Finally, treatment of neurons with P2 resulted in phosphorylation of the ser/thr kinase Akt. Thus, a small peptide mimicking homophilic NCAM interaction is capable of inducing differentiation as reflected by neurite outgrowth in several neuronal cell types and inhibiting...

  19. Neural protein gamma-synuclein interacting with androgen receptor promotes human prostate cancer progression

    Gamma-synuclein (SNCG) has previously been demonstrated to be significantly correlated with metastatic malignancies; however, in-depth investigation of SNCG in prostate cancer is still lacking. In the present study, we evaluated the role of SNCG in prostate cancer progression and explored the underlying mechanisms. First, alteration of SNCG expression in LNCaP cell line to test the ability of SNCG on cellular properties in vitro and vivo whenever exposing with androgen or not. Subsequently, the Dual-luciferase reporter assays were performed to evaluate whether the role of SNCG in LNCaP is through AR signaling. Last, the association between SNCG and prostate cancer progression was assessed immunohistochemically using a series of human prostate tissues. Silencing SNCG by siRNA in LNCaP cells contributes to the inhibition of cellular proliferation, the induction of cell-cycle arrest at the G1 phase, the suppression of cellular migration and invasion in vitro, as well as the decrease of tumor growth in vivo with the notable exception of castrated mice. Subsequently, mechanistic studies indicated that SNCG is a novel androgen receptor (AR) coactivator. It interacts with AR and promotes prostate cancer cellular growth and proliferation by activating AR transcription in an androgen-dependent manner. Finally, immunohistochemical analysis revealed that SNCG was almost undetectable in benign or androgen-independent tissues prostate lesions. The high expression of SNCG is correlated with peripheral and lymph node invasion. Our data suggest that SNCG may serve as a biomarker for predicting human prostate cancer progression and metastasis. It also may become as a novel target for biomedical therapy in advanced prostate cancer

  20. Subcellular distribution of N-methyl-D-aspartic acid receptor subunit 1 in neural stem cells within subventricular zone of adult rats

    Zhining Li; Wenlong Lü; Hongyan Dong; Hongbin Fan; Ruiguo Dong; Tiejun Xu

    2011-01-01

    The subcellular localization of N-methyl-D-aspartic acid receptor subunit 1 in neural stem cells of the subventricular zone of adult rats was detected using electron microscopy, following immunohistochemistry and immunogold-silver double staining. Results confirmed the presence of neural stem cells in the subventricular zone, which is a key neurogenic region in the central nervous system of adult mammals. The expression of N-methyl-D-aspartic acid receptor subunit 1 was higher than that of nestin and mainly distributed in the cell membrane, cytoplasm, rough endoplasmic reticulum and Golgi complex of neural stem cells.

  1. Principal component articial neural network calibration models for the simultaneous spectrophotometric estimation of mefenamic acid and paracetamol in tablets

    RAJAPPAN MANAVALAN

    2006-11-01

    Full Text Available Simultaneous estimation of all drug components in a multicomponent analgesic dosage form with artificial neural networks calibration models using UV spectrophotometry is reported as a simple alternative to using separate models for each component. Anovel approach for calibration using a compund spectral dataset derived from three spectra of each component is described. The spectra of mefenamic acid and paracetamol were recorded as several concentrations within their linear range and used to compute a calibration mixture between the wavelengths 220 to 340 nm. Neural networks trained by a Levenberg–Marquardt algorithm were used for building and optimizing the calibration models using MATALAB® Neural Network Toolbox and were compared with the principal component regression model. The calibration models were throughly evaluated at several concentration levels using 104 spectra obtained for 52 synthetic binary mixtures prepared using orthogonal designs. The optimized model showed sufficient robustness even when the calibration sets were constructed from a different set of pure spectra of the components. The simultaneous prediction of both components by a single neural netwook with the suggested calibration approach was successful. The model could accurately estimate the drugs, with satisfactory precision and accuracy, in tablet dosage with no interference from excipients as indicated by the results of a recovery study.

  2. When folic acid fails: Insights from 20 years of neural tube defect surveillance in South Carolina.

    Bupp, Caleb P; Sarasua, Sara M; Dean, Jane H; Stevenson, Roger E

    2015-10-01

    Neural tube defects (NTDs) are the most common of the severe malformations of the brain and spinal cord. Increased maternal intake of folic acid (FA) during the periconceptional period is known to reduce NTD risk. Data from 1046 NTD cases in South Carolina were gathered over 20 years of surveillance. It was possible to determine maternal periconceptional FA use in 615 NTD-affected pregnancies. In 163 occurrent (26.9%) and two recurrent (22%) NTD cases, the mothers reported periconceptional FA use. These women were older and more likely to be white. Maternal periconceptional FA usage was reported in 40.4% of cases of spina bifida with other anomalies but in only 25.2% of isolated spina bifida cases (P = 0.02). This enrichment for associated anomalies was not noted among cases of anencephaly or of encephalocele. Among the 563 subsequent pregnancies to mothers with previous NTD-affected pregnancies, those taking FA had a 0.4% NTD recurrence rate, but the recurrence without FA was 8.5%. NTDs with other associated findings were less likely to be prevented by FA, suggesting there is a background NTD rate that cannot be further reduced by FA. Nonetheless, the majority (73.9%) of NTDs in pregnancies in which the mothers reported periconceptional FA use were isolated NTDs of usual types. Cases in which FA failed in prevention of NTDs provide potential areas for further study into the causation of NTDs. The measures and techniques implemented in South Carolina can serve as an effective and successful model for prevention of NTD occurrence and recurrence. PMID:26108864

  3. Platinum-nickel catalyst: The effect of promoters in cis-oleic acid adsorption

    Simonetti, S., E-mail: ssimonet@uns.edu.ar [Universidad Tecnologica Nacional, Facultad Regional Bahia Blanca, 11 de Abril 461, 8000 Bahia Blanca (Argentina); Universidad Nacional del Sur-IFISUR-CONICET, Av. Alem 1253, 8000 Bahia Blanca (Argentina); Martirena, M.; Ulacco, S. [Universidad Tecnologica Nacional, Facultad Regional Bahia Blanca, 11 de Abril 461, 8000 Bahia Blanca (Argentina); Brizuela, G. [Universidad Nacional del Sur-IFISUR-CONICET, Av. Alem 1253, 8000 Bahia Blanca (Argentina)

    2013-01-01

    Highlights: Black-Right-Pointing-Pointer C=O adsorption is more favored than C=C adsorption on the PtNi(1 1 1) surface. Black-Right-Pointing-Pointer The adsorption of the olefinic bond is strengthened by K, Mg, Co, B or Pd promoters. Black-Right-Pointing-Pointer The energy of the system and the C=C/surface distances decrease using promoters. Black-Right-Pointing-Pointer The molecule-surface interaction is favored by electron density exchange. Black-Right-Pointing-Pointer Co promoter shows better adsorption properties than K, Mg, B or Pd. - Abstract: The study of the cis-oleic acid adsorption, on clean and promoted (K, Mg, Co, B or Pd) PtNi(1 1 1) surface was performed by quatum chemical calculations. The oleic acid adsorption on PtNi(1 1 1) surface shows a weak molecule-surface interaction. No preferential site for C=C adsorption is computed and only the C=O adsorption is favored on the clean PtNi(1 1 1) surface. The adsorption properties of the PtNi(1 1 1) are improved by promoters. The stability of the system is increased and the C=C/surface distances are reduced when promoters are present. Among the considered promoters, Co has the best performance in terms of system stability. The lowest C p orbital substantially interacts with Pt and Co s, p and d orbitals. The change electron density of metal centers, enhance the C=C adsorption being the Pt-C interaction the more favored. After adsorption, the strength of the C=C, Pt-Pt and Pt-Co bonds decrease while a molecule-surface bond is formed.

  4. Bile acid promotes liver regeneration via farnesoid X receptor signaling pathways in rats.

    Ding, Long; Yang, Yu; Qu, Yikun; Yang, Ting; Wang, Kaifeng; Liu, Weixin; Xia, Weibin

    2015-06-01

    Bile acids, which are synthesized from cholesterol in the hepatocytes of the liver, are amphipathic molecules with a steroid backbone. Studies have shown that bile acid exhibits important effects on liver regeneration. However, the mechanism underlying these effects remains unclear. The aim of the present study was to investigate the effect of bile acid and the farnesoid X receptor (FXR) on hepatic regeneration and lipid metabolism. Rats were fed with 0.2% bile acid or glucose for 7 days and then subjected to a 50 or 70% hepatectomy. Hepatic regeneration rate, serum and liver levels of bile acid, and expression of FXR and Caveolin‑1, were detected at 24, 48 or 72 h following hepatectomy. The expression of proliferating cell nuclear antigen (PCNA) in the liver was measured using immunohistochemistry at the end of the study. Hepatocytes isolated from rats were treated with bile acid, glucose, FXR agonist and FXR antagonist, separately or in combination. Lipid metabolism, the expression of members of the FXR signaling pathway and energy metabolism‑related factors were measured using ELISA kits or western blotting. Bile acid significantly increased the hepatic regeneration rate and the expression of FXR, Caveolin‑1 and PCNA. Levels of total cholesterol and high density lipoprotein were increased in bile acid‑ or FXR agonist‑treated hepatocytes in vitro. Levels of triglyceride, low density lipoprotein and free fatty acid were decreased. In addition, bile acid and FXR agonists increased the expression of bile salt export pump and small heterodimer partner, and downregulated the expression of apical sodium‑dependent bile acid transporter, Na+/taurocholate cotransporting polypeptide and cholesterol 7α‑hydroxylase. These results suggested that physiological concentrations of bile acid may promote liver regeneration via FXR signaling pathways, and may be associated with energy metabolism. PMID:25634785

  5. A negative retinoic acid response element in the rat oxytocin promoter restricts transcriptional stimulation by heterologous transactivation domains.

    Lipkin, S. M.; Nelson, C. A.; Glass, C K; Rosenfeld, M G

    1992-01-01

    Retinoic acid receptors are ligand-dependent transcription factors that stimulate gene transcription from promoters containing retinoic acid or thyroid hormone response elements. We describe a high-affinity binding site from the rat oxytocin promoter that mediates negative transcriptional regulation by the retinoic acid receptor. To examine whether strong, constitutive transactivation domains would be capable of stimulating gene transcription when bound to this DNA binding site that normally ...

  6. Design of stereoelectronically promoted super lewis acids and unprecedented chemistry of their complexes.

    Foroutan-Nejad, Cina; Vicha, Jan; Marek, Radek

    2014-09-01

    A new family of stereoelectronically promoted aluminum and scandium super Lewis acids is introduced on the basis of state-of-the-art computations. Structures of these molecules are designed to minimize resonance electron donation to central metal atoms in the Lewis acids. Acidity of these species is evaluated on the basis of their fluoride-ion affinities relative to the antimony pentafluoride reference system. It is demonstrated that introduced changes in the stereochemistry of the designed ligands increase acidity considerably relative to Al and Sc complexes with analogous monodentate ligands. The high stability of fluoride complexes of these species makes them ideal candidates to be used as weakly coordinating anions in combination with highly reactive cations instead of conventional Lewis acid-fluoride complexes. Further, the interaction of all designed molecules with methane is investigated. All studied acids form stable pentavalent-carbon complexes with methane. In addition, interactions of the strongest acid of this family with very weak bases, namely, H2, N2, carbon oxides, and noble gases were investigated; it is demonstrated that this compound can form considerably stable complexes with the aforementioned molecules. To the best of our knowledge, carbonyl and nitrogen complexes of this species are the first hypothetical four-coordinated carbonyl and nitrogen complexes of aluminum. The nature of bonding in these systems is studied in detail by various bonding analysis approaches. PMID:25055748

  7. Neural network modeling of the photocatalytic degradation of 2,4-di-hydroxybenzoic acid in aqueous solution

    Oliveros, E. [Karlsruhe Univ. (T.H.) (Germany). Lehrstuhl fur Umweltmesstechnik, Engler-Bunte-Institut; Benoit-Marquie, F.; Puech-Costes, E.; Maurette, M.T. [Universite Paul Sabatier, 31 - Toulouse (France). Laboratoire des IMRCP; Nascimento, C.A.O. [Sao Paulo Univ., SP (Brazil). Escola Politecnica

    1998-10-01

    Artificial neural networks have been used for modeling the TiO{sub 2} photocatalytic degradation of 2,4-di-hydroxybenzoic acid, chosen as a model water contaminant, as a function of the concentrations of substrate and catalyst. The experimental design methodology was applied to the choice of an appropriate set of experiments well distributed in the experimental region (Doehlert uniform array). Contrary to a classical treatment of the data, based on apparent rate constants modeled by a quadratic polynomial function, neural network analysis of the same experimental data does not require the use of an kinetic or phenomenological equations and allows the simulation and the prediction of the pollutant degradation as a function of irradiation time, as well as prediction of reaction rates, under varying conditions within the experimental region. (authors) 31 refs.

  8. Indoleacetic acid operon of Pseudomonas syringae subsp. savastanoi: transcription analysis and promoter identification.

    Gaffney, T D; da Costa e Silva, O.; Yamada, T.; Kosuge, T

    1990-01-01

    Expression of the indoleacetic acid (iaa) operon, which contributes to the virulence of the phytopathogenic bacterium Pseudomonas syringae subsp. savastanoi, was monitored by using broad-host-range lacZ reporter gene plasmids. A combination of translational (gene) fusions and transcriptional (operon) fusions of P. syringae subsp. savastanoi sequences to lacZ allowed localization of the iaa operon promoter. RNA recovered from P. syringae subsp. savastanoi strains was mapped with iaa operon-spe...

  9. The Lewis Acid-promoted Novel Cyclization Reactions Towards N-adn O-Containing Heterocycles

    Shoko; Yamazaki

    2007-01-01

    1 Results Nitrogen and oxygen-containing heterocyclic systems are important structures in organic chemistry because of their presence in many biologically active compounds.In this work,a new zinc and indium-promoted conjugate addition-cyclization reaction to afford nitrogen and oxygen-containing five-membered heterocycles has been developed.A Lewis acid-catalyzed cyclization of an ethenetricarboxylate derivative with propargylamines or propargyl alcohols to give methylenepyrrolidines and methylenetetrah...

  10. Valproic acid induces differentiation and inhibition of proliferation in neural progenitor cells via the beta-catenin-Ras-ERK-p21Cip/WAF1 pathway

    Arenas Ernest

    2008-12-01

    Full Text Available Abstract Background Valproic acid (VPA, a commonly used mood stabilizer that promotes neuronal differentiation, regulates multiple signaling pathways involving extracellular signal-regulated kinase (ERK and glycogen synthase kinase3β (GSK3β. However, the mechanism by which VPA promotes differentiation is not understood. Results We report here that 1 mM VPA simultaneously induces differentiation and reduces proliferation of basic fibroblast growth factor (bFGF-treated embryonic day 14 (E14 rat cerebral cortex neural progenitor cells (NPCs. The effects of VPA on the regulation of differentiation and inhibition of proliferation occur via the ERK-p21Cip/WAF1 pathway. These effects, however, are not mediated by the pathway involving the epidermal growth factor receptor (EGFR but via the pathway which stabilizes Ras through β-catenin signaling. Stimulation of differentiation and inhibition of proliferation in NPCs by VPA occur independently and the β-catenin-Ras-ERK-p21Cip/WAF1 pathway is involved in both processes. The independent regulation of differentiation and proliferation in NPCs by VPA was also demonstrated in vivo in the cerebral cortex of developing rat embryos. Conclusion We propose that this mechanism of VPA action may contribute to an explanation of its anti-tumor and neuroprotective effects, as well as elucidate its role in the independent regulation of differentiation and inhibition of proliferation in the cerebral cortex of developing rat embryos.

  11. Sonic hedgehog and retinoic Acid induce bone marrow-derived stem cells to differentiate into glutamatergic neural cells.

    Yu, Zhenhai; Wu, Shixing; Liu, Zhen; Lin, Haiyan; Chen, Lei; Yuan, Xinli; Zhang, Zhiying; Liu, Fang; Zhang, Chuansen

    2015-01-01

    Studies have showed that transplanted stem cells in the inner ear won't regenerate to replace the damaged sensory hair cells. They can spontaneously differentiate into mesenchymal cells and fibrocytes in the damaged inner ear. Only mature sensory cells of MSCs-derived possess the great potency for cell transplantation in the treatment of sensorineural hearing loss. So, we try to establish an efficient generation of the glutamatergic sensory neural phenotype for the cell transplantation of the hearing loss. We isolated MSCs from femoral and tibial bones according to their adherence to culture dishes. After purification, proliferation, and passaged, cells became homogeneous in appearance, showing more uniformity and grew in a monolayer with a typical spindle-shape morphology. The cell surface markers were assessed using FACS to characterize the isolated cells. For neural induction to harvest the glutamatergic sensory neurons, passage 3 MSCs were incubated with preinduced medium for 24 hr, and neural-induced medium for an additional 14 days. The cells exhibit a typical neural shape. RT-PCR analysis indicated that the mRNA levels of the neural cell marker nestin, Tau, MAP-2, β-tubulin III, GluR-3, and GluR-4 were higher compared with primary MSCs. Immunohistochemistry and western-blotting proofed that nestin, MAP-2, β-tubulin III, and GluR-4 proteins indeed exhibit their expression difference in the induced cells compared to the MSCs. We show an efficient protocol by the combined applications of Sonic Hedgehog (Shh) and Retinoic Acid (RA) to induce MSCs to differentiate into the glutamatergic sensory neuron which were identified from the morphological, biochemical, and molecular characteristics. PMID:24547891

  12. Endophytic Fungi Produce Gibberellins and Indoleacetic Acid and Promotes Host-Plant Growth during Stress

    In-Jung Lee

    2012-09-01

    Full Text Available We isolated and examined two endophytic fungi for their potential to secrete phytohormones viz. gibberellins (GAs and indoleacetic acid (IAA and mitigate abiotic stresses like salinity and drought. The endophytic fungi Phoma glomerata LWL2 and Penicillium sp. LWL3 significantly promoted the shoot and allied growth attributes of GAs-deficient dwarf mutant Waito-C and Dongjin-beyo rice. Analysis of the pure cultures of these endophytic fungi showed biologically active GAs (GA1, GA3, GA4 and GA7 in various quantities. The cultures of P. glomerata and Penicillium sp. also contained IAA. The culture application and endophytic-association with host-cucumber plants significantly increased the plant biomass and related growth parameters under sodium chloride and polyethylene glycol induced salinity and drought stress as compared to control plants. The endophytic symbiosis resulted in significantly higher assimilation of essential nutrients like potassium, calcium and magnesium as compared to control plants during salinity stress. Endophytic-association reduced the sodium toxicity and promoted the host-benefit ratio in cucumber plants as compared to non-inoculated control plants. The symbiotic-association mitigated stress by compromising the activities of reduced glutathione, catalase, peroxidase and polyphenol oxidase. Under stress conditions, the endophyte-infection significantly modulated stress through down-regulated abscisic acid, altered jasmonic acid, and elevated salicylic acid contents as compared to control. In conclusion, the two endophytes significantly reprogrammed the growth of host plants during stress conditions.

  13. Gluconic acid production and phosphate solubilization by the plant growth-promoting bacterium Azospirillum spp.

    Rodriguez, Hilda; Gonzalez, Tania; Goire, Isabel; Bashan, Yoav

    2004-11-01

    In vitro gluconic acid formation and phosphate solubilization from sparingly soluble phosphorus sources by two strains of the plant growth-promoting bacteria A. brasilense (Cd and 8-I) and one strain of A. lipoferum JA4 were studied. Strains of A. brasilense were capable of producing gluconic acid when grown in sparingly soluble calcium phosphate medium when their usual fructose carbon source is amended with glucose. At the same time, there is a reduction in pH of the medium and release of soluble phosphate. To a greater extent, gluconic acid production and pH reduction were observed for A. lipoferum JA4. For the three strains, clearing halos were detected on solid medium plates with calcium phosphate. This is the first report of in vitro gluconic acid production and direct phosphate solubilization by A. brasilense and the first report of P solubilization by A. lipoferum. This adds to the very broad spectrum of plant growth-promoting abilities of this genus.

  14. Autophagy induction promotes aristolochic acid-I-induced renal injury in vivo and in vitro

    Graphical abstract: - Highlights: • Aristolochic acid induced autophagy in vivo and in vitro. • Autophagy induced by aristolochic acid could promote cell apoptosis. • Inhibition autophagy by silencing ATG5 could prevent cell from programmed cell death induced by aristolochic acid. - Abstract: Studies have found that ingestion of aristolochic acid (AA) causes nephropathy first by inducing renal tubular cell apoptosis acutely. It is currently unknown whether crosstalk between autophagy and apoptosis orchestrates the fate of tubular cells in acute AA nephropathy. We tested this hypothesis by acute administration of AA in vivo and in vitro. Autophagy was first induced in vivo through enhancing Atg5 and LC3-II expressions in kidneys of AA-I-treated rats. Punctuate LC3-GFP dots and autophagosomes were detected in this acute AA-I nephropathy rat model. We subsequently utilized normal rat renal proximal tubular epithelial cells (NRK52E) to study the autophagy mechanisms involved in acute AA-I nephropathy, with 100 μM AA-I (median lethal dose 50) given in vitro. Cleavage of poly (ADP-ribose) polymerase (PARP), nuclear condensation, and fragmentation were demonstrated in the AA-I-treated NRK52E cells. Furthermore, AA-I induced Atg5 and LC3-II expressions and punctuated LC3-GFP dots. Autophagy flux by using lysosome inhibitor E64 induced the accumulation of LC3-II, which further promoted apoptosis through enhancing PARP cleavage. Inhibition of autophagy by 3-methyl adenine also led to the attenuation of AA-I-induced apoptosis, manifesting as decreased PARP cleavage, nuclei condensation, and decreased the number of cells negative for acridine orange/ethidium bromide staining. In addition, knockdown of Atg5 by short hairpin RNA attenuated LC3-II expression and PARP cleavage in NRK52E cells. Taken together, these findings suggested that the acute phase of AA-I-induced nephropathy is associated with induction of Atg5-dependent autophagy, which promotes renal tubular cell

  15. Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity.

    Entekhabi, Elahe; Haghbin Nazarpak, Masoumeh; Moztarzadeh, Fathollah; Sadeghi, Ali

    2016-12-01

    Given the large differences in nervous tissue and other tissues of the human body and its unique features, such as poor and/or lack of repair, there are many challenges in the repair process of this tissue. Tissue engineering is one of the most effective approaches to repair neural damages. Scaffolds made from electrospun fibers have special potential in cell adhesion, function and cell proliferation. This research attempted to design a high porous nanofibrous scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions for nerve regeneration by applying proper physicochemical and mechanical signals. Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds were measured by FTIR and tensile test. Morphology, swelling behavior, and biodegradability of the scaffolds were evaluated too. Porosity of various layers of scaffolds was measured by image analysis method. To assess the cell-scaffold interaction, SH-SY5Y human neuroblastoma cell line were cultured on the electrospun scaffolds. Taken together, these results suggest that the blended nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet all of the required specifications for neural cells and have potential application in neural tissue engineering. PMID:27612726

  16. Encapsulation of ascorbic acid promotes the reduction of Maillard reaction products in UHT milk.

    Troise, Antonio Dario; Vitiello, Daniele; Tsang, Catherine; Fiore, Alberto

    2016-06-15

    The presence of amino groups and carbonyls renders fortified milk with ascorbic acid particularly susceptible to the reduction of available lysine and to the formation of Maillard reaction products (MRPs), as Nε-(carboxyethyl)-l-lysine (CEL), Nε-(carboxymethyl)-l-lysine (CML), Amadori products (APs) and off-flavors. A novel approach was proposed to control the Maillard reaction (MR) in fortified milk: ascorbic acid was encapsulated in a lipid coating and the effects were tested after a lab scale UHT treatment. Encapsulation promoted a delayed release of ascorbic acid and a reduction in the formation of MRPs. Total lysine increased up to 45% in milk with encapsulated ascorbic acid, while reductions in CML, CEL and furosine ranged from 10% to 53% compared with control samples. The effects were also investigated towards the formation of amide-AGEs (advanced glycation end products) by high resolution mass spectrometry (HRMS) revealing that several mechanisms coincide with the MR in the presence of ascorbic acid. PMID:27240727

  17. Efeito da fortificação com ácido fólico na redução dos defeitos do tubo neural The effect of folic acid fortification on the reduction of neural tube defects

    Leonor Maria Pacheco Santos

    2007-01-01

    Full Text Available Defeitos do tubo neural são malformações que ocorrem na fase inicial do desenvolvimento fetal, levando à anencefalia e espinha bífida; o ácido fólico é o mais importante fator de risco identificado até hoje. A prevalência relatada de defeitos do tubo neural coloca o Brasil no patamar dos países com as mais altas taxas no mundo. Inquéritos sobre consumo de folato entre gestantes brasileiras mostram ingestão altamente deficiente (Neural tube defects are congenital malformations that occur during initial fetal development, leading to anencephaly and spina bifida; folic acid deficiency is the most important risk factor identified to date. Brazil has one of the world's highest neural tube defect rates. Food consumption surveys among pregnant Brazilian women showed a high rate of inadequate folic acid intake (< 0.6mg/day. In 2004, the National Health Surveillance Agency (ANVISA mandated the fortification of corn meal and wheat flour with folic acid (0.15mg/100g. The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16mg folic acid/day. However, while in the South of the country the supply was 144g/day, in the North and Central West it barely reached 70g/day. Folic acid food fortification is mandatory in some 40 countries, but only four have assessed this strategy. The existing studies have all shown a significant impact, ranging from 19 to 78%. Folic acid fortification is an undeniably important intervention for primary prevention, and neural tube defects can now be considered a preventable epidemic.

  18. Myristic Acid (MA) Promotes Adipogenic Gene Expression and the Differentiation of Porcine Intramuscular Adipocyte Precursor Cells

    LU Nai-sheng; ZHANG Yong-liang; JIANG Qing-yan; SHU Gang; XIE Qiu-ping; ZHU Xiao-tong; GAO Ping; ZHOU Gui-xuan; WANG Song-bo; WANG Li-na; XI Qian-yun

    2014-01-01

    Intramuscular fat (IMF) content is considered to be a key factor that affects the marbling, tenderness, juiciness and lfavor of pork. To investigate the effects of myristic acid (MA) on the differentiation of porcine intramuscular adipocytes, cells were isolated from longissimus dorsi muscle (LDM) and treated with 0, 10, 50 or 100μmol L-1 MA. The results showed that MA signiifcantly promotes the differentiation of intramuscular adipocytes in a dose-dependent manner. MA also led to a parallel increase in the expression of peroxisome proliferator activated receptor-γ(PPARγ) and adipose-related genes, such as glucose transporter 1 (GLUT1), lipoprotein lipase (LPL), adipocyte fatty acid binding protein 4 (FABP4/aP2), fatty acid translocase (FAT), acetyl-CoA carboxylaseα(ACCα), adipose triglyceride lipase (ATGL) and fatty acid synthase (FASN). However, no signiifcant effects of MA were observed on the expression of CAAT enhancer binding protein-α(C/EBPα) or hormone sensitive lipase (HSL). The expression of pyruvate dehydrogenase kinase 4 (PDK4) was increased by MA during the early stages of differentiation (day 1-3). In addition, MA also increased the absolute content of C14 (P<0.001) and saturated fatty acids (SFA) (P<0.05) to varying degrees, but no effects were observed on other fatty acids. These results suggest that MA might be able to enhance the IMF content of pork and increase the accumulation of myristic and myristoleic acid in muscle, which might have beneifcial implications for human health.

  19. Gamma-aminobutyric acid promotes human hepatocellular carcinoma growth through overexpressed gamma-aminobutyric acid A receptor α3 subunit

    2008-01-01

    AIM: To investigate the expression pattern of gamma-aminobutyric acid A (GABAA) receptors in hepatocellular carcinoma (HCC) and indicate the relationship among gamma-aminobutyric acid (GABA), gamrna-aminobutyric acid A receptor α3 subunit (GABRA3) and HCC.METHODS: HCC cell line Chang, HepG2, normal liver cell line L-02 and 8 samples of HCC tissues and paired non-cancerous tissues were analyzed with semiquantitative polymerase chain reaction (PCR) for the expression of GABAA receptors. HepG2 cells were treated with gamma-aminobutyric acid (GABA) at serial concentrations (0, 1, 10, 20, 40 and 60 μmol/L), and their proliferating abilities were analyzed with the 3-(4, 5-methylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell doubling time test, colon formation assay, cell cycle analysis and tumor planted in nude mice. Small interfering RNA was used for knocking down the endogenous GABRA3 in HepG2. oliferating abilities of these cells treated with or without GABA were analyzed.RESULTS: We identified the overexpression of GABRA3 in HCC cells. Knockdown of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth, suggesting its role in HCC cell viability. We determined the in vitro and in vivo effect of GABA in the proliferation of GABRA3-positive cell lines, and found that GABA increased HCC growth in a dose-dependent manner. Notably, the addition of GABA into the cell culture medium promoted the proliferation of GABRA3-expressing HepG2 cells, but not GABRA3-knockdown HepG2 cells. This means that GABA stimulates HepG2 cell growth through GABRA3. CONCLUSION: GABA and GABRA3 play important roles in HCC development and progression and can be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.

  20. Chemical modification of chitosan film via surface grafting of citric acid molecular to promote the biomineralization

    Liu, Yang; Shen, Xin; Zhou, Huan; Wang, Yingjun; Deng, Linhong

    2016-05-01

    We develop a novel chitosan-citric acid film (abbreviated as CS-CA) suitable for biomedical applications in this study. In this CS-CA film, the citric acid, which is a harmless organic acid has been extensively investigated as a modifying agent on carbohydrate polymers, was cross-linked by 1-Ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) onto the surface of chitosan (CS) film. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) confirms the graft copolymerization of the modified chitosan film (CS-CA). Surface wettability, moisturizing performance, the capacity of mineralization in vitro and biocompatibility of the films were characterized. After modification, this CS-CA film has good hydrophilicity. It is very evident that the citric acid grafting treatment significantly promotes the biomineralization of the chitosan based substrates. Cell experiments show that the MC3T3-E1 osteoblasts can adhere and proliferate well on the surface of CS-CA film. This CS-CA film, which can be prepared in large quantities and at low cost, should have potential application in bone tissue engineering.

  1. Industry experience in promoting weekly iron-folic acid supplementation in the Philippines.

    Garcia, Josel; Datol-Barrett, Eva; Dizon, Maynilad

    2005-12-01

    After participating in a pilot project under a government-industry partnership to promote the adoption of weekly iron-folic acid supplementation among women of reproductive age in the Philippines in 1998, United Laboratories (UNILAB), the Philippines' largest private pharmaceutical company, decided in April 2002 to launch a weekly iron-folic acid supplement for pregnant and non-pregnant women under the brand name Femina. The business objective set for the Femina brand was to build the category of preventive iron-folic acid supplements in line with the Philippine Department of Health's advocacy on weekly supplementation as an alternate to daily dosing to reduce the prevalence of anemia in the country. The brand was supported with an integrated mix of traditional advertising media with complementary direct-to-consumer educational programs that aimed to create awareness of iron-deficiency anemia, its causes and effects, and the role of weekly intake of iron-folic acid in preventing the condition. Aggressive marketing support for 1 year was successful in creating awareness among the target women. Significant lessons derived from consumers identified opportunity areas that can be further addressed in developing advocacy programs on weekly iron supplementation implemented on a nationwide scale in the future. PMID:16466091

  2. Investigations of Escherichia coli promoter sequences with artificial neural networks: new signals discovered upstream of the transcriptional startpoint

    Pedersen, Anders Gorm; Engelbrecht, Jacob

    1995-01-01

    along the promoter region. The spacing of all signals correspond to the helical periodicity of DNA, meaning that the signals are all present on the same face of the DNA helix in the promoter region. This is consistent with a model where the RNA polymerase contacts the promoter on one side of the DNA...

  3. Membrane properties of neural stem cells after in vitro induced neurogenesis by retinoic acid

    Jelitai, M.; Anděrová, Miroslava; Marko, K.; Madarasz, E.; Syková, Eva

    Praha, 2003. s. 37. ISBN 80-239-0887-1. [IBRO World Congress of Neuroscience /6./. 10.07.2003-15.07.2003, Praha] R&D Projects: GA ČR GA305/02/1528; GA ČR GA305/03/1172; GA MŠk LN00A065 Institutional research plan: CEZ:MSM 111300004 Keywords : neural stem cells Subject RIV: FH - Neurology

  4. Neural differentiation of pluripotent mouse embryonal carcinoma cells by retinoic acid - inhibitory effect of serum

    Pacherník, J.; Bryja, Vítězslav; Ešner, M.; Kubala, Lukáš; Dvořák, Petr; Hampl, Aleš

    2005-01-01

    Roč. 54, - (2005), s. 115-122. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GP524/03/P171; GA MŠk(CZ) LN00A065 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z5039906 Keywords : neural differentiation Subject RIV: FH - Neurology Impact factor: 1.806, year: 2005

  5. Rheb-TOR signaling promotes protein synthesis, but not glucose or amino acid import, in Drosophila

    de la Cruz Aida

    2007-03-01

    Full Text Available Abstract Background The Ras-related GTPase, Rheb, regulates the growth of animal cells. Genetic and biochemical tests place Rheb upstream of the target of rapamycin (TOR protein kinase, and downstream of the tuberous sclerosis complex (TSC1/TSC2 and the insulin-signaling pathway. TOR activity is regulated by nutritional cues, suggesting that Rheb might either control, or respond to, nutrient availability. Results We show that Rheb and TOR do not promote the import of glucose, bulk amino acids, or arginine in Drosophila S2 cells, but that both gene products are important regulators of ribosome biogenesis, protein synthesis, and cell size. S2 cell size, protein synthesis, and glucose import were largely insensitive to manipulations of insulin signaling components, suggesting that cellular energy levels and TOR activity can be maintained through insulin/PI3K-independent mechanisms in S2 cell culture. In vivo in Drosophila larvae, however, we found that insulin signaling can regulate protein synthesis, and thus may affect TOR activity. Conclusion Rheb-TOR signaling controls S2 cell growth by promoting ribosome production and protein synthesis, but apparently not by direct effects on the import of amino acids or glucose. The effect of insulin signaling upon TOR activity varies according to cellular type and context.

  6. Extracorporeal membrane oxygenation promotes long chain fatty acid oxidation in the immature swine heart in vivo

    Kajimoto, Masaki; O' Kelly-Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Isern, Nancy G.; Olson, Aaron; Portman, Michael A.

    2013-09-01

    Extracorporeal membrane oxygenation (ECMO) supports infants and children with severe cardiopulmonary compromise. Nutritional support for these children includes provision of medium- and long-chain fatty acids (FAs). However, ECMO induces a stress response, which could limit the capacity for FA oxidation. Metabolic impairment could induce new or exacerbate existing myocardial dysfunction. Using a clinically relevant piglet model, we tested the hypothesis that ECMO maintains the myocardial capacity for FA oxidation and preserves myocardial energy state. Provision of 13-Carbon labeled medium-chain FA (octanoate), longchain free FAs (LCFAs), and lactate into systemic circulation showed that ECMO promoted relative increases in myocardial LCFA oxidation while inhibiting lactate oxidation. Loading of these labeled substrates at high dose into the left coronary artery demonstrated metabolic flexibility as the heart preferentially oxidized octanoate. ECMO preserved this octanoate metabolic response, but also promoted LCFA oxidation and inhibited lactate utilization. Rapid upregulation of pyruvate dehydrogenase kinase-4 (PDK4) protein appeared to participate in this metabolic shift during ECMO. ECMO also increased relative flux from lactate to alanine further supporting the role for pyruvate dehydrogenase inhibition by PDK4. High dose substrate loading during ECMO also elevated the myocardial energy state indexed by phosphocreatine to ATP ratio. ECMO promotes LCFA oxidation in immature hearts, while maintaining myocardial energy state. These data support the appropriateness of FA provision during ECMO support for the immature heart.

  7. Basic fibroblast growth factor increases the number of endogenous neural stem cells and inhibits the expression of amino methyl isoxazole propionic acid receptors in amyotrophic lateral sclerosis mice

    Weihui Huang; Dawei Zang; Yi Lu; Ping Jiang

    2012-01-01

    This study aimed to investigate the number of amino methyl isoxazole propionic acid (AMPA) re-ceptors and production of endogenous neural stem cells in the SOD1G93AG1H transgenic mouse model of amyotrophic lateral sclerosis, at postnatal day 60 following administration of basic fibroblast growth factor (FGF-2). A radioligand binding assay and immunohistochemistry were used to estimate the number of AMPA receptors and endogenous neural stem cells respectively. Results showed that the number of AMPA receptors and endogenous neural stem cells in the brain stem and sensorimotor cortex were significantly increased, while motor function was significantly decreased at postnatal days 90 and 120. After administration of FGF-2 into mice, numbers of endogenous neural stem cells increased, while expression of AMPA receptors decreased, whilst motor functions were recovered. At postnatal day 120, the number of AMPA receptors was negatively correlated with the number of endogenous neural stem cells in model mice and FGF-2-treated mice. Our experimental findings indicate that FGF-2 can inhibit AMPA receptors and increase the number of endogenous neural stem cells, thus repairing neural injury in amyotrophic lateral sclerosis mice.

  8. A peptide mimetic targeting trans-homophilic NCAM binding sites promotes spatial learning and neural plasticity in the hippocampus

    Kraev, Igor; Henneberger, Christian; Rossetti, Clara; Conboy, Lisa; Kohler, Lene B; Fantin, Martina; Jennings, Alistair; Venero, Cesar; Popov, Victor; Rusakov, Dmitri; Stewart, Michael G; Bock, Elisabeth; Berezin, Vladimir; Sandi, Carmen

    2011-01-01

    The key roles played by the neural cell adhesion molecule (NCAM) in plasticity and cognition underscore this membrane protein as a relevant target to develop cognitive-enhancing drugs. However, NCAM is a structurally and functionally complex molecule with multiple domains engaged in a variety of ...

  9. Enzymatic Depletion of the Polysialic Acid Moiety Associated with the Neural Cell Adhesion Molecule Inhibits Antidepressant Efficacy.

    Wainwright, Steven R; Barha, Cindy K; Hamson, Dwayne K; Epp, Jonathan R; Chow, Carmen; Lieblich, Stephanie E; Rutishauser, Urs; Galea, Liisa Am

    2016-05-01

    Antidepressant drugs are too often ineffective, the exact mechanism of efficacy is still ambiguous, and there has been a paucity of novel targets for pharmacotherapy. In an attempt to understand the pathogenesis of depression and subsequently develop more efficacious antidepressant drugs, multiple theories have been proposed, including the modulation of neurotransmission, the upregulation of neurogenesis and neurotrophic factors, normalizing hypothalamic-pituitary-adrenal reactivity, and the reduction of neuroinflammation; all of which have supporting lines of evidence. Therefore, an ideal molecular target for novel pharmaceutical intervention would function at the confluence of these theories. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM) functions broadly, serving to mediate synaptic plasticity, neurogenesis, neurotrophic factor signaling, and inflammatory signaling throughout the brain; all of which are associated with the pathophysiology and treatment of depression. Moreover, the expression of PSA-NCAM is reduced by depression, and conversely enhanced by antidepressant treatment, particularly within the hippocampus. Here we demonstrate that selectively cleaving the polysialic acid moiety, using the bacteriophage-derived enzyme endoneuraminidase N, completely inhibits the antidepressant efficacy of the selective-serotonin reuptake inhibitor fluoxetine (FLX) in a chronic unpredictable stress model of depression. We also observe a corresponding attenuation of FLX-induced hippocampal neuroplasticity, including decreased hippocampal neurogenesis, synaptic density, and neural activation. These data indicate that PSA-NCAM-mediated neuroplasticity is necessary for antidepressant action; therefore PSA-NCAM represents an interesting, and novel, target for pharmacotherapy. PMID:26530284

  10. Promoters inducible by aromatic amino acids and γ-aminobutyrate (GABA) for metabolic engineering applications in Saccharomyces cerevisiae.

    Kim, Sujin; Lee, Kyusung; Bae, Sang-Jeong; Hahn, Ji-Sook

    2015-03-01

    A wide range of promoters with different strengths and regulatory mechanisms are valuable tools in metabolic engineering and synthetic biology. While there are many constitutive promoters available, the number of inducible promoters is still limited for pathway engineering in Saccharomyces cerevisiae. Here, we constructed aromatic amino-acid-inducible promoters based on the binding sites of Aro80 transcription factor, which is involved in the catabolism of aromatic amino acids through transcriptional activation of ARO9 and ARO10 genes in response to aromatic amino acids. A dynamic range of tryptophan-inducible promoter strengths can be obtained by modulating the number of Aro80 binding sites, plasmid copy numbers, and tryptophan concentrations. Using low and high copy number plasmid vectors and different tryptophan concentrations, a 29-fold range of fluorescence intensities of enhanced green fluorescent protein (EGFP) reporter could be achieved from a synthetic U4C ARO9 promoter, which is composed of four repeats of Aro80 binding half site (CCG) and ARO9 core promoter element. The U4C ARO9 promoter was applied to express alsS and alsD genes from Bacillus subtilis for acetoin production in S. cerevisiae, resulting in a gradual increase in acetoin titers depending on tryptophan concentrations. Furthermore, we demonstrated that γ-aminobutyrate (GABA)-inducible UGA4 promoter, regulated by Uga3, can also be used in metabolic engineering as a dose-dependent inducible promoter. The wide range of controllable expression levels provided by these tryptophan- and GABA-inducible promoters might contribute to fine-tuning gene expression levels and timing for the optimization of pathways in metabolic engineering. PMID:25573467

  11. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region.

    Wang, Haochen; De Steur, Hans; Chen, Gong; Zhang, Xiaotian; Pei, Lijun; Gellynck, Xavier; Zheng, Xiaoying

    2016-01-01

    Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs) through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages) and a control group received ordinary flour (three villages). NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs) method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207-0473, p Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory) folic acid fortification in China. PMID:27005659

  12. Effectiveness of Folic Acid Fortified Flour for Prevention of Neural Tube Defects in a High Risk Region

    Haochen Wang

    2016-03-01

    Full Text Available Despite efforts to tackle folate deficiency and Neural Tube Defects (NTDs through folic acid fortification, its implementation is still lacking where it is needed most, highlighting the need for studies that evaluate the effectiveness of folic acid fortified wheat flour in a poor, rural, high-risk, NTD region of China. One of the most affected regions, Shanxi Province, was selected as a case study. A community intervention was carried out in which 16,648 women of child-bearing age received fortified flour (eight villages and a control group received ordinary flour (three villages. NTD birth prevalence and biological indicators were measured two years after program initiation at endline only. The effect on the NTD burden was calculated using the disability-adjusted life years (DALYs method. In the intervention group, serum folate level was higher than in the control group. NTDs in the intervention group were 68.2% lower than in the control group (OR = 0.313, 95% CI = 0.207–0473, p < 0.001. In terms of DALYs, burden in intervention group was approximately 58.5% lower than in the control group. Flour fortification was associated with lower birth prevalence and burden of NTDs in economically developing regions with a high risk of NTDs. The positive findings confirm the potential of fortification when selecting an appropriate food vehicle and target region. As such, this study provides support for decision makers aiming for the implementation of (mandatory folic acid fortification in China.

  13. Combinatorial Regulation of Photoreceptor Differentiation Factor, Neural Retina Leucine Zipper Gene Nrl, Revealed by in Vivo Promoter Analysis*

    Kautzmann, Marie-Audrey I.; Kim, Douglas S; Felder-Schmittbuhl, Marie-Paule; Swaroop, Anand

    2011-01-01

    Development and homeostasis require stringent spatiotemporal control of gene expression patterns that are established, to a large extent, by combinatorial action of transcription regulatory proteins. The bZIP transcription factor NRL (neural retina leucine zipper) is critical for rod versus cone photoreceptor cell fate choice during retinal development and acts as a molecular switch to produce rods from postmitotic precursors. Loss of Nrl in mouse leads to a cone-only retina, whereas ectopic ...

  14. Plumbagin Promotes the Generation of Astrocytes from Rat Spinal Cord Neural Progenitors Via Activation of the Transcription Factor Stat3

    Luo, Yongquan; Mughal, Mohamed; Ouyang, Xin; Jiang, Haiyang; Luo, Tae-Gen Son Weiming; Yu, Qian-sheng; Greig, Nigel H.; Mattson, Mark P

    2010-01-01

    Plumbagin (5-hydroxy-2-methyl-1,4 naphthoquinone) is a naturally occurring low molecular weight lipophilic phytochemical derived from roots of plants of the Plumbago genus. Plumbagin has been reported to have several clinically relevant biological activities in non-neural cells including antiatherosclerotic, anticoagulant, anticarcinogenic, antitumor and bactericidal effects. In a recent screen of a panel of botanical pesticides we identified plumbagin as having neuroprotective activity. In t...

  15. TNF-α respecifies human mesenchymal stem cells to a neural fate and promotes migration toward experimental glioma

    Ries, Christian; von Baumgarten, Louisa; Schichor, Christian; Berninger, Benedikt; Popp, Tanja; Neth, Peter; Goldbrunner, Roland; Kienast, Yvonne; Winkler, Frank; Jochum, Marianne; Egea, Virginia

    2010-01-01

    Abstract Bone marrow-derived human mesenchymal stem cells (hMSCs) have become valuable candidates for cell-based therapeutical applications including neuroregenerative and anti-tumor strategies. Yet, the molecular mechanisms that control hMSC transdifferentiation to neural cells and hMSC tropism toward glioma remain unclear. Here, we demonstrate that hMSCs incubated with 50 ng/ml TNF-? acquired astroglial cell morphology without affecting proliferation which was increased at 5 ng/m...

  16. A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

    Lam Angeline

    2004-09-01

    Full Text Available Abstract Background Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD. In November 1998, food fortification with folic acid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to assess the benefits and possible adverse effects of this intervention. Methods This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I Determination of rates of NTDs; II Dietary assessment; III Blood analysis; IV Assessment of knowledge and use of folic acid supplements. Results The annual rates of NTDs in Newfoundland varied greatly between 1976 and 1997, with a mean rate of 3.40 per 1,000 births. There was no significant change in the average rates between 1991–93 and 1994–97 (relative risk [RR] 1.01, 95% confidence interval [CI] 0.76–1.34. The rates of NTDs fell by 78% (95% CI 65%–86% after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35. The average dietary intake of folic acid due to fortification was 70 μg/day in women aged 19–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, there were no significant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate status masking haematological manifestations of vitamin B12 deficiency. The proportion of women aged 19–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%. Conclusions Based on these findings, mandatory food fortification in Canada should continue at the

  17. Antisera production to detect indoleacetic acid in cultures of plant-growth promoting bacteria

    Rabbit polyclonal antisera against indoleacetic acid (IAA) bound to nitrocellulose membrane were obtained, which exhibited a high titer and specificity. The dot immunobinding technique with colloidal gold was used to detect auxin production by several strains belonging to Gluconacetobacter, Herbaspirillum, Azospirillum, Pseudomonas, Burkholderia and Bacillus genera, using culture supernatants as antigens. Moreover, auxin production was quantified by the Salkowski's method to corroborate the previous results. It was found that that all the studied microorganisms produce IAA and the feasibility of using these antisera to detect the metabolite was confirmed. Taking into account the potentialities of plant growth promoting bacteria as biofertilizers, the use of these antisera for a rapid and easy detection of IAA in bacteria associated with important crops is thus recommended.

  18. Ursodeoxycholic acid impairs atherogenesis and promotes plaque regression by cholesterol crystal dissolution in mice.

    Bode, Niklas; Grebe, Alena; Kerksiek, Anja; Lütjohann, Dieter; Werner, Nikos; Nickenig, Georg; Latz, Eicke; Zimmer, Sebastian

    2016-09-01

    Atherosclerosis is a chronic inflammatory disease driven primarily by a continuous retention of cholesterol within the subendothelial space where it precipitates to form cholesterol crystals (CC). These CC trigger a complex inflammatory response through activation of the NLRP3 inflammasome and promote lesion development. Here we examined whether increasing cholesterol solubility with ursodeoxycholic acid (UDCA) affects vascular CC formation and ultimately atherosclerotic lesion development. UDCA mediated intracellular CC dissolution in macrophages and reduced IL-1β production. In ApoE(-/-) mice, UDCA treatment not only impaired atherosclerotic plaque development but also mediated regression of established vascular lesions. Importantly, mice treated with UDCA had decreased CC-depositions in atherosclerotic plaques compared to controls. Together, our data demonstrate that UDCA impaired CC and NLRP3 dependent inflammation by increasing cholesterol solubility and diminished atherosclerosis in mice. PMID:27416761

  19. Human platelet releasates combined with polyglycolic acid scaffold promote chondrocyte differentiation and phenotypic maintenance

    Giulia Bernardini; Federico Chellini; Bruno Frediani; Adriano Spreafico; Annalisa Santucci

    2015-03-01

    In the present study, we aimed to demonstrate the differentiating properties of platelet-rich plasma releasates (PRPr) on human chondrocytes seeded on a polygtlycolic acid (PGA) 3D scaffold. Gene expression and biochemical analysis were carried out to assess the improved quality of our PGA-based cartilage constructs supplemented with PRPr. We observed that the use of PRPr as cell cultures supplementation to PGA-chondrocyte constructs may promote chondrocyte differentiation, and thus may contribute to maintaining the chondrogenic phenotype longer than conventional supplementation by increasing high levels of important chondrogenic markers (e.g. sox9, aggrecan and type II collagen), without induction of type I collagen. Moreover, our constructs were analysed for the secretion and deposition of important ECM molecules (sGAG, type II collagen, etc.). Our results indicate that PRPr supplementation may synergize with PGA-based scaffolds to stimulate human articular chondrocyte differentiation, maturation and phenotypic maintenance.

  20. Poly-L-ornithine promotes preferred differentiation of neural stem/progenitor cells via ERK signalling pathway

    Ge, Hongfei; Tan, Liang; Wu, Pengfei; Yin, Yi; Liu, Xin; Meng, Hui; Cui, Gaoyu; Wu, Nan; Lin, Jiangkai; Hu, Rong; Feng, Hua

    2015-10-01

    Neural stem/progenitor cells (NSPCs) replacement therapies are the most attractive strategies to restore an injured brain. Key challenges of such therapies are enriching NSPCs and directing them differentiation into specific neural cell types. Here, three biomaterial substrates Poly-L-ornithine (PO), Poly-L-lysine (PLL) and fibronectin (FN) were investigated for their effects on proliferation and differentiation of rat NSPCs, and the underlying mechanisms were also explored. The results showed PO significantly increased NSPCs proliferation and induced preferred differentiation, compared with PLL and FN. Checking protein markers of several neural cell subtypes, it is showed PO significantly induced NSPCs expressing Doublecortin (DCX) and Olig2, one for neuroblasts and young neurons and the other for young oligodendrocytes. It is suggested the ERK signaling pathway was involving in this process because an ERK antagonist U0126 could inhibit PO’s effects mentioned above, as well as an ERK pathway agonist Ceramide C6 could enhance them. Given that both neurons and oligodendrocytes are the most vulnerable cells in many neurological diseases, PO-induced preferred differentiation into neurons and oligodendrocytes is a potential paradigm for NSPCs-based therapies.

  1. Claulansine F promoted the neuronal differentiation of neural stem and progenitor cells through Akt/GSK-3β/β-catenin pathway.

    Huang, Ju-Yang; Ma, Yin-Zhong; Yuan, Yu-He; Zuo, Wei; Chu, Shi-Feng; Liu, Hang; Du, Guan-Hua; Zhang, Dong-Ming; Chen, Nai-Hong

    2016-09-01

    The persistence of neurogenesis raises the idea that neurons produced by the resident or transplanted neural stem cells could replace the neurons lost from brain injury or neurodegenerative disease. Therefore, compounds or methods for promoting neuronal differentiation become the focus of neurodegenerative disease therapy research. Claulansine F (Clau F), a newly discovered carbazole alkaloid, has been showed to induce neuritogenesis in PC12 cells. Herein, we studied the effect of Clau F on neuronal differentiation of neural stem/progenitor cells (NS/PCs). The current study demonstrated that Clau F initiated neuronal differentiation with a significant increase of TuJ1-positive cells and TuJ1 protein levels. We also found that Clau F promoted the maturity and sustainability of neurons by increasing MAP2-positive cells and MAP2 protein levels. At the same time, Clau F significantly inhibited the proliferation of NS/PCs. The underlying mechanism of Clau F was preliminary explored. Clau F treatment resulted in a profound increase of phosphorylation of Akt and GSK-3β, which led to GSK-3β inhibition and subsequently the nuclear accumulation of β-catenin. Further, the interaction between β-catenin and p300 in the nucleus was enhanced and the transcription of p300/β-catenin responsive genes were increased significantly (c-jun, fra-1) by Clau F. Importantly, the positive effect of Clau F on neuronal differentiation was abolished by Akti-1/2, a specific inhibitor of Akt-1/2 kinase, which indicated the involvement of Akt/GSK-3β in Clau F-mediated neuronal differentiation. In conclusion, these data suggested that Clau F promoted neuronal differentiation through Akt/GSK-3β/β-catenin signaling pathway in NS/PCs. PMID:27179990

  2. Differential Radiosensitizing Effect of Valproic Acid in Differentiation Versus Self-Renewal Promoting Culture Conditions

    Purpose: It has been shown that valproic acid (VA) enhances the proliferation and self-renewal of normal hematopoietic stem cells and that breast cancer stem/progenitor cells can be resistant to radiation. From these data, we hypothesized that VA would fail to radiosensitize breast cancer stem/progenitor cells grown to three-dimensional (3D) mammospheres. Methods and Materials: We used the MCF7 breast cancer cell line grown under stem cell-promoting culture conditions (3D mammosphere) and standard nonstem cell monolayer culture conditions (two-dimensional) to examine the effect of pretreatment with VA on radiation sensitivity in clonogenic survival assays and on the expression of embryonic stem cell transcription factors. Results: 3D-cultured MCF-7 cells expressed higher levels of Oct4, Nanog, and Sox2. The 3D passage enriched self-renewal and increased radioresistance in the 3D mammosphere formation assays. VA radiosensitized adherent cells but radioprotected 3D cells in single-fraction clonogenic assays. Moreover, fractionated radiation sensitized VA-treated adherent MCF7 cells but did not have a significant effect on VA-treated single cells grown to mammospheres. Conclusion: We have concluded that VA might preferentially radiosensitize differentiated cells compared with those expressing stem cell surrogates and that stem cell-promoting culture is a useful tool for in vitro evaluation of novel cancer therapeutic agents and radiosensitizers.

  3. Algae as an electron donor promoting sulfate reduction for the bioremediation of acid rock drainage.

    Ayala-Parra, Pedro; Sierra-Alvarez, Reyes; Field, Jim A

    2016-11-01

    This study assessed bioremediation of acid rock drainage in simulated permeable reactive barriers (PRB) using algae, Chlorella sorokiniana, as the sole electron donor for sulfate-reducing bacteria. Lipid extracted algae (LEA), the residues of biodiesel production, were compared with whole cell algae (WCA) as an electron donor to promote sulfate-reducing activity. Inoculated columns containing anaerobic granular sludge were fed a synthetic medium containing H2SO4 and Cu(2+). Sulfate, sulfide, Cu(2+) and pH were monitored throughout the experiment of 123d. Cu recovered in the column packing at the end of the experiment was evaluated using sequential extraction. Both WCA and LEA promoted 80% of sulfate removal (12.7mg SO4(2-) d(-1)) enabling near complete Cu removal (>99.5%) and alkalinity generation raising the effluent pH to 6.5. No noteworthy sulfate reduction, alkalinity formation and Cu(2+) removal were observed in the endogenous control. In algae amended-columns, Cu(2+) was precipitated with biogenic H2S produced by sulfate reduction. Formation of CuS was evidenced by sequential extraction and X-ray diffraction. LEA and WCA provided similar levels of electron donor based on the COD balance. The results demonstrate an innovative passive remediation system using residual algae biomass from the biodiesel industry. PMID:27318730

  4. Spectroscopic evidence for biochar amendment promoting humic acid synthesis and intensifying humification during composting.

    Wang, Cheng; Tu, Qiaoping; Dong, Da; Strong, P J; Wang, Hailong; Sun, Bin; Wu, Weixiang

    2014-09-15

    Despite the many benefits of biochar amendment in composting, little information is available about its effects on organic matter humification during the process. In this study the analytical results for two in-vessel composting piles were compared, one amended with biochar (VPSB, pig manure+sawdust+biochar) and the other serving as a control (VPS, pig manure+sawdust). During the 74 days of humification, the increased content of humic acid carbon in VPSB is 16.9% more than that of the control. Spectroscopic analyses show a higher O-alkyl C/alkyl C ratio and aromaticity in VPSB at the thermophilic phase, and peak intensities of fulvic-like and humic-like substances were achieved faster in VPSB than VPS. These data inferred that biochar amendment promoted the neo-synthesis of humic acids and intensified the humification of pig manure. Increase in carboxylic groups of biochar as a result of oxidation reactions and sorption of humic substances may correspond to the faster formation of aromatic polymers in biochar-supplemented composting pile. The results suggest that biochar amendment might be a potential method to enhance humification during pig manure composting. PMID:25194558

  5. Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury

    Qun Zhao; Zhi-yue Li; Ze-peng Zhang; Zhou-yun Mo; Shi-jie Chen; Si-yu Xiang; Qing-shan Zhang; Min Xue

    2015-01-01

    A variety of neurotrophic factors have been shown to repair the damaged peripheral nerve. However, in clinical practice, nerve growth factor, neurotrophin-3 and brain-derived neuro-trophic factor are all peptides or proteins that may be rapidly deactivated at the focal injury site;their local effective concentration time following a single medication cannot meet the required time for spinal axons to regenerate and cross the glial scar. In this study, we produced polymer sustained-release microspheres based on the polylactic-co-glycolic acid copolymer; the micro-spheres at 300-µm diameter contained nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor. Six microspheres were longitudinally implanted into the sciatic nerve at the anastomosis site, serving as the experimental group; while the sciatic nerve in the control group was subjected to the end-to-end anastomosis using 10/0 suture thread. At 6 weeks after implanta-tion, the lower limb activity, weight of triceps surae muscle, sciatic nerve conduction velocity and the maximum amplitude were obviously better in the experimental group than in the control group. Compared with the control group, more regenerating nerve ifbers were observed and dis-tributed in a dense and ordered manner with thicker myelin sheaths in the experimental group. More angiogenesis was also visible. Experimental findings indicate that polylactic-co-glycolic acid composite microspheres containing nerve growth factor, neurotrophin-3 and brain-derived neurotrophic factor can promote the restoration of sciatic nerve in rats after injury.

  6. Mangiferin decreases plasma free fatty acids through promoting its catabolism in liver by activation of AMPK.

    Yucun Niu

    Full Text Available Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW decreased dose-dependently FFA and triglycerides (TG levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK phosphorylation and its downstream proteins involved in fatty acid translocase (CD36 and carnitine palmitoyltransferase 1 (CPT1, but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2 expression and acetyl-CoA carboxylase (ACC activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism.

  7. Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury.

    Iwasaki, Motoyuki; Wilcox, Jared T; Nishimura, Yusuke; Zweckberger, Klaus; Suzuki, Hidenori; Wang, Jian; Liu, Yang; Karadimas, Spyridon K; Fehlings, Michael G

    2014-03-01

    While neural stem/progenitor cells (NPCs) show promise for traumatic spinal cord injury (SCI), their efficacy in cervical SCI remains to be established. Moreover, their application to SCI is limited by the challenges posed by the lesion including the glial scar and the post-traumatic cavitation. Given this background, we sought to examine the synergistic effect of self-assembling peptide (SAP) molecules, designed to optimize the post-traumatic CNS microenvironment, and NSCs in a clinically-relevant model of contusive/compressive cervical SCI. We injected K2(QL)6K2 (QL6) SAPs into the lesion epicenter 14 days after bilateral clip compression-induced cervical SCI in rats, combined with simultaneous transplantation of neural stem/progenitor cells (NPCs) intraspinally adjacent to the lesion epicenter. The QL6 SAPs reduced the volume of cystic cavitation in the spinal cord lesion. Simultaneously engrafted NPCs preserved motor neurons and attenuated perilesional inflammation. The combination of QL6 and NPCs promoted forelimb neurobehavioral recovery and was associated with significant improvement in forelimb print area and stride length. In summary, we report for the first time histologic and functional benefits in a clinically-relevant model of cervical SCI through the synergistic effects of combined SAP and NPCs. PMID:24406216

  8. Inhibition of the histone demethylase Kdm5b promotes neurogenesis and derepresses Reln (reelin) in neural stem cells from the adult subventricular zone of mice.

    Zhou, Qiong; Obana, Edwin A; Radomski, Kryslaine L; Sukumar, Gauthaman; Wynder, Christopher; Dalgard, Clifton L; Doughty, Martin L

    2016-02-15

    The role of epigenetic regulators in the control of adult neurogenesis is largely undefined. We show that the histone demethylase enzyme Kdm5b (Jarid1b) negatively regulates neurogenesis from adult subventricular zone (SVZ) neural stem cells (NSCs) in culture. shRNA-mediated depletion of Kdm5b in proliferating adult NSCs decreased proliferation rates and reduced neurosphere formation in culture. When transferred to differentiation culture conditions, Kdm5b-depleted adult NSCs migrated from neurospheres with increased velocity. Whole-genome expression screening revealed widespread transcriptional changes with Kdm5b depletion, notably the up-regulation of reelin (Reln), the inhibition of steroid biosynthetic pathway component genes and the activation of genes with intracellular transport functions in cultured adult NSCs. Kdm5b depletion increased extracellular reelin concentration in the culture medium and increased phosphorylation of the downstream reelin signaling target Disabled-1 (Dab1). Sequestration of extracellular reelin with CR-50 reelin-blocking antibodies suppressed the increase in migratory velocity of Kdm5b-depleted adult NSCs. Chromatin immunoprecipitation revealed that Kdm5b is present at the proximal promoter of Reln, and H3K4me3 methylation was increased at this locus with Kdm5b depletion in differentiating adult NSCs. Combined the data suggest Kdm5b negatively regulates neurogenesis and represses Reln in neural stem cells from the adult SVZ. PMID:26739753

  9. Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

    Zhichun Feng; Jing Liu; Rong Ju

    2013-01-01

    Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats (7 days old) subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2′-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2′- deoxyuridine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

  10. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia

    Xu, Wang-shu; Sun, Xuan; Song, Cheng-guang; Mu, Xiao-peng; Ma, Wen-ping; Zhang, Xing-hu; Zhao, Chuan-sheng

    2016-01-01

    Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These findings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia.

  11. Bumetanide promotes neural precursor cell regeneration and dendritic development in the hippocampal dentate gyrus in the chronic stage of cerebral ischemia

    Wang-shu Xu

    2016-01-01

    Full Text Available Bumetanide has been shown to lessen cerebral edema and reduce the infarct area in the acute stage of cerebral ischemia. Few studies focus on the effects of bumetanide on neuroprotection and neurogenesis in the chronic stage of cerebral ischemia. We established a rat model of cerebral ischemia by injecting endothelin-1 in the left cortical motor area and left corpus striatum. Seven days later, bumetanide 200 µg/kg/day was injected into the lateral ventricle for 21 consecutive days with a mini-osmotic pump. Results demonstrated that the number of neuroblasts cells and the total length of dendrites increased, escape latency reduced, and the number of platform crossings increased in the rat hippocampal dentate gyrus in the chronic stage of cerebral ischemia. These findings suggest that bumetanide promoted neural precursor cell regeneration, dendritic development and the recovery of cognitive function, and protected brain tissue in the chronic stage of ischemia.

  12. TdaA Regulates Tropodithietic Acid Synthesis by Binding to the tdaC Promoter Region ▿ †

    Geng, Haifeng; Belas, Robert

    2011-01-01

    Silicibacter sp. TM1040, a member of the marine Roseobacter clade, produces the antibiotic and quorum signaling molecule tropodithietic acid (TDA), encoded by tdaABCDEF. Here, we showed that an LysR-type transcriptional regulator, TdaA, is a positive regulator of tdaCDE gene expression and binds to the tdaC promoter region.

  13. The effects of fulvic acid on microbial denitrification: promotion of NADH generation, electron transfer, and consumption.

    Li, Mu; Su, Yinglong; Chen, Yinguang; Wan, Rui; Zheng, Xiong; Liu, Kun

    2016-06-01

    The heterotrophic denitrification requires the participation of electrons which are derived from direct electron donor (usually nicotinamide adenine dinucleotide (NADH)), and the electrons are transferred via electron transport system in denitrifiers and then consumed by denitrifying enzymes. Despite the reported electron transfer ability of humic substances (HS), the influences of fulvic acid (FA), an ubiquitous major component of HS, on promoting NADH generation, electron transfer, and consumption in denitrification process have never been reported. The presence of FA, compared with the control, was found not only significantly improved the total nitrogen (TN) removal efficiency (99.9 % versus 74.8 %) but remarkably reduced the nitrite accumulation (0.2 against 43.8 mg/L) and N2O emission (0.003 against 0.240 mg nitrogen/mg TN removed). The mechanisms study showed that FA increased the metabolism of carbon source via glycolysis and tricarboxylic acid (TCA) cycle pathways to produce more available NADH. FA also facilitated the electron transfer activities from NADH to denitrifying enzymes via complex I and complex III in electron transport system, which improved the reduction of nitrate and accelerated the transformations of nitrite and N2O, and lower nitrite and N2O accumulations were therefore observed. In addition, the consumption of electrons in denitrification was enhanced due to FA stimulating the synthesis and the catalytic activity of key denitrifying enzymes, especially nitrite reductase and N2O reductase. It will provide an important new insight into the potential effect of FA on microbial denitrification metabolism process and even nitrogen cycle in nature niches. PMID:26894403

  14. Amino acid deprivation induces CREBZF/Zhangfei expression via an AARE-like element in the promoter.

    Zhang, Yani; Jin, Yaping; Williams, Tegan A; Burtenshaw, Sally M; Martyn, Amanda C; Lu, Rui

    2010-01-15

    CREBZF (also called ZF or Zhangfei) is a basic region-leucine zipper transcription factor that has been implicated in the herpesvirus infection cycle and related cellular processes. Since ATF4 is known to play a key role in cellular responses to various ER stresses as well as amino acid deprivation, we sought to examine the potential involvement of CREBZF in the amino acid response (AAR). We found that the CREBZF protein was induced by amino acid deprivation in the canine MDCK cells. We subsequently cloned a canine CREBZF promoter region (-1767bp to +1bp) that responds to amino acid limitation. Using deletion mapping and site-directed mutagenesis, we identified a 9-bp sequence 5'-ATTCACTCA-3' in the promoter (-1227 to -1219), deletion of which resulted in a complete loss of inducibility by amino acid deprivation. This sequence is similar to the known amino acid response elements (AAREs) found in other AAR-inducible genes, such as CHOP (C/EBP homologous protein, also known as GADD153). These results suggest that CREBZF may be an amino acid stress sensor. Considering the AARE-like sequence found in CREBZF and other similarities between CREBZF and CHOP, we postulate that CREBZF and CHOP may be two sensors that regulate different yet related signaling pathways governing the AAR. PMID:20026304

  15. Identification and characterization of the retinoic acid response elements in the human RIG1 gene promoter

    The expression of retinoic acid-induced gene 1 (RIG1), a class II tumor suppressor gene, is induced in cells treated with retinoids. RIG1 has been shown to express ubiquitously and the increased expression of this gene appears to suppress cell proliferation. Recent studies also demonstrated that this gene may play an important role in cell differentiation and the progression of cancer. In spite of the remarkable regulatory role of this protein, the molecular mechanism of RIG1 expression induced by retinoids remains to be clarified. The present study was designed to study the molecular mechanism underlying the all-trans retinoic acid (atRA)-mediated induction of RIG1 gene expression. Polymerase chain reaction was used to generate a total of 10 luciferase constructs that contain various fragments of the RIG1 5'-genomic region. These constructs were then transfected into human gastric cancer SC-M1 and breast cancer T47D cells for transactivation analysis. atRA exhibited a significant induction in luciferase activity only through the -4910/-5509 fragment of the 5'-genomic region of RIG1 gene relative to the translation initiation site. Further analysis of this promoter fragment indicated that the primary atRA response region is located in between -5048 and -5403 of the RIG1 gene. Within this region, a direct repeat sequence with five nucleotide spacing, 5'-TGACCTctattTGCCCT-3' (DR5, -5243/-5259), and an inverted repeat sequence with six nucleotide spacing, 5'-AGGCCAtggtaaTGGCCT-3' (IR6, -5323/-5340), were identified. Deletion and mutation of the DR5, but not the IR6 element, abolished the atRA-mediated activity. Electrophoretic mobility shift assays with nuclear extract from atRA-treated cells indicated the binding of retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers specifically to this response element. In addition to the functional DR5, the region contains many other potential sequence elements that are required to maximize the at

  16. Promotion of Intestinal Epithelial Cell Turnover by Commensal Bacteria: Role of Short-Chain Fatty Acids.

    Jung-Ha Park

    Full Text Available The life span of intestinal epithelial cells (IECs is short (3-5 days, and its regulation is thought to be important for homeostasis of the intestinal epithelium. We have now investigated the role of commensal bacteria in regulation of IEC turnover in the small intestine. The proliferative activity of IECs in intestinal crypts as well as the migration of these cells along the crypt-villus axis were markedly attenuated both in germ-free mice and in specific pathogen-free (SPF mice treated with a mixture of antibiotics, with antibiotics selective for Gram-positive bacteria being most effective in this regard. Oral administration of chloroform-treated feces of SPF mice to germ-free mice resulted in a marked increase in IEC turnover, suggesting that spore-forming Gram-positive bacteria contribute to this effect. Oral administration of short-chain fatty acids (SCFAs as bacterial fermentation products also restored the turnover of IECs in antibiotic-treated SPF mice as well as promoted the development of intestinal organoids in vitro. Antibiotic treatment reduced the phosphorylation levels of ERK, ribosomal protein S6, and STAT3 in IECs of SPF mice. Our results thus suggest that Gram-positive commensal bacteria are a major determinant of IEC turnover, and that their stimulatory effect is mediated by SCFAs.

  17. Promotion of Intestinal Epithelial Cell Turnover by Commensal Bacteria: Role of Short-Chain Fatty Acids.

    Park, Jung-Ha; Kotani, Takenori; Konno, Tasuku; Setiawan, Jajar; Kitamura, Yasuaki; Imada, Shinya; Usui, Yutaro; Hatano, Naoya; Shinohara, Masakazu; Saito, Yasuyuki; Murata, Yoji; Matozaki, Takashi

    2016-01-01

    The life span of intestinal epithelial cells (IECs) is short (3-5 days), and its regulation is thought to be important for homeostasis of the intestinal epithelium. We have now investigated the role of commensal bacteria in regulation of IEC turnover in the small intestine. The proliferative activity of IECs in intestinal crypts as well as the migration of these cells along the crypt-villus axis were markedly attenuated both in germ-free mice and in specific pathogen-free (SPF) mice treated with a mixture of antibiotics, with antibiotics selective for Gram-positive bacteria being most effective in this regard. Oral administration of chloroform-treated feces of SPF mice to germ-free mice resulted in a marked increase in IEC turnover, suggesting that spore-forming Gram-positive bacteria contribute to this effect. Oral administration of short-chain fatty acids (SCFAs) as bacterial fermentation products also restored the turnover of IECs in antibiotic-treated SPF mice as well as promoted the development of intestinal organoids in vitro. Antibiotic treatment reduced the phosphorylation levels of ERK, ribosomal protein S6, and STAT3 in IECs of SPF mice. Our results thus suggest that Gram-positive commensal bacteria are a major determinant of IEC turnover, and that their stimulatory effect is mediated by SCFAs. PMID:27232601

  18. A review: Health promoting lactic acid bacteria in traditional Indonesian fermented foods

    Lilis Nuraida

    2015-06-01

    Full Text Available Traditional Indonesian fermented foods can be used as potential sources of probiotics as they commonly contain lactic acid bacteria (LAB, including species of Lactobacillus, Pediococcus, Enterococcus, Weisella and Leuconostoc. The occurrence of LAB in Indonesian fermented foods is not only limited to lactic fermented foods but is also present in foods with molds as the main starter culture. This review aims to describe the significance of Indonesian fermented foods as potential sources of probiotics and the potential of LAB from fermented foods to promote beneficial health effects. A number of in vitro studies have been carried out to assess the probiotic potential of LAB from fermented foods. Many LAB strains have met the basic requirements for them to be considered as probiotics and possess some functional properties contributing to positive health impacts. Hypocholesterolemic effects, stimulation of the immune system, and prevention of diarrhea by some probiotic strains have been shown in animal studies. However, human studies on the efficacy of probiotic strains are still limited. Two strains isolated from dadih, a fermented buffalo milk, are examples of promising probiotic strains that have gone through human studies. The potential probiotic properties of LAB in Indonesian fermented foods still need to be fully investigated to assess their impact on human health. The studies should also consider factors that may influence the functional properties of probiotics, both in foods and in humans.

  19. Ellagic acid promotes A{beta}42 fibrillization and inhibits A{beta}42-induced neurotoxicity

    Feng, Ying [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Yang, Shi-gao; Du, Xue-ting; Zhang, Xi; Sun, Xiao-xia; Zhao, Min [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China); Sun, Gui-yuan, E-mail: sungy2004@sohu.com [Department of Histology and Embryology, College of Basic Medical Science, China Medical University, Shenyang 110001 (China); Liu, Rui-tian, E-mail: rtliu@tsinghua.edu.cn [Tsinghua University School of Medicine, Haidian District, Beijing 100084 (China)

    2009-12-25

    Smaller, soluble oligomers of {beta}-amyloid (A{beta}) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of A{beta} oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against A{beta} neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on A{beta}42 aggregation and neurotoxicity in vitro. EA promoted A{beta} fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited A{beta} aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in A{beta}42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic A{beta} aggregates to render them harmless, our MTT results showed that EA could significantly reduce A{beta}42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  20. Enantioselective Hydrolysis of Amino Acid Esters Promoted by Bis(β-cyclodextrin) Copper Complexes

    Xue, Shan-Shan; Zhao, Meng; Ke, Zhuo-Feng; Cheng, Bei-Chen; Su, Hua; Cao, Qian; Cao, Zhen-Kun; Wang, Jun; Ji, Liang-Nian; Mao, Zong-Wan

    2016-02-01

    It is challenging to create artificial catalysts that approach enzymes with regard to catalytic efficiency and selectivity. The enantioselective catalysis ranks the privileged characteristic of enzymatic transformations. Here, we report two pyridine-linked bis(β-cyclodextrin) (bisCD) copper(II) complexes that enantioselectively hydrolyse chiral esters. Hydrolytic kinetic resolution of three pairs of amino acid ester enantiomers (S1-S3) at neutral pH indicated that the “back-to-back” bisCD complex CuL1 favoured higher catalytic efficiency and more pronounced enantioselectivity than the “face-to-face” complex CuL2. The best enantioselectivity was observed for N-Boc-phenylalanine 4-nitrophenyl ester (S2) enantiomers promoted by CuL1, which exhibited an enantiomer selectivity of 15.7. We observed preferential hydrolysis of L-S2 by CuL1, even in racemic S2, through chiral high-performance liquid chromatography (HPLC). We demonstrated that the enantioselective hydrolysis was related to the cooperative roles of the intramolecular flanking chiral CD cavities with the coordinated copper ion, according to the results of electrospray ionization mass spectrometry (ESI-MS), inhibition experiments, rotating-frame nuclear Overhauser effect spectroscopy (ROESY), and theoretical calculations. Although the catalytic parameters lag behind the level of enzymatic transformation, this study confirms the cooperative effect of the first and second coordination spheres of artificial catalysts in enantioselectivity and provides hints that may guide future explorations of enzyme mimics.

  1. Ellagic acid promotes Aβ42 fibrillization and inhibits Aβ42-induced neurotoxicity

    Smaller, soluble oligomers of β-amyloid (Aβ) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of Aβ oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against Aβ neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on Aβ42 aggregation and neurotoxicity in vitro. EA promoted Aβ fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited Aβ aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in Aβ42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic Aβ aggregates to render them harmless, our MTT results showed that EA could significantly reduce Aβ42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.

  2. Gamma-aminobutyric acid (GABA) and neuropeptides in neural areas mediating motion-induced emesis

    Damelio, F.; Daunton, Nancy G.; Fox, Robert A.

    1991-01-01

    Immunocytochemical methods were employed to localize the neurotransmitter amino acid gamma-aminobutyric acid and the neuropeptides substance P and Met-enkephalin in the area postrema (AP), area subpostrema (ASP), nucleus of the tractus solitarius (NTS), dorsal motor nucleus of the vagus nerve (DMNV), and lateral vestibular nucleus (LVN). Glutamic acid decarboxylase immunoreactive (GAD-IR) terminals and fibers were observed in the AP and particularly in the ASP. A gradual decrease in the density of terminals was seen towards the solitary complex. The DMNV revealed irregularly scattered GAD-IR terminals within the neuropil or closely surrounding neuronal cell bodies. The LVN, particularly the dorsal division, showed numerous axon terminals which were mostly localize around large neurons and their proximal dendrites. Substance P immunoreactive (SP-IR) terminals and fibers showed high density in the solitary complex, in particular within the lateral division. The ASP showed medium to low density of SP-IR fibers and terminals. The AP exhibited a small number of fibers and terminals irregularly distributed. The DMNV revealed a high density of SP-IR terminals and fibers that were mainly concentrated in the periphery. Very few terminals were detected in the LVN. Met-enkephalin immunoreactive (Met-Enk-IR) fibers and terminals showed high density and uniform distribution in the DMNV. Scattered terminals and fibers were observed in the AP, ASP, and NTS (particularly the lateral division). The very few fibers were observed in the LVN surrounded the neuronal cell bodies. The present report is part of a study designed to investigate the interaction between neuropeptides and conventional neurotransmitters under conditions producing motion sickness and in the process of sensory-motor adaptation.

  3. Estimation of Wear Resistance in Acid Solution of Dental Ceramics by Neural Network

    Lisjak, D.; Čurković, L.; Živko-Babić, J.; Jakovac, M.

    2002-01-01

    It is known that exposure to acid causes damage to the glass surface. The aim of this study was to examine wear resistance, measuring the mass change of dental ceramics after contact with 10-3 mol dm-3 HCl at temperature of 50°C. Four samples of dental ceramics were analyzed: feldspatic ceramic, hydrothermal ceramic, glass ceramic for staining and glass ceramic for layering. The mass concentrations of eluted Na+, K+ and Ca2+ were determined by ion chromatography (IC) and mass concentration...

  4. IGF-1 promotes Brn-4 expression and neuronal differentiation of neural stem cells via the PI3K/Akt pathway.

    Xinhua Zhang

    Full Text Available Our previous studies indicated that transcription factor Brn-4 is upregulated in the surgically denervated hippocampus in vivo, promoting neuronal differentiation of hippocampal neural stem cells (NSCs in vitro. The molecules mediating Brn-4 upregulation in the denervated hippocampus remain unknown. In this study we examined the levels of insulin-like growth factor-1 (IGF-1 in hippocampus following denervation. Surgical denervation led to a significant increase in IGF-1 expression in vivo. We also report that IGF-1 treatment on NSCs in vitro led to a marked acceleration of Brn-4 expression and cell differentiation down neuronal pathways. The promotion effects were blocked by PI3K-specific inhibitor (LY294002, but not MAPK inhibitor (PD98059; levels of phospho-Akt were increased by IGF-1 treatment. In addition, inhibition of IGF-1 receptor (AG1024 and mTOR (rapamycin both attenuated the increased expression of Brn-4 induced by IGF-1. Together, the results demonstrated that upregulation of IGF-1 induced by hippocampal denervation injury leads to activation of the PI3K/Akt signaling pathway, which in turn gives rise to upregulation of the Brn-4 and subsequent stem cell differentiation down neuronal pathways.

  5. Omega 3 fatty acids reduce myeloid progenitor cell frequency in the bone marrow of mice and promote progenitor cell differentiation

    Sollars Vincent E

    2009-03-01

    Full Text Available Abstract Background Omega 3 fatty acids have been found to inhibit proliferation, induce apoptosis, and promote differentiation in various cell types. The processes of cell survival, expansion, and differentiation are of key importance in the regulation of hematopoiesis. We investigated the role of omega 3 fatty acids in controlling the frequency of various myeloid progenitor cells in the bone marrow of mice. Increased progenitor cell frequency and blocked differentiation are characteristics of hematopoietic disorders of the myeloid lineage, such as myeloproliferative diseases and myeloid leukemias. Results We found that increasing the proportion of omega 3 fatty acids relative to the proportion of omega 6 fatty acids in the diet caused increased differentiation and reduced the frequency of myeloid progenitor cells in the bone marrow of mice. Furthermore, this had no adverse effect on peripheral white blood cell counts. Conclusion Our results indicate that omega 3 fatty acids impact hematopoietic differentiation by reducing myeloid progenitor cell frequency in the bone marrow and promoting progenitor cell differentiation. Further exploration of this discovery could lead to the use of omega 3 fatty acids as a therapeutic option for patients that have various disorders of hematopoiesis.

  6. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context

    Laura Bindila; Antoni Pastor; Margarita Pérez-Martín; Rafael De La Torre; Juan Suarez

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3+ or BrdU+ cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3+), astroglia (GFAP+), and microglia (Iba1+ cells) were analyzed in the hippocampus, hypothalamus and striatum o...

  7. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.

    Rivera, Patricia; Bindila, Laura; Pastor, Antoni; Pérez-Martín, Margarita; Pavón, Francisco J.; Serrano, Antonia; de la Torre, Rafael; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and ...

  8. NR2B-containing NMDA receptors promote neural progenitor cell proliferation through CaMKIV/CREB pathway

    Highlights: → The NR2B component of the NMDARs is important for the NSPC proliferation. → pCaMKIV and pCREB exist in NSPCs. → The CaMKIV/CREB pathway mediates NSPC proliferation. -- Abstract: Accumulating evidence indicates the involvement of N-methyl-D-aspartate receptors (NMDARs) in regulating neural stem/progenitor cell (NSPC) proliferation. Functional properties of NMDARs can be markedly influenced by incorporating the regulatory subunit NR2B. Here, we aim to analyze the effect of NR2B-containing NMDARs on the proliferation of hippocampal NSPCs and to explore the mechanism responsible for this effect. NSPCs were shown to express NMDAR subunits NR1 and NR2B. The NR2B selective antagonist, Ro 25-6981, prevented the NMDA-induced increase in cell proliferation. Moreover, we demonstrated that the phosphorylation levels of calcium/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein (CREB) were increased by NMDA treatment, whereas Ro 25-6981 decreased them. The role that NR2B-containing NMDARs plays in NSPC proliferation was abolished when CREB phosphorylation was attenuated by CaMKIV silencing. These results suggest that NR2B-containing NMDARs have a positive role in regulating NSPC proliferation, which may be mediated through CaMKIV phosphorylation and subsequent induction of CREB activation.

  9. Human neural stem cells differentiate and promote locomotor recovery in an early chronic spinal cord injury NOD-scid mouse model.

    Desirée L Salazar

    Full Text Available BACKGROUND: Traumatic spinal cord injury (SCI results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns were prospectively isolated based on fluorescence-activated cell sorting for a CD133(+ and CD24(-/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery. METHODS AND FINDINGS: hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein. CONCLUSIONS: The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the "window of opportunity" for

  10. Alpha-Lipoic acid counteracts the promoted oxidative DNA damage in the liver of septic rats

    Viral, parasitic infections and chemical carcinogens are among the etiological factors of liver cancer. It seems important to study the initiating and promoting agents to evaluate the etiology and prevention of such life threatening disease. Intestine-derived bacteria product, lipopolysaccharide (LPS), is mainly detoxified by the liver. It has shown to induce a state of oxidative DNA damage is not fully investigated. Increased oxidative DNA damage and rate of cell proliferation may initiate or even promote cancer. In the present work, the capability of LPS to induce 8-hydroxydeoxyguanosine (8-HDG), a specific DNA adduct for oxidative DNA damage, in rat livers is tested. Furthermore, a possible protective effect of alpha lipoic acid (ALA) is also assessed. Investigated parameters are liver contents of glutathione (GSH), lipid peroxides (MDA), nitric oxide (NO) and 8-HDG in the liver-extracted DNA. Serum activities of ALT, AST and GGT as liver-function markers as well as IL2 are assessed. Moreover, liver histology is examined. LPS was given doses of 1, 3, 5, 7 and 9 mg/kg once i.p. while, the rat mortality was examined 24 hours later. ALA was given in doses of 50, 100 and 200 mg/kg once i.p. 3h before LPS is found to be 5mg/kg. LPS increased the level of 8-HDG, MDA and NO in the liver. It also induced acute liver necrosis and inflammatory cell infiltration as shown in liver-histopathology and in the significant increase in the activities of ALT, AST and GGT. LPS increased the serum level of IL2 as well. The dose 200mg/kg of ALA revealed a 100% protection against LPS-induced lethality. It also, prevented the LPS-induced increase in 8-HDG in liver extracted DNA, the liver contents of MDA and NO. ALA also rescued the LPS-induced GSH depletion. It corrected the liver function as shown by the prevention of increases in the activity of ALT, AST and GGT with a remarkable improvement in the liver histology. Moreover, it prevented the increase in serum level of IL2. These

  11. Effect of gamma-aminobutyric acid on neurally mediated contraction of guinea pig trachealis smooth muscle.

    Tamaoki, J; Graf, P D; Nadel, J A

    1987-10-01

    To determine whether gamma-aminobutyric acid (GABA) affects the contractile properties of airway smooth muscle and, if so, what the mechanism of action is, the authors studied guinea pig tracheal rings under isometric conditions in vitro. GABA and related substances, baclofen and muscimol, had no effect on the resting tension but reversibly depressed contractions induced by electrical field stimulation in a dose-dependent fashion, IC50 values (mean +/- S.E.) being 5.6 +/- 1.4 X 10(-6) M, 6.8 +/- 0.9 X 10(-6) M and 8.5 +/- 1.5 X 10(-5) M, respectively. In contrast, GABA did not alter the response to exogenous acetylcholine or the nonadrenergic noncholinergic inhibitory component. Pretreatment of tissues with bicuculline antagonized the inhibitory effect of GABA as well as that of baclofen. This inhibitory effect was not modified by propranolol, phentolamine, hemicholinium-3 or naloxone, but it was blocked by the Cl channel blocker furosemide and by the substitution of external Cl. These results suggest that GABA decreases the contractile response of airway smooth muscle to cholinergic nerve stimulation by inhibiting the evoked release of acetylcholine and that this effect is exerted by activating Cl-dependent, bicuculline-sensitive GABA receptors. PMID:3668869

  12. Use of recurrent neural networks for determination of 7-epiclusianone acidity constants in ethanol-water mixtures; Uso de redes neurais recorrentes na determinacao das constantes de acidez para a 7-epiclusianona em misturas etanol-agua

    Costa, Ederson D' Martin; Lemes, Nelson Henrique Teixeira, E-mail: nelson.lemes@unifal-mg.edu.br [Instituto de Ciencias Exatas, Universidade Federal de Alfenas, Alfenas, MG (Brazil); Santos, Marcelo Henrique dos [Instituto de Ciencias Farmaceuticas, Universidade Federal de Alfenas, Alfenas, MG (Brazil); Braga, Joao Pedro [Departamento de Quimica, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2012-07-01

    This work propose a recursive neural network to solve inverse equilibrium problem. The acidity constants of 7-epiclusianone in ethanol-water binary mixtures were determined from multiwavelength spectrophotometric data. A linear relationship between acidity constants and the % w/v of ethanol in the solvent mixture was observed. The proposed method efficiency is compared with the Simplex method, commonly used in nonlinear optimization techniques. The neural network method is simple, numerically stable and has a broad range of applicability. (author)

  13. Neural progenitor cell transplantation promotes neuroprotection, enhances hippocampal neurogenesis, and improves cognitive outcomes after traumatic brain injury.

    Blaya, Meghan O; Tsoulfas, Pantelis; Bramlett, Helen M; Dietrich, W Dalton

    2015-02-01

    Transplantation of neural progenitor cells (NPCs) may be a potential treatment strategy for traumatic brain injury (TBI) due to their intrinsic advantages, including the secretion of neurotrophins. Neurotrophins are critical for neuronal survival and repair, but their clinical use is limited. In this study, we hypothesized that pericontusional transplantation of NPCs genetically modified to secrete a synthetic, human multineurotrophin (MNTS1) would overcome some of the limitations of traditional neurotrophin therapy. MNTS1 is a multifunctional neurotrophin that binds all three tropomyosin-related kinase (Trk) receptors, recapitulating the prosurvival activity of 3 endogenous mature neurotrophins. NPCs obtained from rat fetuses at E15 were transduced with lentiviral vectors containing MNTS1 and GFP constructs (MNTS1-NPCs) or fluorescent constructs alone (control GFP-NPCs). Adult rats received fluid percussion-induced TBI or sham surgery. Animals were transplanted 1week later with control GFP-NPCs, MNTS1-NPCs, or injected with saline (vehicle). At five weeks, animals were evaluated for hippocampal-dependent spatial memory. Six weeks post-surgery, we observed significant survival and neuronal differentiation of MNTS1-NPCs and injury-activated tropism toward contused regions. NPCs displayed processes that extended into several remote structures, including the hippocampus and contralateral cortex. Both GFP- and MNTS1-NPCs conferred significant preservation of pericontusional host tissues and enhanced hippocampal neurogenesis. NPC transplantation improved spatial memory capacity on the Morris water maze (MWM) task. Transplant recipients exhibited escape latencies approximately half that of injured vehicle controls. While we observed greater transplant survival and neuronal differentiation of MNTS1-NPCs, our collective findings suggest that MNTS1 may be superfluous in terms of preserving the cytoarchitecture and rescuing behavioral deficits given the lack of significant

  14. Short term morphine exposure in vitro alters proliferation and differentiation of neural progenitor cells and promotes apoptosis via mu receptors.

    Dafna Willner

    Full Text Available Chronic morphine treatment inhibits neural progenitor cell (NPC progression and negatively effects hippocampal neurogenesis. However, the effect of acute opioid treatment on cell development and its influence on NPC differentiation and proliferation in vitro is unknown. We aim to investigate the effect of a single, short term exposure of morphine on the proliferation, differentiation and apoptosis of NPCs and the mechanism involved.Cell cultures from 14-day mouse embryos were exposed to different concentrations of morphine and its antagonist naloxone for 24 hours and proliferation, differentiation and apoptosis were studied. Proliferating cells were labeled with bromodeoxyuridine (BrdU and cell fate was studied with immunocytochemistry.Cells treated with morphine demonstrated decreased BrdU expression with increased morphine concentrations. Analysis of double-labeled cells showed a decrease in cells co-stained for BrdU with nestin and an increase in cells co-stained with BrdU and neuron-specific class III β-tubuline (TUJ1 in a dose dependent manner. Furthermore, a significant increase in caspase-3 activity was observed in the nestin- positive cells. Addition of naloxone to morphine-treated NPCs reversed the anti-proliferative and pro-apoptotic effects of morphine.Short term morphine exposure induced inhibition of NPC proliferation and increased active caspase-3 expression in a dose dependent manner. Morphine induces neuronal and glial differentiation and decreases the expression of nestin- positive cells. These effects were reversed with the addition of the opioid antagonist naloxone. Our results demonstrate the effects of short term morphine administration on the proliferation and differentiation of NPCs and imply a mu-receptor mechanism in the regulation of NPC survival.

  15. Roles of Salicylic Acid-responsive Cis-acting Elements and W-boxes in Salicylic Acid Induction of VCH3 Promoter in Transgenic Tobaccos

    Hai-Yan LI; Wei WEI; Yu LI

    2006-01-01

    A salicylic acid (SA)-inducible VCH3 promoter was recently identified from grapevine (Vitis amurensis) that contains two inverse SA-responsive cis-acting elements and four W-boxes. To further demonstrate the roles of these elements, four fragments with lengths from -1187, -892, -589, -276 to +7 bp were fused with the β-glucuronidase (GUS) reporter gene and transferred to Nicotiana tobacum,together with another four VCH3 promoter fragments with mutation in the two inverse SA-responsive elements. The functions of each promoter fragment were examined by analysis of GUS activity in the transgenic tobacco root treated with SA. Enhanced GUS activity was shown in the roots of transgenic tobaccos with the VCH3 (-1187)-GUS construct containing two SA-responsive cis-acting elements and four W-boxes. However, GUS activity directed by the VCH3 (-892)-GUS construct, containing one SA cisacting element and four W-boxes, was reduced by up to 35% compared with that in tobaccos transformed with the VCH3 (-1187)-GUS construct, indicating that the SA cis-acting element plays an important role in SA induction of the VCH3 promoter. Neither the m2VCH3 (-1187)-GUS nor the m VCH3 (-892)-GUSconstruct, with mutation on the SA-responsive elements, abolished the expression of GUS activity, demonstrating that the W-boxes in the VCH3 promoter are also involved in SA induction. Histochemical analysis of GUS activity directed by each of the eight VCH3 promoter fragments showed that GUS was expressed specifically in vascular tissue. It was concluded that both the SA-responsive cis-acting elements and the Wboxes are important for the SA induction of the VCH3 promoter. This promoter might have a potential use in plant genetic engineering.

  16. Heteropoly acid promoted V2O5/TiO2 catalysts for NO abatement with ammonia in alkali containing flue gases

    Putluru, Siva Sankar Reddy; Jensen, Anker Degn; Riisager, Anders;

    2011-01-01

    catalytic reduction (SCR) of NO with ammonia. The SCR activity of heteropoly acid promoted catalysts was found to be much higher than for unpromoted catalysts. The stability of heteropoly acid promoted catalysts is dependent on calcination temperature and there is a gradual decrease in SCR activity and...... acidity with increase in calcination temperatures. Furthermore, the heteropoly acid promoted V2O5/TiO2 catalysts showed excellent alkali deactivation resistance and might therefore be alternative deNOx catalysts in biomass fired power plants.......V2O5/TiO2 and heteropoly acid promoted V2O5/TiO2 catalysts were prepared and characterized by N2 physisorption, XRPD and NH3-TPD. The influence of the calcination temperature from 400 to 700 1C on crystallinity and acidic properties was studied and compared with the activity for the selective...

  17. S6K Promotes Dopaminergic Neuronal Differentiation Through PI3K/Akt/mTOR-Dependent Signaling Pathways in Human Neural Stem Cells.

    Lee, Jeong Eun; Lim, Mi Sun; Park, Jae Hyun; Park, Chang Hwan; Koh, Hyun Chul

    2016-08-01

    It has recently been reported that the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway regulates neuronal differentiation of neural stem cells (NSCs) derived from rats or mice and is essential for the self-renewal of human embryonic stem cells (hESCs). However, the roles of PI3K/Akt/mTOR signaling pathways during proliferation and dopaminergic neuronal differentiation of human neural stem cells (hNSCs) are poorly understood. In this study, we examined the effect of regulation of these intracellular signaling pathways in hNSCs on the potential to maintain proliferation and induce dopaminergic neuronal differentiation. Dopaminergic neuronal differentiation depended on the concentration of insulin in our culture system. Inhibition of PI3K/Akt with LY294002 reduced proliferation and inhibited dopaminergic neuronal differentiation of these cells. We also found that rapamycin, a specific inhibitor of mTOR, significantly reduced neuronal differentiation without affecting proliferation. Inhibition of the Akt/mTOR signaling pathway led to inhibition of p70 ribosomal S6 kinase (S6K) signaling, which reduced dopaminergic neuronal differentiation in hNSCs. Inhibition of S6K by a specific chemical inhibitor, PF-4708671 inhibited dopaminergic neuronal differentiation of hNSCs. As expected, transduction with a dominant negative S6K1 (S6K1-DN) construct impaired dopaminergic neuronal differentiation of hNSCs. Conversely, overexpression of constitutively active S6K1 (S6K1-CA) promoted dopaminergic neuronal differentiation of these cells. In a survival study, 4 weeks after transplantation, no or very few donor cells were viable in striata grafted with S6K1-DN-transduced hNSCs. In contrast, S6K1-CA-transduced hNSCs survived, integrated into striata to generate tubular masses of grafts and differentiated toward TH-positive cells. Taken together, these data demonstrated that insulin promotes dopaminergic neuronal differentiation through a PI

  18. Erythorbic acid promoted formation of CdS QDs in a tube-in-tube micro-channel reactor

    Liang, Yan; Tan, Jiawei; Wang, Jiexin; Chen, Jianfeng [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029 (China); Sun, Baochang, E-mail: sunbc@mail.buct.edu.cn [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029 (China); Shao, Lei, E-mail: shaol@mail.buct.edu.cn [State Key Laboratory of Organic–Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029 (China); Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029 (China)

    2014-12-15

    Erythorbic acid assistant synthesis of CdS quantum dots (QDs) was conducted by homogeneous mixing of two continuous liquids in a high-throughput microporous tube-in-tube micro-channel reactor (MTMCR) at room temperature. The effects of the micropore size of the MTMCR, liquid flow rate, mixing time and reactant concentration on the size and size distribution of CdS QDs were investigated. It was found that the size and size distribution of CdS QDs could be tuned in the MTMCR. A combination of erythorbic acid promoted formation technique with the MTMCR may be a promising pathway for controllable mass production of QDs.

  19. Promotion of radiation peroxidation in models of lipid membranes by caesium and rubidium counter-ions: micellar linolenic acids

    Caesium and rubidium counter-ions increase peroxidation in irradiated micelles of linoleic (18 : 2) and linolenic (18 :3) acids. The effect was specific to Cs+ and Rb+ in the alkali metal series. The effect was independent of the salts used (Cl-, NO3-, Cl04-) and, therefore, independent of the chaotropic nature, and reactivity with hydroxyl radicals of Cl-, NO3- and ClO4-. The promotion of peroxidation by Cs+ and Rb+ is interpreted in terms of their effect on fatty acid micelle structure. The dependence of radiation peroxidation on lipid structure in the micelles may be significant for studies of peroxidation in highly structured cell membranes. (author)

  20. Effects of Lewis acidity of metal oxide promoters on the activity and selectivity of Co-based Fischer–Tropsch synthesis catalysts

    Johnson, Gregory R.; Bell, Alexis T. (LBNL); (UCB)

    2016-06-17

    Metal oxides of Ce, Gd, La, Mn, and Zr were investigated as promoters for improving the activity and selectivity of Co-based FTS catalysts. The extent to which these promoters decrease the selectivity toward CH4 and increase the selectivity toward C5+ hydrocarbons was found to depend on both the loading and the composition of the oxide promoter. Elemental mapping by STEM–EDS revealed that the propensity for a given metal oxide to associate with Co affects the sensitivity of the product distribution to changes in promoter loading. For all promoters, a sufficiently high loading resulted in the product distributions becoming insensitive to further increases in promoter loading, very likely due to the formation of a half monolayer of promoter oxide over the Co surface. Simulations suggest that the fraction of Co active sites that are adjacent to the promoter moieties approaches unity at this degree of coverage. The oxidation state of the promoter metal cation under reaction conditions, determined by in situ XANES measurements, was used to calculate relative Lewis acidity of the promoter metal cation. A strong positive correlation was found between the C5+ product selectivity and the Lewis acidity of the promoter metal cations, suggesting that the promotional effects are a consequence of Lewis acid–base interactions between the reaction intermediates and the promoter metal cations. Rate data obtained at different pressures were used to estimate the apparent rate coefficient and the CO adsorption constant appearing in the Langmuir–Hinshelwood expression that describes the CO consumption kinetics for both unpromoted and the metal oxide-promoted catalysts. Both parameters exhibited positive correlations with the promoter Lewis acidity. In conclusion, these results are consistent with the hypothesis that the metal cations of the promoter act as Lewis acids that interact with the O atom of adsorbed CO to facilitate CO adsorption and

  1. Perlecan is required for FGF-2 signaling in the neural stem cell niche

    Aurelien Kerever

    2014-03-01

    Full Text Available In the adult subventricular zone (neurogenic niche, neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis.

  2. EFFECTS OF SP1 SITE TO hTERT PROMOTER ACTIVITY AND ITS RESPONSE TO RETINOID ACID

    应磊; 戴冰冰; 王楚; 卢健; 钱关祥

    2005-01-01

    Objective To investigate the function of Sp1 consensus sites to human telomerase reverse transcriptase (hTERT) promoter in different cell lines and in TRA-treated Held cell. Methods Different length of hTERT promoter was cloned and inserted into pGL3/basic reporter plasmid. The last four Sp1 sites were deleted by PCR and pGL3 B/TRTP413 A reporter plasmid was constructed. All reporter plasmids were transiently transfected into 293, A549, Hela and HepG2 cell lines. 48 h after transfection, luciferase activity was analyzed. hTERT promoter activity of Held cell which was treated with trans-retinoid acid (TRA) was tested too. Total RNA of these cells were extracted and reverse transcript. hTERT mRNA level was analyzed in all tested cells. c-Myc and Sp1 expression were examined in Hela cell before and after TRA treatment. U937 was used as a positive control in TRA treatment.Results hTERT was expressed at different level in all tested cell lines. 207bp promoter upstream of transcription start site maintained complete activity. Deletion of last 4 Sp1 sites greatly decreased activity of hTERT promoter, and almost eliminated its activity in HepG2. TRA increased the activity of different length hTERT promoters in Hela cell,but the activity of Sp1 site-deleted promoter decreased by 3 times. Unlike U937 cell, hTERT expression of Held cell increased after TRA treatment, and c-Myc and Sp1 mRNA level were relatively stable. Conclusion Sp1 site was required for transactivation of hTERT promoter and played an important role during TRA treatment.

  3. Pd-catalyzed ethylene methoxycarbonylation with Brønsted acid ionic liquids as promoter and phase-separable reaction media

    Garcia-Suarez, Eduardo J.; Khokarale, Santosh Govind; Nguyen van Buu, Olivier;

    2014-01-01

    Brønsted acid ionic liquids (BAILs) were prepared and applied as combined acid promoters and reaction media in Pd–phosphine catalyzed methoxycarbonylation of ethylene to produce methyl propionate. The BAILs served as alternatives to common mineral acids required for the reaction, e.g. methanesulf...

  4. Transplantation of mesenchymal stem cells promotes the functional recovery of the central nervous system following cerebral ischemia by inhibiting myelin-associated inhibitor expression and neural apoptosis

    FENG, NIANPING; HAO, GUANG; YANG, FENGGANG; QU, FUJUN; ZHENG, HAIHONG; LIANG, SONGLAN; JIN, YONGHUA

    2016-01-01

    Cerebral ischemia, which may lead to cerebral hypoxia and damage of the brain tissue, is a leading cause of human mortality and adult disability. Mesenchymal stem cells (MSCs) are a class of adult progenitor cells with the ability to differentiate into multiple cell types. The transplantation of bone marrow-derived MSCs is a potential therapeutic strategy for cerebral ischemia. However, the underlying mechanism has yet to be elucidated. In the present study, primary MSCs were isolated from healthy rats, labeled and transplanted into the brains of middle cerebral artery occlusion rat models. The location of the labeled MSCs in the rat brains were determined by fluorescent microscopy, and the neurological functions of the rats were scored. Immunohistochemical analyses demonstrated that the protein expression levels of myelin-associated inhibitors of regeneration, including Nogo-A, oligodendrocyte myelin glycoprotein and myelin-associated glycoprotein, were decreased following transplantation of the bone marrow-derived MSCs. Furthermore, the mRNA expression levels of Capase-3 and B-cell lymphoma 2, as determined by reverse transcription-quantitative polymerase chain reactions, were downregulated and upregulated, respectively, in the MSC-transplanted rats; thus suggesting that neural apoptosis was inhibited. The results of the present study suggested that the transplantation of bone marrow-derived MSCs was able to promote the functional recovery of the central nervous system following cerebral ischemia. Accordingly, inhibitors targeting myelin-associated inhibitors and apoptosis may be of clinical significance for cerebral ischemia in the future.

  5. Feline Neural Progenitor Cells II: Use of Novel Plasmid Vector and Hybrid Promoter to Drive Expression of Glial Cell Line-Derived Neurotrophic Factor Transgene

    X. Joann You

    2012-01-01

    Full Text Available Sustained transgene expression is required for the success of cell transplant-based gene therapy. Most widely used are lentiviral-based vectors which integrate into the host genome and thereby maintain sustained transgene expression. This requires integration into the nuclear genome, and potential risks include activation of oncogenes and inactivation of tumor suppressor genes. Plasmids have been used; however lack of sustained expression presents an additional challenge. Here we used the pCAG-PyF101-eGFP plasmid to deliver the human GDNF gene to cat neural progenitor cells (cNPCs. This vector consists of a CAGG composite promoter linked to the polyoma virus mutant enhancer PyF101. Expression of an episomal eGFP reporter and GDNF transgene were stably maintained by the cells, even following induction of differentiation. These genetically modified cells appear suitable for use in allogeneic models of cell-based delivery of GDNF in the cat and may find veterinary applications should such strategies prove clinically beneficial.

  6. Mycogenic Mn(II) oxidation promotes remediation of acid mine drainage and other anthropogenically impacted environments

    Santelli, C. M.; Chaput, D.; Hansel, C. M.; Burgos, W. D.

    2014-12-01

    Manganese is a pollutant in worldwide environments contaminated with metals and organics, such as acid mine drainage (AMD), freshwater ponds, and agricultural waste storage sites. Microorganisms contribute to the removal of dissolved Mn compounds in the environment by promoting Mn(II) oxidation reactions. The oxidation of Mn(II) results in the precipitation of sparingly soluble Mn(IV) oxide minerals, effectively removing the metal from the aqueous milieu (e.g., groundwater or wastewater streams). In recent years, our research has identified a diversity of Mn(II)-oxidizing fungi inhabiting these polluted environments, however their overall contribution to the remediation process in situ remains poorly understood. Here we present results of culture-based and Next Generation Sequencing (NGS) studies in AMD treatment systems actively remediating Mn and other metals where we profile the bacterial, fungal, algal and archaeal communities to determine the overall community diversity and to establish the relative abundance of known Mn(II) oxidizers. A variety of treatment systems with varying Mn-removal efficiencies were sampled to understand the relationship between remediation efficiency and microbial community composition and activity. Targeted-amplicon sequencing of DNA and RNA of the 16S rRNA genes (bacteria and archaea), 23S rRNA genes (algae) and ITS region (fungi) was performed using both 454 pyrosequencing and Illumina platforms. Results showed that only the fungal taxonomic profiles significantly differed between sites that removed the majority of influent Mn and those that did not. Specifically, Ascomycota (which include known Mn(II) oxidizers isolated from these treatment systems) dominated greater efficiency systems whereas less efficient systems were dominated by Basidiomycota. Furthermore, known Mn(II) oxidizers accounted for only a minor proportion of bacterial sequences but a far greater proportion of fungal sequences. These culture-independent studies lend

  7. Phosphazene-promoted metal-free ring-opening polymerization of ethylene oxide initiated by carboxylic acid

    Zhao, Junpeng

    2014-03-11

    The effectiveness of carboxylic acid as initiator for the anionic ring-opening polymerization of ethylene oxide was investigated with a strong phosphazene base (t-BuP4) used as promoter. Kinetic study showed an induction period, i.e., transformation of carboxylic acid to hydroxyl ester, followed by slow chain growth together with simultaneous and fast end-group transesterification, which led to poly(ethylene oxide) (PEO) consisting of monoester (monohydroxyl), diester, and dihydroxyl species. An appropriate t-BuP4/acid ratio was proven to be essential to achieve better control over the polymerization and low dispersity of PEO. This work provides important information and enriches the toolbox for macromolecular and biomolecular engineering with protic initiating sites. © 2014 American Chemical Society.

  8. Noncytotoxic and Antitumour-Promoting Activities of Garcinia Acid Esters from Garcinia atroviridis Griff. ex T. Anders (Guttiferae

    Mukram M. Mackeen

    2012-01-01

    Full Text Available The in vitro antitumour-promoting, cytotoxic, and antioxidant activities of two ester derivatives of garcinia acid, that is, 2-(butoxycarbonylmethyl-3-butoxycarbonyl-2-hydroxy-3-propanolide (1 and 1′,1′′-dibutyl methyl hydroxycitrate (2, that had been previously isolated from the fruits of Garcinia atroviridis Griff. ex T. Anders (Guttiferae, were examined. Based on the inhibition of Epstein-Barr virus early antigen (EBV-EA activation, compound 1 (IC50: 70 μM showed much higher (8-fold antitumour-promoting activity than compound 2 (IC50: 560 μM. In addition, both compounds were nontoxic towards CEM-SS (human T-lymphoblastic leukemia cells (CD50: >100 μM, Raji (human B-lymphoblastoid cells (CD50: >600 μM, and brine shrimp (LD50: >300 μM. Although the antitumour-promoting activity of compound 1 is moderate compared with the known antitumour promoter genistein, its non-toxicity suggests the potential of compound 1 and related structures as chemopreventive agents. The weak antioxidant activity displayed by both compounds also suggested that the primary antitumour-promoting mechanism of compound 1 did not involve oxidative-stress quenching.

  9. Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor

    Krall, Abigail S.; Xu, Shili; Graeber, Thomas G.; Braas, Daniel; Christofk, Heather R.

    2016-01-01

    Cellular amino acid uptake is critical for mTOR complex 1 (mTORC1) activation and cell proliferation. However, the regulation of amino acid uptake is not well-understood. Here we describe a role for asparagine as an amino acid exchange factor: intracellular asparagine exchanges with extracellular amino acids. Through asparagine synthetase knockdown and altering of media asparagine concentrations, we show that intracellular asparagine levels regulate uptake of amino acids, especially serine, arginine and histidine. Through its exchange factor role, asparagine regulates mTORC1 activity and protein synthesis. In addition, we show that asparagine regulation of serine uptake influences serine metabolism and nucleotide synthesis, suggesting that asparagine is involved in coordinating protein and nucleotide synthesis. Finally, we show that maintenance of intracellular asparagine levels is critical for cancer cell growth. Collectively, our results indicate that asparagine is an important regulator of cancer cell amino acid homeostasis, anabolic metabolism and proliferation. PMID:27126896

  10. Depletion of Retinoic Acid Receptors Initiates a Novel Positive Feedback Mechanism that Promotes Teratogenic Increases in Retinoic Acid

    Enrico D'Aniello; Rydeen, Ariel B.; Jane L Anderson; Amrita Mandal; Waxman, Joshua S.

    2013-01-01

    Author Summary Retinoic acid (RA) is the most active metabolic product of Vitamin A. Appropriate levels of RA are required for proper embryonic development and tissue maintenance in all vertebrates. Inappropriate levels of RA in human embryos can cause congenital defects that affect many organs, including the heart and limbs, and lead to numerous types of cancers. Understanding how animals maintain appropriate RA levels and the consequences of inappropriate RA signaling will therefore provide...

  11. Garcinone D, a natural xanthone promotes C17.2 neural stem cell proliferation: Possible involvement of STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway.

    Yang, Xiaohong; Wang, Shengnan; Ouyang, Ying; Tu, Yaling; Liu, Anmin; Tian, Yinghong; He, Mingliang; Pi, Rongbiao

    2016-07-28

    Garcinia mangostana L. (Mangosteen) has been used to treat various pathological conditions, including inflammation and urinary tract infections. Here, we observed that garcinone D, a natural xanthone from mangosteen, promoted the proliferation of C17.2 neural progenitor cells and also resulted in a larger percentage of cells in S phase compared with the control group. Moreover, garcinone D increased the protein levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and Cyclin D1 in concentration- and time- dependent manners. Garcinone D also increased the protein levels of nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in concentration- and time- dependent manners, and inhibiting Nrf2 activation by brusatol could partly reverse garcinone D-induced C17.2 cell proliferation. Taken together, it is the first time to show that garcinone D promotes the proliferation of C17.2 neural stem cells, which may involve the STAT3/Cyclin D1 pathway and Nrf2/HO-1 pathway. It would provide new inspiration to develop garcinone D as a lead compound to promote the proliferation of endogenous neural stem cells (NSCs). PMID:27177723

  12. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice.

    Silvennoinen, Reija; Quesada, Helena; Kareinen, Ilona; Julve, Josep; Kaipiainen, Leena; Gylling, Helena; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-05-11

    Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. PMID:25969465

  13. Effects of Fish Oil Supplementation during the Suckling Period on Auditory Neural Conduction in n-3 Fatty Acid-Deficient Rat Pups

    vida rahimi

    2014-07-01

    Full Text Available Abstract Introduction: Omega 3 fatty acid especially in the form of fish oil, has structural and biological role in the body's various systems especially nervous system. Numerous studies have tried to research about it. Auditory is one of the affected systems. Omega 3 deficiency can have devastating effects on the nervous system and auditory. This study aimed to evaluate neural conduction in n-3 fatty acid-deficient rat pups following the supplementation of fish oil consumption during the suckling period Materials and Methods: In this interventional and experimental study, one sources of omega3 fatty acid (fish oil were fed to rat pups of n-3 PUFA-deficient dams to compare changes in their auditory neural conduction with that of control and n-3 PUFA-deficient groups, using Auditory Brainstem Response (ABR. The parameters of interest were P1, P3, P4 absolute latency, P1-P3, P1-P4 and P3-P4 IPL , P4/P1 amplitude ratio . The rat pups were given oral fish oil, 5 Ml /g weight for 17 days, between the age of 5 and 21 days. Results There were no significant group differences in P1 and P3 absolute latency (p > 0.05. but the result in P4 was significant(P ≤ 0.05 . The n-3 PUFA deficient +vehicle had the most prolonged (the worst P1-P4 IPL and P3-P4 IPL compared with control and n-3 PUFA deficient + FO groups. There was no significant difference in P1-P4 IPL and P3-P4 IPL between n-3 PUFA deficient + FO and control groups (p > 0.05.There was a significant effect of diet on P1-P4 IPL and P3-P4 IPL between groups (P ≤ 0.05. Conclusion: The results of present study showed the effect of omega3 deficiency on auditory neural structure during pregnancy and lactation period. Additionally, we observed the reduced devastating effects on neural conduction in n-3 fatty acid-deficient rat pups following the supplementation of fish oil during the suckling period

  14. Regulation of carnitine palmitoyltransferase (CPT) I during fasting in rainbow trout (Oncorhynchus mykiss) promotes increased mitochondrial fatty acid oxidation.

    Morash, Andrea J; McClelland, Grant B

    2011-01-01

    Periods of fasting, in most animals, are fueled principally by fatty acids, and changes in the regulation of fatty acid oxidation must exist to meet this change in metabolic substrate use. We examined the regulation of carnitine palmitoyltransferase (CPT) I, to help explain changes in mitochondrial fatty acid oxidation with fasting. After fasting rainbow trout (Oncorhynchus mykiss) for 5 wk, the mitochondria were isolated from red muscle and liver to determine (1) mitochondrial fatty acid oxidation rate, (2) CPT I activity and the concentration of malonyl-CoA needed to inhibit this activity by 50% (IC(50)), (3) mitochondrial membrane fluidity, and (4) CPT I (all five known isoforms) and peroxisome proliferator-activated receptor (PPARα and PPARβ) mRNA levels. Fatty acid oxidation in isolated mitochondria increased during fasting by 2.5- and 1.75-fold in liver and red muscle, respectively. Fasting also decreased sensitivity of CPT I to malonyl-CoA (increased IC(50)), by two and eight times in red muscle and liver, respectively, suggesting it facilitates the rate of fatty acid oxidation. In the liver, there was also a significant increase CPT I activity per milligram mitochondrial protein and in whole-tissue PPARα and PPARβ mRNA levels. However, there were no changes in mitochondrial membrane fluidity in either tissue, indicating that the decrease in CPT I sensitivity to malonyl-CoA is not due to bulk fluidity changes in the membrane. However, there were significant differences in CPT I mRNA levels during fasting. Overall, these data indicate some important changes in the regulation of CPT I that promote the increased mitochondrial fatty acid oxidation that occurs during fasting in trout. PMID:22030855

  15. GENETIC MODIFICATION OF GIBBERELLIC ACID SIGNALING TO PROMOTE CARBON SEQUESTRATION IN TREE ROOTS AND STEMS

    Busov, Victor

    2013-03-05

    poplar GA 2-oxidases predominantly expressed in roots also decreased lateral root formation. GAs negatively affected lateral root formation by inhibiting lateral root primordium initiation. A whole-genome microarray analysis of root development in GA-modified transgenic plants revealed 2069 genes with significantly altered expression. The expression of 1178 genes, including genes that promote cell proliferation, growth, and cell wall loosening, corresponded to the phenotypic severity of the root traits when transgenic events with differential phenotypic expression were compared. The array data and direct hormone measurements suggested crosstalk of GA signaling with other hormone pathways, including auxin and abscisic acid. Transgenic modification of a differentially expressed gene encoding an auxin efflux carrier suggests that GA modulation of lateral root development is at least partly imparted by polar auxin transport modification. These results suggest a mechanism for GA-regulated modulation of lateral root proliferation associated with regulation of plant allometry during the stress response. Here we summarize progress in identification of three classes of genes useful for control of plant architecture: those affecting hormone metabolism and signaling; transcription and other regulatory factors; and the cell cycle. We focus on strong modifiers of stature and form that may be useful for directed modification of plant architecture, rather than the detailed mechanisms of gene action. Gibberellin (GA) metabolic and response genes are particularly attractive targets for manipulation because many act in a dose-dependent manner; similar phenotypic effects can be readily achieved in heterologous species; and induced pleiotropic effects--such as on nitrogen assimilation, photosynthesis, and lateral root production--are usually positive with respect to crop performance. Genes encoding transcription factors represent strong candidates for manipulation of plant architecture. For

  16. Macrophage reprogramming by mycolic acid promotes a tolerogenic response in experimental asthma

    Korf, Johanna E.; Pynaert, Gwenda; Tournoy, Kurt; Boonefaes, Tom; Van Oosterhout, Antoon; Ginneberge, Daisy; Haegeman, Anuschka; Verschoor, Jan A.; De Baetselier, Patrick; Grooten, Johan

    2006-01-01

    Rationale: Mycolic acid (MA) constitutes a major and distinguishing cell wall biolipid from Mycobacterium tuberculosis. MA interferes with the lipid homeostasis of alveolar macrophages, inducing differentiation into foamy macrophages exhibiting increased proinflammatory function. Objectives: We veri

  17. Impacto de la fortificación de alimentos con ácido fólico en los defectos del tubo neural en Costa Rica Impact of the fortification of food with folic acid on neural tube defects in Costa Rica

    María de la Paz Barboza Argüello

    2011-07-01

    Full Text Available OBJETIVO: Evaluar el impacto de la fortificación de alimentos con ácido fólico en las tendencias de las prevalencias de los defectos del tubo neural (DTN y la tasa de mortalidad infantil (TMI por este trastorno en Costa Rica. MÉTODOS: Se analizaron los datos de vigilancia del Centro de Registro de Enfermedades Congénitas y el Centro Centroamericano de Población. Se consideraron defectos del tubo neural la anencefalia, la espina bífida y el encefalocele. Se examinaron las tendencias durante 1987-2009, así como las diferencias de tasas (intervalo de confianza [IC] 95% de prevalencia y mortalidad antes de la fortificación de alimentos con ácido fólico y hasta 12 años después de su implementación. Se determinó el aporte de la fortificación al descenso en la TMI general. RESULTADOS: En 1987-1997, previo al período de fortificación de alimentos con ácido fólico, la prevalencia de DTN fue de 12/10 000 nacidos (IC95%: 11,1-12,8, mientras que en 2009 fue de 5,1/10 000 nacidos (3,3-6,5. La TMI por DTN en 1997 fue de 0,64/1 000 nacimientos (46-0,82 y en 2009 de 0,19/1 000 (0,09-0,3. La TMI por DTN y su prevalencia disminuyeron en forma significativa, 71% y 58% respectivamente (P OBJECTIVE: Evaluate the impact of the fortification of food with folic acid on prevalence trends for neural tube defects (NTD and the infant mortality rate (IMR associated with this disorder in Costa Rica. METHODS: The surveillance data from the Congenital Disease Registry Center and the Central American Population Center were analyzed. The neural tube defects considered were anencephaly, spina bifida, and encephalocele. The trends from 1987-2009, as well as the differences in prevalence and mortality rates prior to and up to 12 years after food fortification with folic acid, were examined (95% confidence interval [CI]. The contribution of fortification to the decrease in the overall IMR was determined. RESULTS: During 1987-1997, prior to the period of food

  18. RAGE is a nucleic acid receptor that promotes inflammatory responses to DNA

    Sirois, Cherilyn M.; Jin, Tengchuan; Miller, Allison L.; Bertheloot, Damien; Nakamura, Hirotaka; Horvath, Gabor L.; Mian, Abubakar; Jiang, Jiansheng; Schrum, Jacob; Bossaller, Lukas; Pelka, Karin; Garbi, Natalio; Brewah, Yambasu; Tian, Jane; Chang, ChewShun

    2013-01-01

    Recognition of DNA and RNA molecules derived from pathogens or self-antigen is one way the mammalian immune system senses infection and tissue damage. Activation of immune signaling receptors by nucleic acids is controlled by limiting the access of DNA and RNA to intracellular receptors, but the mechanisms by which endosome-resident receptors encounter nucleic acids from the extracellular space are largely undefined. In this study, we show that the receptor for advanced glycation end-products...

  19. Noncytotoxic and Antitumour-Promoting Activities of Garcinia Acid Esters from Garcinia atroviridis Griff. ex T. Anders (Guttiferae)

    Abdul M. Ali; Nashriyah Mat; Lajis, Nordin H.; Mooi, Lim Y.; Mohidin Amran; Mackeen, Mukram M.

    2012-01-01

    The in vitro antitumour-promoting, cytotoxic, and antioxidant activities of two ester derivatives of garcinia acid, that is, 2-(butoxycarbonylmethyl)-3-butoxycarbonyl-2-hydroxy-3-propanolide (1) and 1′,1′′-dibutyl methyl hydroxycitrate (2), that had been previously isolated from the fruits of Garcinia atroviridis Griff. ex T. Anders (Guttiferae), were examined. Based on the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation, compound 1 (IC50: 70  μ M) showed much higher (8-fol...

  20. Group X Secreted Phospholipase A2 Releases ω3 Polyunsaturated Fatty Acids, Suppresses Colitis, and Promotes Sperm Fertility.

    Murase, Remi; Sato, Hiroyasu; Yamamoto, Kei; Ushida, Ayako; Nishito, Yasumasa; Ikeda, Kazutaka; Kobayashi, Tetsuyuki; Yamamoto, Toshinori; Taketomi, Yoshitaka; Murakami, Makoto

    2016-03-25

    Within the secreted phospholipase A2(sPLA2) family, group X sPLA2(sPLA2-X) has the highest capacity to hydrolyze cellular membranes and has long been thought to promote inflammation by releasing arachidonic acid, a precursor of pro-inflammatory eicosanoids. Unexpectedly, we found that transgenic mice globally overexpressing human sPLA2-X (PLA2G10-Tg) displayed striking immunosuppressive and lean phenotypes with lymphopenia and increased M2-like macrophages, accompanied by marked elevation of free ω3 polyunsaturated fatty acids (PUFAs) and their metabolites. Studies usingPla2g10-deficient mice revealed that endogenous sPLA2-X, which is highly expressed in the colon epithelium and spermatozoa, mobilized ω3 PUFAs or their metabolites to protect against dextran sulfate-induced colitis and to promote fertilization, respectively. In colitis, sPLA2-X deficiency increased colorectal expression of Th17 cytokines, and ω3 PUFAs attenuated their production by lamina propria cells partly through the fatty acid receptor GPR120. In comparison, cytosolic phospholipase A2(cPLA2α) protects from colitis by mobilizing ω6 arachidonic acid metabolites, including prostaglandin E2 Thus, our results underscore a previously unrecognized role of sPLA2-X as an ω3 PUFA mobilizerin vivo, segregated mobilization of ω3 and ω6 PUFA metabolites by sPLA2-X and cPLA2α, respectively, in protection against colitis, and the novel role of a particular sPLA2-X-driven PUFA in fertilization. PMID:26828067

  1. Performance of a neural-network-based determination of amino acid class and secondary structure from 1H-15N NMR data

    A neural network which can determine both amino acid class and secondary structure using NMR data from 15N-labeled proteins is described. We have included nitrogen chemical shifts,3JHNHα coupling constants, α-proton chemical shifts, and side-chain proton chemical shifts as input to a three-layer feed-forward network. The network was trained with 456 spin systems from several proteins containing various types of secondary structure, and tested on human ubiquitin, which has no sequence homology with any of the proteins in the training set. A very limited set of data,representative of those from a TOCSY-HSQC and HNHA experiment, was used.Nevertheless, in 60% of the spin systems the correct amino acid class was among the top two choices given by the network, while in 96% of the spin systems the secondary structure was correctly identified. The performance of this network clearly shows the potential of the neural network algorithm in the automation of NMR spectral analysis

  2. Origins of selectivity in Brønsted acid-promoted diazoalkane-azomethine reactions (the aza-Darzens aziridine synthesis).

    Troyer, Timothy L; Muchalski, Hubert; Hong, Ki Bum; Johnston, Jeffrey N

    2011-04-01

    The mechanism of the Brønsted acid-catalyzed aza-Darzens reaction is explored by charting the stereochemical outcome of the triflic acid-promoted conversion of trans-triazolines to cis-aziridines. These experiments are consistent with the intermediacy of an α-diazonium-β-amino ester intermediate. PMID:21366339

  3. Total synthesis of gracilioether F. Development and application of Lewis acid promoted ketene–alkene [2+2] cycloadditions and late-stage C—H oxidation

    Rasik, Christopher M. [Indiana Univ., Bloomington, IN (United States); Brown, M. Kevin [Indiana Univ., Bloomington, IN (United States)

    2014-12-22

    The first synthesis of gracilioether F, a polyketide natural product with an unusual tricyclic core and five contiguous stereocenters, is described. Key steps of the synthesis include a Lewis acid promoted ketene–alkene [2+2] cycloaddition and a late-stage carboxylic acid directed C(sp³)—H oxidation. The synthesis requires only eight steps from norbornadiene.

  4. Phenytoin enhances the phosphorylation of epidermal growth factor receptor and fibroblast growth factor receptor in the subventricular zone and promotes the proliferation of neural precursor cells and oligodendrocyte differentiation.

    Galvez-Contreras, Alma Y; Gonzalez-Castaneda, Rocio E; Campos-Ordonez, Tania; Luquin, Sonia; Gonzalez-Perez, Oscar

    2016-01-01

    Phenytoin is a widely used antiepileptic drug that induces cell proliferation in several tissues, such as heart, bone, skin, oral mucosa and neural precursors. Some of these effects are mediated via fibroblast growth factor receptor (FGFR) and epidermal growth factor receptor (EGFR). These receptors are strongly expressed in the adult ventricular-subventricular zone (V-SVZ), the main neurogenic niche in the adult brain. The aim of this study was to determine the cell lineage and cell fate of V-SVZ neural progenitors expanded by phenytoin, as well as the effects of this drug on EGFR/FGFR phosphorylation. Male BALB/C mice received 10 mg/kg phenytoin by oral cannula for 30 days. We analysed the proliferation of V-SVZ neural progenitors by immunohistochemistry and western blot. Our findings indicate that phenytoin enhanced twofold the phosphorylation of EGFR and FGFR in the V-SVZ, increased the number of bromodeoxyuridine (BrdU)+/Sox2+ and BrdU+/doublecortin+ cells in the V-SVZ, and expanded the population of Olig2-expressing cells around the lateral ventricles. After phenytoin removal, a large number of BrdU+/Receptor interacting protein (RIP)+ cells were observed in the olfactory bulb. In conclusion, phenytoin enhanced the phosphorylation of FGFR and EGFR, and promoted the expression of neural precursor markers in the V-SVZ. In parallel, the number of oligodendrocytes increased significantly after phenytoin removal. PMID:26370587

  5. Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid.

    Enrico D'Aniello

    Full Text Available Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1, a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA.

  6. Phenazine-1-Carboxylic Acid Promotes Bacterial Biofilm Development via Ferrous Iron Acquisition▿†

    Wang, Yun; Wilks, Jessica C.; Danhorn, Thomas; Ramos, Itzel; Croal, Laura; Newman, Dianne K.

    2011-01-01

    The opportunistic pathogen Pseudomonas aeruginosa forms biofilms, which render it more resistant to antimicrobial agents. Levels of iron in excess of what is required for planktonic growth have been shown to promote biofilm formation, and therapies that interfere with ferric iron [Fe(III)] uptake combined with antibiotics may help treat P. aeruginosa infections. However, use of these therapies presumes that iron is in the Fe(III) state in the context of infection. Here we report the ability o...

  7. Efeito da fortificação alimentar com ácido fólico na prevalência de defeitos do tubo neural Efecto de la fortificación alimentaria con ácido fólico en la prevalencia de defectos del tubo neural Effects of folic acid fortification on the prevalence of neural tube defects

    Sâmya Silva Pacheco

    2009-08-01

    defectos del cierre del tubo neural fueron definidos de acuerdo con el Códigos Internacional de Enfermedades- 10ª Revisión: anencefalia, encefalocele y espina bífida. Se compararon las prevalencias en los períodos anterior (2000 - 2004 y posterior (2005-2006 al período obligatorio de fortificación. Se analizó la tendencia temporal de las prevalencias trimestrales de defectos del cierre del tubo neural por las pruebas de Mann-Kendall y Sen's Slope. RESULTADOS: No se identificó tendencia de reducción en la ocurrencia del hecho (Teste de Mann-Kendall; p= 0,270; Sen's Slope = - 0,008 en el período estudiado. No hubo diferencia estadísticamente significativa entre las prevalencias de defectos de cierre del tubo neural en los períodos anterior y posterior a la fortificación de los alimentos con ácido fólico de acuerdo con las características maternas. CONCLUSIONES: A pesar de que no haya sido observada reducción de los defectos de cierre del tubo neural posterior al período obligatorio de fortificación de alimentos con ácido fólico, los resultados encontrados no permiten descartar el beneficio del mismo en la prevención de esta malformación. Son necesarios estudios evaluando mayor período y considerando el nivel de consumo de los productos fortificados por las mujeres en edad fértil.OBJECTIVE:To analyze the effect of folic acid-fortified foods on the prevalence of neural tube defects in live newborns. METHODS: Longitudinal study with newborns from the city of Recife, Northeastern Brazil, between 2000 and 2006. Data analyzed were obtained from the Sistema Nacional de Informações de Nascidos Vivos (National Information System on Live Births. Neural tube defects were defined in accordance with the International Classification of Diseases, 10th revision (ICD-10: anencephaly, encephalocele, and spina bifida. Prevalences from the periods before (2000-2004 and after (2005-2006 the mandatory fortification period were compared. Time trend of three

  8. Taurolithocholic acid promotes intrahepatic cholangiocarcinoma cell growth via muscarinic acetylcholine receptor and EGFR/ERK1/2 signaling pathway

    AMONYINGCHAROEN, SUMET; SURIYO, TAWIT; THIANTANAWAT, APINYA; WATCHARASIT, PIYAJIT; SATAYAVIVAD, JUTAMAAD

    2015-01-01

    Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract and its occurrence is associated with chronic cholestasis which causes an elevation of bile acids in the liver and bile duct. The present study aimed to investigate the role and mechanistic effect of bile acids on the CCA cell growth. Intrahepatic CCA cell lines, RMCCA-1 and HuCCA-1, were treated with bile acids and their metabolites to determine the growth promoting effect. Cell viability, cell cycle analysis, EdU incorporation assays were conducted. Intracellular signaling proteins were detected by western immunoblotting. Among eleven forms of bile acids and their metabolites, only taurolithocholic acid (TLCA) concentration dependently (1–40 μM) increased the cell viability of RMCCA-1, but not HuCCA-1 cells. The cell cycle analysis showed induction of cells in the S phase and the EdU incorporation assay revealed induction of DNA synthesis in the TLCA-treated RMCCA-1 cells. Moreover, TLCA increased the phosphorylation of EGFR, ERK 1/2 and also increased the expression of cyclin D1 in RMCCA-1 cells. Furthermore, TLCA-induced RMCCA-1 cell growth could be inhibited by atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, AG 1478, a specific EGFR inhibitor, or U 0126, a specific MEK 1/2 inhibitor. These results suggest that TLCA induces CCA cell growth via mAChR and EGFR/EKR1/2 signaling pathway. Moreover, the functional presence of cholinergic system plays a certain role in TLCA-induced CCA cell growth. PMID:25815516

  9. Cloning and Analyzing of Xenopus Mespo Promoter in Retinoic Acid Regulated Mespo Expression

    Jin-Hu WANG; Xiao-Yan DING

    2006-01-01

    Juring vertebrate embryogenesis, presomitic mesoderm cells enter a segmental program to generate somite, a process termed somitogenesis. Mespo, a member of the bHLH transcription factor family,plays important roles in this process. However, how Mespo expression is regulated remains unclear. To address this question, we isolated a genomic DNA sequence containing 4317 bp of Mespo 5' flanking region in Xenopus. Luciferase assays show that this upstream sequence has transcription activity. Transgenic assay shows that this genomic contig is sufficient to recapitulate the dynamic stage- and tissue-specific expression pattern of endogenous Mespo from the gastrula to the tailbud stage. We further mapped a 326 bp DNA sequence responding to retinoic acid signaling. These results shed light on how Mespo expression is regulated,and suggest that retinoic acid signaling pathways play roles in somitogenesis through regulating Mespo.

  10. Strecker degradation of amino acids promoted by a camphor-derived sulfonamide.

    Carvalho, M Fernanda N N; Ferreira, M João; Knittel, Ana S O; Oliveira, Maria da Conceição; Costa Pessoa, João; Herrmann, Rudolf; Wagner, Gabriele

    2016-01-01

    A camphor-derived sulfonimine with a conjugated carbonyl group, oxoimine 1 (O2SNC10H13O), reacts with amino acids (glycine, L-alanine, L-phenylalanine, L-leucine) to form a compound O2SNC10H13NC10H14NSO2 (2) which was characterized by spectroscopic means (MS and NMR) and supported by DFT calculations. The product, a single diastereoisomer, contains two oxoimine units connected by a -N= bridge, and thus has a structural analogy to the colored product Ruhemann´s purple obtained by the ninhydrin reaction with amino acids. A plausible reaction mechanism that involves zwitterions, a Strecker degradation of an intermediate imine and water-catalyzed tautomerizations was developed by means of DFT calculations on potential transition states. PMID:27340465

  11. Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

    Ferreira, M João; Knittel, Ana S O; Oliveira, Maria da Conceição; Costa Pessoa, João; Herrmann, Rudolf; Wagner, Gabriele

    2016-01-01

    Summary A camphor-derived sulfonimine with a conjugated carbonyl group, oxoimine 1 (O2SNC10H13O), reacts with amino acids (glycine, L-alanine, L-phenylalanine, L-leucine) to form a compound O2SNC10H13NC10H14NSO2 (2) which was characterized by spectroscopic means (MS and NMR) and supported by DFT calculations. The product, a single diastereoisomer, contains two oxoimine units connected by a –N= bridge, and thus has a structural analogy to the colored product Ruhemann´s purple obtained by the ninhydrin reaction with amino acids. A plausible reaction mechanism that involves zwitterions, a Strecker degradation of an intermediate imine and water-catalyzed tautomerizations was developed by means of DFT calculations on potential transition states.

  12. Adipose Overexpression of Desnutrin Promotes Fatty Acid Use and Attenuates Diet-Induced Obesity

    Ahmadian, Maryam; Duncan, Robin E.; Varady, Krista A.; Frasson, Danubia; Hellerstein, Marc K.; Birkenfeld, Andreas L.; Samuel, Varman T.; Shulman, Gerald I.; Wang, Yuhui; Kang, Chulho; Sul, Hei Sook

    2009-01-01

    OBJECTIVE To investigate the role of desnutrin in adipose tissue triacylglycerol (TAG) and fatty acid metabolism. RESEARCH DESIGN AND METHODS We generated transgenic mice overexpressing desnutrin (also called adipose triglyceride lipase [ATGL]) in adipocytes (aP2-desnutrin) and also performed adenoviral-mediated overexpression of desnutrin in 3T3-L1CARΔ1 adipocytes. RESULTS aP2-desnutrin mice were leaner with decreased adipose tissue TAG content and smaller adipocyte size. Overexpression of d...

  13. Ascorbic acid improves embryonic cardiomyoblast cell survival and promotes vascularization in potential myocardial grafts in vivo

    Martinez, E. C.; Wang, J; Gan, S U; Singh, R.; Lee, C. N.; Kofidis, T

    2010-01-01

    Organ restoration via cell therapy and tissue transplantation is limited by impaired graft survival. We tested the hypothesis that ascorbic acid (AA) reduces cell death in myocardial grafts both in vitro and in vivo and introduced a new model of autologous graft vascularization for later transplantation. Luciferase (Fluc)- and green fluorescent protein (GFP)-expressing H9C2 cardiomyoblasts were seeded in gelatin scaffolds to form myocardial artificial grafts (MAGs). MAGs were supplemented wit...

  14. Retinoic Acid Promotes Interleukin-4 Plasmid-Dimethylsulfoxide Topical Transdermal Delivery for Treatment of Psoriasis

    Chen, Zhong-Wen; Zhang, Yin-Bing; Chen, Xaing-Jun; Liu, Xiao; Wang, Zhen; Zhou, Xi-Kun; Qiu, Ji; Zhang, Nan-Nan; Teng, Xiu; MAO, YONG-QIU; Liu, Chang-Yong; Wei, Yu-quan; Li, Jiong

    2015-01-01

    Background Psoriasis is an autoimmune disease that is caused by a shift in the Th1/Th2 balance toward Th1-dominant immunity. It has been established as an effective treatment to counteract psoriasis by subcutaneous injection of recombinant interleukin (IL)-4, and IL-4 gene therapy by topical transdermal penetration has shown its antipsoriatic effect in mice. Retinoic acid (RA) and dimethylsulfoxide can increase the efficiency of gene transfection in the topical transdermal delivery system. Ob...

  15. High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation

    Ulf Gustafsson; Staffan Sahlin; Curt Einarsson

    2003-01-01

    AIM: To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile.METHODS: Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing cholecystectomy. Clinical data, biliary lipids, bile acid composition,presence of crystals and nucleation time were analyzed.RESULTS: A subgroup of gallstone patients displayeda higher proportion of DCA in bile than gallstone free subjects.By choosing a cut-off level of the 90th percentile, a group of 13 gallstone patients with high DCA levels (mean 50percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids)were obtained. The mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age: 62 years vs45 years) and so was the mean BMI (28.3 vs. 24.7). Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA group. There was no difference in biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA.CONCLUSION: Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal DCA. The two groups of patients did not differ with respect to biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals. It is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients.

  16. The promoting effects of geniposidic acid and aucubin in Eucommia ulmoides Oliver leaves on collagen synthesis.

    Li, Y; Sato, T; Metori, K; Koike, K; Che, Q M; Takahashi, S

    1998-12-01

    We have reported that collagen synthesis was stimulated by the administration of a hot water extract from the leaves of Eucommia ulmoides OLIVER, Eucommiaceae (Du-Zhong leaves) in false aged model rats. In this paper, we set out to examine the compounds in Du-Zhong leaves that stimulated collagen synthesis in false aged model rats. In experiment 1, a methanol extract of Du-Zhong leaves also stimulated collagen synthesis in aged model rats. An acetone fraction was derived from the methanol extract by silica gel chromatography in experiment 2. The acetone fraction mainly contained iridoides mono-glycosides such as geniposidic acid and aucubin. The administration of geniposidic acid or aucubin stimulated collagen synthesis in aged model rats in experiments 3 and 4 (significance (p<0.05)). The reported pharmacological effects of Du-Zhong leaves, including healing organs and strengthening bone and muscle, are closely related to collagen metabolism. It appears that geniposidic acid and aucubin are the actual compounds in Du-Zhong which caused the effect in our experiments. PMID:9881644

  17. Post-harvest induced production of salvianolic acids and significant promotion of antioxidant properties in roots of Salvia miltiorrhiza (Danshen).

    Zhou, Guo-Jun; Wang, Wei; Xie, Xiao-Mei; Qin, Min-Jian; Kuai, Ben-Ke; Zhou, Tong-Shui

    2014-01-01

    Danshen, the dried roots of Salvia miltiorrhiza, is an extremely valued Traditional Chinese Medicine. Previously, we have demonstrated that salvianolic acid B (SaB), the important bioactive ingredient in this herb, was a post-harvest product. Here, we further reported that all salvianolic acids (SAs) in the roots were post-harvest products of the drying process. In addition, the results of various radical scavenging activity assays, including lipid peroxidation (1), DPPH (2), hydroxyl (3) and superoxide (4), were significantly increased along with the accumulation of total salvianolic acids in the process. The contents of chemical targets and antioxidant activities both reached the highest value under thermal treatment at 130 °C for 80 min. In this dehydration period, contents of SaB, and sum of nine SAs increased from 0.01% to 5.51%, and 0.20% to 6.61%; and IC50 of antioxidant activity decreased from 4.85 to 2.69 (1); 7.75 to 0.43 (2); 2.57 to 1.13 (3) and 17.25 to 1.10 mg/mL. These results further supported the hypothesis that the newly harvested plant roots were still physiologically active and the secondary metabolites might be produced due to dehydration stress after harvest. Our findings supplied an important and useful theoretical basis for promoting the quality of Danshen and other medicinal plant materials. PMID:24886944

  18. Post-Harvest Induced Production of Salvianolic Acids and Significant Promotion of Antioxidant Properties in Roots of Salvia miltiorrhiza (Danshen

    Guo-Jun Zhou

    2014-05-01

    Full Text Available Danshen, the dried roots of Salvia miltiorrhiza, is an extremely valued Traditional Chinese Medicine. Previously, we have demonstrated that salvianolic acid B (SaB, the important bioactive ingredient in this herb, was a post-harvest product. Here, we further reported that all salvianolic acids (SAs in the roots were post-harvest products of the drying process. In addition, the results of various radical scavenging activity assays, including lipid peroxidation (1, DPPH (2, hydroxyl (3 and superoxide (4, were significantly increased along with the accumulation of total salvianolic acids in the process. The contents of chemical targets and antioxidant activities both reached the highest value under thermal treatment at 130 °C for 80 min. In this dehydration period, contents of SaB, and sum of nine SAs increased from 0.01% to 5.51%, and 0.20% to 6.61%; and IC50 of antioxidant activity decreased from 4.85 to 2.69 (1; 7.75 to 0.43 (2; 2.57 to 1.13 (3 and 17.25 to 1.10 mg/mL. These results further supported the hypothesis that the newly harvested plant roots were still physiologically active and the secondary metabolites might be produced due to dehydration stress after harvest. Our findings supplied an important and useful theoretical basis for promoting the quality of Danshen and other medicinal plant materials.

  19. Deficiencia de folatos y su asociación con defectos de cierre del tubo neural en el norte de México Folic acid deficiency and its relationship with neural tube defects in northern Mexico

    Martha Rodríguez-Morán

    1998-11-01

    Full Text Available Objetivo. Valorar la asociación de la deficiencia de folatos y otros factores de riesgo con la ocurrencia de defectos de cierre del tubo neural (DCTN, en la población rural del norte de México (Chihuahua, Durango y Zacatecas. Material y métodos. Se hizo un estudio multicéntrico de casos y controles. Se consideraron como casos a los recién nacidos vivos (RNV y a los muertos con DCTN, y como controles, a los RNV sanos, no malformados. Se determinó la exposición a factores de riesgo conocidos, estableciendo su asociación con los DCTN, con un modelo de análisis múltiple de regresión logística. Resultados. Los factores de riesgo asociados a DCTN fueron: la deficiencia de folatos (RM 11.1; IC95% 1.2-106.2, p= 0.04; el antecedente, en embarazos previos, de productos con DCTN (RM 3.3; IC95% 1.1-18.8, p= 0.05, y óbitos (RM 7.1; IC95% 1.1-46.3, p= 0.04. Conclusiones. La deficiencia de folatos constituye uno de los principales factores de riesgo asociado a los DCTN en la población rural del norte de México. Es necesario llevar a cabo más investigaciones para determinar la contribución de otros factores de riesgo y establecer las medidas preventivas adecuadas.Objective. To evaluate folic acid deficiency and other risk factors and their relationship with the occurrence of neural tube defects (NTD, in the rural population of northern Mexico (Chihuahua, Durango and Zacatecas. Material and methods. A multicentric case-control study was performed. Cases were both live and stillborn with NTD, and controls were healthy newborns without congenital malformations. Exposure to known risk factors was determined, establishing its association with NTD using multiple logistic regression analysis. Results. Risk factors associated to NTD were: folic acid deficiency (OR 11.1; CI 95% 1.2-106.2, p= 0.04; the antecedents of previous NTD pregnancies (OR 3.3; CI 95% 1.1-18.8, p= 0.05 and stillbirths (OR 7.1; CI 95% 1.1-46.3, p= 0.04. Conclusions. Folic acid

  20. 9-Cis Retinoic Acid Promotes Lymphangiogenesis and Enhances Lymphatic Vessel Regeneration: Therapeutic Implications of 9-Cis Retinoic Acid for Secondary Lymphedema

    Choi, Inho; Lee, Sunju; Chung, Hee Kyoung; Lee, Yong Suk; Kim, Kyu Eui; Choi, Dongwon; Park, Eun Kyung; Yang, Dongyun; Ecoiffier, Tatiana; Monahan, John; Chen, Wen; Aguilar, Berenice; Lee, Ha Neul; Yoo, Jaehyuk; Koh, Chester J.; Chen, Lu; Wong, Alex K.; Hong, Young-Kwon

    2012-01-01

    Background The lymphatic system plays a key role in tissue fluid homeostasis and lymphatic dysfunction due to genetic defects or lymphatic vessel obstruction can cause lymphedema, disfiguring tissue swellings often associated with fibrosis and recurrent infections without available cures to date. In this study, retinoic acids (RAs) were determined to be a potent therapeutic agent that is immediately applicable to reduce secondary lymphedema. Methods and Results We report that RAs promote proliferation, migration and tube formation of cultured lymphatic endothelial cells (LECs) by activating FGF-receptor signaling. Moreover, RAs control the expression of cell-cycle checkpoint regulators such as p27Kip1, p57Kip2 and the aurora kinases through both an Akt-mediated non-genomic action and a transcription-dependent genomic action that is mediated by Prox1, a master regulator of lymphatic development. Moreover, 9-cisRA was found to activate in vivo lymphangiogenesis in animals based on mouse trachea, matrigel plug and cornea pocket assays. Finally, we demonstrate that 9-cisRA can provide a strong therapeutic efficacy in ameliorating the experimental mouse tail lymphedema by enhancing lymphatic vessel regeneration. Conclusions These in vitro and animal studies demonstrate that 9-cisRA potently activates lymphangiogenesis and promotes lymphatic regeneration in an experimental lymphedema model, presenting it as a promising novel therapeutic agent to treat human lymphedema patients. PMID:22275501

  1. Neural Tube Defects

    Greene, Nicholas D. E.; Copp, Andrew J.

    2014-01-01

    Neural tube defects (NTDs), including spina bifida and anencephaly, are severe birth defects of the central nervous system that originate during embryonic development when the neural tube fails to close completely. Human NTDs are multifactorial, with contributions from both genetic and environmental factors. The genetic basis is not yet well understood, but several nongenetic risk factors have been identified as have possibilities for prevention by maternal folic acid supplementation. Mechani...

  2. Oleic acid content of a meal promotes oleoylethanolamide response and reduces subsequent energy intake in humans.

    Mennella, Ilario; Savarese, Maria; Ferracane, Rosalia; Sacchi, Raffaele; Vitaglione, Paola

    2015-01-01

    Animal data suggest that dietary fat composition may influence endocannabinoid (EC) response and dietary behavior. This study tested the hypothesis that fatty acid composition of a meal can influence the short-term response of ECs and subsequent energy intake in humans. Fifteen volunteers on three occasions were randomly offered a meal containing 30 g of bread and 30 mL of one of three selected oils: sunflower oil (SO), high oleic sunflower oil (HOSO) and virgin olive oil (VOO). Plasma EC concentrations and appetite ratings over 2 h and energy intake over 24 h following the experimental meal were measured. Results showed that after HOSO and VOO consumption the circulating oleoylethanolamide (OEA) was significantly higher than after SO consumption; a concomitantly significant reduction of energy intake was found. For the first time the oleic acid content of a meal was demonstrated to increase the post-prandial response of circulating OEA and to reduce energy intake at subsequent meals in humans. PMID:25347552

  3. Chlorogenic acid ameliorates endotoxin-induced liver injury by promoting mitochondrial oxidative phosphorylation.

    Zhou, Yan; Ruan, Zheng; Zhou, Lili; Shu, Xugang; Sun, Xiaohong; Mi, Shumei; Yang, Yuhui; Yin, Yulong

    2016-01-22

    Acute or chronic hepatic injury is a common pathology worldwide. Mitochondrial dysfunction and the depletion of adenosine triphosphate (ATP) play important roles in liver injury. Chlorogenic acids (CGA) are some of the most abundant phenolic acids in human diet. This study was designed to test the hypothesis that CGA may protect against chronic lipopolysaccharide (LPS)-induced liver injury by modulating mitochondrial energy generation. CGA decreased the activities of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase. The contents of ATP and adenosine monophosphate (AMP), as well as the ratio of AMP/ATP, were increased after CGA supplementation. The activities of enzymes that are involved in glycolysis were reduced, while those of enzymes involved in oxidative phosphorylation were increased. Moreover, phosphorylated AMP-activated protein kinase (AMPK), and mRNA levels of AMPK-α, peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1, and mitochondrial DNA transcription factor A were increased after CGA supplementation. Collectively, these findings suggest that the hepatoprotective effect of CGA might be associated with enhanced ATP production, the stimulation of mitochondrial oxidative phosphorylation and the inhibition of glycolysis. PMID:26740181

  4. Photoelectrocatalytic oxidation of glucose at a ruthenium complex modified titanium dioxide electrode promoted by uric acid and ascorbic acid for photoelectrochemical fuel cells

    Lu, Shuo-Jian; Ji, Shi-Bo; Liu, Jun-Chen; Li, Hong; Li, Wei-Shan

    2015-01-01

    The simultaneous presence of uric acid (UA) and ascorbic acid (AA) is first found to largely promote the photoelectrocatalytic oxidation of glucose (GLU) at an indium-tin oxide (ITO) or TiO2 nanoparticles/ITO electrode modified with [Ru(tatp)3]2+ (tatp = 1,4,8,9-tetra-aza-triphenylene) possessing good redox activity and nanoparticle size distribution. A well-defined electrocatalytic peak for GLU oxidation is shown at 0.265 V (vs. SCE) under approximate physiological conditions upon incorporation of UA and AA. The [Ru(tatp)3]2+/ITO electrode exhibits attractive amperometric oxidation responses towards GLU, UA and AA, while controlled potentiostatically at 0.3 V, 0.7 V and 1.0 V, respectively, indicating high sensitivity and excellent reproducibility. On basis of the photoelectrocatalysis of [Ru(tatp)3]2+/TiO2/ITO anode, a GLU concentration-dependent photoelectrochemical fuel cell vs. SCE is elaborately assembled. The proposed free-enzyme photoelectrochemical fuel cell employing 0.1 M GLU associated with 0.01 M UA and 0.01 M AA as fuel shows open-circuit photovoltage of 0.608 V, short-circuit photocurrent density of 124.5 μA cm-2 and maximum power density of 21.75 μW cm-2 at 0.455 V, fill factor of 0.32 and photoenergy conversion efficiency of 36.65%, respectively.

  5. Retinoic-acid signalling in node ectoderm and posterior neural plate directs left–right patterning of somitic mesoderm

    Sirbu, Ioan Ovidiu; Duester, Gregg

    2006-01-01

    Somitogenesis requires bilateral rhythmic segmentation of paraxial mesoderm along the antero-posterior axis1. The location of somite segmentation depends on opposing signalling gradients of retinoic acid (generated by retinaldehyde dehydrogenase-2; Raldh2) anteriorly and fibroblast growth factor (FGF; generated by Fgf8) posteriorly2,3. Retinoic-acid-deficient embryos exhibit somite left–right asymmetry4–6, but it remains unclear how retinoic acid mediates left–right patterning. Here, we demon...

  6. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells.

    Reigstad, Christopher S; Salmonson, Charles E; Rainey, John F; Szurszewski, Joseph H; Linden, David R; Sonnenburg, Justin L; Farrugia, Gianrico; Kashyap, Purna C

    2015-04-01

    Gut microbiota alterations have been described in several diseases with altered gastrointestinal (GI) motility, and awareness is increasing regarding the role of the gut microbiome in modulating GI function. Serotonin [5-hydroxytryptamine (5-HT)] is a key regulator of GI motility and secretion. To determine the relationship among gut microbes, colonic contractility, and host serotonergic gene expression, we evaluated mice that were germ-free (GF) or humanized (HM; ex-GF colonized with human gut microbiota). 5-HT reduced contractile duration in both GF and HM colons. Microbiota from HM and conventionally raised (CR) mice significantly increased colonic mRNAs Tph1 [(tryptophan hydroxylase) 1, rate limiting for mucosal 5-HT synthesis; P cell numbers (cells producing 5-HT) were unchanged. Short-chain fatty acids (SCFAs) promoted TPH1 transcription in BON cells (human EC cell model). Thus, gut microbiota acting through SCFAs are important determinants of enteric 5-HT production and homeostasis. PMID:25550456

  7. Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

    Davide Bello

    2015-10-01

    Full Text Available A new method for the preparation of α-fluorovinyl thioethers is reported which involves the hydrofluorination of alkynyl sulfides with 3HF·Et3N, a process that requires Lewis acid activation using BF3·Et2O and TiF4. The method gives access to a range of α-fluorovinyl thioethers, some in high stereoselectivity with the Z-isomer predominating over the E-isomer. The α-fluorovinyl thioether motif has prospects as a steric and electronic mimetic of thioester enols and enolates, important intermediates in enzymatic C–C bond forming reactions. The method opens access to appropriate analogues for investigations in this direction.

  8. Retinoic acid receptor beta2 promotes functional regeneration of sensory axons in the spinal cord.

    Wong, Liang-Fong; Yip, Ping K; Battaglia, Anna; Grist, John; Corcoran, Jonathan; Maden, Malcolm; Azzouz, Mimoun; Kingsman, Susan M; Kingsman, Alan J; Mazarakis, Nicholas D; McMahon, Stephen B

    2006-02-01

    The embryonic CNS readily undergoes regeneration, unlike the adult CNS, which has limited axonal repair after injury. Here we tested the hypothesis that retinoic acid receptor beta2 (RARbeta2), critical in development for neuronal growth, may enable adult neurons to grow in an inhibitory environment. Overexpression of RARbeta2 in adult rat dorsal root ganglion cultures increased intracellular levels of cyclic AMP and stimulated neurite outgrowth. Stable RARbeta2 expression in DRG neurons in vitro and in vivo enabled their axons to regenerate across the inhibitory dorsal root entry zone and project into the gray matter of the spinal cord. The regenerated neurons enhanced second-order neuronal activity in the spinal cord, and RARbeta2-treated rats showed highly significant improvement in sensorimotor tasks. These findings show that RARbeta2 induces axonal regeneration programs within injured neurons and may thus offer new therapeutic opportunities for CNS regeneration. PMID:16388307

  9. Promoted degradation of perfluorooctanic acid by persulfate when adding activated carbon

    Highlights: • PFOA removal and defluorination with AC/PS are 12 and 19 times higher than PS only • AC can activate PS to accelerate the decomposition and mineralization of PFOA. • With AC/PS, a lower reaction temperature and a shorter reaction time would suffice • A 2-cycle schematic reaction mechanism was proposed to describe PS oxidation of PFOA. -- Abstract: Treatment of persistent perfluorooctanoic acid (PFOA) in water using persulfate (PS) oxidation typically requires an elevated temperature or UV irradiation, which is energy-consuming. Under relatively low temperatures of 25–45 °C, activated carbon (AC) activated PS oxidation of PFOA was evaluated for its potential of practical applications. With presence of AC in PS oxidation, PFOA removal efficiency at 25 °C reached 682% with a high defluorination efficiency of 549% after 12 h and few intermediates of short-chain perfluorinated carboxylic acids (PFCAs) were found. The removal and defluorination rates with the combined AC/PS system were approximately 12 and 19 times higher than those of the PS-only system, respectively. Activated carbon not only removes PFOA through adsorption, but also activates PS to form sulfate radicals that accelerate the decomposition and mineralization of PFOA. The activation energy for PS oxidation of PFOA was reduced from 668 to 261 kJ/mol by the catalytic effect of AC, which implies a lower reaction temperature and a shorter reaction time would suffice. A 2-cycle schematic reaction mechanism was used to describe PS oxidation of PFOA with the generation of various intermediates and end-products

  10. Promoted degradation of perfluorooctanic acid by persulfate when adding activated carbon

    Lee, Yu-Chi [Research Center for Environmental Pollution Prevention and Control Technology, Graduate Institute of Environmental Engineering, National Taiwan University, 71, Chou-Shan Rd., Taipei 106, Taiwan, ROC (China); Lo, Shang-Lien, E-mail: sllo@ntuedu.tw [Research Center for Environmental Pollution Prevention and Control Technology, Graduate Institute of Environmental Engineering, National Taiwan University, 71, Chou-Shan Rd., Taipei 106, Taiwan, ROC (China); Kuo, Jeff [Department of Civil and Environmental Engineering, California State University, 800 North, State College Blvd., Fullerton (United States); Huang, Chin-Pao [Department of Civil and Environmental Engineering, University of Delaware, Newark, DE 19716 (United States)

    2013-10-15

    Highlights: • PFOA removal and defluorination with AC/PS are 12 and 19 times higher than PS only • AC can activate PS to accelerate the decomposition and mineralization of PFOA. • With AC/PS, a lower reaction temperature and a shorter reaction time would suffice • A 2-cycle schematic reaction mechanism was proposed to describe PS oxidation of PFOA. -- Abstract: Treatment of persistent perfluorooctanoic acid (PFOA) in water using persulfate (PS) oxidation typically requires an elevated temperature or UV irradiation, which is energy-consuming. Under relatively low temperatures of 25–45 °C, activated carbon (AC) activated PS oxidation of PFOA was evaluated for its potential of practical applications. With presence of AC in PS oxidation, PFOA removal efficiency at 25 °C reached 682% with a high defluorination efficiency of 549% after 12 h and few intermediates of short-chain perfluorinated carboxylic acids (PFCAs) were found. The removal and defluorination rates with the combined AC/PS system were approximately 12 and 19 times higher than those of the PS-only system, respectively. Activated carbon not only removes PFOA through adsorption, but also activates PS to form sulfate radicals that accelerate the decomposition and mineralization of PFOA. The activation energy for PS oxidation of PFOA was reduced from 668 to 261 kJ/mol by the catalytic effect of AC, which implies a lower reaction temperature and a shorter reaction time would suffice. A 2-cycle schematic reaction mechanism was used to describe PS oxidation of PFOA with the generation of various intermediates and end-products.