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Sample records for hypoxic cell sensitizers

  1. Inhibition of JNK Sensitizes Hypoxic Colon Cancer Cells to DNA Damaging Agents

    Science.gov (United States)

    Vasilevskaya, Irina A.; Selvakumaran, Muthu; Hierro, Lucia Cabal; Goldstein, Sara R.; Winkler, Jeffrey D.; O'Dwyer, Peter J.

    2015-01-01

    Purpose We showed previously that in HT29 colon cancer cells, modulation of hypoxia-induced stress signaling affects oxaliplatin cytotoxicity. To further study the significance of hypoxia-induced signaling through JNK, we set out to investigate how modulation of kinase activities influences cellular responses of hypoxic colon cancer cells to cytotoxic drugs. Experimental design In a panel of cell lines we investigated effects of pharmacological and molecular inhibition of JNK on sensitivity to oxaliplatin, SN-38 and 5-FU. Combination studies for the drugs and JNK inhibitor CC-401 were carried out in vitro and in vivo. Results Hypoxia-induced JNK activation was associated with resistance to oxaliplatin. CC-401 in combination with chemotherapy demonstrates synergism in colon cancer cell lines, though synergy is not always hypoxia-specific. A more detailed analysis focused on HT29 and SW620 (responsive), and HCT116 (non-responsive) lines. In HT29 and SW620 cells CC-401 treatment results in greater DNA damage in the sensitive cells. In vivo, potentiation of bevacizumab, oxaliplatin, and the combination by JNK inhibition was confirmed in HT29-derived mouse xenografts, where tumor growth delay was greater in the presence of CC-401. Finally, stable introduction of a dominant negative JNK1, but not JNK2, construct into HT29 cells rendered them more sensitive to oxaliplatin under hypoxia, suggesting differing input of JNK isoforms in cellular responses to chemotherapy. Conclusions These findings demonstrate that signaling through JNK is a determinant of response to therapy in colon cancer models, and support the testing of JNK inhibition to sensitize colon tumors in the clinic. PMID:26023085

  2. EVALUATION OF THE CLINICAL USE OF HYPOXIC CELL SENSITIZERS IN RADIATION THERAPY OF MALIGNANT EPITHELIAL SKIN TUMORS

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    P. Yu. Polyakov

    2015-01-01

    Full Text Available Aim: To increase the efficacy of radiation therapy of malignant epithelial cell skin neoplasms with the use of radiation sensitizers of hypoxic tumor cells.Materials and methods: The study was performed in 517 patients with basal cell (n = 361 and squamous cell (n = 156 skin cancer, 274 (53% of whom had T2 and 243 (47%, T3 tumors. Patients with locally advanced and metastatic tumors were excluded from the study. The following treatment modalities were used: distant gamma-therapy, short-distance radiation therapy and combined radiation therapy with the use of non-conventional dose fractioning at total local doses equal to 72–73 Gr. The sensibilization of hypoxic tumor cells to radiation therapy with metronidazole was done by targeted delivery of the drug to the tumor by means of topical application of Coletex-M drapes impregnated with metronidazole in a high concentration (up to 20 mcg/cm². The second method of radiosensibilization of hypoxic tumor cells was based on a preliminary use of low intensity laser radiation onto the tumor. As a source this radiation, a helium neon laser was used with the power of up to 12 mVt and the wave length of 0.63 to 0.89 mcm, duration of sessions from 3 to 15 minutes. The control group comprised 192 skin cancer patients who underwent radiation therapy without the use of radiation sensitizers. Results: The use of metronidazole and low intensity laser radiation within the radiation therapy of T3 skin cancer patients, compared to the treatment without the radiation modifiers, significantly improved the immediate cure rates (full tumor regression at 1 to 1.5 months after completion of radiation from 75.5 ± 3.1% to 89.2 ± 1.9% (р < 0.05. In the group with basal cell skin cancer that underwent radiation therapy combined with metronidazole, there was an association of its radio-modifying effect and tumor size. Short-distance roentgenotherapy of patients with T2 basal cell skin cancer and tumor size of < 4 cm was

  3. Clusterin and chemotherapy sensitivity under normoxic and graded hypoxic conditions in colorectal cancer.

    LENUS (Irish Health Repository)

    Kevans, David

    2012-06-01

    In vitro studies have shown that clusterin modulates treatment sensitivity in a number of human cancers; however, the interaction between clusterin expression and hypoxia in controlling treatment response in CRC has not previously been examined. The aim of this study was to assess the effect of clusterin overexpression in CRC cells on sensitivity to 5-fluorouracil (5-FU), oxaliplatin and FOLFOX treatment under normoxic and graded hypoxic conditions.

  4. Evaluation of nitrobenzimidazoles as hypoxic cell radiosensitizers

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    Wright, J.; Frank, L.R.; Bush, D.; Harrison, G.H.

    1983-07-01

    Radiobiological and pharmacokinetic assays were performed to determine the potential of 2-nitrobenzimidazole (NBI) as a hypoxic cell radiosensitizing agent. As judged by comparing survival curve slopes of Serratia marcescens irradiated under aerated and hypoxic conditions, the NBI enhancement ratio (ER) at 2 mM concentration was 2.4 +/- 0.2, compared with an oxygen enhancement ratio of 3.3 +/- 0.3. 2,5-Dinitrobenzimidazole (DNBI) was investigated in vitro; its ER was 3.0 +/- 0.3 at 4 mM concentration. Very poor tissue penetration of DNBI precluded further testing in vivo. Acute toxic signs appeared in C3H/HeJ mice following ip injection of NBI at 100 mg/kg. These would be partly attributable to the stress caused by the high pH of the injection vehicle. The LD50 was estimated to be 125-150 mg/kg. Mammary adenocarcinoma tumors grown in the flanks of these mice exhibited maximum NBI levels at 5 min postinjection (ip). Peak tumor radiosensitization occurred in the interval between 5 and 10 min postinjection. The ER for tumor regrowth delay was 2.1 +/- 0.3 following 50 mg/kg injected into mice 5 min before irradiation. Functional evaluation up to 40 days after treatment revealed no evidence of neurological deficit.

  5. The lethal interaction of x ray and penicillin induced lesions following x-irradiation of Escherichia coli B/r in the presence of hypoxic cell sensitizers

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    Gillies, N.E.; Obioha, F.I.

    1982-03-01

    When Escherichia coli B/r were x-irradiated under anoxia in the presence of different electron-affinic sensitizers and then incubated in broth containing penicillin (at a concentration that did not kill unirradiated cells) additional killing of the bacteria occurred provided the sensitizers were of relatively high lipophilicity. The overall effect was to increase the efficiency of these sensitizers. It is concluded that sensitizer-dependent latent radiation lesions(s) are produced in membrane components of the cell envelope that interact with damage caused by penicillin in the peptidoglycan layer and this causes the additional lethality.

  6. Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells.

    Science.gov (United States)

    Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao; Asai, Kiyofumi; Imaizumi, Yuji

    2016-08-05

    The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4-5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba(2+)-sensitive inward rectifier K(+) current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca(2+) imaging study revealed that the hypoxic stress enhanced store-operated Ca(2+) (SOC) entry, which was significantly reduced in the presence of 100 μM Ba(2+). On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba(2+). We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca(2+) entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Role of a novel KCa opener in regulating K+ channels of hypoxic human pulmonary vascular cells.

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    Peng, W; Hoidal, J R; Farrukh, I S

    1999-04-01

    Hypoxic pulmonary vasoconstriction (HPVC) is mediated, in part, via membrane depolarization and inhibition of K+ channels. We recently observed that the naturally occurring steroid dehydroepiandrosterone (DHEA) reversed and prevented HPVC in isolated perfused and ventilated ferret lungs. In the current study, we investigated the effects of DHEA on the major K+ channels of chronically hypoxic human pulmonary smooth-muscle cells (HPSMC). K+ channels were recorded by using the patch-clamp technique in whole-cell and single-channel configurations. Single-channel recordings were performed in inside-out and outside-out excised patches, and in intact HPSMC in cell-attached configuration. Using whole-cell current recording, chronic hypoxia decreased the high-amplitude, high-noise, and charybdotoxin-sensitive Ca2+-dependent K+ channels (KCa). DHEA reversed the effect of chronic hypoxia on KCa, but had no effect on the low-amplitude, low-noise, and 4-aminopyridine-sensitive delayed rectifying K+ channels. In the cell-attached configuration, chronic hypoxia caused a decrease in KCa sensitivity to membrane potential (Em). DHEA reversed the effect of hypoxia on KCa sensitivity to Em and caused a mean of 40-mV left shift in voltage-dependent activation of KCa. DHEA increased KCa activation from both sides of membrane patches of hypoxic HPSMC via a cyclic adenosine monophosphate- and cyclic guanosine monophosphate-independent pathway. We concluded that DHEA is a novel KCa opener of the human pulmonary vasculature.

  8. Hypoxic stress up-regulates Kir2.1 expression and facilitates cell proliferation in brain capillary endothelial cells

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    Yamamura, Hideto; Suzuki, Yoshiaki; Yamamura, Hisao [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Imaizumi, Yuji, E-mail: yimaizum@phar.nagoya-cu.ac.jp [Department of Molecular & Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya (Japan)

    2016-08-05

    The blood-brain barrier (BBB) is mainly composed of brain capillary endothelial cells (BCECs), astrocytes and pericytes. Brain ischemia causes hypoxic encephalopathy and damages BBB. However, it remains still unclear how hypoxia affects BCECs. In the present study, t-BBEC117 cells, an immortalized bovine brain endothelial cell line, were cultured under hypoxic conditions at 4–5% oxygen for 72 h. This hypoxic stress caused hyperpolarization of resting membrane potential. Patch-clamp recordings revealed a marked increase in Ba{sup 2+}-sensitive inward rectifier K{sup +} current in t-BBEC117 cells after hypoxic culture. Western blot and real-time PCR analyses showed that Kir2.1 expression was significantly up-regulated at protein level but not at mRNA level after the hypoxic culture. Ca{sup 2+} imaging study revealed that the hypoxic stress enhanced store-operated Ca{sup 2+} (SOC) entry, which was significantly reduced in the presence of 100 μM Ba{sup 2+}. On the other hand, the expression of SOC channels such as Orai1, Orai2, and transient receptor potential channels was not affected by hypoxic stress. MTT assay showed that the hypoxic stress significantly enhanced t-BBEC117 cell proliferation, which was inhibited by approximately 60% in the presence of 100 μM Ba{sup 2+}. We first show here that moderate cellular stress by cultivation under hypoxic conditions hyperpolarizes membrane potential via the up-regulation of functional Kir2.1 expression and presumably enhances Ca{sup 2+} entry, resulting in the facilitation of BCEC proliferation. These findings suggest potential roles of Kir2.1 expression in functional changes of BCECs in BBB following ischemia. -- Highlights: •Hypoxic culture of brain endothelial cells (BEC) caused membrane hyperpolarization. •This hyperpolarization was due to the increased expression of Kir2.1 channels. •Hypoxia enhanced store-operated Ca{sup 2+} (SOC) entry via Kir2.1 up-regulation. •Expression levels of putative SOC

  9. Radiation-induced changes in nucleoid halo diameteres of aerobic and hypoxic SF-126 human brain tumor cells

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    Wang, J.; Basu, H.S.; Hu, L.; Feuerstein, B.G.; Deen, D.F. [Univ. of California, San Francisco, CA (United States)] [and others

    1995-02-01

    Nucleoid halo diameters were measured to assay changes in DNA supercoiling in human brain tumor cell line SF-126 after irradiation under aerobic or hypoxic conditions. In unirradiated aerobic cells, a typical propidium iodide titration curve showed that with increasing concentrations of propodium iodide, the halo diameter increased and then decreased with the unwinding and subsequent rewinding of DNA supercoils. In irradiated cells, the rewinding of DNA supercoils was inhibited, resulting in an increased halo diameter, in a radiation dose-dependent manner. To produce equal increases in halo diameter required about a threefold higher radiation dose in hypoxic cells than in aerobic cells. Quantitatively similiar differences in the radiation sensitivities of hypoxic and aerobic cells were demonstrated by a colony-forming efficiency assay. These findings suggest that the nucleoid halo assay may be used as a rapid measure of the inherent radiation sensitivity of human tumors. 22 refs., 5 figs.

  10. Hypoxic Preconditioning Increases Survival and Pro-Angiogenic Capacity of Human Cord Blood Mesenchymal Stromal Cells In Vitro.

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    Andreas Matthäus Bader

    Full Text Available Hypoxic preconditioning was shown to improve the therapeutic efficacy of bone marrow-derived multipotent mesenchymal stromal cells (MSCs upon transplantation in ischemic tissue. Given the interest in clinical applications of umbilical cord blood-derived MSCs, we developed a specific hypoxic preconditioning protocol and investigated its anti-apoptotic and pro-angiogenic effects on cord blood MSCs undergoing simulated ischemia in vitro by subjecting them to hypoxia and nutrient deprivation with or without preceding hypoxic preconditioning. Cell number, metabolic activity, surface marker expression, chromosomal stability, apoptosis (caspases-3/7 activity and necrosis were determined, and phosphorylation, mRNA expression and protein secretion of selected apoptosis and angiogenesis-regulating factors were quantified. Then, human umbilical vein endothelial cells (HUVEC were subjected to simulated ischemia in co-culture with hypoxically preconditioned or naïve cord blood MSCs, and HUVEC proliferation was measured. Migration, proliferation and nitric oxide production of HUVECs were determined in presence of cord blood MSC-conditioned medium. Cord blood MSCs proved least sensitive to simulated ischemia when they were preconditioned for 24 h, while their basic behavior, immunophenotype and karyotype in culture remained unchanged. Here, "post-ischemic" cell number and metabolic activity were enhanced and caspase-3/7 activity and lactate dehydrogenase release were reduced as compared to non-preconditioned cells. Phosphorylation of AKT and BAD, mRNA expression of BCL-XL, BAG1 and VEGF, and VEGF protein secretion were higher in preconditioned cells. Hypoxically preconditioned cord blood MSCs enhanced HUVEC proliferation and migration, while nitric oxide production remained unchanged. We conclude that hypoxic preconditioning protects cord blood MSCs by activation of anti-apoptotic signaling mechanisms and enhances their angiogenic potential. Hence, hypoxic

  11. Development of a real-time imaging system for hypoxic cell apoptosis

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    Go Kagiya

    2016-01-01

    Full Text Available Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting the hypoxic cells is one of the most crucial challenges for cancer regression. Screening potential candidates for effective diagnostic modalities even under a hypoxic environment would be an important first step. In this study, we describe the development of a real-time imaging system to monitor hypoxic cell apoptosis for such screening. The imaging system is composed of a cyclic luciferase (luc gene under the control of an improved hypoxic-responsive promoter. The cyclic luc gene product works as a caspase-3 (cas-3 monitor as it gains luc activity in response to cas-3 activation. The promoter composed of six hypoxic responsible elements and the CMV IE1 core promoter drives the effective expression of the cyclic luc gene in hypoxic conditions, enhancing hypoxic cell apoptosis visualization. We also confirmed real-time imaging of hypoxic cell apoptosis in the spheroid, which shares properties with the tumor. Thus, this constructed system could be a powerful tool for the development of effective anticancer diagnostic modalities.

  12. Metabolic profiling of hypoxic cells revealed a catabolic signature required for cell survival.

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    Christian Frezza

    Full Text Available Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography-mass spectrometry (LC-MS, to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours.

  13. Hypoxic radiosensitization: adored and ignored

    DEFF Research Database (Denmark)

    Overgaard, Jens

    2007-01-01

    Since observations from the beginning of the last century, it has become well established that solid tumors may contain oxygen-deficient hypoxic areas and that cells in such areas may cause tumors to become radioresistant. Identifying hypoxic cells in human tumors has improved by the help of new...... resistance can be eliminated or modified by normobaric or hyperbaric oxygen or by the use of nitroimidazoles as hypoxic radiation sensitizers. More recently, attention has been given to hypoxic cytotoxins, a group of drugs that selectively or preferably destroys cells in a hypoxic environment. An updated.......71 to 0.86) for the outcome of locoregional control and with an associated significant overall survival benefit (odds ratio = 0.87; 95% CI, 0.80 to 0.95). No significant influence was found on the incidence of distant metastases or on the risk of radiation-related complications. Ample data exist...

  14. Stem Cell Therapy for Neonatal Hypoxic-Ischemic Encephalopathy

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    Gabriel eGonzales-Portillo

    2014-08-01

    Full Text Available Treatments for neonatal hypoxic ischemic encephalopathy (HIE have been limited. The aim of this paper is to offer translational research guidance on stem cell therapy for neonatal HIE by examining clinically relevant animal models, practical stem cell sources, safety and efficacy of endpoint assays, as well as a general understanding of modes of action of this cellular therapy. In order to do so, we discuss the clinical manifestations of HIE, highlighting its overlapping pathologies with stroke providing insights on the potential of cell therapy, currently investigated in stroke, for HIE. To this end, we draw guidance from recommendations outlined in Stem cell Therapeutics as an Emerging Paradigm for Stroke or STEPS, which have been recently modified to Baby STEPS to cater for the neonatal symptoms of HIE. These guidelines recognized that neonatal HIE exhibits distinct disease symptoms from adult stroke in need of an innovative translational approach that facilitates the entry of cell therapy in the clinic. Finally, new information about recent clinical trials, and insights into combination therapy are provided with the vision that stem cell therapy may benefit from available treatments, such as hypothermia, already being tested in children diagnosed with HIE.

  15. Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status.

    NARCIS (Netherlands)

    Sprong, D.; Janssen, H.L.K.; Vens, C.; Begg, A.C.

    2006-01-01

    PURPOSE: To determine the role of DNA repair in hypoxic radioresistance. METHODS AND MATERIALS: Chinese hamster cell lines with mutations in homologous recombination (XRCC2, XRCC3, BRAC2, RAD51C) or nonhomologous end-joining (DNA-PKcs) genes were irradiated under normoxic (20% oxygen) and hypoxic

  16. Normoxic cells remotely regulate the acid-base balance of cells at the hypoxic core of connexin-coupled tumor growths.

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    Dovmark, Tobias H; Hulikova, Alzbeta; Niederer, Steven A; Vaughan-Jones, Richard D; Swietach, Pawel

    2017-09-07

    ATP fuels the removal of metabolic end-products, including H(+) ions that profoundly modulate biological activities. Energetic resources in hypoxic tumor regions are constrained by low-yielding glycolysis, and any means of reducing the cost of acid extrusion, without compromising pH homeostasis, would therefore be advantageous for cancer cells. Some cancers express connexin channels that allow solute exchange between cells, and we propose that, via this route, normoxic cells supply hypoxic neighbors with acid-neutralizing HCO3(-) ions. This hypothesis was tested by imaging cytoplasmic pH in spheroidal tissue growths of connexin43-positive pancreatic cancer Colo357 cells during light-controlled H(+) uncaging at the hypoxic core. Cytoplasmic acid retention at the core was halved in the presence of CO2/HCO3(-), but this process requires a restorative HCO3(-) flux. The effect of CO2/HCO3(-) was ablated by connexin43 inhibition or knockdown. In connexin-decoupled spheroids, 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), an inhibitor of HCO3(-) uptake, had no effect on cytoplasmic [H(+)] in the H(+)-uncaging region, indicating that DIDS-sensitive transport is not an adequate pH-regulatory strategy therein. With intact connexin-coupling, acid retention at the core increased upon DIDS treatment, indicating that HCO3(-) ions are taken up actively by peripheral cells and then transmitted passively to cells at the hypoxic core. Thus, the energetic burden of pH regulation is offloaded from hypoxic cells onto metabolically altruistic normoxic neighbors.-Dovmark, T. H., Hulikova, A., Niederer, S. A., Vaughan-Jones, R. D., Swietach, P. Normoxic cells remotely regulate the acid-base balance of cells at the hypoxic core of connexin-coupled tumor growths. © FASEB.

  17. Effects of hypoxic culture conditions on umbilical cord-derived human mesenchymal stem cells

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    Hass Ralf

    2010-07-01

    Full Text Available Abstract Following cultivation of distinct mesenchymal stem cell (MSC populations derived from human umbilical cord under hypoxic conditions (between 1.5% to 5% oxygen (O2 revealed a 2- to 3-fold reduced oxygen consumption rate as compared to the same cultures at normoxic oxygen levels (21% O2. A simultaneous measurement of dissolved oxygen within the culture media from 4 different MSC donors ranged from 15 μmol/L at 1.5% O2 to 196 μmol/L at normoxic 21% O2. The proliferative capacity of the different hypoxic MSC populations was elevated as compared to the normoxic culture. This effect was paralleled by a significantly reduced cell damage or cell death under hypoxic conditions as evaluated by the cellular release of LDH whereby the measurement of caspase3/7 activity revealed little if any differences in apoptotic cell death between the various cultures. The MSC culture under hypoxic conditions was associated with the induction of hypoxia-inducing factor-alpha (HIF-1α and an elevated expression of energy metabolism-associated genes including GLUT-1, LDH and PDK1. Concomitantly, a significantly enhanced glucose consumption and a corresponding lactate production could be observed in the hypoxic MSC cultures suggesting an altered metabolism of these human stem cells within the hypoxic environment.

  18. Targeting the tumour vasculature: exploitation of low oxygenation and sensitivity to NOS inhibition by treatment with a hypoxic cytotoxin.

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    Jennifer H E Baker

    Full Text Available Many cancer research efforts focus on exploiting genetic-level features that may be targeted for therapy. Tissue-level features of the tumour microenvironment also represent useful therapeutic targets. Here we investigate the presence of low oxygen tension and sensitivity to NOS inhibition of tumour vasculature as potential tumour-specific features that may be targeted by hypoxic cytotoxins, a class of therapeutics currently under investigation. We have previously demonstrated that tirapazamine (TPZ mediates central vascular dysfunction in tumours. TPZ is a hypoxic cytotoxin that is also a competitive inhibitor of NOS. Here we further investigated the vascular-targeting activity of TPZ by combining it with NOS inhibitor L-NNA, or with low oxygen content gas breathing. Tumours were analyzed via multiplex immunohistochemical staining that revealed irreversible loss of perfusion and enhanced tumour cell death when TPZ was combined with either low oxygen or a NOS inhibitor. Tumour growth rate was reduced by TPZ + NOS inhibition, and tumours previously resistant to TPZ-mediated vascular dysfunction were sensitized by low oxygen breathing. Additional mapping analysis suggests that tumours with reduced vascular-associated stroma may have greater sensitivity to these effects. These results indicate that poorly oxygenated tumour vessels, also being abnormally organized and with inadequate smooth muscle, may be successfully targeted for significant anti-cancer effects by inhibition of NOS and hypoxia-activated prodrug toxicity. This strategy illustrates a novel use of hypoxia-activated cytotoxic prodrugs as vascular targeting agents, and also represents a novel mechanism for targeting tumour vessels.

  19. CD44 Interacts with HIF-2α to Modulate the Hypoxic Phenotype of Perinecrotic and Perivascular Glioma Cells

    DEFF Research Database (Denmark)

    Johansson, Elinn; Grassi, Elisa S.; Pantazopoulou, Vasiliki

    2017-01-01

    correlated with CD44. The CD44ICD was sufficient to induce hypoxic signaling at perivascular oxygen tensions, and blocking CD44 cleavage decreased HIF-2α stabilization in CD44-expressing cells. Our data indicate that the stem cell marker CD44 modulates the hypoxic response of glioma cells and that the pseudo......-hypoxic phenotype of stem-like glioma cells is achieved by stabilization of HIF-2α through interaction with CD44, independently of oxygen....

  20. The anti-protozoan drug nifurtimox preferentially inhibits clonogenic tumor cells under hypoxic conditions.

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    Li, Quhuan; Lin, Qun; Kim, Hoon; Yun, Zhong

    2017-01-01

    Tumor hypoxia is an independent prognostic indicator of tumor malignant progression and poor patient survival. Therefore, eradication of hypoxic tumor cells is of paramount importance for successful disease control. In this study, we have made a new discovery that nifurtimox, a clinically approved drug to treat Chagas disease caused by the parasitic protozoan trypanosomes, can function as a hypoxia-activated cytotoxin. We have found that nifurtimox preferentially kill clonogenic tumor cells especially under the hypoxic conditions of ≤0.1% O2. Mechanistically, nifurtimox becomes activated after tumor cells enter into a fully hypoxic state, as shown by the stabilization of the Hypoxia-Inducible Factor 1α (HIF-1α). Nifurtimox specifically induces the formation of 53BP1 foci, a hallmark of DNA double-stranded breaks, in hypoxic tumor cells. Hypoxia-dependent activation of nifurtimox involves P450 (cytochrome) oxidoreductase. The anti-protozoan drug nifurtimox holds promise as a new hypoxia-activated cytotoxin with the potential to preferentially eliminates severely hypoxic tumor cells.

  1. Erythropoietin and a nonerythropoietic peptide analog promote aortic endothelial cell repair under hypoxic conditions: role of nitric oxide

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    Heikal L

    2016-08-01

    Full Text Available Lamia Heikal,1 Pietro Ghezzi,1 Manuela Mengozzi,1 Blanka Stelmaszczuk,2 Martin Feelisch,2 Gordon AA Ferns1 1Brighton and Sussex Medical School, Falmer, Brighton, 2Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital and Institute for Life Sciences, Southampton, UK Abstract: The cytoprotective effects of erythropoietin (EPO and an EPO-related nonerythropoietic analog, pyroglutamate helix B surface peptide (pHBSP, were investigated in an in vitro model of bovine aortic endothelial cell injury under normoxic (21% O2 and hypoxic (1% O2 conditions. The potential molecular mechanisms of these effects were also explored. Using a model of endothelial injury (the scratch assay, we found that, under hypoxic conditions, EPO and pHBSP enhanced scratch closure by promoting cell migration and proliferation, but did not show any effect under normoxic conditions. Furthermore, EPO protected bovine aortic endothelial cells from staurosporine-induced apoptosis under hypoxic conditions. The priming effect of hypoxia was associated with stabilization of hypoxia inducible factor-1α, EPO receptor upregulation, and decreased Ser-1177 phosphorylation of endothelial nitric oxide synthase (NOS; the effect of hypoxia on the latter was rescued by EPO. Hypoxia was associated with a reduction in nitric oxide (NO production as assessed by its oxidation products, nitrite and nitrate, consistent with the oxygen requirement for endogenous production of NO by endothelial NOS. However, while EPO did not affect NO formation in normoxia, it markedly increased NO production, in a manner sensitive to NOS inhibition, under hypoxic conditions. These data are consistent with the notion that the tissue-protective actions of EPO-related cytokines in pathophysiological settings associated with poor oxygenation are mediated by NO. These findings may be particularly relevant to atherogenesis and postangioplasty restenosis. Keywords

  2. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells.

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    Ding, Fengan; Li, Yiping; Liu, Jing; Liu, Lei; Yu, Wenmin; Wang, Zhi; Ni, Haifeng; Liu, Bicheng; Chen, Pingsheng

    2014-01-01

    Gold nanoparticles (GNPs) can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells. Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet-visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM) to human renal proximal tubular cells (HK-2) by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM) treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the production of reactive oxygen species, the loss of mitochondrial membrane potential (ΔΨM), and an increase in apoptosis and autophagic cell death. Our results demonstrate that renal tubular epithelial cells presented different responses under normoxic and hypoxic environments, which provide an important basis for understanding the risks associated with GNP

  3. Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions

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    Paschke Reinhard

    2011-09-01

    Full Text Available Abstract Background Betulinic acid (BA is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas, the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. Methods In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays and protein expression was examined with Western blot analyses. Results Under normoxic conditions, a half maximal inhibitory concentration (IC50 of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively and U343MG cells (p Conclusion Our results suggest that BA is capable of improving the effects of tumor therapy in human malignant glioma cells, particularly under hypoxic conditions. Further investigations are necessary to characterize its potential as a radiosensitizer.

  4. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Li, Ying-Bo; Wang, Yan; Tang, Ji-Ping; Chen, Di; Wang, Sha-Li

    2015-05-01

    Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 μM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 μM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  5. Neuroprotective effects of ginsenoside Rg1-induced neural stem cell transplantation on hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Ying-bo Li

    2015-01-01

    Full Text Available Ginsenoside Rg1 is the major pharmacologically active component of ginseng, and is reported to have various therapeutic actions. To determine whether it induces the differentiation of neural stem cells, and whether neural stem cell transplantation after induction has therapeutic effects on hypoxic-ischemic encephalopathy, we cultured neural stem cells in 10-80 µM ginsenoside Rg1. Immunohistochemistry revealed that of the concentrations tested, 20 mM ginsenoside Rg1 had the greatest differentiation-inducing effect and was the concentration used for subsequent experiments. Whole-cell patch clamp showed that neural stem cells induced by 20 µM ginsenoside Rg1 were more mature than non-induced cells. We then established neonatal rat models of hypoxic-ischemic encephalopathy using the suture method, and ginsenoside Rg1-induced neural stem cells were transplanted via intracerebroventricular injection. These tests confirmed that neural stem cells induced by ginsenoside had fewer pathological lesions and had a significantly better behavioral capacity than model rats that received saline. Transplanted neural stem cells expressed neuron-specific enolase, and were mainly distributed in the hippocampus and cerebral cortex. The present data suggest that ginsenoside Rg1-induced neural stem cells can promote the partial recovery of complicated brain functions in models of hypoxic-ischemic encephalopathy.

  6. Development of an ultrasound sensitive oxygen carrier for oxygen delivery to hypoxic tissue.

    Science.gov (United States)

    Eisenbrey, John R; Albala, Lorenzo; Kramer, Michael R; Daroshefski, Nick; Brown, David; Liu, Ji-Bin; Stanczak, Maria; O'Kane, Patrick; Forsberg, Flemming; Wheatley, Margaret A

    2015-01-15

    Radiation therapy is frequently used in the treatment of malignancies, but tumors are often more resistant than the surrounding normal tissue to radiation effects, because the tumor microenvironment is hypoxic. This manuscript details the fabrication and characterization of an ultrasound-sensitive, injectable oxygen microbubble platform (SE61O2) for overcoming tumor hypoxia. SE61O2 was fabricated by first sonicating a mixture of Span 60 and water-soluble vitamin E purged with perfluorocarbon gas. SE61O2 microbubbles were separated from the foam by flotation, then freeze dried under vacuum to remove all perfluorocarbon, and reconstituted with oxygen. Visually, SE61O2 microbubbles were smooth, spherical, with an average diameter of 3.1 μm and were reconstituted to a concentration of 6.5 E7 microbubbles/ml. Oxygen-filled SE61O2 provides 16.9 ± 1.0 dB of enhancement at a dose of 880 μl/l (5.7 E7 microbubbles/l) with a half-life under insonation of approximately 15 min. In in vitro release experiments, 2 ml of SE61O2 (1.3 E8 microbubbles) triggered with ultrasound was found to elevate oxygen partial pressures of 100ml of degassed saline 13.8 mmHg more than untriggered bubbles and 20.6 mmHg more than ultrasound triggered nitrogen-filled bubbles. In preliminary in vivo delivery experiments, triggered SE61O2 resulted in a 30.4 mmHg and 27.4 mmHg increase in oxygen partial pressures in two breast tumor mouse xenografts. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Loss of CSL Unlocks a Hypoxic Response and Enhanced Tumor Growth Potential in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eike-Benjamin Braune

    2016-05-01

    Full Text Available Notch signaling is an important regulator of stem cell differentiation. All canonical Notch signaling is transmitted through the DNA-binding protein CSL, and hyperactivated Notch signaling is associated with tumor development; thus it may be anticipated that CSL deficiency should reduce tumor growth. In contrast, we report that genetic removal of CSL in breast tumor cells caused accelerated growth of xenografted tumors. Loss of CSL unleashed a hypoxic response during normoxic conditions, manifested by stabilization of the HIF1α protein and acquisition of a polyploid giant-cell, cancer stem cell-like, phenotype. At the transcriptome level, loss of CSL upregulated more than 1,750 genes and less than 3% of those genes were part of the Notch transcriptional signature. Collectively, this suggests that CSL exerts functions beyond serving as the central node in the Notch signaling cascade and reveals a role for CSL in tumorigenesis and regulation of the cellular hypoxic response.

  8. The anti-protozoan drug nifurtimox preferentially inhibits clonogenic tumor cells under hypoxic conditions

    OpenAIRE

    Li, Quhuan; Lin, Qun; Kim, Hoon; Yun, Zhong

    2017-01-01

    Tumor hypoxia is an independent prognostic indicator of tumor malignant progression and poor patient survival. Therefore, eradication of hypoxic tumor cells is of paramount importance for successful disease control. In this study, we have made a new discovery that nifurtimox, a clinically approved drug to treat Chagas disease caused by the parasitic protozoan trypanosomes, can function as a hypoxia-activated cytotoxin. We have found that nifurtimox preferentially kill clonogenic tumor cells e...

  9. Hypoxic conditions induce a cancer-like phenotype in human breast epithelial cells.

    Directory of Open Access Journals (Sweden)

    Marica Vaapil

    Full Text Available INTRODUCTION: Solid tumors are less oxygenated than their tissue of origin. Low intra-tumor oxygen levels are associated with worse outcome, increased metastatic potential and immature phenotype in breast cancer. We have reported that tumor hypoxia correlates to low differentiation status in breast cancer. Less is known about effects of hypoxia on non-malignant cells. Here we address whether hypoxia influences the differentiation stage of non-malignant breast epithelial cells and potentially have bearing on early stages of tumorigenesis. METHODS: Normal human primary breast epithelial cells and immortalized non-malignant mammary epithelial MCF-10A cells were grown in a three-dimensional overlay culture on laminin-rich extracellular matrix for up to 21 days at normoxic or hypoxic conditions. Acinar morphogenesis and expression of markers of epithelial differentiation and cell polarization were analyzed by immunofluorescence, immunohistochemistry, qPCR and immunoblot. RESULTS: In large ductal carcinoma in situ patient-specimens, we find that epithelial cells with high HIF-1α levels and multiple cell layers away from the vasculature are immature compared to well-oxygenated cells. We show that hypoxic conditions impaired acinar morphogenesis of primary and immortalized breast epithelial cells grown ex vivo on laminin-rich matrix. Normoxic cultures formed polarized acini-like spheres with the anticipated distribution of marker proteins associated with mammary epithelial polarization e.g. α6-integrin, laminin 5 and Human Milk Fat Globule/MUC1. At hypoxia, cells were not polarized and the sub-cellular distribution pattern of the marker proteins rather resembled that reported in vivo in breast cancer. The hypoxic cells remained in a mitotic state, whereas proliferation ceased with acinar morphogenesis at normoxia. We found induced expression of the differentiation repressor ID1 in the undifferentiated hypoxic MCF-10A cell structures. Acinar

  10. Design considerations for open-well microfluidic platforms for hypoxic cell studies.

    Science.gov (United States)

    Byrne, Matthew B; Leslie, Matthew T; Patel, Heeral S; Gaskins, H Rex; Kenis, Paul J A

    2017-09-01

    Regions of hypoxia are common in solid tumors and are associated with enhanced malignancy, metastasis, and chemo/radio resistance. Real-time hypoxic cellular experimentation is challenging due to the constant need for oxygen control. Most microfluidic platforms developed thus far for hypoxic cell studies are burdened by complex design parameters and are difficult to use for uninitiated investigators. However, open-well microfluidic platforms enable short and long term hypoxic cell studies with an ease of use workflow. Specifically, open-well platforms enable manipulation and addition of cells, media, and reagents using a micropipette for hypoxic cell studies in tunable dissolved oxygen concentrations as low 0.3 mg/l. We analyzed design considerations for open-well microfluidic platforms such as media height, membrane thickness, and impermeable barriers to determine their effects on the amount of dissolved oxygen within the platform. The oxygen concentration was determined by experimental measurements and computational simulations. To examine cell behavior under controlled oxygen conditions, hypoxia-induced changes to hypoxia inducible factor activity and the mitochondrial redox environment were studied. A fluorescent reporter construct was used to monitor the stabilization of hypoxia inducible factors 1α and 2α throughout chronic hypoxia. Reporter construct fluorescence intensity inversely correlated with dissolved oxygen in the medium, as expected. Additionally, the glutathione redox poise of the mitochondrial matrix in living cancer cells was monitored throughout acute hypoxia with a genetically encoded redox probe and was observed to undergo a reductive response to hypoxia. Overall, these studies validate an easy to use open-well platform suitable for studying complex cell behaviors in hypoxia.

  11. Quantitative measurement of redox potential in hypoxic cells using SERS nanosensors.

    Science.gov (United States)

    Jiang, Jing; Auchinvole, Craig; Fisher, Kate; Campbell, Colin J

    2014-10-21

    Hypoxia is considered to be a reductive disorder of cells that is caused either by a lack of oxygen or by the dysregulation of metabolic pathways and is thought to play a role in the pathology of diseases including stroke and cancer. One aspect of hypoxia that remains poorly investigated is the dysregulation of cellular redox potential and its role in controlling biological pathway activation. Since there is currently no way of quantitatively measuring the intracellular redox potential of hypoxic cells, this provided us with the motivation to develop optical nanosensors whose Surface-Enhanced Raman (SER) spectrum provides a quantitative measure of redox potential in hypoxic cells. Our nanosensors are made from organic reporter molecules that show oxidation-state-dependent changes in the Raman spectrum and are chemically adsorbed onto gold nanoshells. These nanosensors can be taken up by cells, and by collecting the SER spectrum we can calculate the localised intracellular redox potential from single hypoxic cells in a non-invasive, reversible way.

  12. Galectin-3 up-regulation in hypoxic and nutrient deprived microenvironments promotes cell survival.

    Directory of Open Access Journals (Sweden)

    Rafael Yamashita Ikemori

    Full Text Available Galectin-3 (gal-3 is a β-galactoside binding protein related to many tumoral aspects, e.g. angiogenesis, cell growth and motility and resistance to cell death. Evidence has shown its upregulation upon hypoxia, a common feature in solid tumors such as glioblastoma multiformes (GBM. This tumor presents a unique feature described as pseudopalisading cells, which accumulate large amounts of gal-3. Tumor cells far from hypoxic/nutrient deprived areas express little, if any gal-3. Here, we have shown that the hybrid glioma cell line, NG97ht, recapitulates GBM growth forming gal-3 positive pseudopalisades even when cells are grafted subcutaneously in nude mice. In vitro experiments were performed exposing these cells to conditions mimicking tumor areas that display oxygen and nutrient deprivation. Results indicated that gal-3 transcription under hypoxic conditions requires previous protein synthesis and is triggered in a HIF-1α and NF-κB dependent manner. In addition, a significant proportion of cells die only when exposed simultaneously to hypoxia and nutrient deprivation and demonstrate ROS induction. Inhibition of gal-3 expression using siRNA led to protein knockdown followed by a 1.7-2.2 fold increase in cell death. Similar results were also found in a human GBM cell line, T98G. In vivo, U87MG gal-3 knockdown cells inoculated subcutaneously in nude mice demonstrated decreased tumor growth and increased time for tumor engraftment. These results indicate that gal-3 protected cells from cell death under hypoxia and nutrient deprivation in vitro and that gal-3 is a key factor in tumor growth and engraftment in hypoxic and nutrient-deprived microenvironments. Overexpression of gal-3, thus, is part of an adaptive program leading to tumor cell survival under these stressing conditions.

  13. Fetal stress and programming of hypoxic/ischemic-sensitive phenotype in the neonatal brain: mechanisms and possible interventions.

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-08-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxic-ischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other brain disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Arginine-vasopressin marker copeptin is a sensitive plasma surrogate of hypoxic exposure

    Directory of Open Access Journals (Sweden)

    Ostergaard L

    2014-09-01

    ultimately survived. Their systemic blood pressure fell with acute (5 minutes hypoxia but was partially recovered over time. In contrast, right ventricular pressures increased with acute (5 minutes hypoxia and normalized after 16 hours. No signs of pulmonary inflammation or edema were found despite prolonged hypoxia. Whereas copeptin levels increased significantly after acute (5 minutes hypoxia and then returned to near baseline after 16 hours, mid-regional proANP levels were even further increased after 16 hours of exposure to hypoxia. Conclusion: Plasma copeptin is a sensitive marker of acute (5 minutes exposure to severe hypoxia, and subsequent regulation can indicate recovery. Copeptin levels can therefore reflect clinical and physiological changes in response to hypoxia and indicate recovery from ongoing hypoxic exposure. Keywords: vasoactive peptides, hypoxia, copeptin, atrial natriuretic peptide, acclimatization, adaptation, critical illness

  15. Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

    2011-01-01

    Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxic...... (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media....

  16. Induction of dormancy in hypoxic human papillomavirus-positive cancer cells

    OpenAIRE

    Hoppe-Seyler, Karin; Bossler, Felicitas; Lohrey, Claudia; Bulkescher, Julia; Rösl, Frank; Jansen, Lars; Mayer, Arnulf; Vaupel, Peter; Dürst, Matthias; Hoppe-Seyler, Felix

    2017-01-01

    Human papillomaviruses (HPVs) are major human carcinogens. It is widely assumed that HPV-positive tumor cells must sustain viral E6/E7 oncogene expression to continuously block the tumor-suppressive senescence response of the host cell. Consequently, E6/E7 are considered attractive therapeutic targets for immunotherapy or for functional inhibition. Here we show that hypoxic conditions, as often found in HPV-positive cancers, allow the cells to induce a dormant state in which E6/E7 is down-reg...

  17. The Antiproliferative and Colony-suppressive Activities of STAT3 Inhibitors in Human Cancer Cells Is Compromised Under Hypoxic Conditions.

    Science.gov (United States)

    Tian, Jilai; Xiao, Hui; Wu, Ruohan; Cao, Yang; Li, Chenglong; Xu, Ronald; Pierson, Christopher R; Finlay, Jonathan L; Yang, Fang; Gu, Ning; Lin, Jiayuh

    2017-02-01

    Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been indicated as a novel cancer drug target, since it plays an important role in diverse oncogenic processes including survival, cell proliferation and migration. Emerging STAT3 inhibitors have demonstrated efficacy in cancer cells and animal tumor models. It is well known that most solid tumors are characterized by hypoxia, but it is not clear if hypoxic conditions affect activity of STAT3 inhibitors. To examine this, two STAT3 inhibitors were tested to investigate their inhibitory efficacy in cancer cells grown under hypoxic conditions compared with those without hypoxia. Cell proliferation, colony formation and western blot assays were performed to examine the differences in the cell viability, proliferation and proteins in the STAT3 pathway. Under hypoxic conditions, the half-maximal inhibitory concentration values for both STAT3 inhibitors were increased compared to normoxic conditions in human pancreatic cancer, medulloblastoma and sarcoma cell lines. In addition, the ability of both STAT3 inhibitors to inhibit colony formation in pancreatic cancer, medulloblastoma and sarcoma cell lines was reduced under hypoxic conditions when compared to cells under normoxic conditions. Furthermore, there was an increase in phosphorylated STAT3 levels in cancer cells under hypoxic conditions, suggesting this may be one of the mechanisms of resistance. In summary, the results presented here provide a novel finding of STAT3 inhibitor activity under hypoxic conditions and indicate that under such low oxygen conditions, the anticancer efficacy of STAT3 inhibitors was indeed hampered. These results highlight the need to develop new therapeutic strategies to overcome the resistance of cancer cells to STAT3 inhibitors under hypoxic conditions. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  18. Hypoxic preconditioning of human cardiosphere-derived cell sheets enhances cellular functions via activation of the PI3K/Akt/mTOR/HIF-1α pathway.

    Science.gov (United States)

    Tanaka, Yuya; Hosoyama, Tohru; Mikamo, Akihito; Kurazumi, Hiroshi; Nishimoto, Arata; Ueno, Koji; Shirasawa, Bungo; Hamano, Kimikazu

    2017-01-01

    Cell sheet technology is a promising therapeutic strategy for the treatment of ischemic diseases such as myocardial infarction. We recently developed a novel protocol, termed "hypoxic preconditioning," capable of augmenting the therapeutic efficacy of cell sheets. Following this protocol, the pro-angiogenic and anti-fibrotic activity of cell sheets were enhanced by brief incubation of cell sheets under hypoxic culture conditions. However, the precise molecular mechanism underlying the hypoxic preconditioning of cell sheets is unclear. In the present study, we examined signal transducers in cell sheets to identify those responsive to hypoxic preconditioning, using cardiosphere-derived cell (CDC) sheets. We initially tested whether sheet-like structures were suitable for hypoxic preconditioning by comparing them with individual cells. Hypoxic preconditioning was more effective in sheeted cells than in individual cells. Expression of hypoxia inducible factor-1α (HIF-1α) and mammalian target of rapamycin (mTOR) were induced upon hypoxic preconditioning of cell sheets, as was the phosphoinositide 3-kinase (PI3K)/Akt pathway. In addition, hypoxic preconditioning increased phosphorylation of epidermal growth factor receptor (EGFR) and heat shock protein 60 (HSP60) in CDC sheets. Our findings provide novel insights into the utility of hypoxic preconditioning in cell sheet-based technologies for the treatment of ischemic diseases.

  19. Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells prevents long-lasting learning impairment following neonatal hypoxic-ischemic brain insult in rats.

    Science.gov (United States)

    Katsuragi, Shinji; Ikeda, Tomoaki; Date, Isao; Shingo, Tetsuro; Yasuhara, Takao; Mishima, Kenichi; Aoo, Naoya; Harada, Kazuhiko; Egashira, Nobuaki; Iwasaki, Katsunori; Fujiwara, Michihiro; Ikenoue, Tsuyomu

    2005-04-01

    Implantation of encapsulated glial cell line-derived neurotrophic factor-secreting cells into brain parenchyma reduces histological brain damage following hypoxic-ischemic stress in neonatal rats. We examined the effect of glial cell line-derived neurotrophic factors on long-term learning and memory impairment and morphological changes up to 18 weeks after hypoxic-ischemic stress in neonatal rats. Baby hamster kidney cells were transfected with expression vector either including (glial cell line-derived neurotrophic factor-hypoxic-ischemic group; n = 10) or not including (control-hypoxic-ischemic group; n = 8) human glial cell line-derived neurotrophic factor cDNA, encapsulated in semipermeable hollow fibers, and implanted into the left brain parenchyma of 7-day-old Wistar rats. Two days after implantation the rats received hypoxic-ischemic stress, and their behavior was then examined in several learning tasks: the 8-arm radial maze, choice reaction time, and water maze tasks, which examine short-term working memory, attention process, and long-term reference memory, respectively. The rats were killed 18 weeks after the hypoxic-ischemic insult for evaluation of brain damage. Two additional control groups were used: the control group (n = 15), which underwent no treatment, and the glial cell line-derived neurotrophic factor group (n = 6), which underwent implantation of the glial cell line-derived neurotrophic factor capsule but did not undergo hypoxic-ischemic stress. The decrease in the size of the cerebral hemisphere was significantly less in the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, compared with the control-hypoxic-ischemic group, and improved performance was observed in all three tasks for the glial cell line-derived neurotrophic factor-hypoxic-ischemic group: for the control-hypoxic-ischemic group versus the glial cell line-derived neurotrophic factor-hypoxic-ischemic group, respectively, in the 8-arm radial maze test, average

  20. Fetal Stress and Programming of Hypoxic/Ischemic-Sensitive Phenotype in the Neonatal Brain: Mechanisms and Possible Interventions

    Science.gov (United States)

    Li, Yong; Gonzalez, Pablo; Zhang, Lubo

    2012-01-01

    Growing evidence of epidemiological, clinical and experimental studies has clearly shown a close link between adverse in utero environment and the increased risk of neurological, psychological and psychiatric disorders in later life. Fetal stresses, such as hypoxia, malnutrition, and fetal exposure to nicotine, alcohol, cocaine and glucocorticoids may directly or indirectly act at cellular and molecular levels to alter the brain development and result in programming of heightened brain vulnerability to hypoxic-ischemic encephalopathy and the development of neurological diseases in the postnatal life. The underlying mechanisms are not well understood. However, glucocorticoids may play a crucial role in epigenetic programming of neurological disorders of fetal origins. This review summarizes the recent studies about the effects of fetal stress on the abnormal brain development, focusing on the cellular, molecular and epigenetic mechanisms and highlighting the central effects of glucocorticoids on programming of hypoxicischemic-sensitive phenotype in the neonatal brain, which may enhance the understanding of brain pathophysiology resulting from fetal stress and help explore potential targets of timely diagnosis, prevention and intervention in neonatal hypoxic-ischemic encephalopathy and other for brain disorders. PMID:22627492

  1. Contribution of oxygen-sensitive neurons of the rostral ventrolateral medulla to hypoxic cerebral vasodilatation in the rat

    Science.gov (United States)

    Golanov, E. V.; Reis, D. J.

    1996-01-01

    1. We sought to determine whether hypoxic stimulation of neurons of the rostral ventrolateral reticular nucleus (RVL) would elevate regional cerebral blood flow (rCBF) in anaesthetized paralysed rats. 2. Microinjection of sodium cyanide (NaCN; 150-450 pmol) into the RVL rapidly (within 1-2 s), transiently, dose-dependently and site-specifically elevated rCBF1 measured by laser Doppler flowmetry, by 61.3 +/- 22.1% (P cerebral cortex (by 172.6 +/- 15.6%; P cerebral glucose utilization (rCGU), measured autoradiographically with 14C-2-deoxyglucose (Sokoloff method), was increased in proportion to rCBF in the mid-line thalamus (165.6 +/- 17.8%, P cerebral cortex by hypoxaemia is in large measure neurogenic, mediated trans-synaptically over intrinsic neuronal pathways, and initiated by excitation of oxygen sensitive neurons in the RVL.

  2. Radiosensitization of normoxic and hypoxic h1339 lung tumor cells by heat shock protein 90 inhibition is independent of hypoxia inducible factor-1α.

    Directory of Open Access Journals (Sweden)

    Daniela Schilling

    Full Text Available Ionizing irradiation is a commonly accepted treatment modality for lung cancer patients. However, the clinical outcome is hampered by normal tissue toxicity and tumor hypoxia. Since tumors often have higher levels of active heat shock protein 90 (Hsp90 than normal tissues, targeting of Hsp90 might provide a promising strategy to sensitize tumors towards irradiation. Hsp90 client proteins include oncogenic signaling proteins, cell cycle activators, growth factor receptors and hypoxia inducible factor-1α (HIF-1α. Overexpression of HIF-1α is assumed to promote malignant transformation and tumor progression and thus might reduce the accessibility to radiotherapy.Herein, we describe the effects of the novel Hsp90 inhibitor NVP-AUY922 and 17-allylamino-17-demethoxygeldanamycin (17-AAG, as a control, on HIF-1α levels and radiosensitivity of lung carcinoma cells under normoxic and hypoxic conditions. NVP-AUY922 exhibited a similar biological activity to that of 17-AAG, but at only 1/10 of the dose. As expected, both inhibitors reduced basal and hypoxia-induced HIF-1α levels in EPLC-272H lung carcinoma cells. However, despite a down-regulation of HIF-1α upon Hsp90 inhibition, sensitivity towards irradiation remained unaltered in EPLC-272H cells under normoxic and hypoxic conditions. In contrast, treatment of H1339 lung carcinoma cells with NVP-AUY922 and 17-AAG resulted in a significant up-regulation of their initially high HIF-1α levels and a concomitant increase in radiosensitivity.In summary, our data show a HIF-1α-independent radiosensitization of normoxic and hypoxic H1339 lung cancer cells by Hsp90 inhibition.

  3. Relaxing the formation of hypoxic bottom water with sediment microbial fuel cells.

    Science.gov (United States)

    Touch, Narong; Hibino, Tadashi; Morimoto, Yuki; Kinjo, Nobutaka

    2017-12-01

    The method of improving bottom water environment using industrial wastes to suppress diffusion substances from bottom sediment has recently captured the attention of many researchers. In this study, wastewater discharge-derived sediment was used to examine an alternative approach involving the use of sediment microbial fuel cells (SMFCs) in relaxing the formation of hypoxic bottom water, and removing reduced substances from sediment. Concentrations of dissolved oxygen (DO) and other ions were measured in overlying water and sediment pore water with and without the application of SMFCs. The results suggest that SMFCs can markedly reduce hydrogen sulfide and manganese ion concentrations in overlying water, and decrease the depletions of redox potential and DO concentration. In addition, SMFCs can dissolve ferric compounds in the sediment and thereby release the ferric ion available to fix phosphate in the sediment. Our results indicate that SMFCs can be used as an alternative method to relax the formation of hypoxic bottom water and to remove reduced substances from the sediment, thus improving the quality of both water and sediment environments.

  4. Important role of PLC-γ1 in hypoxic increase in intracellular calcium in pulmonary arterial smooth muscle cells.

    Science.gov (United States)

    Yadav, Vishal R; Song, Tengyao; Joseph, Leroy; Mei, Lin; Zheng, Yun-Min; Wang, Yong-Xiao

    2013-02-01

    An increase in intracellular calcium concentration ([Ca(2+)](i)) in pulmonary arterial smooth muscle cells (PASMCs) induces hypoxic cellular responses in the lungs; however, the underlying molecular mechanisms remain incompletely understood. We report, for the first time, that acute hypoxia significantly enhances phospholipase C (PLC) activity in mouse resistance pulmonary arteries (PAs), but not in mesenteric arteries. Western blot analysis and immunofluorescence staining reveal the expression of PLC-γ1 protein in PAs and PASMCs, respectively. The activity of PLC-γ1 is also augmented in PASMCs following hypoxia. Lentiviral shRNA-mediated gene knockdown of mitochondrial complex III Rieske iron-sulfur protein (RISP) to inhibit reactive oxygen species (ROS) production prevents hypoxia from increasing PLC-γ1 activity in PASMCs. Myxothiazol, a mitochondrial complex III inhibitor, reduces the hypoxic response as well. The PLC inhibitor U73122, but not its inactive analog U73433, attenuates the hypoxic vasoconstriction in PAs and hypoxic increase in [Ca(2+)](i) in PASMCs. PLC-γ1 knockdown suppresses its protein expression and the hypoxic increase in [Ca(2+)](i). Hypoxia remarkably increases inositol 1,4,5-trisphosphate (IP(3)) production, which is blocked by U73122. The IP(3) receptor (IP(3)R) antagonist 2-aminoethoxydiphenyl borate (2-APB) or xestospongin-C inhibits the hypoxic increase in [Ca(2+)](i). PLC-γ1 knockdown or U73122 reduces H(2)O(2)-induced increase in [Ca(2+)](i) in PASMCs and contraction in PAs. 2-APB and xestospongin-C produce similar inhibitory effects. In conclusion, our findings provide novel evidence that hypoxia activates PLC-γ1 by increasing RISP-dependent mitochondrial ROS production in the complex III, which causes IP(3) production, IP(3)R opening, and Ca(2+) release, playing an important role in hypoxic Ca(2+) and contractile responses in PASMCs.

  5. Oxygen tension-independent protection against hypoxic cell killing in rat liver by low sodium

    Directory of Open Access Journals (Sweden)

    Andrea Ferrigno

    2017-05-01

    Full Text Available The role of Na+ in hypoxic injury was evaluated by a time-course analysis of damage in isolated livers perfused with N2-saturated buffer containing standard (143 mM or low (25 mM Na+ levels. Trypan blue uptake was used to detect non-viable cells. Under hypoxia with standard-Na+, trypan blue uptake began at the border between pericentral areas and periportal regions and increased in the latter zone; using a low-Na+ buffer, no trypan blue zonation occurred but a homogenous distribution of dye was found associated with sinusoidal endothelial cell (SEC staining. A decrease in hyaluronic acid (HA uptake, index of SEC damage, was observed using a low-Na+ buffer. A time dependent injury was confirmed by an increase in LDH and TBARS levels with standard-Na+ buffer. Using low-Na+ buffer, SEC susceptibility appears elevated under hypoxia and hepatocytes was protected, in an oxygen independent manner.

  6. Signal transduction mechanisms and nitric oxide in hypoxic and ischemic human cardiac ventricular cell.

    Science.gov (United States)

    Corbucci, G C; Ricchi, A; Lettieri, B; Mastronardi, P

    2001-11-01

    Nitric oxide (NO) plays a well-known role in regulating endocellular adaptive changes to acute hypoxia and ischemia. The reversible inhibition of complex IV of the mitochondrial respiratory chain fulfils a cytoprotective function, whereas the progressive inhibition of complex I and II reveals the onset of irreversible oxidative damage due to persistent NO production in response to prolonged hypoxia and/or ischemia. In hypoxic or ischemic human myocardial cells, death may be caused by apoptosis or necrosis following the activation of the biomolecular signal transduction mechanisms. The activation of MAPK (mitogen-activated protein kinase) followed by ERK (extracellular regulated kinase) and p21waf is necessary in this respect. The myocardial cell is well known for its postmitotic nature and through their activation these kinases aim to repair DNA damaged by oxidative stress in order to guarantee the survival of the cell itself. A direct correlation has been found between the activation of these kinases and NO production. It was decided to carry out this study in hypoxic and ischemic human heart ventricular tissue in order to confirm this connection. In 10 patients undergoing cardiac valvular replacement, ventricular samples were collected before aortic clamping, after 15 min of ischemia and after 60 minutes during which the patients received doses of hematic cardioplegic solution at regular intervals. The results show a rapid increase in NO production in response to ischemia followed by a tendency for levels of this element to fall. MAPK, ERK and p21waf activation was parallel to No production, irrespective of the repeated administration of hematic cardioplegic solution. The heart tissue examined 60 minutes after aortic clamping came from a ventricular area subject to preconditioning mechanisms. In view of this, the data obtained must be seen in terms of the close correlation between the mitochondrial action played by NO and the contemporary and consequent

  7. Prolyl hydroxylase PHD3 enhances the hypoxic survival and G1 to S transition of carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Heidi Högel

    Full Text Available Hypoxia restricts cell proliferation and cell cycle progression at the G1/S interface but at least a subpopulation of carcinoma cells can escape the restriction. In carcinoma hypoxia may in fact select for cells with enhanced hypoxic survival and increased aggressiveness. The cellular oxygen sensors HIF proline hydroxylases (PHDs adapt the cellular functions to lowered environmental oxygen tension. PHD3 isoform has shown the strongest hypoxic upregulation among the family members. We detected a strong PHD3 mRNA expression in tumors of head and neck squamous cell carcinoma (HNSCC. The PHD3 expression associated with expression of hypoxic marker gene. Using siRNA in cell lines derived from HNSCC we show that specific inhibition of PHD3 expression in carcinoma cells caused reduced cell survival in hypoxia. The loss of PHD3, but not that of PHD2, led to marked cell number reduction. Although caspase-3 was activated at early hypoxia no induction of apoptosis was detected. However, hypoxic PHD3 inhibition caused a block in cell cycle progression. Cell population in G1 phase was increased and the population in S phase reduced demonstrating a block in G1 to S transition under PHD3 inhibition. In line with this, the level of hyperphosphorylated retinoblastoma protein Rb was reduced by PHD3 knock-down in hypoxia. PHD3 loss led to increase in cyclin-dependent kinase inhibitor p27 expression but not that of p21 or p16. The data demonstrated that increased PHD3 expression under hypoxia enhances cell cycle progression and survival of carcinoma cells.

  8. DNA damage in wounded, hypoxic and acidotic human skin fibroblast cell cultures after low laser irradiation

    Science.gov (United States)

    Hawkins Evans, D.; Mbene, A.; Zungu, I.; Houreld, N.; Abrahamse, H.

    2009-02-01

    Phototherapy has become more popular and widely used in the treatment of a variety of medical conditions. To ensure sound results as evidence of its effectiveness, well designed experiments must be conducted when determining the effect of phototherapy. Cell culture models such as hypoxic, acidotic and wounded cell cultures simulating different disease conditions including ischemic heart disease, diabetes and wound healing were used to determine the effect of laser irradiation on the genetic integrity of the cell. Even though phototherapy has been found to be beneficial in a wide spectrum of conditions, it has been shown to induce DNA damage. However, this damage appears to be repairable. The risk lies in the fact that phototherapy may help the medical condition initially but damage DNA at the same time leaving undetected damage that may result in late onset, more severe, induced medical conditions including cancer. Human skin fibroblasts were cultured and used to induce a wound (by the central scratch model), hypoxic (by incubation in an anaerobic jar, 95% N2 and 5% O2) and acidotic (reducing the pH of the media to 6.7) conditions. Different models were irradiated using a Helium-Neon (632.8 nm) laser with a power density of 2.07 mW/cm2 and a fluence of 5 J/cm2 or 16 J/cm2. The effect of the irradiation was determined using the Comet assay 1 and 24 h after irradiation. In addition, the Comet assay was performed with the addition of formamidopyrimidine glycosylase (FPG) obviating strand brakes in oxidized bases at a high fluence of 16 J/cm2. A significant increase in DNA damage was seen in all three injured models at both 1 and 24 h post-irradiation when compared to the normal un-injured cells. However, when compared to non-irradiated controls the acidotic model showed a significant decrease in DNA damage 24 h after irradiation indicating the possible induction of cellular DNA repair mechanisms. When wounded cells were irradiated with higher fluences of 16 J/cm2

  9. Dye Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Di Wei

    2010-03-01

    Full Text Available Dye sensitized solar cell (DSSC is the only solar cell that can offer both the flexibility and transparency. Its efficiency is comparable to amorphous silicon solar cells but with a much lower cost. This review not only covers the fundamentals of DSSC but also the related cutting-edge research and its development for industrial applications. Most recent research topics on DSSC, for example, applications of nanostructured TiO2, ZnO electrodes, ionic liquid electrolytes, carbon nanotubes, graphene and solid state DSSC have all been included and discussed.

  10. HIF1α is a regulator of hematopoietic progenitor and stem cell development in hypoxic sites of the mouse embryo

    Science.gov (United States)

    Imanirad, Parisa; Kartalaei, Parham Solaimani; Crisan, Mihaela; Vink, Chris; Yamada-Inagawa, Tomoko; de Pater, Emma; Kurek, Dorota; Kaimakis, Polynikis; van der Linden, Reiner; Speck, Nancy; Dzierzak, Elaine

    2014-01-01

    Hypoxia affects many physiologic processes during early stages of mammalian ontogeny, particularly placental and vascular development. In the adult, the hypoxic bone marrow microenvironment plays a role in regulating hematopoietic stem cell (HSC) function. HSCs are generated from the major vasculature of the embryo, but whether the hypoxic response affects the generation of these HSCs is as yet unknown. Here we examined whether Hypoxia Inducible Factor1-alpha (HIF1α), a key modulator of the response to hypoxia, is essential for HSC development. We found hypoxic cells in embryonic tissues that generate and expand hematopoietic cells (aorta, placenta and fetal liver), and specifically aortic endothelial and hematopoietic cluster cells. A Cre/loxP conditional knockout (cKO) approach was taken to delete HIF1α in Vascular Endothelial-Cadherin expressing endothelial cells, the precursors to definitive hematopoietic cells. Functional assays show that HSC and hematopoietic progenitor cells (HPC) are significantly reduced in cKO aorta and placenta. Moreover, decreases in phenotypic aortic hematopoietic cluster cells in cKO embryos indicate that HIF1α is necessary for generation and/or expansion of HPC and HSCs. cKO adult BM HSCs are also affected under transplantation conditions. Thus, HIF1α is a regulator of HSC generation and function beginning at the earliest embryonic stages. PMID:24141110

  11. HIF1α is a regulator of hematopoietic progenitor and stem cell development in hypoxic sites of the mouse embryo

    Directory of Open Access Journals (Sweden)

    Parisa Imanirad

    2014-01-01

    Full Text Available Hypoxia affects many physiologic processes during early stages of mammalian ontogeny, particularly placental and vascular development. In the adult, the hypoxic bone marrow microenvironment plays a role in regulating hematopoietic stem cell (HSC function. HSCs are generated from the major vasculature of the embryo, but whether the hypoxic response affects the generation of these HSCs is as yet unknown. Here we examined whether Hypoxia Inducible Factor1-alpha (HIF1α, a key modulator of the response to hypoxia, is essential for HSC development. We found hypoxic cells in embryonic tissues that generate and expand hematopoietic cells (aorta, placenta and fetal liver, and specifically aortic endothelial and hematopoietic cluster cells. A Cre/loxP conditional knockout (cKO approach was taken to delete HIF1α in Vascular Endothelial-Cadherin expressing endothelial cells, the precursors to definitive hematopoietic cells. Functional assays show that HSC and hematopoietic progenitor cells (HPCs are significantly reduced in cKO aorta and placenta. Moreover, decreases in phenotypic aortic hematopoietic cluster cells in cKO embryos indicate that HIF1α is necessary for generation and/or expansion of HPCs and HSCs. cKO adult BM HSCs are also affected under transplantation conditions. Thus, HIF1α is a regulator of HSC generation and function beginning at the earliest embryonic stages.

  12. A flavonoid chrysin suppresses hypoxic survival and metastatic growth of mouse breast cancer cells.

    Science.gov (United States)

    Lirdprapamongkol, Kriengsak; Sakurai, Hiroaki; Abdelhamed, Sherif; Yokoyama, Satoru; Maruyama, Takeyuki; Athikomkulchai, Sirivan; Viriyaroj, Amornrat; Awale, Suresh; Yagita, Hideo; Ruchirawat, Somsak; Svasti, Jisnuson; Saiki, Ikuo

    2013-11-01

    Tumor hypoxia commonly occurs in solid tumors, and correlates with metastasis. Current cancer therapies are inefficient in curing metastatic disease. Herein, we examined effect of Thai propolis extract and its major constituent, chrysin, on hypoxic survival of 4T1 mouse breast cancer cells in vitro, and investigated its underlying mechanism. In vivo effect of chrysin on metastatic progression of cancer cells was studied, both as a single agent and in combination with another antimetastatic agent, agonistic monoclonal antibody targeting the DR5 TRAIL receptor (DR5 mAb). Thai propolis extract and chrysin decreased survival of 4T1 cells after exposure to hypoxia (1% O2), for 2 days. Immunoblot analysis revealed that chrysin inhibited hypoxia-induced STAT3 phosphorylation without affecting HIF-1α protein level. Chrysin also abrogated hypoxia-induced VEGF gene expression as determined by qRT-PCR. The in vivo effect of chrysin was determined in a spontaneous metastasis mouse model of breast cancer, either alone or in combination with DR5 mAb. Daily oral administration of chrysin in Balb/c mice implanted with 4T1 cells significantly suppressed growth of lung metastatic colonies. Moreover, antimetastatic activity of DR5 mAb was enhanced when given in combination with chrysin. We demonstrate that chrysin has potential in controlling metastatic progression.

  13. Prolonged hypoxic culture and trypsinization increase the pro-angiogenic potential of human adipose tissue-derived stem cells

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Grøndahl; Frøbert, Ole; Pilgaard, Linda

    2011-01-01

    Transplantation of mesenchymal stromal cells (MSC), including adipose tissue-derived stem cells (ASC), is a promising option in the treatment of vascular disease. Short-term hypoxic culture of MSC augments secretion of anti-apoptotic and angiogenic cytokines. We hypothesized that prolonged hypoxi...... (1% and 5% oxygen) culture and trypsinization would augment ASC expression of anti-apoptotic and angiogenic cytokines and increase the angiogenic potential of ASC-conditioned media....

  14. Effects of YC-1 on hypoxia-inducible factor 1 alpha in hypoxic human bladder transitional carcinoma cell line T24 cells.

    Science.gov (United States)

    Li, Yangle; Zhao, Xiaokun; Tang, Huiting; Zhong, Zhaohui; Zhang, Lei; Xu, Ran; Li, Songchao; Wang, Yi

    2012-01-01

    It was the aim of this study to explore the effects of 3-(5'-hydroxymethyl-2'-furyl)-l-benzyl indazole (YC-1) on transcription activity, cell proliferation and apoptosis of hypoxic human bladder transitional carcinoma cells (BTCC), mediated by hypoxia-inducible factor 1α (HIF-1α). BTCC cell line T24 cells were incubated under normoxic or hypoxic conditions, adding different doses of YC-1. The protein expression of HIF-1α and HIF-1α-mediated genes was detected by Western blotting. RT-PCR was used to detect HIF-1α mRNA expression. Cell proliferation, apoptosis and migration activity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell migration assay. The cells were pretreated by two ERK/p38 MAPK pathway-specific inhibitors, PD98059 or SB203580, and then incubated with YC-1 treatment under hypoxic condition. HIF-1α protein expression was detected by Western blotting. Hypoxic T24 cells expressed a higher level of HIF-1α, vascular endothelial growth factor, matrix metalloproteinases-2, B-cell lymphoma/leukemia-2 protein and HIF-1α mRNA compared with normoxic controls, in which the above-mentioned expression was downregulated by YC-1 in a dose-dependent manner. Cell proliferation and migration activity were inhibited while apoptosis was induced by YC-1 under hypoxic condition. Moreover, YC-1-downregulated HIF-1α expression was reversed by PD98059 and SB203580, respectively. YC-1 inhibits HIF-1α and HIF-1α-mediated gene expression, cell proliferation and migration activity and induces apoptosis in hypoxic BTCC. The ERK/p38 MAPK pathway may be involved in YC-1-mediated inhibition of HIF-1α. Copyright © 2011 S. Karger AG, Basel.

  15. Transcriptional signature of human adipose tissue-derived stem cells (hASCs) preconditioned for chondrogenesis in hypoxic conditions

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    Pilgaard, L.; Lund, P.; Duroux, M. [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark); Lockstone, H.; Taylor, J. [Bioinformatics and Statistical Genetics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom); Emmersen, J.; Fink, T. [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark); Ragoussis, J. [Genomics, Wellcome Trust Centre for Human Genetics, Oxford University, Roosevelt Drive, Oxford, OX3 7BN (United Kingdom); Zachar, V., E-mail: vlaz@hst.aau.dk [Laboratory for Stem Cell Research, Aalborg University, Fredrik Bajers Vej 3B, 9220 Aalborg (Denmark)

    2009-07-01

    Hypoxia is an important factor involved in the control of stem cells. To obtain a better insight into the phenotypical changes brought about by hypoxic preconditioning prior to chondrogenic differentiation; we have investigated growth, colony-forming and chondrogenic capacity, and global transcriptional responses of six adipose tissue-derived stem cell lines expanded at oxygen concentrations ranging from ambient to 1%. The assessment of cell proliferation and colony-forming potential revealed that the hypoxic conditions corresponding to 1% oxygen played a major role. The chondrogenic inducibility, examined by high-density pellet model, however, did not improve on hypoxic preconditioning. While the microarray analysis revealed a distinctive inter-donor variability, the exposure to 1% hypoxia superseded the biological variability and produced a specific expression profile with 2581 significantly regulated genes and substantial functional enrichment in the pathways of cell proliferation and apoptosis. Additionally, exposure to 1% oxygen resulted in upregulation of factors related to angiogenesis and cell growth. In particular, leptin (LEP), the key regulator of body weight and food intake was found to be highly upregulated. In conclusion, the results of this investigation demonstrate the significance of donor demographics and the importance of further studies into the use of regulated oxygen tension as a tool for preparation of ASCs in order to exploit their full potential.

  16. HIF1α represses cell stress pathways to allow proliferation of hypoxic fetal cardiomyocytes

    Science.gov (United States)

    Guimarães-Camboa, Nuno; Stowe, Jennifer; Aneas, Ivy; Sakabe, Noboru; Cattaneo, Paola; Henderson, Lindsay; Kilberg, Michael S.; Johnson, Randall S.; Chen, Ju; McCulloch, Andrew D.; Nobrega, Marcelo A.; Evans, Sylvia M.; Zambon, Alexander C.

    2015-01-01

    Summary Transcriptional mediators of cell stress pathways, including HIF1α, ATF4, and p53, are key to normal development and play critical roles in disease, including ischemia and cancer. Despite their importance, mechanisms by which pathways mediated by these transcription factors interact with each other are not fully understood. In addressing the controversial role of HIF1α in cardiomyocytes (CMs) during heart development, we have discovered a mid-gestational requirement for HIF1α for proliferation of hypoxic CMs, involving metabolic switching and a complex interplay between HIF1α, ATF4 and p53. Loss of HIF1α resulted in activation of ATF4 and p53, the latter inhibiting CM proliferation. Bioinformatic and biochemical analyses revealed unexpected mechanisms by which HIF1α intersects with ATF4 and p53 pathways. Our results highlight previously undescribed roles of HIF1α and interactions between major cell stress pathways that could be targeted to enhance proliferation of CMs in ischemia, and may have relevance to other diseases, including cancer. PMID:26028220

  17. Inhibition of IRE1 modifies hypoxic regulation of G6PD, GPI, TKT, TALDO1, PGLS and RPIA genes expression in U87 glioma cells

    Directory of Open Access Journals (Sweden)

    O. H. Minchenko

    2017-02-01

    Full Text Available We have studied the effect of hypoxia on the expression level of mRNA of the basic enzymes of pentose-phosphate cycle (G6PD, TKT, TALDO1, PGLS and RPIA and glucose-6-phosphate isomerase (GPI in U87 glioma cells in relation to inhibition of IRE1 (inositol requiring enzyme 1. It was shown that hypoxia leads to up-regulation of the expression of GPI and PGLS genes and to down-regulation of TALDO1 and RPIA genes in control glioma cells. Changes for GPI gene were more significant than for other genes. At the same time, inhibition of IRE1 modified the effect of hypoxia on the expression of all studied genes. In particular, it increased sensitivity to hypoxia of G6PD and TKT genes expression and suppressed the effect of hypoxia on the expression of GPI and RPIA genes. Additionally, inhibition of IRE1 eliminated hypoxic regulation of PGLS gene and did not change significantly effect of hypoxia on the expression of TALDO1 gene in glioma cells. Present study demonstrated that hypoxia, which often contributes to tumor growth, affects the expression of most studied genes and inhibition of IRE1 modified the hypoxic regulation of pentose-phosphate cycle gene expressions in a gene specific manner and thus possibly contributes to slower glioma growth, but several aspects of this regulation warrant further investigation.

  18. Hypoxic treatment inhibits insulin-induced chondrogenesis of ATDC5 cells despite upregulation of DEC1

    DEFF Research Database (Denmark)

    Chen, Li; Fink, Trine; Ebbesen, Peter

    2006-01-01

    Chondrogenesis occurs in vivo in a hypoxic environment, in which the hypoxia inducible factor 1, HIF-1, plays a regulatory role, possibly mediated through the transcription factor DEC1. We have analyzed the effect of hypoxia (1% oxygen) alone and in combination with insulin on the chondrogenic di...... blocked hypertrophic differentiation. Paradoxically, the transcriptional activation of DEC1 was invariably enhanced by the hypoxic exposure....

  19. Transplantation of hypoxic preconditioned neural stem cells benefits functional recovery via enhancing neurotrophic secretion after spinal cord injury in rats.

    Science.gov (United States)

    Fan, Wei-Li; Liu, Peng; Wang, Guan; Pu, Jung-Ang; Xue, Xin; Zhao, Jian-Hua

    2017-09-08

    Spinal cord injury (SCI) is a debilitating, costly, and common pathological condition that affects the function of central nervous system (CNS). To date, there are few promising therapeutic strategies available for SCI. To look for a suitable therapeutic strategy, we have developed a sublethal hypoxic preconditioning procedure using Fluorescence-activated cell sorting (FACS) analysis, LDH releasing and cell viability assays in vitro. Meanwhile, we have examined the benefits of neural stem cells (NSCs) transplantation prior to hypoxic preconditioning on functional recovery and potential mechanism via MRI screening, H&E and Nissl staining, immunofluorescence staining and Elisa assays. Our data showed that transplantation of hypoxic prconditioned NSCs could enhance neuronal survival, especially 5-TH(+) and ChAT(+) neurons, in the injured spinal cord to reinforce functional benefits. The hypoxia exposure upregulated HIF-1α, neurotrophic and growth factors including neurotrophin-3 (NT-3), glial cell-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) in vitro and in vivo. Furthermore, functional recovery, including locomotor and hypersensitivities to mechanical and thermal stimulation assessed via behavioral and sensory tests, improved significantly in rats with engraftment of NSCs after hypoxia exposure from day 14 post-SCI, compared with the control and N-NSCs groups. In short, the approach employed in this study could result in functional recovery via upregulating neurotrophic and growth factors, which implies that hypoxic preconditioning strategy could serve as an effective and feasible strategy for cell-based therapy in the treatment of SCI in rats. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  20. Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction.

    Science.gov (United States)

    Liu, Yihua; Yang, Xiaoxi; Maureira, Pablo; Falanga, Aude; Marie, Vanessa; Gauchotte, Guillaume; Poussier, Sylvain; Groubatch, Frederique; Marie, Pierre-Yves; Tran, Nguyen

    2017-01-01

    The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs). This study sought to address (i) the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii) the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI) in rats. rat BMSCs were harvested and cultured in normoxic (21% O2, n=27) or hypoxic conditions (5% O2, n=27) until Passage 4 (P4). Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6) or hypoxia (n=6) were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography (PET) imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization. Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility. Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting angiogenesis. © 2017 The Author(s). Published by S. Karger AG

  1. Permanently Hypoxic Cell Culture Yields Rat Bone Marrow Mesenchymal Cells with Higher Therapeutic Potential in the Treatment of Chronic Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Yihua Liu

    2017-11-01

    Full Text Available Background: The mismatch between traditional in vitro cell culture conditions and targeted chronic hypoxic myocardial tissue could potentially hamper the therapeutic effects of implanted bone marrow mesenchymal stem cells (BMSCs. This study sought to address (i the extent of change to BMSC biological characteristics in different in vitro culture conditions and (ii the effectiveness of permanent hypoxic culture for cell therapy in treating chronic myocardial infarction (MI in rats. Methods: rat BMSCs were harvested and cultured in normoxic (21% O2, n=27 or hypoxic conditions (5% O2, n=27 until Passage 4 (P4. Cell growth tests, flow cytometry, and Bio-Plex assays were conducted to explore variations in the cell proliferation, phenotype, and cytokine expression, respectively. In the in vivo set-up, P3-BMSCs cultured in normoxia (n=6 or hypoxia (n=6 were intramyocardially injected into rat hearts that had previously experienced 1-month-old MI. The impact of cell therapy on cardiac segmental viability and hemodynamic performance was assessed 1 month later by 2-Deoxy-2[18F]fluoro-D-glucose (18F-FDG positron emission tomography (PET imaging and pressure-volume catheter, respectively. Additional histomorphological examinations were conducted to evaluate inflammation, fibrosis, and neovascularization. Results: Hypoxic preconditioning significantly enhanced rat BMSC clonogenic potential and proliferation without altering the multipotency. Different profiles of inflammatory, fibrotic, and angiogenic cytokine secretion were also documented, with a marked correlation observed between in vitro and in vivo proangiogenic cytokine expression and tissue neovessels. Hypoxic-preconditioned cells presented a beneficial effect on the myocardial viability of infarct segments and intrinsic contractility. Conclusion: Hypoxic-preconditioned BMSCs were able to benefit myocardial perfusion and contractility, probably by modulating the inflammation and promoting

  2. A Hybrid Nanomaterial for the Controlled Generation of Free Radicals and Oxidative Destruction of Hypoxic Cancer Cells.

    Science.gov (United States)

    Shen, Song; Zhu, Chunlei; Huo, Da; Yang, Miaoxin; Xue, Jiajia; Xia, Younan

    2017-07-17

    Anticancer modalities based on oxygen free radicals, including photodynamic therapy and radiotherapy, have emerged as promising treatments in the clinic. However, the hypoxic environment in tumor tissue prevents the formation of oxygen free radicals. Here we introduce a novel strategy that employs oxygen-independent free radicals generated from a polymerization initiator for eradicating cancer cells. The initiator is mixed with a phase-change material and loaded into the cavities of gold nanocages. Upon irradiation by a near-infrared laser, the phase-change material is melted due to the photothermal effect of gold nanocages, leading to the release and decomposition of the loaded initiator to generate free radicals. The free radicals produced in this way are highly effective in inducing apoptosis in hypoxic cancer cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The role of heat shock protein (HSP as inhibitor apoptosis in hypoxic conditions of bone marrow stem cell culture

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    Sri Wigati Mardi Mulyani

    2014-03-01

    Full Text Available Background: The concept of stem cell therapy is one of the new hope as a medical therapy on salivary gland defect. However, the lack of viability of the transplanted stem cells survival rate led to the decrease of effectiveness of stem cell therapy. The underlying assumption in the decrease of viability and function of stem cells is an increase of apoptosis incidence. It suggests that the microenvironment in the area of damaged tissues is not conducive to support stem cell viability. One of the microenvironment is the hypoxia condition. Several scientific journals revealed that the administration of hypoxic cell culture can result in stress cells but on the other hand the stress condition of the cells also stimulates heat shock protein 27 (HSP 27 as antiapoptosis through inhibition of caspase 9. Purpose: The purpose of this study was to examine the role of heat shock protein 27 as inhibitor apoptosis in hypoxic conditions of bone marrow stem cell culture. Methods: Stem cell culture was performed in hypoxic conditions (O2 1% and measured the resistance to apoptosis through HSP 27 and caspase 9 expression of bone marrow mesenchymal stem cells by using immunoflorecence and real time PCR. Results: The result of study showed that preconditioning hypoxia could inhibit apoptosis through increasing HSP 27 and decreasing level of caspase 9. Conclusion: The study suggested that hypoxic precondition could reduce apoptosis by increasing amount of heat shock protein 27 and decreasing caspase 9.Latar belakang: Konsep terapi stem cell merupakan salah satu harapan baru sebagai terapi medis kelainan kelenjar ludah. Namun, rendahnya viabilitas stem cell yang ditransplantasikan menyebabkan penurunan efektivitas terapi. Asumsi yang mendasari rendahnya viabilitas dan fungsi stem cell adalah tingginya kejadian apoptosis. Hal ini menunjukkan bahwa lingkungan mikro di daerah jaringan yang rusak tidak kondusif untuk mendukung viabilitas stem cell. Salah satu lingkungan

  4. Metabolic effects of fructose 1,6-bisphosphate in normoxic and hypoxic states of MG63 osteosarcoma cells.

    Science.gov (United States)

    Adah, Ameze; Benghuzzi, Hamed; Tucci, Michelle; Huang, Derek; Franklin, Laura; Adah, Felix

    2006-01-01

    Glycolysis is a very important process which contains very intricate steps that play a role in cellular performance and viability. Fructose 1,6-bisphosphate (FBP) is a glycolytic intermediate that has proven to improve cellular conditions under hypoxic and ischemic conditions. Osteoblasts are key regulators of skeletal matrix synthesis and degradation. Thus, considering FBP's positive effects on ameliorating hypoxia-induced injuries, the objective of this study was to determine its effects and comparative effects on osteoblast cells under normoxic and hypoxic states. MG63 osteoblast-like cells were cultured in 24-well culture plates and treated with high, medium and low dosages of FBP at 24, 48, and 72 hours. At the end of each time period, cellular number, damage by a malondialdehyde assay (MDA), and glutathione levels were evaluated. There was a significant increase in cell number for the low level of FBP in normoxia at 48 hours (p < 0.05). For the cells in hypoxia, there was a significant decrease in cell number for the medium level at 48 hours (p < 0.05). At 48 hours there was a significant decrease in cell damage through MDA measurement for the cells in normoxia and hypoxia when compared to the control. Cellular damage was not evident in the supernatant in either oxygen condition for the duration of the study. A significant decrease in glutathione levels was also noted for the cells in hypoxia. Cellular morphology included multiple nucleoli, vacuolated cytoplasm, abnormal cells, and web-like cytoplasm. The results indicate that FBP does protect bone cells exposed to hypoxic injuries, and while doing so, ameliorating the states of the cells in shock.

  5. Neurogenin-2-transduced human neural progenitor cells attenuate neonatal hypoxic-ischemic brain injury.

    Science.gov (United States)

    Lee, Il-Shin; Koo, Kyo Yeon; Jung, Kwangsoo; Kim, Miri; Kim, Il-Sun; Hwang, Kyujin; Yun, Seokhwan; Lee, Haejin; Shin, Jeong Eun; Park, Kook In

    2017-05-01

    Neonatal hypoxic-ischemic (HI) brain injury leads to high mortality and neurodevelopmental disabilities. Multipotent neural progenitor cells (NPCs) with self-renewing capacity have the potential to reduce neuronal loss and improve the compromised environment in the HI brain injury. However, the therapeutic efficacy of neuronal-committed progenitor cells and the underlying mechanisms of recovery are not yet fully understood. Therefore, this study investigated the regenerative ability and action mechanisms of neuronally committed human NPCs (hNPCs) transduced with neurogenin-2 (NEUROG2) in neonatal HI brain injury. NEUROG2- or green fluorescent protein (GFP)-encoding adenoviral vector-transduced hNPCs (NEUROG2- or GFP-NPCs) were transplanted into neonatal mouse brains with HI injury. Grafted NEUROG2-NPCs showed robust dispersion and engraftment, prolonged survival, and neuronal differentiation in HI brain injury. NEUROG2-NPCs significantly improved neurological behaviors, decreased cellular apoptosis, and increased the neurite outgrowth and axonal sprouting in HI brain injury. In contrast, GFP-NPC grafts moderately enhanced axonal extension with limited behavioral recovery. Notably, NEUROG2-NPCs showed increased secretion of multiple factors, such as nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3 (NTF3), fibroblast growth factor 9 (FGF9), ciliary neurotrophic factor (CNTF), and thrombospondins 1 and 2 (THBS 1/2), which promoted SH-SY5Y neuroblastoma cell survival and neurite outgrowth. Thus, we postulate that NEUROG2-expressing human NPCs facilitate functional recovery after neonatal HI brain injury via their ability to secrete multiple factors that enhance neuronal survival and neuroplasticity. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Biochemical and morphological changes in endothelial cells in response to hypoxic interstitial edema

    Directory of Open Access Journals (Sweden)

    Miserocchi Giuseppe

    2006-01-01

    Full Text Available Abstract Background A correlation between interstial pulmonary matrix disorganization and lung cellular response was recently documented in cardiogenic interstitial edema as changes in the signal-cellular transduction platforms (lipid microdomains: caveoale and lipid rafts. These findings led to hypothesize a specific "sensing" function by lung cells resulting from a perturbation in cell-matrix interaction. We reason that the cell-matrix interaction may differ between the cardiogenic and the hypoxic type of lung edema due to the observed difference in the sequential degradation of matrix proteoglycans (PGs family. In cardiogenic edema a major fragmentation of high molecular weight PGs of the interfibrillar matrix was found, while in hypoxia the fragmentation process mostly involved the PGs of the basement membrane controlling microvascular permeability. Based on these considerations, we aim to describe potential differences in the lung cellular response to the two types of edema. Methods We analysed the composition of plasma membrane and of lipid microdomains in lung tissue samples from anesthetized rabbits exposed to mild hypoxia (12 % O2 for 3–5 h causing interstitial lung edema. Lipid analysis was performed by chromatographic techniques, while protein analysis by electrophoresis and Western blotting. Lipid peroxidation was assessed on total plasma membranes by a colorimetric assay (Bioxytech LPO-586, OxisResearch. Plasma membrane fluidity was also assessed by fluorescence. Lipid microdomains were isolated by discontinuous sucrose gradient. We also performed a morphometric analysis on lung cell shape on TEM images from lung tissue specimen. Results After hypoxia, phospholipids content in plasma membranes remained unchanged while the cholesterol/phospholipids ratio increased significantly by about 9% causing a decrease in membrane fluidity. No significant increase in lipid peroxidation was detected. Analysis of lipid microdomains showed a

  7. Reverse TCA cycle flux through isocitrate dehydrogenases 1 and 2 is required for lipogenesis in hypoxic melanoma cells.

    Science.gov (United States)

    Filipp, Fabian V; Scott, David A; Ronai, Ze'ev A; Osterman, Andrei L; Smith, Jeffrey W

    2012-05-01

    The tricarboxylic acid (TCA) cycle is the central hub of oxidative metabolism, running in the classic forward direction to provide carbon for biosynthesis and reducing agents for generation of ATP. Our metabolic tracer studies in melanoma cells showed that in hypoxic conditions the TCA cycle is largely disconnected from glycolysis. By studying the TCA branch point metabolites, acetyl CoA and citrate, as well as the metabolic endpoint glutamine and fatty acids, we developed a comprehensive picture of the rewiring of the TCA cycle that occurs in hypoxia. Hypoxic tumor cells maintain proliferation by running the TCA cycle in reverse. The source of carbon for acetyl CoA, citrate, and fatty acids switches from glucose in normoxia to glutamine in hypoxia. This hypoxic flux from glutamine into fatty acids is mediated by reductive carboxylation. This reductive carboxylation is catalyzed by two isocitrate dehydrogenases, IDH1 and IDH2. Their combined action is necessary and sufficient to effect the reverse TCA flux and maintain cellular viability. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

  8. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Mylonis, Ilias; Lakka, Achillia; Tsakalof, Andreas [Laboratory of Biochemistry, School of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa (Greece); Institute of Biomedical Research and Technology (BIOMED), 51 Papanastasiou str., 41222 Larissa (Greece); Simos, George, E-mail: simos@med.uth.gr [Laboratory of Biochemistry, School of Medicine, University of Thessaly, BIOPOLIS, 41110 Larissa (Greece); Institute of Biomedical Research and Technology (BIOMED), 51 Papanastasiou str., 41222 Larissa (Greece)

    2010-07-16

    Research highlights: {yields} Kaempferol inhibits HIF-1 activity in hepatocarcinoma cells; {yields} Kaempferol causes cytoplasmic mislocalization of HIF-1{alpha} by impairing the MAPK pathway. {yields} Viability of hepatocarcinoma cells under hypoxia is reduced by kaempferol. -- Abstract: Hepatocellular carcinoma (HCC) is characterized by high mortality rates and resistance to conventional treatment. HCC tumors usually develop local hypoxia, which stimulates proliferation of cancer cells and renders them resilient to chemotherapy. Adaptation of tumor cells to the hypoxic conditions depends on the hypoxia-inducible factor 1 (HIF-1). Over-expression of its regulated HIF-1{alpha} subunit, an important target of anti-cancer therapy, is observed in many cancers including HCC and is associated with severity of tumor growth and poor patient prognosis. In this report we investigate the effect of the dietary flavonoid kaempferol on activity, expression levels and localization of HIF-1{alpha} as well as viability of human hepatoma (Huh7) cancer cells. Treatment of Huh7 cells with kaempferol under hypoxic conditions (1% oxygen) effectively inhibited HIF-1 activity in a dose-dependent manner (IC{sub 50} = 5.16 {mu}M). The mechanism of this inhibition did not involve suppression of HIF-1{alpha} protein levels but rather its mislocalization into the cytoplasm due to inactivation of p44/42 MAPK by kaempferol (IC{sub 50} = 4.75 {mu}M). Exposure of Huh7 cells to 10 {mu}{Mu} kaempferol caused significant reduction of their viability, which was remarkably more evident under hypoxic conditions. In conclusion, kaempferol, a non-toxic natural food component, inhibits both MAPK and HIF-1 activity at physiologically relevant concentrations (5-10 {mu}M) and suppresses hepatocarcinoma cell survival more efficiently under hypoxia. It has, therefore, potential as a therapeutic or chemopreventive anti-HCC agent.

  9. Gene expression profiles in hypoxic preconditioning using cDNA microarray analysis: altered expression of an angiogenic factor, carcinoembryonic antigen-related cell adhesion molecule 1.

    Science.gov (United States)

    Chen, Wen-Jone; Chen, Huei-Wen; Yu, Sung-Liang; Huang, Chien-Hua; Wang, Tzung-Dau; Chen, Jeremy J W; Chien, Chiang-Ting; Chen, Hsuan-Yu; Yang, Pan-Chyr; Lee, Yuan-Teh

    2005-08-01

    Hypoxic preconditioning has been shown to exhibit cardioprotective effects on myocardium from ischemic or reperfusion injury. The specific regulated gene involved in the hypoxia-induced cardioprotective effects is profiled in this study. Young male Wistar rats and ICR mice were exposed to sea level (as normal control) or simulated high altitude for 15 h/day for 2, 4, or 8 weeks, or for 4 weeks at high altitude after 2 weeks at sea level. The left ventricles of the animals were isolated for mRNA isolation and cDNA microarray analysis. Our data demonstrated that hypoxic preconditioning significantly ameliorated cardiac ischemic injury by minimizing the infarct size. After cluster analysis of expression profiles after different courses of hypoxic preconditioning (0, 2, 4, and 8 weeks), 386 genes showed an ascending pattern, whereas 301 genes showed a descending pattern. The ascending genes include several angiogenic factors: FGF receptor 4, vascular endothelial growth factor (vEGF), and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1). The microvessel density was also significantly increased in hypoxic hearts. Using Western blotting and immunohistochemical analysis, the protein expression level and localization of CEACAM-1 were observed in hypoxic myocardium. The results also indicated that CEACAM-1 was upregulated as with other hypoxic angiogenic factors, heme oxygenase 1 (HO-1) and hypoxia inducible factor-1alpha (HIF-1alpha), in in vitro cultured cardiomyocytes (H9c2) after hypoxia treatment and in vivo hypoxic preconditioning. Furthermore, incubation with recombinant vEGF could also increase the expression level of CEACAM-1 in H9c2 cells. These results demonstrated that hypoxic preconditioning resulted in transcriptional changes, and some of these genes have been correlated with angiogenesis. The HIF-1/vEGF/CEACAM-1 pathway might be important for hypoxia-induced angiogenesis in the heart during hypoxic preconditioning.

  10. Nicotine promotes vascular endothelial growth factor secretion by human trophoblast cells under hypoxic conditions and improves the proliferation and tube formation capacity of human umbilical endothelial cells.

    Science.gov (United States)

    Zhao, Hongbo; Wu, Lanxiang; Wang, Yahui; Zhou, Jiayi; Li, Ruixia; Zhou, Jiabing; Wang, Zehua; Xu, Congjian

    2017-04-01

    Pre-eclampsia, characterized as defective uteroplacental vascularization, remains the major cause of maternal and fetal mortality and morbidity. Previous epidemiological studies demonstrated that cigarette smoking reduced the risk of pre-eclampsia. However, the molecular mechanism remains elusive. In the present study, it is demonstrated that a low dose of nicotine decreased soluble vascular endothelial growth factor receptor 1 (sFlt1) secretion in human trophoblast cells under hypoxic conditions. Nicotine was then observed to promote vascular endothelial growth factor (VEGF) secretion by reducing sFlt1 secretion and increasing VEGF mRNA transcription. Further data showed that nicotine enhanced hypoxia-mediated hypoxia-inducible factor-1α (HIF-1α) expression and HIF-1α small interfering RNA abrogated nicotine-induced VEGF secretion, indicating that HIF-1α may be responsible for nicotine-mediated VEGF transcription under hypoxic conditions. Moreover, conditioned medium from human trophoblast cells treated with nicotine under hypoxic conditions promoted the proliferation and tube formation capacity of human umbilical endothelial cells (HUVEC) by promoting VEGF secretion. These findings indicate that nicotine may promote VEGF secretion in human trophoblast cells under hypoxic conditions by reducing sFlt1 secretion and up-regulating VEGF transcription and improve the proliferation and tube formation of HUVEC cells, which may contribute to elucidate the protective effect of cigarette smoking against pre-eclampsia. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  11. [Beta-adrenoceptor-mediated cyclic AMP signal in different types of cultured nerve cells in normoxic and hypoxic conditions].

    Science.gov (United States)

    Jóźwiak-Bębenista, M; Wiktorowska-Owczarek, A; Kowalczyk, E

    2016-01-01

    β-adrenergic neurotransmission is an important factor regulating brain activity such as neuronal and glial survival, plasticity, membrane transport or cellular metabolism. Intracellular β-adrenergic signaling, via a stimulatory G protein (Gs), activates two major down-stream effectors, i.e., adenylyl cyclase (AC) and cAMP-dependent protein kinase A (PKA). The aim of this work was to study the ability of endogenous (adrenaline and noradrenaline) and exogenous (isoprenaline) β-adrenergic receptor agonists to increase cAMP in different types of nerve cells. Moreover, we wanted to precisely identify the receptor isoform involved in the observed phenomenon using selective β1-, β2- β3-adrenoceptor blockers. In an additional study, the negative influence of hypoxia on the AC/cAMP intracellular signaling system was tested. The study was conducted in parallel on rat primary glial (astrocytes) cultures, primary neuronal cultures, C6 glioma cells and human T98G glioma cells. The formation of [^(3)H] cAMP by agonists and antagonists was measured in [^(3)H] adenine prelabeled cells under normoxic and hypoxic conditions. The obtained results revealed that adrenaline, noradrenaline and isoprenaline strongly stimulated cAMP production in all tested cell types (with highest potency in C6 glioma cells). In glial and neuronal cells the adrenaline-evoked cAMP effect was mediated mainly by the β1-adrenoceptor, whereas in tumor cells the effect was probably mediated by all three β-subtype specific drugs. The AC/cAMP intracellular signaling system is affected by hypoxic conditions. Considering both physiological and therapeutic importance of β-family receptors the present work characterized the β-adrenoceptor-mediated cAMP signal transduction pathway in different nerve cells in normoxic and hypoxic conditions. The proposed in vitro model of hypoxic conditions may serve as a good model system to study the biological effects of endogenous catecholamines as well as potential

  12. Exosomes from hypoxic endothelial cells have increased collagen crosslinking activity through up-regulation of lysyl oxidase-like 2.

    Science.gov (United States)

    de Jong, Olivier G; van Balkom, Bas W M; Gremmels, Hendrik; Verhaar, Marianne C

    2016-02-01

    Exosomes are important mediators of intercellular communication. Additionally, they contain a variety of components capable of interacting with the extracellular matrix (ECM), including integrins, matrix metalloproteinases and members of the immunoglobin superfamily. Despite these observations, research on exosome-ECM interactions is limited. Here, we investigate whether the exosome-associated lysyl oxidase family member lysyl oxidase-like 2 (LOXL2) is involved in ECM remodelling. We found that LOXL2 is present on the exterior of endothelial cell (EC)-derived exosomes, placing it in direct vicinity of the ECM. It is up-regulated twofold in EC-derived exosomes cultured under hypoxic conditions. Intact exosomes from hypoxic EC and LOXL2 overexpressing EC show increased activity in a fluorometric lysyl oxidase enzymatic activity assay as well as in a collagen gel contraction assay. Concordantly, knockdown of LOXL2 in exosome-producing EC in both normal and hypoxic conditions reduces activity of exosomes in both assays. Our findings show for the first time that ECM crosslinking by EC-derived exosomes is mediated by LOXL2 under the regulation of hypoxia, and implicate a role for exosomes in hypoxia-regulated focal ECM remodelling, a key process in both fibrosis and wound healing. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. Dye Sensitized Solar Cell, DSSC

    Directory of Open Access Journals (Sweden)

    Pongsatorn Amornpitoksuk

    2003-07-01

    Full Text Available A dye sensitized solar cell is a new type of solar cell. The operating system of this solar cell type is similar to plant’s photosynthesis process. The sensitizer is available for absorption light and transfer electrons to nanocrystalline metal oxide semiconductor. The ruthenium(II complexes with polypyridyl ligands are usually used as the sensitizers in solar cell. At the present time, the complex of [Ru(2,2',2'’-(COOH3- terpy(NCS3] is the most efficient sensitizer. The total photon to current conversion efficiency was approximately 10% at AM = 1.5.

  14. Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Wei, E-mail: detachedy@yahoo.com.cn [Department of Radiobiology, School of Radiological Medicine and Protection, Soochow University, Suzhou (China); Sun, Ting [Brain and Nerve Research Laboratory, The First Affiliated Hospital, Soochow University, Suzhou (China); Cao, Jianping; Liu, Fenju [Department of Radiobiology, School of Radiological Medicine and Protection, Soochow University, Suzhou (China); Tian, Ye [Department of Radiotherapy and Oncology, The Second Affiliated Hospital, Soochow University, Suzhou (China); Zhu, Wei [Department of Radiobiology, School of Radiological Medicine and Protection, Soochow University, Suzhou (China)

    2012-05-01

    Hypoxia is a common feature of solid tumors and an important contributor to tumor radioresistance. miR-210 is the most consistently and robustly induced microRNA under hypoxia in different types of tumor cells and normal cells. In the present study, to explore the feasibility of miR-210 as an effective therapeutic target, lentiviral-mediated anti-sense miR-210 gene transfer technique was employed to downregulate miR-210 expression in hypoxic human hepatoma SMMC-7721, HepG2 and HuH7 cells, and phenotypic changes of which were analyzed. Hypoxia led to an increased hypoxia inducible factor-1{alpha} (HIF-1{alpha}) and miR-210 expression and cell arrest in the G{sub 0}/G{sub 1} phase in all cell lines. miR-210 downregulation significantly suppressed cell viability, induced cell arrest in the G{sub 0}/G{sub 1} phase, increased apoptotic rate and enhanced radiosensitivity in hypoxic human hepatoma cells. Moreover, apoptosis-inducing factor, mitochondrion-associated, 3 (AIFM3) was identified as a direct target gene of miR-210. AIFM3 downregulation by siRNA attenuated radiation induced apoptosis in miR-210 downregulated hypoxic human hepatoma cells. Taken together, these data suggest that miR-210 might be a potential therapeutic target and specific inhibition of miR-210 expression in combination with radiotherapy might be expected to exert strong anti-tumor effect on hypoxic human hepatoma cells. -- Highlights: Black-Right-Pointing-Pointer miR-210 downregulation radiosensitized hypoxic hepatoma. Black-Right-Pointing-Pointer AIFM3 was identified as a direct target gene of miR-210. Black-Right-Pointing-Pointer miR-210 might be a therapeutic target to hypoxic hepatoma.

  15. Oxidative Stress Promotes Doxorubicin-Induced Pgp and BCRP Expression in Colon Cancer Cells Under Hypoxic Conditions.

    Science.gov (United States)

    Pinzón-Daza, Martha L; Cuellar-Saenz, Yenith; Nualart, Francisco; Ondo-Mendez, Alejandro; Del Riesgo, Lilia; Castillo-Rivera, Fabio; Garzón, Ruth

    2017-07-01

    P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) are ATP binding cassette (ABC) transporters that are overexpressed in different drug-resistant cancer cell lines. In this study, we investigated whether doxorubicin promotes Pgp and/or BCRP expression to induce drug resistance in colon cancer cells under hypoxic conditions. We analyzed HIF-1α activity via ELISA, Pgp, and BCRP expression by qRT-PCR and the relationship between doxorubicin uptake and ABC transporter expression via confocal microscopy in HT-29WT and HT-29 doxorubicin-resistant colon cancer cells (HT-29DxR). These cells were treated with doxorubicin and/or CoCl2 (chemical hypoxia), and reactive oxygen species inductors. We found that the combination of chemically induced hypoxia and doxorubicin promoted Pgp mRNA expression within 24 h in HT-29WT and HT-29DxR cells. Both doxorubicin and CoCl2 alone or in combination induced Pgp and BCRP expression, as demonstrated via confocal microscopy in each of the above two cell lines. Thus, we surmised that Pgp and BCRP expression may result from synergistic effects exerted by the combination of doxorubicin-induced ROS production and HIF-1α activity under hypoxic conditions. However, HIF-1α activity disruption via the administration of E3330, an APE-1 inhibitor, downregulated Pgp expression and increased doxorubicin delivery to HT-29 cells, where it served as a substrate for Pgp, indicating the existence of an indirect relationship between Pgp expression and doxorubicin accumulation. Thus, we concluded that Pgp and BCRP expression can be regulated via cross-talk between doxorubicin and hypoxia, promoting drug resistance in HT-29 WT, and HT-29DxR cells and that this process may be ROS dependent. J. Cell. Biochem. 118: 1868-1878, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Inhibition of IRE1 signaling affects the expression of genes encoded glucocorticoid receptor and some related factors and their hypoxic regulation in U87 glioma cells.

    Science.gov (United States)

    Minchenko, D O; Riabovol, O O; Tsymbal, D O; Ratushna, O O; Minchenko, O H

    2016-07-01

    The aim of the present investigation was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoding glucocorticoid receptor (NR3C1) and some related proteins (SGK1, SGK3, NCOA1, NCOA2, ARHGAP35, NNT) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of the glioma growth. The expression of NR3C1,SGK1,SGK3, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by quantitative polymerase chain reaction. Inhibition of IRE1 signaling enzyme function up-regulates the expression of NR3C1, SGK1, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells in comparison with the control glioma cells, with more significant changes for NR3C1, SGK1, and NNT genes. At the same time, the expression of SGK3 gene is strongly down-regulated in glioma cells upon inhibition of IRE1. We have also shown that hypoxia increases the expression of NR3C1, SGK1, NCOA2, ARHGAP35, and NNT genes but decreases SGK3 and NCOA1 genes expression in control glioma cells. Moreover, the inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in U87 glioma cells enhances the eff ect of hypoxia on the expression of SGK1, SGK3, and NNT genes, but decreases the sensitivity of NR3C1 gene to hypoxic condition. Furthermore, the expression of NCOA1 gene is resistant to hypoxia in control glioma cells, but NCOA2 and ARHGAP35 genes are resistant to this condition in glioma cells without functional activity of IRE1 signaling enzyme. Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NR3C1, SGK1, SGK3, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells

  17. The Proteasome Inhibitor MG-132 Protects Hypoxic SiHa Cervical Carcinoma Cells after Cyclic Hypoxia/Reoxygenation from Ionizing Radiation

    Directory of Open Access Journals (Sweden)

    Frank Pajonk

    2006-12-01

    Full Text Available INTRODUCTION: Transient hypoxia and subsequent reoxygenation are common phenomena in solid tumors that greatly influence the outcome of radiation therapy. This study was designed to determine how varying cycles of hypoxia/reoxygenation affect the response of cervical carcinoma cells irradiated under oxic and hypoxic conditions and whether this could be modulated by proteasome inhibition. MATERIALS AND METHODS: Plateau-phase SiHa cervical carcinoma cells in culture were exposed to varying numbers of 30-minute cycles of hypoxia/reoxygenation directly before irradiation under oxic or hypoxic conditions. 26S Proteasome activity was blocked by addition of MG-132. Clonogenic survival was measured by a colonyforming assay. RESULTS: Under oxic conditions, repeated cycles of hypoxia/reoxygenation decreased the clonogenic survival of SiHa cells. This effect was even more pronounced after the inhibition of 26S proteasome complex. In contrast, under hypoxic conditions, SiHa cells were radioresistant, as expected, but this was increased by proteasome inhibition. CONCLUSIONS: Proteasome inhibition radiosensitizes oxygenated tumor cells but may also protect tumor cells from ionizing radiation under certain hypoxic conditions.

  18. Lecithin-Bound Iodine Prevents Disruption of Tight Junctions of Retinal Pigment Epithelial Cells under Hypoxic Stress

    Directory of Open Access Journals (Sweden)

    Masahiko Sugimoto

    2016-01-01

    Full Text Available Aim. We investigated whether lecithin-bound iodine (LBI can protect the integrity of tight junctions of retinal pigment epithelial cells from hypoxia. Method. Cultured human retinal pigment epithelial (ARPE-19 cells were pretreated with LBI. To mimic hypoxic conditions, cells were incubated with CoCl2. We compared the integrity of the tight junctions (TJs of control to cells with either LBI alone, CoCl2 alone, or LBI + CoCl2. The levels of cytokines in the conditioned media were also determined. Results. Significant decrease in the zonula occludens-1 (ZO-1 intensity in the CoCl2 group compared to the control (5787.7 ± 4126.4 in CoCl2 group versus 29244.6 ± 2981.2 in control; average ± standard deviation. But the decrease was not significant in the LBI + CoCl2 (27189.0 ± 11231.1. The levels of monocyte chemoattractant protein-1 (MCP-1 and Chemokine (C-C Motif Ligand 11 (CCL-11 were significantly higher in the CoCl2 than in the control (340.8 ± 43.3 versus 279.7 ± 68.3 pg/mL for MCP-1, and 15.2 ± 12.9 versus 12.5 ± 6.1 pg/mL for CCL-11. With LBI pretreatment, the levels of both cytokines were decreased to 182.6 ± 23.8 (MCP-1 and 5.46 ± 1.9 pg/mL for CCL-11. Blockade of MCP-1 or CCL-11 also shows similar result representing TJ protection from hypoxic stress. Conclusions. LBI results in a protective action from hypoxia.

  19. Dye Sensitized Tandem Photovoltaic Cells

    Energy Technology Data Exchange (ETDEWEB)

    Barber, Greg D.

    2009-12-21

    This work provided a new way to look at photoelectrochemical cells and their performance. Although thought of as low efficiency, a the internal efficiency of a 9% global efficiency dye sensitized solar cell is approximately equal to an 18% efficient silicon cell when each is compared to their useful spectral range. Other work undertaken with this contract also reported the first growth oriented titania and perovskite columns on a transparent conducting oxide. Other work has shown than significant performance enhancement in the performance of dye sensitized solar cells can be obtained through the use of coupling inverse opal photonic crystals to the nanocrystalline dye sensitized solar cell. Lastly, a quick efficient method was developed to bond titanium foils to transparent conducting oxide substrates for anodization.

  20. Bone marrow-derived mesenchymal stem cells propagate immunosuppressive/anti-inflammatory macrophages in cell-to-cell contact-independent and -dependent manners under hypoxic culture.

    Science.gov (United States)

    Takizawa, Naoki; Okubo, Naoto; Kamo, Masaharu; Chosa, Naoyuki; Mikami, Toshinari; Suzuki, Keita; Yokota, Seiji; Ibi, Miho; Ohtsuka, Masato; Taira, Masayuki; Yaegashi, Takashi; Ishisaki, Akira; Kyakumoto, Seiko

    2017-09-15

    Immunosuppressive/anti-inflammatory macrophage (Mφ), M2-Mφ that expressed the typical M2-Mφs marker, CD206, and anti-inflammatory cytokine, interleukin (IL)-10, is beneficial and expected tool for the cytotherapy against inflammatory diseases. Here, we demonstrated that bone marrow-derived lineage-positive (Lin+) blood cells proliferated and differentiated into M2-Mφs by cooperation with the bone marrow-derived mesenchymal stem cells (MSCs) under hypoxic condition: MSCs not only promoted proliferation of undifferentiated M2-Mφs, pre-M2-Mφs, in the Lin+ fraction via a proliferative effect of the MSCs-secreted macrophage colony-stimulating factor, but also promoted M2-Mφ polarization of the pre-M2-Mφs through cell-to-cell contact with the pre-M2-Mφs. Intriguingly, an inhibitor for intercellular adhesion molecule (ICAM)-1 receptor/lymphocyte function-associated antigen (LFA)-1, Rwj50271, partially suppressed expression of CD206 in the Lin+ blood cells but an inhibitor for VCAM-1 receptor/VLA-4, BIO5192, did not, suggesting that the cell-to-cell adhesion through LFA-1 on pre-M2-Mφs and ICAM-1 on MSCs was supposed to promoted the M2-Mφ polarization. Thus, the co-culture system consisting of bone marrow-derived Lin+ blood cells and MSCs under hypoxic condition was a beneficial supplier of a number of M2-Mφs, which could be clinically applicable to inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The effects of short-term hypoxia on human mesenchymal stem cell proliferation, viability and p16INK4A mRNA expression: Investigation using a simple hypoxic culture system with a deoxidizing agent

    Directory of Open Access Journals (Sweden)

    Ito A

    2015-05-01

    Full Text Available A hypoxic environment is thought to be important for the maintenance of stemness and suppressing cell senescence, in stem cells. Therefore, a hypoxic condition is induced during cell expansion and/or induction of intended differentiation. However, the induction of these conditions requires a specially equipped hypoxia chamber and expensive gas mixtures, which are expensive and space-consuming. Owing to these restrictions, appropriate hypoxic conditions cannot be provided during cell transportation, which is increasingly required for regenerative medicine. Hence, a simple and economical culture system is required. The purpose of this study was to investigate the effects of short-term hypoxic conditions on human mesenchymal stem cell (MSC proliferation, viability, and senescence, utilizing the CulturePal system (CulturePal-Zero and CulturePal-Five, a novel and simple hypoxic culture system with a built-in deoxidizing agent. The O2 concentration in the CulturePal-Zero was observed to reduce to <0.1% within 1 h, and to 5% within 24 h in the CulturePal-Five system. Cell proliferation under these hypoxic conditions showed a sharp increase at 5% O2 concentration, and no noticeable cell death was observed even at severe hypoxic conditions (<0.1% O2 up to 72h. The p16INK4A (cell senescence marker mRNA expression was retained under hypoxic conditions up to 72h, but it was up-regulated under normoxic conditions. Interestingly, the p16INK4A expression altered proportionately to the O2 concentration. These results indicated that the short-term hypoxic condition, at an approximate O2 concentration of 5%, would be suitable for promoting cell proliferation and repressing cell senescence, without aggravating the MSC viability. Therefore, the CulturePal systems may be suitable for providing an appropriate hypoxic condition in stem cell research and transportation.

  2. The effects of short-term hypoxia on human mesenchymal stem cell proliferation, viability and p16INK4A mRNA expression: Investigation using a simple hypoxic culture system with a deoxidizing agent

    Science.gov (United States)

    Ito, Akira; Aoyama, Tomoki; Yoshizawa, Makoto; Nagai, Momoko; Tajino, Junichi; Yamaguchi, Shoki; Iijima, Hirotaka; Zhang, Xiangkai; Kuroki, Hiroshi

    2015-01-01

    A hypoxic environment is thought to be important for the maintenance of stemness and suppressing cell senescence, in stem cells. Therefore, a hypoxic condition is induced during cell expansion and/or induction of intended differentiation. However, the induction of these conditions requires a specially equipped hypoxia chamber and expensive gas mixtures, which are expensive and space-consuming. Owing to these restrictions, appropriate hypoxic conditions cannot be provided during cell transportation, which is increasingly required for regenerative medicine. Hence, a simple and economical culture system is required. The purpose of this study was to investigate the effects of short-term hypoxic conditions on human mesenchymal stem cell (MSC) proliferation, viability, and senescence, utilizing the CulturePal system (CulturePal-Zero and CulturePal-Five), a novel and simple hypoxic culture system with a built-in deoxidizing agent. The O2 concentration in the CulturePal-Zero was observed to reduce to <0.1% within 1 h, and to 5% within 24h in the CulturePal-Five system. Cell proliferation under these hypoxic conditions showed a sharp increase at 5% O2 concentration, and no noticeable cell death was observed even at severe hypoxic conditions (<0.1% O2) up to 72h. The p16INK4A (cell senescence marker) mRNA expression was retained under hypoxic conditions up to 72h, but it was up-regulated under normoxic conditions. Interestingly, the p16INK4A expression altered proportionately to the O2 concentration. These results indicated that the short-term hypoxic condition, at an approximate O2 concentration of 5%, would be suitable for promoting cell proliferation and repressing cell senescence, without aggravating the MSC viability. Therefore, the CulturePal systems may be suitable for providing an appropriate hypoxic condition in stem cell research and transportation. PMID:26195892

  3. Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells.

    Science.gov (United States)

    Cho, Sung-Yun; Lee, Hyo-Jeong; Lee, Hyo-Jung; Jung, Deok-Beom; Kim, Hyunseok; Sohn, Eun Jung; Kim, Bonglee; Jung, Ji Hoon; Kwon, Byoung-Mog; Kim, Sung-Hoon

    2013-01-01

    Here, antitumor mechanism of cinnamaldehyde derivative CB-PIC was elucidated in human SW620 colon cancer cells. CB-PIC significantly exerted cytotoxicity, increased sub-G1 accumulation, and cleaved PARP with apoptotic features, while it enhanced the phosphorylation of AMPK alpha and ACC as well as activated the ERK in hypoxic SW620 cells. Furthermore, CB-PIC suppressed the expression of HIF1 alpha, Akt, and mTOR and activated the AMPK phosphorylation in hypoxic SW620 cells. Conversely, silencing of AMPK α blocked PARP cleavage and ERK activation induced by CB-PIC, while ERK inhibitor PD 98059 attenuated the phosphorylation of AMPK α in hypoxic SW620 cells, implying cross-talk between ERK and AMPK α . Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1 α and Akt/mTOR and the activation of AMPK α and pACC in hypoxic SW620 cells. In addition, CB-PIC suppressed the growth of SW620 cells inoculated in BALB/c athymic nude mice, and immunohistochemistry revealed that CB-PIC treatment attenuated the expression of Ki-67, CD34, and CAIX and increased the expression of pAMPK α in CB-PIC-treated group. Interestingly, CP-PIC showed better antitumor activity in SW620 colon cancer cells under hypoxia than under normoxia, since it may be applied to chemoresistance. Overall, our findings suggest that activation of AMPK α and ERK mediates CB-PIC-induced apoptosis in hypoxic SW620 colon cancer cells.

  4. Activation of AMP-Activated Protein Kinase α and Extracelluar Signal-Regulated Kinase Mediates CB-PIC-Induced Apoptosis in Hypoxic SW620 Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sung-Yun Cho

    2013-01-01

    Full Text Available Here, antitumor mechanism of cinnamaldehyde derivative CB-PIC was elucidated in human SW620 colon cancer cells. CB-PIC significantly exerted cytotoxicity, increased sub-G1 accumulation, and cleaved PARP with apoptotic features, while it enhanced the phosphorylation of AMPK alpha and ACC as well as activated the ERK in hypoxic SW620 cells. Furthermore, CB-PIC suppressed the expression of HIF1 alpha, Akt, and mTOR and activated the AMPK phosphorylation in hypoxic SW620 cells. Conversely, silencing of AMPKα blocked PARP cleavage and ERK activation induced by CB-PIC, while ERK inhibitor PD 98059 attenuated the phosphorylation of AMPKα in hypoxic SW620 cells, implying cross-talk between ERK and AMPKα. Furthermore, cotreatment of CB-PIC and metformin enhanced the inhibition of HIF1α and Akt/mTOR and the activation of AMPKα and pACC in hypoxic SW620 cells. In addition, CB-PIC suppressed the growth of SW620 cells inoculated in BALB/c athymic nude mice, and immunohistochemistry revealed that CB-PIC treatment attenuated the expression of Ki-67, CD34, and CAIX and increased the expression of pAMPKα in CB-PIC-treated group. Interestingly, CP-PIC showed better antitumor activity in SW620 colon cancer cells under hypoxia than under normoxia, since it may be applied to chemoresistance. Overall, our findings suggest that activation of AMPKα and ERK mediates CB-PIC-induced apoptosis in hypoxic SW620 colon cancer cells.

  5. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

    Science.gov (United States)

    Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

    2015-10-28

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

  6. Physiological and hypoxic oxygen concentration differentially regulates human c-Kit+ cardiac stem cell proliferation and migration.

    Science.gov (United States)

    Bellio, Michael A; Rodrigues, Claudia O; Landin, Ana Marie; Hatzistergos, Konstantinos E; Kuznetsov, Jeffim; Florea, Victoria; Valasaki, Krystalenia; Khan, Aisha; Hare, Joshua M; Schulman, Ivonne Hernandez

    2016-12-01

    Cardiac stem cells (CSCs) are being evaluated for their efficacy in the treatment of heart failure. However, numerous factors impair the exogenously delivered cells' regenerative capabilities. Hypoxia is one stress that contributes to inadequate tissue repair. Here, we tested the hypothesis that hypoxia impairs cell proliferation, survival, and migration of human CSCs relative to physiological and room air oxygen concentrations. Human endomyocardial biopsy-derived CSCs were isolated, selected for c-Kit expression, and expanded in vitro at room air (21% O2). To assess the effect on proliferation, survival, and migration, CSCs were transferred to physiological (5%) or hypoxic (0.5%) O2 concentrations. Physiological O2 levels increased proliferation (P air and hypoxia, a significant reduction of β-galactosidase activity (-4,203 fluorescent units, P air and hypoxia, and treatment with mesenchymal stem cell-conditioned media rescued CSC migration under hypoxia to levels comparable to physiological O2 migration (2-fold, P air may diminish cell regenerative potential. This study provides novel insights into the modulatory effects of O2 concentration on CSC biology and has important implications for refining stem cell therapies. Copyright © 2016 the American Physiological Society.

  7. Digoxin Downregulates NDRG1 and VEGF through the Inhibition of HIF-1α under Hypoxic Conditions in Human Lung Adenocarcinoma A549 Cells

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    Dong Wei

    2013-04-01

    Full Text Available Digoxin, an inhibitor of Na+/K+ ATPase, has been used in the treatment of heart-related diseases (such as congestive heart failure and atrial arrhythmia for decades. Recently, it was reported that digoxin is also an effective HIF-1α inhibitor. We investigated whether digoxin could suppress tumor cell growth through HIF-1α in non-small cell lung cancer cells (A549 cells under hypoxic conditions. An MTT assay was used to measure cell viability. RT-PCR and western blotting were performed to analyze the mRNA and protein expression of VEGF, NDRG1, and HIF-1α. HIF-1α nuclear translocation was then determined by EMSA. Digoxin was found to inhibit the proliferation of A549 cells under hypoxic conditions. Our results showed that hypoxia led to the upregulation of VEGF, NDRG1, and HIF-1α both at the mRNA and protein levels. We also found that the hypoxia-induced overexpression of VEGF, NDRG1, and HIF-1α was suppressed by digoxin in a concentration-dependent manner. As expected, our EMSA results demonstrated that under hypoxic conditions HIF-1α nuclear translocation was also markedly reduced by digoxin in a concentration-dependent manner. Our results suggest that digoxin downregulated hypoxia-induced overexpression of VEGF and NDRG1 at the transcriptional level probably through the inhibition of HIF-1α synthesis in A549 cells.

  8. Inhibition of Hypoxia Inducible Factor Alpha and Astrocyte-Elevated Gene-1 Mediates Cryptotanshinone Exerted Antitumor Activity in Hypoxic PC-3 Cells

    Directory of Open Access Journals (Sweden)

    Hyo-Jeong Lee

    2012-01-01

    Full Text Available Although cryptotanshinone (CT was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1α in CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1α accumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1α siRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1α during hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1α to VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1α, AEG1, and VEGF as a potent chemotherapeutic agent.

  9. HIF-1α inhibition by siRNA or chetomin in human malignant glioma cells: effects on hypoxic radioresistance and monitoring via CA9 expression

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    Bache Matthias

    2010-11-01

    Full Text Available Abstract Background Hypoxia induces activation of the HIF-1 pathway and is an essential characteristic of malignant gliomas. Hypoxia has been linked to tumor progression, therapy resistance and poor prognosis. However, little is known about the impact of HIF-1α inhibition on radioresistance of malignant glioma. Methods In this study, we investigated the effects of the inhibition of HIF-1α on cell survival and radiosensitivity in U251MG and U343MG glioma cells, using two different strategies. HIF-1α inhibition was achieved by siRNA targeting of HIF-1α or via chetomin, a disruptor of interactions between HIF-1α and p300. The inhibition of the HIF-1 pathway was monitored by quantitative real-time PCR and Western blot analyses of the expression levels of HIF-1α and CA9. CA9 expression was investigated as a potential indicator of the efficacy of HIF-1 inhibition and the resulting radiosensitivity of malignant glioma cell lines was determined by clonogenic assay after irradiation under normoxic (2-10 Gy or hypoxic (2-15 Gy conditions. Results Although siRNA and chetomin show distinct modes of action, both attenuated the hypoxia-induced radioresistance of malignant glioma cell lines U251MG (DMF10: 1.35 and 1.18 and U343MG (DMF10: 1.78 and 1.48. However, siRNA and chetomin showed diverse effects on radiosensitivity under normoxic conditions in U251MG (DMF10: 0.86 and 1.35 and U343MG (DMF10: 1.33 and 1.02 cells. Conclusions Results from this in vitro study suggest that inhibition of HIF-1α is a promising strategy to sensitize human malignant gliomas to radiotherapy and that CA9 could serve as an indicator of effective HIF-1-related radiosensitization.

  10. Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice.

    Science.gov (United States)

    Wei, Ning; Yu, Shan Ping; Gu, Xiaohuan; Taylor, Tammi M; Song, Denise; Liu, Xin-Feng; Wei, Ling

    2013-01-01

    Stem cell transplantation therapy has emerged as a potential treatment for ischemic stroke and other neurodegenerative diseases. Effective delivery of exogenous cells and homing of these cells to the lesion region, however, have been challenging issues that hinder the efficacy and efficiency of cell-based therapy. In the present investigation, we tested a delayed treatment of noninvasive and brain-targeted intranasal delivery of bone marrow mesenchymal stem cells (BMSCs) in a mouse focal cerebral ischemia model. The investigation tested the feasibility and effectiveness of intranasal delivery of BMSCs to the ischemic cortex. Hypoxia preconditioning (HP) of BMSCs was performed before transplantation in order to promote their survival, migration, and homing to the ischemic brain region after intranasal transplantation. Hoechst dye-labeled normoxic- or hypoxic-pretreated BMSCs (1 × 10(6) cells/animal) were delivered intranasally 24 h after stroke. Cells reached the ischemic cortex and deposited outside of vasculatures as early as 1.5 h after administration. HP-treated BMSCs (HP-BMSCs) showed a higher level of expression of proteins associated with migration, including CXC chemokine receptor type 4 (CXCR4), matrix metalloproteinase 2 (MMP-2), and MMP-9. HP-BMSCs exhibited enhanced migratory capacities in vitro and dramatically enhanced homing efficiency to the infarct cortex when compared with normoxic cultured BMSCs (N-BMSCs). Three days after transplantation and 4 days after stroke, both N-BMSCs and HP-BMSCs decreased cell death in the peri-infarct region; significant neuroprotection of reduced infarct volume was seen in mice that received HP-BMSCs. In adhesive removal test of sensorimotor functional assay performed 3 days after transplantation, HP-BMSC-treated mice performed significantly better than N-BMSC- and vehicle-treated animals. These data suggest that delayed intranasal administration of stem cells is feasible in the treatment of stroke and hypoxic

  11. Bcl-2 regulates HIF-1alpha protein stabilization in hypoxic melanoma cells via the molecular chaperone HSP90.

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    Daniela Trisciuoglio

    Full Text Available BACKGROUND: Hypoxia-Inducible Factor 1 (HIF-1 is a transcription factor that is a critical mediator of the cellular response to hypoxia. Enhanced levels of HIF-1alpha, the oxygen-regulated subunit of HIF-1, is often associated with increased tumour angiogenesis, metastasis, therapeutic resistance and poor prognosis. It is in this context that we previously demonstrated that under hypoxia, bcl-2 protein promotes HIF-1/Vascular Endothelial Growth Factor (VEGF-mediated tumour angiogenesis. METHODOLOGY/PRINCIPAL FINDINGS: By using human melanoma cell lines and their stable or transient derivative bcl-2 overexpressing cells, the current study identified HIF-1alpha protein stabilization as a key regulator for the induction of HIF-1 by bcl-2 under hypoxia. We also demonstrated that bcl-2-induced accumulation of HIF-1alpha protein during hypoxia was not due to an increased gene transcription or protein synthesis. In fact, it was related to a modulation of HIF-1alpha protein expression at a post-translational level, indeed its degradation rate was faster in the control lines than in bcl-2 transfectants. The bcl-2-induced HIF-1alpha stabilization in response to low oxygen tension conditions was achieved through the impairment of ubiquitin-dependent HIF-1alpha degradation involving the molecular chaperone HSP90, but it was not dependent on the prolyl hydroxylation of HIF-1alpha protein. We also showed that bcl-2, HIF-1alpha and HSP90 proteins form a tri-complex that may contribute to enhancing the stability of the HIF-1alpha protein in bcl-2 overexpressing clones under hypoxic conditions. Finally, by using genetic and pharmacological approaches we proved that HSP90 is involved in bcl-2-dependent stabilization of HIF-1alpha protein during hypoxia, and in particular the isoform HSP90beta is the main player in this phenomenon. CONCLUSIONS/SIGNIFICANCE: We identified the stabilization of HIF-1alpha protein as a mechanism through which bcl-2 induces the

  12. Small interfering RNA targeting HIF-1{alpha} reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Staab, Adrian [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Paul Scherrer Institute (PSI), Villigen (Switzerland); Fleischer, Markus [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Wuerzburg Univ. (Germany). Medical Clinic II; Loeffler, Juergen; Einsele, Herrmann [Wuerzburg Univ. (Germany). Medical Clinic II; Said, Harun M.; Katzer, Astrid; Flentje, Michael [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Plathow, Christian [Freiburg Univ. (Germany). Dept. of Nuclear Medicine; Vordermark, Dirk [Wuerzburg Univ. (Germany). Dept. of Radiation Oncology; Halle-Wittenberg Univ. (Germany). Dept. of Radiation Oncology

    2011-04-15

    Background: Hypoxia inducible factor-1 has been identified as a potential target to overcome hypoxia-induced radioresistance The aim of the present study was to investigate whether selective HIF-1 inhibition via small interfering RNA (siRNA) targeting hypoxia-inducible factor 1{alpha} (HIF-1{alpha}) affects hypoxia-induced radioresistance in HT 1080 human fibrosarcoma cells. Material and Methods: HIF-1{alpha} expression in HT 1080 human fibrosarcoma cells in vitro was silenced using HIF-1{alpha} siRNA sequence primers. Quantitative real-time polymerase chain reaction assay was performed to quantify the mRNA expression of HIF-1{alpha}. HIF-1{alpha} protein levels were studied by Western blotting at 20% (air) or after 12 hours at 0.1% O{sub 2} (hypoxia). Cells were assayed for clonogenic survival after irradiation with 2, 5, or 10 Gy, under normoxic or hypoxic conditions in the presence of HIF-1{alpha}-targeted or control siRNA sequences. A modified oxygen enhancement ratio (OER') was calculated as the ratio of the doses to achieve the same survival at 0.1% O{sub 2} as at ambient oxygen tensions. OER' was obtained at cell survival levels of 50%, 37%, and 10%. Results: HIF-1{alpha}-targeted siRNA enhanced radiation treatment efficacy under severely hypoxic conditions compared to tumor cells treated with scrambled control siRNA. OER was reduced on all survival levels after treatment with HIF-1{alpha}-targeted siRNA, suggesting that inhibition of HIF-1 activation by using HIF-1{alpha}-targeted siRNA increases radiosensitivity of hypoxic tumor cells in vitro. Conclusion: Inhibition of HIF-1 activation by using HIF-1{alpha}-targeted siRNA clearly acts synergistically with radiotherapy and increase radiosensitivity of hypoxic cells in vitro. (orig.)

  13. Cell Death Conversion under Hypoxic Condition in Tumor Development and Therapy

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    Yu Qiu

    2015-10-01

    Full Text Available Hypoxia, which is common during tumor progression, plays important roles in tumor biology. Failure in cell death in response to hypoxia contributes to progression and metastasis of tumors. On the one hand, the metabolic and oxidative stress following hypoxia could lead to cell death by triggering signal cascades, like LKB1/AMPK, PI3K/AKT/mTOR, and altering the levels of effective components, such as the Bcl-2 family, Atg and p62. On the other hand, hypoxia-induced autophagy can serve as a mechanism to turn over nutrients, so as to mitigate the adverse condition and then avoid cell death potentially. Due to the effective role of hypoxia, this review focuses on the crosstalk in cell death under hypoxia in tumor progression. Additionally, the illumination of cell death in hypoxia could shed light on the clinical applications of cell death targeted therapy.

  14. Induction of cancer cell death by proton beam in tumor hypoxic region

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. M.; Hur, T. R.; Lee, K. B.; Jeong, M. H.; Park, J. W. [Kyungbook National Univ., Daegu (Korea, Republic of)

    2007-04-15

    Proton beam induced apoptosis significantly in Lewis lung carcinoma cells and hepatoma HepG2 cells in a dose- and time-dependent manner, but slightly in leukemia Molt-4 cells. Relative biological effectiveness (RBE) values for death rate relative to gamma ray were ranged from 1.3 to 2.1 in LLC or HepG2 but 0.7 in Molt-4 cells at 72h after irradiation. The typical apoptosis was observed by nuclear DNA staining with DAPI. By FACS analysis after stained with PI, sub-G1 cell fraction was significantly increased but G2/M phase was not altered by proton beam irradiation measured at 24 h after irradiation. Proton beam-irradiated tumor cells induced cleavage of PARP-1 and procaspases (-3 and -9) and increased the level of p53 and p21. decreased pro-lamin B. Acitivity of caspases was significantly increased after proton beam irradiation. Furthermore, ROS were significantly increased and N-acetyl cystein (NAC) pretreatment restored the apoptotic cell death induced in proton beam-irradiated cells. In conclusion, single treatment of low energy proton beam with SOBP induced apoptosis of solid tumor cells via increased ROS, active caspase -3,-9 and p53, p2.

  15. mtDNA as a Mediator for Expression of Hypoxia-Inducible Factor 1α and ROS in Hypoxic Neuroblastoma Cells

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    Chung-Wen Kuo

    2017-06-01

    Full Text Available Mitochondria consume O2 to produce ATP and are critical for adaption of hypoxia, but the role of mitochondria in HIF-1α pathway is as yet unclear. In this study, mitochondrial DNA (mtDNA enriched (SK-N-AS and depleted (ρ0 cells of neuroblastoma were cultured in a hypoxic chamber to simulate a hypoxic condition and then the major components involved in mitochondrial related pathways, hypoxia-inducible factor 1α (HIF-1α and reactive oxygen species (ROS were measured. The results showed that hypoxia-stimulated exposure elevated expression of HIF-1α, which was additionally influenced by level of generated ROS within the cytosol. Moreover, elevation of HIF-1α also resulted in increases of lactate dehydrogenase A (LDH-A and pyruvate dehydrogenase kinase 1 (PDK1 in both hypoxic cells. The expression of mitochondrial biogenesis related proteins and metabolic components were noted to increase significantly in hypoxic SK-N-AS cells, indicating that mtDNA was involved in mitochondrial retrograde signaling and metabolic pathways. An analysis of dynamic proteins found elevated levels of HIF-1α causing an increased expression of dynamin-related protein 1 (DRP1 during hypoxia; further, the existence of mtDNA also resulted in higher expression of DRP1 during hypoxia. By using siRNA of HIF-1α or DRP1, expression of DRP1 decreased after suppression of HIF-1α; moreover, the expression of HIF-1α was also affected by the suppression of DRP1. In this study, we demonstrated that mtDNA is a mediator of HIF-1α in eliciting metabolic reprogramming, and mitochondrial biogenesis. Identification of a mutual relationship between HIF-1α and DRP1 may be a critical tool in the future development of clinical applications.

  16. Up-Regulation of ENO1 by HIF-1α in Retinal Pigment Epithelial Cells after Hypoxic Challenge Is Not Involved in the Regulation of VEGF Secretion.

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    Feihui Zheng

    Full Text Available Alpha-enolase (ENO1, a major glycolytic enzyme, is reported to be over-expressed in various cancer tissues. It has been demonstrated to be regulated by the Hypoxia-inducible factor 1-α (HIF-1α, a crucial transcriptional factor implicated in tumor progression and cancer angiogenesis. Choroidal neovascularization (CNV, which is a leading cause of severe vision loss caused by newly formed blood vessels in the choroid, is also engendered by hypoxic stress. In this report, we investigated the expression of ENO1 and the effects of its down-regulation upon cobalt (II chloride-induced hypoxia in retinal pigment epithelial cells, identified as the primary source of ocular angiogenic factors.HIF-1α-diminished retinal pigment epithelial cells were generated by small interfering RNA (siRNA technology in ARPE-19 cells, a human retinal pigment epithelial cell line. Both normal and HIF-1α-diminished ARPE-19 cells were then subjected to hypoxic challenge using cobalt (II chloride (CoCl2 or anaerobic chamber. The relation between ENO1 expression and vascular endothelial growth factor (VEGF secretion by retinal pigment epithelial cells were examined. Protein levels of HIF-1α and ENO1 were analyzed using Western Blot, while VEGF secretion was essayed by enzyme-linked immunosorbent assay (ELISA. Cytotoxicity after hypoxia was detected by Lactate Dehydrogenase (LDH Assay.Upon 24 hr of CoCl2-induced hypoxia, the expression levels of ENO1 and VEGF were increased along with HIF-1α in ARPE-19 cells, both of which can in turn be down-regulated by HIF-1α siRNA application. However, knockdown of ENO1 alone or together with HIF-1α did not help suppress VEGF secretion in hypoxic ARPE-19 cells.ENO1 was demonstrated to be up-regulated by HIF-1α in retinal pigment epithelial cells in response to hypoxia, without influencing VEGF secretion.

  17. Hypoxic conditions induce a cancer-like phenotype in human breast epithelial cells

    DEFF Research Database (Denmark)

    Vaapil, Marica; Helczynska, Karolina; Villadsen, René

    2012-01-01

    Solid tumors are less oxygenated than their tissue of origin. Low intra-tumor oxygen levels are associated with worse outcome, increased metastatic potential and immature phenotype in breast cancer. We have reported that tumor hypoxia correlates to low differentiation status in breast cancer. Less...... is known about effects of hypoxia on non-malignant cells. Here we address whether hypoxia influences the differentiation stage of non-malignant breast epithelial cells and potentially have bearing on early stages of tumorigenesis....

  18. Cardiac biomarkers in neonatal hypoxic ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, D

    2012-04-01

    Following a perinatal hypoxic-ischaemic insult, term infants commonly develop cardiovascular dysfunction. Troponin-T, troponin-I and brain natriuretic peptide are sensitive indicators of myocardial compromise. The long-term effects of cardiovascular dysfunction on neurodevelopmental outcome following perinatal hypoxic ischaemia remain controversial. Follow-up studies are warranted to ensure optimal cardiac function in adulthood. CONCLUSION: Cardiac biomarkers may improve the diagnosis of myocardial injury, help guide management, estimate mortality risk and may also aid in longterm neurodevelopmental outcome prediction following neonatal hypoxic-ischaemia.

  19. Hypoxic chondrogenic differentiation of human cord blood stem cells in structurally-graded polycaprolactone scaffolds

    DEFF Research Database (Denmark)

    Munir, Samir; Søballe, Kjeld; Ulrich-Vinther, Michael

    in standard micromass pellet system, layered on calcium polyphosphate (CPP), and on semi-permeable polytetrafluoroethane membranes with and without collagen type I, II or IV pre-coating. Findings / Results: The MPLC cell line used in this study possessed poor chondrogenic potency overall, but membrane...

  20. Aglycemia keeps mitochondrial oxidative phosphorylation under hypoxic conditions in HepG2 cells

    Czech Academy of Sciences Publication Activity Database

    Plecitá-Hlavatá, Lydie; Ježek, Jan; Ježek, Petr

    2015-01-01

    Roč. 47, č. 6 (2015), s. 467-476 ISSN 0145-479X R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GA13-02033S; GA MŠk(CZ) LH11055 Institutional support: RVO:67985823 Keywords : cancer mitochondria * non-canonical response to hypoxia * hypoxia-inducible factor * glutaminolysis * HepG2 cells Subject RIV: ED - Physiology Impact factor: 2.080, year: 2015

  1. Using stem cell oxygen physiology to optimize blastocyst culture while minimizing hypoxic stress.

    Science.gov (United States)

    Bolnick, Alan; Awonuga, Awoniyi O; Yang, Yu; Abdulhasan, Mohammed; Xie, Yufen; Zhou, Sichang; Puscheck, Elizabeth E; Rappolee, Daniel A

    2017-10-01

    This review is a response to the Fellows Forum on testing 2% oxygen for best culture of human blastocysts (J Ass Reprod Gen 34:303-8, 1; J Ass Reprod Gen 34:309-14, 2) prior to embryo transfer. It is a general analysis in support of the position that an understanding of stem cell physiology and responses to oxygen are necessary for optimization of blastocyst culture in IVF and to enhance reproductive success in fertile women.

  2. Hypoxic preconditioning with cobalt of bone marrow mesenchymal stem cells improves cell migration and enhances therapy for treatment of ischemic acute kidney injury.

    Directory of Open Access Journals (Sweden)

    Xiaofang Yu

    Full Text Available Mesenchymal stem cell (MSC administration is known to enhance the recovery of the kidney following injury. Here we tested the potential of hypoxic-preconditioned-MSC transplantation to enhance the efficacy of cell therapy on acute kidney injury (AKI by improving MSC migration to the injured kidney. Cobalt was used as hypoxia mimetic preconditioning (HMP. MSC were subjected to HMP through 24 h culture in 200 µmol/L cobalt. Compared to normoxia cultured MSC (NP-MSC, HMP significantly increased the expression of HIF-1α and CXCR4 in MSC and enhanced the migration of MSC in vitro. This effect was lost when MSC were treated with siRNA targeting HIF-1α or CXCR4 antagonist. SPIO labeled MSC were administered to rats with I/R injury followed immediately by magnetic resonance imaging. Imaging clearly showed that HMP-MSC exhibited greater migration and a longer retention time in the ischemic kidney than NP-MSC. Histological evaluation showed more HMP-MSC in the glomerular capillaries of ischemic kidneys than in the kidneys receiving NP-MSC. Occasional tubules showed iron labeling in the HMP group, while no tubules had iron labeling in NP group, indicating the possibility of tubular transdifferentiation after HMP. These results were also confirmed by fluorescence microscopy study using CM-DiI labeling. The increased recruitment of HMP-MSC was associated with reduced kidney injury and enhanced functional recovery. This effect was also related to the increased paracrine action by HMP-MSC. Thus we suggest that by enhancing MSC migration and prolonging kidney retention, hypoxic preconditioning of MSC may be a useful approach for developing AKI cell therapy.

  3. Generation of oxidants by hypoxic human pulmonary and coronary smooth-muscle cells.

    Science.gov (United States)

    Mehta, Jinesh P; Campian, Jian Li; Guardiola, Juan; Cabrera, Jesus A; Weir, E Kenneth; Eaton, John W

    2008-06-01

    Pulmonary vasoconstriction in response to hypoxia is unusual inasmuch as local exposure of nonpulmonary vasculature to hypoxia results in vasodilation. It has been suggested that pulmonary artery smooth-muscle cells may relax in response to intracellular generation of reactive oxygen species (ROS) and that the production of ROS decreases under hypoxia. However, other workers report increased ROS production in human pulmonary artery smooth-muscle cells (HPASMC) during hypoxia. Using dihydrodichlorofluorescein diacetate, dihydroethidium, and Amplex Red (Molecular Probes; Eugene, OR), we estimated ROS generation by confluent primary cultures of HPASMC and human coronary artery smooth-muscle cells (HCASMC) under normoxia (20%) and acute hypoxia (5%). All three assay systems showed that HPASMC production of ROS is decreased under hypoxia and to a greater extent than the decrease in ROS production by HCASMC. A substantially greater percentage of normoxic ROS production by HPASMC is mitochondrial (> 60%) compared to HCASMC (< 30%). These results support the conclusion that ROS generation decreases, rather than increases, in HPASMC during hypoxia. However, as ROS production also decreases in HCASMC during hypoxia, the reason for the opposite change in vascular tone is not yet apparent.

  4. Prediction of radiotherapy effect in patients with non-small cell lung cancer by Tc-99m hypoxic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun; Ahn, S. J.; Bom, H. S.; Heo, Y. J. [Chonnam National University Hospital, Gwangju (Korea, Republic of); Kim, S. M. [Chugnam National University Hospital, Daejeon (Korea, Republic of); Kim, C. K. [Wongkwang University Hospital, Iksan (Korea, Republic of)

    2005-07-01

    Hypoxia predicts poor response to radiation therapy. This study aimed to compare Tc-99m-EC-metronidazole (Tc-MN) uptake with F-18 FDG uptake in tumors and predict the therapeutic response to radiation therapy in patients with non-small cell lung cancer. Eight patients with non-small cell lung cancer underwent Tc-MN SPECT (20 mCi) and F-18 FDG PET (15.4 {+-}2.6 mCi) before the initiation of radiation therapy. Tumor-to-contralateral normal lung uptake ratios of MN and FDG and standardized uptake value (SUV) were on Tc-MN SPECT and F-18 FDG images. Response to therapy was assessed on follow-up chest CT and F-18 FDG PET after completion of radiation therapy. FDG and MN uptakes were found in all lung cancer. FDG SUV widely ranged from 9.9 to 53.5 (mean {+-} S.D: 23.3 {+-} 15.4), and tumor-to-contralateral normal lung uptake ratios of FDG were ranged from to 7.68 to 1.04 (mean {+-} S.D:14.59 {+-} 4.75). Tumor-to-contralateral normal lung uptake ratios of MN were ranged from to 2.28 to 4.41 (mean {+-} S.D: 3.45 {+-} 0.87). There was no significant correlation of NM with SUV and tumor-to-normal uptake ratios of FDG (r = -0.257, p =0.623; r = -0.143, p =0.787, respectively). One patent died during radiation therapy, and other 7 patients completed radiation therapy. Four patients showed partial response to radiation therapy, 3 patients complete remission. Tc-MN uptakes were variable and not significantly correlated with therapy response. However, its uptakes were lower in non-small cell lung cancer patients with good response to radiation therapy. Tc-MN could be available in the detection of intratumoral hypoxic tissues before radiation therapy and SPECT with Tc-MN may become useful in prediction of the prognosis in patients with non-small cell lung cancer.

  5. Hypoxic pretreatment of human umbilical cord mesenchymal stem cells regulating macrophage polarization

    Directory of Open Access Journals (Sweden)

    Chuan TONG

    2016-08-01

    Full Text Available Objective  To investigate the effect of human umbilical cord mesenchymal stem cells (hUC-MSCs on macrophage polarization under hypoxia. Methods  hUC-MSCs were obtained by explants adherent culture and cultured under normoxia (21% O2 and hypoxia (5% O2. The multi-directional differentiation of hUC-MSCs was observed by osteogenic and adipogenic differentiation induction. Live/death staining was performed to detect the cell viability, and ELISA was executed to detect the protein content in supernatant of hUC-MSCs. Transwell chamber was employed to co-culture the hUC-MSCs cultured under normoxia and hypoxia and macrophage (THP-1 stimulated by lipopolysaccharide (IPS, then the polarization of THP-1 was detected by immunofluorescence, and the secretions of inflammatory factor and anti-inflammatory factor of THP-1 were detected by ELISA. Results  hUC-MSCs cultured under hypoxia showed the ability of osteogenic and adipogenic multi-directional differentiation. Live/death staining showed the high cell viability of hUC-MSCs cultured under normoxia and hypoxia. The expression levels of prostaglandin E2 (PGE2 and indoleamine 2,3-dioxygenase (IDO were significantly higher in the hUC-MSCs cultured under hypoxia than in those cultured under normoxia. hUCMSCs cultured under hypoxia promoted the polarization of THP-1 to M2, obviously reduced the expression of TNF-α and IL-1β, and increased the expression of IL-10 significantly. Conclusion hUC-MSCs cultured under hypoxia may promote the polarization of THP-1 to M2 and improve the viability of anti-inflammatory. DOI: 10.11855/j.issn.0577-7402.2016.07.01

  6. Hypoxia-Specific Drug Tirapazamine Does Not Abrogate Hypoxic Tumor Cells in Combination Therapy with Irinotecan and Methylselenocysteine in Well-Differentiated Human Head and Neck Squamous Cell Carcinoma A253 Xenografts

    Directory of Open Access Journals (Sweden)

    Arup Bhattacharya

    2008-08-01

    Full Text Available Well-differentiated hypoxic regions in head and neck squamous cell carcinoma like in A253 xenografts are avascular and, therefore, hinder drug delivery leading to drug resistance and tumor regrowth. Methylselenocysteine (MSC, 0.2 mg/mouse per day per oral for 35 days starting 7 days before the first irinotecan (CPT-11 has been found to increase efficacy of a wide variety of chemotherapeutic agents including CPT-11 (100 mg/kg per week x 4 intravenously. Whereas CPT-11 leads to a 10% complete response (CR in A253 xenografts, the combination of MSC and CPT-11 increased the CR to 70%. Surviving tumors were found to consist largely of avascular hypoxic regions. Here, we investigated the combination of tirapazamine (TPZ, 70 mg/kg per week intraperitoneal x 4 administered 3 or 72 hours before CPT-11, a bioreductive drug in clinical trial with selective toxicity for hypoxic cells, with MSC and CPT-11 in further enhancing the cure rates. Tumor response, change in tumor hypoxic regions, and DNA damage were monitored in vivo. Tirapazamine administered 3 hours before CPT-11 in combination with MSC + CPT-11 led to a lower tumor burden. Tirapazamine did not increase cure rate beyond that of MSC + CPT-11 combination and was instead found to decrease cures with no evidence of an increased DNA damage or a significant reduction in avascular hypoxic tumor regions. CD31 immunostaining in A253 demonstrated disruption of tumor vessels by TPZ that could lower cytotoxic drug delivery to carbonic anhydrase IX-positive hypoxic tumor cells and may explain at least partially these unexpected results.

  7. Inhibition of IRE1 signaling affects the expression of genes encoded glucocorticoid receptor and some related factors and their hypoxic regulation in U87 glioma cells

    Directory of Open Access Journals (Sweden)

    Minchenko D.O.

    2016-07-01

    Full Text Available Objective. The aim of the present investigation was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1, which is a central mediator of the unfolded protein response on the expression of genes encoding glucocorticoid receptor (NR3C1 and some related proteins (SGK1, SGK3, NCOA1, NCOA2, ARHGAP35, NNT and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of the glioma growth.

  8. [Silencing hypoxia inducible factor-2α gene by small interference RNA inhibits the growth of mammosphere cells in nude mice under hypoxic microenvironment].

    Science.gov (United States)

    Qu, Hong-bo; Fan, Yuan-ming; Han, Ming-li; Zeng, Ni; Zhu, Zhi-kun; Liu, Hong; Xie, Jia; Wu, Cheng-yi; Tang, Wei-xue

    2013-04-16

    To explore the effects of silencing hypoxia inducible factor-2α (HIF-2α) by small interference RNA on the growth of mammosphere cells in nude mice under hypoxic microenvironment. The empty and interference vectors were transfected into MCF-7 cell. Then G418 was added to screen the positive cells to obtain stable cell line. The empty and interference vectors were inoculated subcutaneously into left and right back near hind limb of nude mice. The volume and weight of tumors were calculated respectively. The expressions of HIF-2α, CD44, OCT-4 and KLF-4 protein in xenograft tumor tissues were detected by Western blot. The expression vector of HIF-2α-siRNA was successfully established. The formation of mammosphere was lowered by silencing HIF-2α gene expression. In contract to empty vector group cell, there were obvious decreases in the volumes and weights of tumors in interference group (P interference group (0.42 ± 0.01) was much lower than that of the empty vector group (0.89 ± 0.03, P interference group (0.21 ± 0.01) was much lower than the empty vector group (0.78 ± 0.03, P interference group (0.42 ± 0.01)was much lower than the empty vector group (0.68 ± 0.03, P interference group (0.34 ± 0.01) was much lower than the empty vector group (0.72 ± 0.03, P < 0.05). Silencing HIF-2α gene can effectively inhibit the growth of breast cancer stem cells in nude mice under hypoxic microenvironment. Its mechanism may be through inhibited capacity for self-renewal and proliferation of breast cancer stem cells in vivo through the down-regulated expressions of markers associated with stem cells. HIF-2α is expected to become a new target for gene therapy of breast cancer.

  9. Preterm Hypoxic Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Krishna G Gopagondanahalli

    2016-10-01

    Full Text Available Hypoxic ischemic encephalopathy (HIE is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic ischemic episode before or during birth. However, in the preterm infant, defining hypoxic ischemic injury, its clinical course, monitoring and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic ischemic insult in preterm infants is probably higher than recognized, and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies.

  10. Optical molecular imaging of hypoxic breast cancer - From prospect to preclinical practice

    OpenAIRE

    van Brussel, A.S.A.

    2013-01-01

    Current imaging modalities for breast cancer diagnosis and therapy monitoring either lack sensitivity, specificity, make use of radiation and/or give images of limited resolution. Optical molecular imaging is a novel technique that detects light emitted by (breast)cancer-specific probes with a sensitive camera. As hypoxia is a common condition in solid tumors, proteins upregulated in hypoxic cells are of special interest as target for molecular imaging of breast cancer. In this thesis we revi...

  11. Role of hypoxia and glycolysis in the development of multi-drug resistance in human tumor cells and the establishment of an orthotopic multi-drug resistant tumor model in nude mice using hypoxic pre-conditioning

    Directory of Open Access Journals (Sweden)

    Duan Zhenfeng

    2011-02-01

    Full Text Available Abstract Background The development of multi-drug resistant (MDR cancer is a significant challenge in the clinical treatment of recurrent disease. Hypoxia is an environmental selection pressure that contributes to the development of MDR. Many cancer cells, including MDR cells, resort to glycolysis for energy acquisition. This study aimed to explore the relationship between hypoxia, glycolysis, and MDR in a panel of human breast and ovarian cancer cells. A second aim of this study was to develop an orthotopic animal model of MDR breast cancer. Methods Nucleic and basal protein was extracted from a panel of human breast and ovarian cancer cells; MDR cells and cells pre-exposed to either normoxic or hypoxic conditions. Western blotting was used to assess the expression of MDR markers, hypoxia inducible factors, and glycolytic proteins. Tumor xenografts were established in the mammary fat pad of nu/nu mice using human breast cancer cells that were pre-exposed to either hypoxic or normoxic conditions. Immunohistochemistry was used to assess the MDR character of excised tumors. Results Hypoxia induces MDR and glycolysis in vitro, but the cellular response is cell-line specific and duration dependent. Using hypoxic, triple-negative breast cancer cells to establish 100 mm3 tumor xenografts in nude mice is a relevant model for MDR breast cancer. Conclusion Hypoxic pre-conditiong and xenografting may be used to develop a multitude of orthotopic models for MDR cancer aiding in the study and treatment of the disease.

  12. Comparative Study on the Protective Effects of Salidroside and Hypoxic Preconditioning for Attenuating Anoxia-Induced Apoptosis in Pheochromocytoma (PC12) Cells.

    Science.gov (United States)

    Hu, Yao; Lv, Xiumei; Zhang, Jing; Meng, Xianli

    2016-10-30

    BACKGROUND Hypoxia is an important sign that can result from body injuries or a special condition such as being at a high altitude or deep water diving. In the current studies, hypoxic preconditioning (HPC) plays a key role in reducing hypoxia-induced apoptosis. We aimed to study the pharmacologic preconditioning effects of salidroside versus those of HPC in hypoxia-/anoxia-induced apoptosis in PC12 cells (pheochromocytoma). MATERIAL AND METHODS PC12 cells were treated by different experimental conditions: control condition, hypoxia condition, HPC condition, low-/middle-/high-dose condition of salidroside, cyclosporine A (CsA), and oratractyloside (ATR). The cell viability, lactate dehydrogenase (LDH) activity, apoptosis, mitochondrial membrane potential (MMP), intracellular Ca2+, caspase-3 activity, and expression of Bcl-2 were detected in PC12 cells after the hypoxia treatment. Salidroside, extracted from the traditional Chinese herb Rhodiola rosea L, plays an essential role in reducing hypoxia-induced apoptosis in PC12 cells by the mitochondrial pathway. RESULTS Salidroside decreased the apoptosis and increased the viability of hypoxia-induced PC12 cells more effectively than HPC Moreover, salidroside markedly stabilized MMP and intracellular Ca2+, reduced or inhibited LDH and caspase-3 activity, and up-regulated Bcl-2; CsA and ATR showed corresponding function. CONCLUSIONS Salidroside administration restrains apoptosis induced by hypoxia in PC12 cells. The protective effects are mediated by preservation of mitochondrial integrity and MMP to inhibit the excessive Ca2+ influx and caspase-3 activity and to promote the Bcl-2 expression, providing a potential clinical and effective therapeutic mechanism to reduce deaths from ischemic or hypoxic injury.

  13. (II) complexes as sensitizers for dye sensitized solar cells

    Indian Academy of Sciences (India)

    electrical conversion efficiency. (η) of 10% at AM 1·5 solar radiation.12 Although. Z907 sensitized solar cell resulted in low efficiency. *For correspondence. J. Chem. Sci., Vol. 123, No. 1, January 2011, pp. 37–46. * Indian Academy of Sciences. 37 ...

  14. The Long Non-coding RNA HIF1A-AS2 Facilitates the Maintenance of Mesenchymal Glioblastoma Stem-like Cells in Hypoxic Niches

    Directory of Open Access Journals (Sweden)

    Marco Mineo

    2016-06-01

    Full Text Available Long non-coding RNAs (lncRNAs have an undefined role in the pathobiology of glioblastoma multiforme (GBM. These tumors are genetically and phenotypically heterogeneous with transcriptome subtype-specific GBM stem-like cells (GSCs that adapt to the brain tumor microenvironment, including hypoxic niches. We identified hypoxia-inducible factor 1 alpha-antisense RNA 2 (HIF1A-AS2 as a subtype-specific hypoxia-inducible lncRNA, upregulated in mesenchymal GSCs. Its deregulation affects GSC growth, self-renewal, and hypoxia-dependent molecular reprogramming. Among the HIF1A-AS2 interactome, IGF2BP2 and DHX9 were identified as direct partners. This association was needed for maintenance of expression of their target gene, HMGA1. Downregulation of HIF1A-AS2 led to delayed growth of mesenchymal GSC tumors, survival benefits, and impaired expression of HMGA1 in vivo. Our data demonstrate that HIF1A-AS2 contributes to GSCs’ speciation and adaptation to hypoxia within the tumor microenvironment, acting directly through its interactome and targets and indirectly by modulating responses to hypoxic stress depending on the subtype-specific genetic context.

  15. Gene sensitizes cancer cells to chemotherapy drugs

    Science.gov (United States)

    NCI scientists have found that a gene, Schlafen-11 (SLFN11), sensitizes cells to substances known to cause irreparable damage to DNA.  As part of their study, the researchers used a repository of 60 cell types to identify predictors of cancer cell respons

  16. Nitric oxide metabolites in goldfish under normoxic and hypoxic conditions

    DEFF Research Database (Denmark)

    Hansen, Marie N.; Jensen, Frank Bo

    2010-01-01

    levels was assessed from metabolic and respiratory variables. In normoxic goldfish, the concentrations of NO metabolites in plasma and tissues were comparable with values reported in mammals, indicative of similar NOS activity. Exposure to hypoxia [at PO2 (partial pressure of O2) values close......) in multiple tissues of a non-mammalian vertebrate (goldfish) under normoxic and hypoxic conditions. NO metabolites were measured in blood (plasma and red cells) and heart, brain, gill, liver, kidney and skeletal muscle, using highly sensitive reductive chemiluminescence. The severity of the chosen hypoxia...

  17. Dye-sensitized solar cells based on purple corn sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Phinjaturus, Kawin [Materials Science and Nanotechnology Program, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Maiaugree, Wasan [Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Suriharn, Bhalang [Department of Plant Science and Agricultural Resources, Faculty of Agriculture, Khon Kaen University, Khon Kaen 40002 (Thailand); Pimanpaeng, Samuk; Amornkitbamrung, Vittaya [Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Integrated Nanotechnology Research Center (INRC), Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Swatsitang, Ekaphan, E-mail: ekaphan@kku.ac.th [Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Integrated Nanotechnology Research Center (INRC), Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen 40002 (Thailand); Nanotec-KKU Center of Excellence on Advanced Nanomaterials for Energy Production and Storage, Khon Kaen 40002 (Thailand)

    2016-09-01

    Graphical abstract: - Highlights: • Extract from husk, cob and silk of purple corn was used as a photosensitizer in DSSC. • Effect of solvents i.e. acetone, ethanol and DI water on DSSC efficiency was studied. • The highest efficiency of 1.06% was obtained in DSSC based on acetone extraction. - Abstract: Natural dye extracted from husk, cob and silk of purple corn, were used for the first time as photosensitizers in dye sensitized solar cells (DSSCs). The dye sensitized solar cells fabrication process has been optimized in terms of solvent extraction. The resulting maximal efficiency of 1.06% was obtained from purple corn husk extracted by acetone. The ultraviolet–visible (UV–vis) spectroscopy, Fourier transform infrared spectroscopy (FTIR), electrochemical impedance spectroscopy (EIS) and incident photon-to-current efficiency (IPCE) were employed to characterize the natural dye and the DSSCs.

  18. Fruit based Dye Sensitized Solar Cells

    Science.gov (United States)

    Ung, M. C.; Sipaut, C. S.; Dayou, J.; Liow, K. S.; Kulip, J.; Mansa, R. F.

    2017-07-01

    Dye Sensitized Solar Cell (DSSC) was first discovered in 1991 by O’regan and Gratzel. This new type of solar cell was reported to have lower production cost with efficiency as high as 12% which is comparable to conventional silicon solar cell. Initially, it uses ruthenium dye as light sensitizer for the operation. However, DSSC with ruthenium dyes are facing environment friendly issues due to the toxic chemicals and costly purification in processing ruthenium dye. Regardless of the poor performance in DSSC, natural dyes which are easy to prepare, cheap and environmental friendly still appear to be an alternative as dye sensitizer. In this study, dye sensitized solar cells (DSSCs) were fabricated using anthocyanin source dyes extracted from several local fruits. All the extracts absorb a wide range of the visible light and ultraviolet spectrum. Therefore, all of the natural dyes show light absorption properties which is important for a dye sensitizer. A DSSC is comprised of conductive substrate, nanoporous semiconductor TiO2 layer, dye sensitizer, electrolyte with redox couple and a counter electrode with catalyst. In this study, the effect of different light source and different counter electrode are been investigated. However, it is vital to know that further research need to do more on the locally Borneo sourced dyes to evaluate and enhance their performance in Dye Sensitized Solar Cell.

  19. Hypoxia in Tumor Angiogenesis and Metastasis: Evaluation of VEGF and MMP Over-expression and Down-Regulation of HIF-1alpha with RNAi in Hypoxic Tumor Cells

    Science.gov (United States)

    Shah, Shruti

    Background: As tumor mass grows beyond a few millimeters in diameter, the angiogenic "switch" is turned on leading to recruitment of blood vessels from surrounding artery and veins. However, the tumor mass is poorly perfused and there are pockets of hypoxia or lower oxygen concentrations relative to normal tissue. Hypoxia-inducing factor-1a (HIF-1a), a transcription factor, is activated when the oxygen concentration is low. Upon activation of HIF-1a, a number of other genes also turn on that allows the tumor to become more aggressive and resistant to therapy. Purpose: The main objectives of this study were to evaluate the effect of hypoxia-induced HIF-1a followed by over-expression of angiogenic and metastatic markers in tumor cells and down-regulation of HIF-1a using nanoparticle-delivered RNA interference therapy. Methods: Human ovarian (SKOV3) and breast (MDA-MB-231) adenocarcinoma cells were incubated under normoxic and hypoxic conditions. Following hypoxia treatment of the cells, HIF-1α, vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), and MMP-9 expression was analyzed qualitatively and quantitatively. For intracellular delivery of HIF-1a gene silencing small interfering RNA (siRNA), type B gelatin nanoparticles were fabricated using the solvent displacement method and the surface was modified with poly(ethylene glycol) (PEG, Mol. wt. 2kDa). Cellular uptake and distribution of the nanoparticles was observed with Cy3-siRNA loaded, FITC-conjugated gelatin nanoparticles. Cytotoxicity of the nanoparticle formulations was evaluated in both the cell lines. siRNA was transfected in the gelatin nanoparticles under hypoxic conditions. Total cellular protein and RNA were extracted for analysis of HIF1a, VEGF, MMP-2 and MMP-9 expression. Results: MDA-MB-231 and SKOV3 cells show increased expression of HIF1a under hypoxic conditions compared to baseline levels at normoxic conditions. ELISA and western blots of VEGF, MMP-2 and MMP-9 appear to

  20. Non-radioactive 2-deoxy-2-fluoro-D-glucose inhibits glucose uptake in xenograft tumours and sensitizes HeLa cells to doxorubicin in vitro.

    Science.gov (United States)

    Niccoli, Sarah; Boreham, Douglas R; Phenix, Christopher P; Lees, Simon J

    2017-01-01

    A glucose analog called 2-deoxy-D-glucose (2DG) has been successfully used to sensitize cancer cells to ROS-inducing cancer treatments such as ionizing radiation, through the inhibition of glycolysis. However, the use of 2DG can be limited by several factors such as availability, non-specific cytotoxicity, and chemoresistance under hypoxic conditions. The purpose of this study was to investigate the use of non-radioactive 2-deoxy-2-fluoro-D-glucose (19FDG), a drug that potentially addresses current limitations of 2DG. The effectiveness of using either 2DG or 19FDG in combination with doxorubicin (Dox) in HeLa cells was determined in both normoxia and hypoxia. We have also shown that under both oxygen conditions, 19FDG-treated cells produce less lactate than 2DG-treated cells, an important finding that suggests improved inhibition of glycolysis, the preferential pathway for cancerous cells. When used in combination with Dox, we have demonstrated a significant decrease in the number of viable cells, with the effect of 19FDG remaining stable across both normoxic and hypoxic conditions. Moreover, the assessment of apoptosis and necrosis revealed that 19FDG maintained its ability to sensitize HeLa cells to Dox in hypoxia, but 2DG was only effective under normoxic conditions. The retained effectiveness of 19FDG in combination with Dox under hypoxic conditions, suggests that 19FDG may be efficacious for sensitizing hypoxic regions of solid tumour masses. Importantly, the ability of 19FDG to inhibit glucose uptake in vivo was also confirmed using positron emission tomography (PET) of xenograft tumours. The results displayed here suggest 19FDG is a promising combination therapy, which may lead to decreased ROS scavenging via glycolysis, and enhanced treatment success.

  1. Shear Stress Induces Differentiation of Endothelial Lineage Cells to Protect Neonatal Brain from Hypoxic-Ischemic Injury through NRP1 and VEGFR2 Signaling

    Directory of Open Access Journals (Sweden)

    Chia-Wei Huang

    2015-01-01

    Full Text Available Neonatal hypoxic-ischemic (HI brain injuries disrupt the integrity of neurovascular structure and lead to lifelong neurological deficit. The devastating damage can be ameliorated by preserving the endothelial network, but the source for therapeutic cells is limited. We aim to evaluate the beneficial effect of mechanical shear stress in the differentiation of endothelial lineage cells (ELCs from adipose-derived stem cells (ASCs and the possible intracellular signals to protect HI injury using cell-based therapy in the neonatal rats. The ASCs expressed early endothelial markers after biochemical stimulation of endothelial growth medium. The ELCs with full endothelial characteristics were accomplished after a subsequential shear stress application for 24 hours. When comparing the therapeutic potential of ASCs and ELCs, the ELCs treatment significantly reduced the infarction area and preserved neurovascular architecture in HI injured brain. The transplanted ELCs can migrate and engraft into the brain tissue, especially in vessels, where they promoted the angiogenesis. The activation of Akt by neuropilin 1 (NRP1 and vascular endothelial growth factor receptor 2 (VEGFR2 was important for ELC migration and following in vivo therapeutic outcomes. Therefore, the current study demonstrated importance of mechanical factor in stem cell differentiation and showed promising protection of brain from HI injury using ELCs treatment.

  2. Sensitive-cell-based fish chromatophore biosensor

    Science.gov (United States)

    Plant, Thomas K.; Chaplen, Frank W.; Jovanovic, Goran; Kolodziej, Wojtek; Trempy, Janine E.; Willard, Corwin; Liburdy, James A.; Pence, Deborah V.; Paul, Brian K.

    2004-07-01

    A sensitive biosensor (cytosensor) has been developed based on color changes in the toxin-sensitive colored living cells of fish. These chromatophores are highly sensitive to the presence of many known and unknown toxins produced by microbial pathogens and undergo visible color changes in a dose-dependent manner. The chromatophores are immobilized and maintained in a viable state while potential pathogens multiply and fish cell-microbe interactions are monitored. Low power LED lighting is used to illuminate the chromatophores which are magnified using standard optical lenses and imaged onto a CCD array. Reaction to toxins is detected by observing changes is the total area of color in the cells. These fish chromatophores are quite sensitive to cholera toxin, Staphococcus alpha toxin, and Bordatella pertussis toxin. Numerous other toxic chemical and biological agents besides bacterial toxins also cause readily detectable color effects in chromatophores. The ability of the chromatophore cell-based biosensor to distinguish between different bacterial pathogens was examined. Toxin producing strains of Salmonella enteritis, Vibrio parahaemolyticus, and Bacillus cereus induced movement of pigmented organelles in the chromatophore cells and this movement was measured by changes in the optical density over time. Each bacterial pathogen elicited this measurable response in a distinctive and signature fashion. These results suggest a chromatophore cell-based biosensor assay may be applicable for the detection and identification of virulence activities associated with certain air-, food-, and water-borne bacterial pathogens.

  3. Protective Effects of N-Acetyl-L-Cysteine in Human Oligodendrocyte Progenitor Cells and Restoration of Motor Function in Neonatal Rats with Hypoxic-Ischemic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Dongsun Park

    2015-01-01

    Full Text Available Objective. Since oligodendrocyte progenitor cells (OPCs are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE, the present study was aimed at investigating the protective effects of N-acetyl-L-cysteine (NAC, a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats. Methods. In in vitro study, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. In in vivo study, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed. Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE. Conclusion. The results indicate that NAC exerts neuroprotective effects in vitro and in vivo by preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

  4. Hypoxic pulmonary vasoconstriction.

    Science.gov (United States)

    Swenson, Erik R

    2013-06-01

    Hypoxic pulmonary vasoconstriction (HPV) continues to fascinate cardiopulmonary physiologists and clinicians since its definitive description in 1946. Hypoxic vasoconstriction exists in all vertebrate gas exchanging organs. This fundamental response of the pulmonary vasculature in air breathing animals has relevance to successful fetal transition to air breathing at birth and as a mechanism of ventilation-perfusion matching in health and disease. It is a complex process intrinsic to the vascular smooth muscle, but with in vivo modulation by a host of factors including the vascular endothelium, erythrocytes, pulmonary innervation, circulating hormones and acid-base status to name only a few. This review will provide a broad overview of HPV and its mechansms and discuss the advantages and disadvantages of HPV in normal physiology, disease and high altitude.

  5. [Effects of bone marrow mesenchymal stem cells on learning and memory functional recovery in neonatal rats with hypoxic-ischemic brain damage].

    Science.gov (United States)

    Liu, Yang; Zhang, Xuan; Dai, Ying; Shu, Chang; Qu, Ping; Liu, You-xue; Yang, Li; Li, Ting-yu

    2008-09-01

    Neonatal hypoxic-ischemic brain damage (HIBD) causes acute death and chronic nervous system sequelae in newborn infants and children. Whereas there have been no specific treatment towards it up to now. Studies have shown that bone marrow mesenchymal stem cells (MSCs) have the therapeutic potential in many nervous system diseases and the authors previously found that retinoid acid (RA), which plays an important role in brain development, could enhance the neural differentiation of rat MSCs (rMSCs) in vitro. This study aimed to examine effects of rMSCs and RA-preinduced rMSC on learning and memory functional recovery after HIBD in neonatal rats in order to explore a new treatment strategy for clinical application, and explore the mechanism of action of rMSCs. Rat MSCs were isolated and purified from the whole bone marrow of juvenile Wistar rats by removing the non-adherent cells in primary and passage cultures. Neonatal hypoxic-ischemic brain damage rat models were built according to the methods described by Rice: the right carotid artery of 7-day-postnatal Wistar rats was ligated under anesthesia, and then the rats were exposed to 8% - 9% O2 in a container. At 5 days after hypoxia-ischemia, the HIBD neonatal rats were randomly divided into 3 groups and respectively transplanted with saline, BrdU marked rMSCs (1 - 2 x 10(5)) or RA-preinduced rMSCs (1 - 2 x 10(5)) into their lateral cerebral ventricle. Immunohistochemistry for nestin, neuron-specific enolase (NSE), neurofilament protein-heavy chain (NF-H) and glial fibrillary acidic protein (GFAP) were used to identify cells derived from rMSCs at 14 days and 42 days after transplantation. Shuttle box test was performed to evaluate the condition of learning and memory functional recovery when animals were 7 weeks old. Neurotrophin and receptors cDNA microarray were also employed at 14 days after transplantation to investigate the underlying action mechanisms of rMSCs treatment. Real-time PCR was used to confirm some of

  6. Recent Advances in Dye Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Umer Mehmood

    2014-01-01

    Full Text Available Solar energy is an abundant and accessible source of renewable energy available on earth, and many types of photovoltaic (PV devices like organic, inorganic, and hybrid cells have been developed to harness the energy. PV cells directly convert solar radiation into electricity without affecting the environment. Although silicon based solar cells (inorganic cells are widely used because of their high efficiency, they are rigid and manufacturing costs are high. Researchers have focused on organic solar cells to overcome these disadvantages. DSSCs comprise a sensitized semiconductor (photoelectrode and a catalytic electrode (counter electrode with an electrolyte sandwiched between them and their efficiency depends on many factors. The maximum electrical conversion efficiency of DSSCs attained so far is 11.1%, which is still low for commercial applications. This review examines the working principle, factors affecting the efficiency, and key challenges facing DSSCs.

  7. Semiconductor quantum dot-sensitized solar cells

    Directory of Open Access Journals (Sweden)

    Jianjun Tian

    2013-10-01

    Full Text Available Semiconductor quantum dots (QDs have been drawing great attention recently as a material for solar energy conversion due to their versatile optical and electrical properties. The QD-sensitized solar cell (QDSC is one of the burgeoning semiconductor QD solar cells that shows promising developments for the next generation of solar cells. This article focuses on recent developments in QDSCs, including 1 the effect of quantum confinement on QDSCs, 2 the multiple exciton generation (MEG of QDs, 3 fabrication methods of QDs, and 4 nanocrystalline photoelectrodes for solar cells. We also make suggestions for future research on QDSCs. Although the efficiency of QDSCs is still low, we think there will be major breakthroughs in developing QDSCs in the future.

  8. Plasmonic Dye-Sensitized Solar Cells

    KAUST Repository

    Ding, I-Kang

    2010-12-14

    This image presents a scanning electron microscopy image of solid state dye-sensitized solar cell with a plasmonic back reflector, overlaid with simulated field intensity plots when monochromatic light is incident on the device. Plasmonic back reflectors, which consist of 2D arrays of silver nanodomes, can enhance absorption through excitation of plasmonic modes and increased light scattering, as reported by Michael D. McGehee, Yi Cui, and co-workers.

  9. Hypoxic conditions and iron restriction affect the cell-wall proteome of Candida albicans grown under vagina-simulative conditions

    NARCIS (Netherlands)

    Sosinska, Grazyna J.; de Groot, Piet W. J.; Teixeira de Mattos, M. Joost; Dekker, Henk L.; de Koster, Chris G.; Hellingwerf, Klaas J.; Klis, Frans M.

    2008-01-01

    Proteins that are covalently linked to the skeletal polysaccharides of the cell wall of Candida albicans play a major role in the colonization of the vaginal mucosal surface, which may result in vaginitis. Here we report on the variability of the cell-wall proteome of C. albicans as a function of

  10. USING OXYGEN-CONSUMING THERMOSET PLASTICS TO GENERATE HYPOXIC CONDITIONS IN MICROFLUIDIC DEVICES FOR POTENTIAL CELL CULTURE APPLICATIONS

    DEFF Research Database (Denmark)

    Sticker, Drago; Rothbauer, Mario; Ehgartner, Josef

    The precise control of the oxygen concentration in a cellular environment allows the study of cells under physiologically relevant conditions. This work reports on a novel method for the generation of reduced dissolved oxygen concentrations in microfluidic chambers for cell- and organ-on-chip app...

  11. Anaerobic respiration sustains mitochondrial membrane potential in a prolyl hydroxylase pathway-activated cancer cell line in a hypoxic microenvironment.

    Science.gov (United States)

    Takahashi, Eiji; Sato, Michihiko

    2014-02-15

    To elucidate how tumor cells produce energy in oxygen-depleted microenvironments, we studied the possibility of mitochondrial electron transport without oxygen. We produced well-controlled oxygen gradients (ΔO2) in monolayer-cultured cells. We then visualized oxygen levels and mitochondrial membrane potential (ΔΦm) in individual cells by using the red shift of green fluorescent protein (GFP) fluorescence and a cationic fluorescent dye, respectively. In this two-dimensional tissue model, ΔΦm was abolished in cells >500 μm from the oxygen source [the anoxic front (AF)], indicating limitations in diffusional oxygen delivery. This result perfectly matched GFP-determined ΔO2. In cells pretreated with dimethyloxaloylglycine (DMOG), a prolyl hydroxylase domain-containing protein (PHD) inhibitor, the AF was expanded to 1,500-2,000 μm from the source. In these cells, tissue ΔO2 was substantially decreased, indicating that PHD pathway activation suppressed mitochondrial respiration. The expansion of the AF and the reduction of ΔO2 were much more prominent in a cancer cell line (Hep3B) than in the equivalent fibroblast-like cell line (COS-7). Hence, the results indicate that PHD pathway-activated cells can sustain ΔΦm, despite significantly decreased electron flux to complex IV. Complex II inhibition abolished the effect of DMOG in expanding the AF, although tissue ΔO2 remained shallow. Separate experiments demonstrated that complex II plays a substantial role in sustaining ΔΦm in DMOG-pretreated Hep3B cells with complex III inhibition. From these results, we conclude that PHD pathway activation can sustain ΔΦm in an otherwise anoxic microenvironment by decreasing tissue ΔO2 while activating oxygen-independent electron transport in mitochondria.

  12. Sphingosine Kinase-1 Involves the Inhibitory Action of HIF-1α by Chlorogenic Acid in Hypoxic DU145 Cells

    Directory of Open Access Journals (Sweden)

    Myoung-Sun Lee

    2017-02-01

    Full Text Available Hypoxia enhances cancer development in a solid tumor. Hypoxia-inducible factor-1 α (HIF-1α is a transcription factor that is dominantly expressed under hypoxia in solid tumor cells and is a key factor that regulates tumor. HIF-1α regulates several target genes involved in many aspects of cancer progression, including angiogenesis, metastasis, anti-apoptosis and cell proliferation as well as imparts resistance to cancer treatment. In this study, we assessed Crataegus Pinnatifida Bunge var. typical Schneider ethanol extract (CPE for its anti-cancer effects in hypoxia-induced DU145 human prostate cancer cell line. CPE decreased the abundance of HIF-1α and sphingosine kinase-1 (SPHK-1 in hypoxia-induced prostate cancer DU145 cells. CPE decreased HIF-1α and SPHK-1 as well as SPHK-1 activity. Chlorogenic acid (CA is one of four major compounds of CPE. Compared to CPE, CA significantly decreased the expression of HIF-1α and SPHK-1 as well as SPHK-1 activity in hypoxia-induced DU145 cells. Furthermore, CA decreased phosphorylation AKT and GSK-3β, which are associated with HIF-1α stabilization and affected SPHK-1 in a concentration-dependent manner. We confirmed the mechanism of CA-induced inhibition of HIF-1α by SPHK-1 signaling pathway using SPHK-1 siRNA and SPHK inhibitor (SKI. CA decreased the secretion and cellular expression of VEGF, thus inhibiting hypoxia-induced angiogenesis. Treatment of DU145cells with SPHK1 siRNA and CA for 48 h decreased cancer cell growth, and the inhibitory action of SPHK siRNA and CA on cell growth was confirmed by decrease in the abundance of Proliferating cell nuclear antigen (PCNA.

  13. Review of Recent Progress in Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Fan-Tai Kong

    2007-01-01

    Full Text Available We introduced the structure and the principle of dye-sensitized solar cell (DSC. The latest results about the critical technology and the industrialization research on dye-sensitized solar cells were reviewed. The development of key components, including nanoporous semiconductor films, dye sensitizers, redox electrolyte, counter electrode, and conducting substrate in dye-sensitized solar cells was reviewed in detail. The developing progress and prospect of dye-sensitized solar cells from small cells in the laboratory to industrialization large-scale production were reviewed. At last, the future development of DSC was prospective for the tendency of dye-sensitized solar cells.

  14. Sensitizers for Aqueous-Based Solar Cells.

    Science.gov (United States)

    Li, Chun-Ting; Lin, Ryan Yeh-Yung; Lin, Jiann T

    2017-03-02

    Aqueous dye-sensitized solar cells (DSSCs) are attractive due to their sustainability, the use of water as a safe solvent for the redox mediators, and their possible applications in photoelectrochemical water splitting. However, the higher tendency of dye leaching by water and the lower wettability of dye molecules are two major obstacles that need to be tackled for future applications of aqueous DSSCs. Sensitizers designed for aqueous DSSCs are discussed based on their functions, such as modification of the molecular skeleton and the anchoring group for better stability against dye leaching by water, and the incorporation of hydrophilic entities into the dye molecule or the addition of a surfactant to the system to increase the wettability of the dye for more facile dye regeneration. Surface treatment of the photoanode to deter dye leaching or improve the wettability of the dye molecule is also discussed. Redox mediators designed for aqueous DSSCs are also discussed. The review also includes quantum-dot-sensitized solar cells, with a focus on improvements in QD loading and suppression of interfacial charge recombination at the photoanode. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Scintigraphic imaging of focal hypoxic tissue: development and clinical applications of {sup 123} I-IAZA

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I.; McEwan, Alexander J.B. [Alberta Univ., Edmonton (Canada); Cross Cancer Institute, Edmonton (Canada); E-mail: leonard.wiebe@ualberta.ca

    2002-09-01

    Affected tissues in a number of diseases, including cancer, stroke, cardiac infarction and diabetes, develop focal tissue hypoxia during their progression. Tbe presence of hypoxic tissue may make the disease refractory to therapy, as in the case of solid tumor therapy using low LET ionizing radiation. In other pathologies, the detection of viable but hypoxic tissues may serve as a prodromal indicator of developing disease (e.g. diabetes), or as a prognostic indicator for management of the disease (e.g. stroke). Over the past two decades a number of hypoxia radio imaging agents have been developed and tested clinically. Of these, {sup 18} F-Fm iso and {sup 123} I - IAZA are the most widely used radiotracers for PET and SPECT/planar imaging, respectively. IAZA and Fm iso are a 2-nitroimidazoles that chemically bind to subcellular components of viable hypoxic tissues. They sensitize hypoxic tumor to the killing effects of ionizing radiation via mechanisms that mimic the radiosensitizing effects of oxygen, and are therefore called oxygen mimetic. The oxygen mimetic effect is attributable in large part to the covalent binding of reductively-activated nitroimidazole intermediates to critical cellular macromolecules. Nitroimidazoles labelled with gamma-emitting radionuclides (e.g. {sup 18} F-Fm iso and {sup 123} I -IAZA) have been used as scintigraphic markers of tumour hypoxia, based on the need to identify radioresistant hypoxic tumour cells as part of the radiotherapy planning process. Broader interest in non-invasive, imaging-based identification of focal hypoxia in a number of diseases has extended hypoxia studies to include peripheral vascular disease associated with diabetes, rheumatoid arthritis, stroke, myocardial ischaemia, brain trauma and oxidative stress. In this review, the current status of hypoxia-selective studies with {sup 123} I - IAZA, an experimental diagnostic radiopharmaceutical, is reviewed with respect to its pre-clinical development and clinical

  16. Hypoxic mitochondria: accomplices in resistance.

    Science.gov (United States)

    Mazure, N M; Brahimi-Horn, M C; Pouysségur, J

    2011-05-01

    Mitochondria originated from a distant ancestor: the α-proteobacteria. They evolved over millions of years in a symbiotic relationship in eukaryotic cells by favoring consumption of oxygen by the electron transport chain with production of ATP. Contemporary mitochondria still play a crucial role in providing energy but also in apoptosis. Because of this symbiotic relationship and their pivotal function, mitochondria undoubtedly participate in tumorigenesis. Genetic defects in mitochondrial DNA, blockade of oxidative phosphorylation and mitophagy in tumor cells modify the production of damaging reactive oxygen species and restrain apoptosis. As the environment of tumor cells becomes more and more hypoxic, the hypoxia-inducible factor (HIF) is stabilized and participates in the reprogramming of cell metabolism. Recently, we became interested in asking whether HIF and hypoxia affect mitochondrial function. In this review, we show that hypoxia induces enlargement of mitochondria, due to abnormal fusion, which results in resistance to apoptosis and thus in survival. The role of hypoxia-induced BNIP3 and BNIP3L, proteins recently described as pro-survival proteins, in survival is also discussed.

  17. Cell death sensitization of leukemia cells by opioid receptor activation.

    Science.gov (United States)

    Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Fichtner, Iduna; Alt, Andreas; Hilger, Ralf A; Debatin, Klaus-Michael; Miltner, Erich

    2013-05-01

    Cyclic AMP (cAMP) regulates a number of cellular processes and modulates cell death induction. cAMP levels are altered upon stimulation of specific G-protein-coupled receptors inhibiting or activating adenylyl cyclases. Opioid receptor stimulation can activate inhibitory Gi-proteins which in turn block adenylyl cyclase activity reducing cAMP. Opioids such as D,L-methadone induce cell death in leukemia cells. However, the mechanism how opioids trigger apoptosis and activate caspases in leukemia cells is not understood. In this study, we demonstrate that downregulation of cAMP induced by opioid receptor activation using the opioid D,L-methadone kills and sensitizes leukemia cells for doxorubicin treatment. Enhancing cAMP levels by blocking opioid-receptor signaling strongly reduced D,L-methadone-induced apoptosis, caspase activation and doxorubicin-sensitivity. Induction of cell death in leukemia cells by activation of opioid receptors using the opioid D,L-methadone depends on critical levels of opioid receptor expression on the cell surface. Doxorubicin increased opioid receptor expression in leukemia cells. In addition, the opioid D,L-methadone increased doxorubicin uptake and decreased doxorubicin efflux in leukemia cells, suggesting that the opioid D,L-methadone as well as doxorubicin mutually increase their cytotoxic potential. Furthermore, we found that opioid receptor activation using D,L-methadone alone or in addition to doxorubicin inhibits tumor growth significantly in vivo. These results demonstrate that opioid receptor activation via triggering the downregulation of cAMP induces apoptosis, activates caspases and sensitizes leukemia cells for doxorubicin treatment. Hence, opioid receptor activation seems to be a promising strategy to improve anticancer therapies.

  18. [Effects of RNAi on hypoxia inducible factor-1alpha activity and proliferation of hypoxic pulmonary artery smooth muscle cells in rat].

    Science.gov (United States)

    Zhang, Wei; Cao, Yue; Zhang, Yu; Ma, Qi-Sheng; Ma, Lan; Ge, Ri-Li

    2006-02-25

    Pulmonary vascular remodeling is one of the major characteristics of hypoxia-induced pulmonary hypertension, mainly represented by over-proliferation of pulmonary artery smooth muscle cells (PASMCs). Hypoxia inducible factor-1alpha (HIF-1alpha) is a transcription factor which is produced by the cells exposed to hypoxia. HIF-1alpha up-regulates the expression of many hypoxia response genes (HRGs) for the body to adapt to hypoxia and maintain homeostasis. The expression of HIF-1alpha in the PASMCs is remarkably elevated under hypoxic condition and it stimulates the proliferation of PASMCs. In this experiment, we used gene clone technology to design and synthesize two siRNAs based on the sequence of HIF-1alpha mRNA. They were separately subcloned into the plasmid of pGenesil-1 containing U6 promoter. The pGenesil-1 vector of the RNA interference eukaryotic expression vector specific to HIF-1alpha gene was constructed. DNA sequencing of the plasmid verified the successful construction of the HIF-1alpha RNAi. We isolated and cultured the PASMCs of rat. The pGenesil-1 vector was transferred into the PASMCs with METAFECTENE in vitro. The positive cell clones transfected with pGenesil-1 were obtained after being screened with 400 mug/ml G418. These PASMCs were cultured in normoxia and hypoxia. After 48 h, the effects of RNAi on the expression of HIF-1alpha mRNA were detected by RT-PCR. The cellular growth activities were assayed by MTT colorimetry and flow cytometry in vitro. The results showed that for the PASMCs cultured in hypoxia for 48 h, the cell proliferation of blank group and control group were remarkably increased and the HIF-1alpha mRNA expressions were up-regulated, while the cell proliferation of the treatment groups did not increase and the HIF-1alpha mRNA expressions were not up-regulated. In conclusion, we successfully constructed the recombinant plasmid of RNAi and transfected them into the PASMCs in vitro. The RNAi inhibited the expression of HIF-1alpha m

  19. Protons sensitize epithelial cells to mesenchymal transition.

    Science.gov (United States)

    Wang, Minli; Hada, Megumi; Saha, Janapriya; Sridharan, Deepa M; Pluth, Janice M; Cucinotta, Francis A

    2012-01-01

    Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1.

  20. Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Shang-Lang [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chao, Chuck C.-K., E-mail: cckchao@mail.cgu.edu.tw [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan (China)

    2015-06-16

    A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug.

  1. The oncolytic activity of Newcastle disease virus in clear cell renal carcinoma cells in normoxic and hypoxic conditions: the interplay between von Hippel-Lindau and interferon-β signaling.

    Science.gov (United States)

    Ch'ng, Wei-Choong; Stanbridge, Eric J; Yusoff, Khatijah; Shafee, Norazizah

    2013-07-01

    Viral-mediated oncolysis is a promising cancer therapeutic approach offering an increased efficacy with less toxicity than the current therapies. The complexity of solid tumor microenvironments includes regions of hypoxia. In these regions, the transcription factor, hypoxia inducible factor (HIF), is active and regulates expression of many genes that contribute to aggressive malignancy, radio-, and chemo-resistance. To investigate the oncolytic efficacy of a highly virulent (velogenic) Newcastle disease virus (NDV) in the presence or absence of HIF-2α, renal cell carcinoma (RCC) cell lines with defective or reconstituted wild-type (wt) von Hippel-Lindau (VHL) activity were used. We show that these RCC cells responded to NDV by producing only interferon (IFN)-β, but not IFN-α, and are associated with increased STAT1 phosphorylation. Restoration of wt VHL expression enhanced NDV-induced IFN-β production, leading to prolonged STAT1 phosphorylation and increased cell death. Hypoxia augmented NDV oncolytic activity regardless of the cells' HIF-2α levels. These results highlight the potential of oncolytic NDV as a potent therapeutic agent in the killing of hypoxic cancer cells.

  2. Differential functions of C- and N-terminal hepatitis B x protein in liver cells treated with doxorubicin in normoxic or hypoxic condition.

    Directory of Open Access Journals (Sweden)

    Davor Kin-Fan Chau

    Full Text Available Hepatitis viral B x protein (HBx, a hepatocarcinogen, is frequently mutated. Hypoxia influences the growth of HCC and also the sensitivity of tumor cells to treatments. We aimed to test the role of HBx and acute hypoxia in the efficacy of chemotherapy. In this study, we established 4 Chang liver cell lines with the full-length HBx (HBx, the first 50 amino acids of N-terminal HBx (HBx/50, the last 104 amino acids of C-terminal HBx (HBx/51 and empty vector (CL, respectively. MTT and TNUEL assays were used to assess cell viability and apoptosis respectively. Western blot was used to determine the expression of relevant proteins. Results showed that among 4 cell lines, doxorubicin was most effective in decreasing the viability and enhancing apoptosis in HBx/51 cells, while HBx/50 cells were most resistant to the treatment. Cells in hypoxia were more susceptible to doxorubicin than cells in normoxia. Hypoxia facilitated the Bid cleavage especially in HBx/51 cells via phosphorylating p38 MAPK. p38 MAPK inhibitor significantly reduced the tBid level and increased cell viability. In conclusion, N-terminal HBx and C-terminal HBx function differentially in their ability to regulate cell growth, with the former being promotive but the latter being inhibitory. The acute hypoxia may overcome the HBx-induced resistance and facilitate the chemotherapy.

  3. Ruthenium Sensitizers and Their Applications in Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Yuancheng Qin

    2012-01-01

    Full Text Available Dye-sensitized solar cells (DSSCs have attracted considerable attention in recent years due to the possibility of low-cost conversion of photovoltaic energy. The DSSCs-based ruthenium complexes as sensitizers show high efficiency and excellent stability, implying potential practical applications. This review focuses on recent advances in design and preparation of efficient ruthenium sensitizers and their applications in DSSCs, including thiocyanate ruthenium sensitizers and thiocyanate-free ruthenium sensitizers.

  4. Performance of Caesalpinia sappan heartwood extract as photo sensitizer for dye sensitized solar cells

    Science.gov (United States)

    Ananth, S.; Vivek, P.; Saravana Kumar, G.; Murugakoothan, P.

    2015-02-01

    A natural dye extracted from Caesalpinia sappan heartwood was used as photo sensitizer for the first time to fabricate titanium dioxide (TiO2) nanoparticles based dye sensitized solar cells. Brazilin and brazilein are the major pigments present in the natural dye and their optimized molecular structure were calculated using Density functional theory (DFT) at 6-31G (d) level. The HOMO-LUMO were performed to reveal the energy gap using optimized structure. Pure TiO2 nanoparticles in anatase phase were synthesized by sol-gel technique. The pure and natural dye sensitized TiO2 nanoparticles were subjected to structural, optical, spectral and morphological studies. Low cost and environment friendly dye sensitized solar cells were fabricated using natural dye sensitized TiO2 based photo anode. The solar light to electron conversion efficiency of Caesalpinia sappan heartwood extract sensitized dye sensitized solar cell is 1.1%.

  5. Hypoxia-inducible factor-1β (HIF-1β) is upregulated in a HIF-1α-dependent manner in 518A2 human melanoma cells under hypoxic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Mandl, Markus, E-mail: mmandl@mail.austria.com; Kapeller, Barbara; Lieber, Roman; Macfelda, Karin

    2013-04-26

    Highlights: •HIF-1β is a hypoxia-responsive protein in 518A2 human melanoma cells. •HIF-1β is upregulated in a HIF-1α-dependent manner under hypoxic conditions. •HIF-1β is not elevated due to heterodimerization with HIF-1α per se. •HIF-1β inducibility has a biological relevance as judged in Het-CAM model. -- Abstract: Solid tumors include hypoxic areas due to excessive cell proliferation. Adaptation to low oxygen levels is mediated by the hypoxia-inducible factor (HIF) pathway promoting invasion, metastasis, metabolic alterations, chemo-resistance and angiogenesis. The transcription factor HIF-1, the major player within this pathway consists of HIF-1α and HIF-1β. The alpha subunit is continuously degraded under normoxia and becomes stabilized under reduced oxygen supply. In contrast, HIF-1β is generally regarded as constitutively expressed and being present in excess within the cell. However, there is evidence that the expression of this subunit is more complex. The aim of this study was to investigate the role of HIF-1β in human melanoma cells. Among a panel of five different cell lines, in 518A2 cells exposed to the hypoxia-mimetic cobalt chloride HIF-1β was rapidly elevated on protein level. Knockdown experiments performed under cobalt chloride-exposure and hypoxia revealed that this effect was mediated by HIF-1α. The non-canonical relationship between these subunits was further confirmed by pharmacologic inhibition of HIF-1α and by expression of a dominant-negative HIF mutant. Overexpression of HIF-1α showed a time delay in HIF-1β induction, thus arguing for HIF-1β de novo synthesis rather than protein stabilization by heterodimerization. A Hen’s egg test-chorioallantoic membrane model of angiogenesis and invasion indicated a local expression of HIF-1β and implies a biological relevance of these findings. In summary, this study demonstrates the HIF-1α-dependent regulation of HIF-1β under hypoxic conditions for the first time. The

  6. Sensitivity of several cell systems to acrylamide

    NARCIS (Netherlands)

    Hooisma, J.; Groot, D.M.G.de; Magchielse, T.; Muijser, H.

    1980-01-01

    Chick spinal ganglia, chick muscle cells combined with mouse spinal cord explants, C1300 neuroblastoma cells, Chinese hamster ovary cells and newborn rat cerebral cells were exposed to various concentrations of acrylamide in culture. Four morphological and 1 electrophysiological parameter were

  7. Sensitivity Analysis of Centralized Dynamic Cell Selection

    DEFF Research Database (Denmark)

    Lopez, Victor Fernandez; Alvarez, Beatriz Soret; Pedersen, Klaus I.

    2016-01-01

    Centralized architectures with fronthauls can be used to deal with some of the problems inherently associated with dense small cell deployments. This study examines a joint cell assignment and scheduling solution for the downlink to increase the users’ data rates, based on cell switching and a su...... with two different traffic models, and it is not necessary to be able to connect to a large number of cells in order to reap most of the benefits of the centralized dynamic cell selection....

  8. Hypoxic hepatopathy: pathophysiology and prognosis.

    Science.gov (United States)

    Birrer, Richard; Takuda, Yasuharu; Takara, Tsuyoshi

    2007-01-01

    Dramatic transient elevation in serum concentrations of hepatic enzymes occurs in some patients following a hypo-perfusion state. This entity is variously termed "shock liver" or "ischemic hepatitis", since the pathogenesis is considered to be ischemia. However, hypotension or shock is not always present. We analyzed the medical records of 293 patients (322 episodes) who had a hypoxic state and were admitted to the critical care units of two general hospitals over a 13-year period. Hepatic injury was identified in about 1% of patients in critical care admissions. In addition to hypotension, the causes for hepatic injury were a low flow state secondary to congestive heart failure and hypoxia from sepsis or respiratory failure and hypoxemia from a variety of etiologies. These values were mostly normalized within several days when the hypoxic etiology was corrected and a serious co-morbid state did not intervene. Marked elevation of hepatic enzymes can be identified not only in patients with hypotension, but also in normotensive patients in hypoxic state. Thus, the condition is appropriately termed hypoxic hepatopathy.

  9. IAEA-HypoX. A randomized multicenter study of the hypoxic radiosensitizer nimorazole concomitant with accelerated radiotherapy in head and neck squamous cell carcinoma

    DEFF Research Database (Denmark)

    Metwally, Mohamed Ahmed Hassan; Ali, Rubina; Kuddu, Maire

    2015-01-01

    multicenter randomized trial in patients with HNSCC. Tumors were treated to a dose of 66-70Gy, 33-35 fractions, 6 fractions per week. NIM was administered in a dose of 1.2gperm(2), 90min before the first daily RT fraction. The primary endpoint was loco-regional failure. The trial was closed prematurely...... failed to achieve persistent loco-regional tumor control, and a total of 45 patients had died. The use of NIM improved the loco-regional tumor control with an 18month post-randomization cumulative failure rate of 33% versus 51% in the control arm, yielding a risk difference of 18% (CI -3% to 39%; P=0.......10). The corresponding values for overall death was 43% versus 62%, yielding a risk difference of 19% (CI -3% to 42%; P=0.10). Sixteen patients, out of 55 patients analyzed for hypoxic gene expression, were classified as having more hypoxic tumors. Such patients, if treated with RT alone, had a higher loco...

  10. A low protein diet increases the hypoxic tolerance in Drosophila.

    Directory of Open Access Journals (Sweden)

    Paul Vigne

    2006-12-01

    Full Text Available Dietary restriction is well known to increase the life span of a variety of organisms from yeast to mammals, but the relationships between nutrition and the hypoxic tolerance have not yet been considered. Hypoxia is a major cause of cell death in myocardial infarction and stroke. Here we forced hypoxia-related death by exposing one-day-old male Drosophila to chronic hypoxia (5% O(2 and analysed their survival. Chronic hypoxia reduced the average life span from 33.6 days to 6.3 days when flies were fed on a rich diet. A demographic analysis indicated that chronic hypoxia increased the slope of the mortality trajectory and not the short-term risk of death. Dietary restriction produced by food dilution, by yeast restriction, or by amino acid restriction partially reversed the deleterious action of hypoxia. It increased the life span of hypoxic flies up to seven days, which represented about 25% of the life time of an hypoxic fly. Maximum survival of hypoxic flies required only dietary sucrose, and it was insensitive to drugs such as rapamycin and resveratrol, which increase longevity of normoxic animals. The results thus uncover a new link between protein nutrition, nutrient signalling, and resistance to hypoxic stresses.

  11. Mammalian target of rapamycin complex 1 activation sensitizes human glioma cells to hypoxia-induced cell death.

    Science.gov (United States)

    Thiepold, Anna-Luisa; Lorenz, Nadja I; Foltyn, Martha; Engel, Anna L; Divé, Iris; Urban, Hans; Heller, Sonja; Bruns, Ines; Hofmann, Ute; Dröse, Stefan; Harter, Patrick N; Mittelbronn, Michel; Steinbach, Joachim P; Ronellenfitsch, Michael W

    2017-10-01

    Glioblastomas are characterized by fast uncontrolled growth leading to hypoxic areas and necrosis. Signalling from EGFR via mammalian target of rapamycin complex 1 (mTORC1) is a major driver of cell growth and proliferation and one of the most commonly altered signalling pathways in glioblastomas. Therefore, epidermal growth factor receptor and mTORC1 signalling are plausible therapeutic targets and clinical trials with inhibitors are in progress. However, we have previously shown that epidermal growth factor receptor and mTORC1 inhibition triggers metabolic changes leading to adverse effects under the conditions of the tumour microenvironment by protecting from hypoxia-induced cell death. We hypothesized that conversely mTORC1 activation sensitizes glioma cells to hypoxia-induced cell death. As a model for mTORC1 activation we used gene suppression of its physiological inhibitor TSC2 (TSC2sh). TSC2sh glioma cells showed increased sensitivity to hypoxia-induced cell death that was accompanied by an earlier ATP depletion and an increase in reactive oxygen species. There was no difference in extracellular glucose consumption but an altered intracellular metabolic profile with an increase of intermediates of the pentose phosphate pathway. Mechanistically, mTORC1 upregulated the first and rate limiting enzyme of the pentose phosphate pathway, G6PD. Furthermore, an increase in oxygen consumption in TSC2sh cells was detected. This appeared to be due to higher transcription rates of genes involved in mitochondrial respiratory function including PPARGC1A and PPARGC1B (also known as PGC-1α and -β). The finding that mTORC1 activation causes an increase in oxygen consumption and renders malignant glioma cells susceptible to hypoxia and nutrient deprivation could help identify glioblastoma patient cohorts more likely to benefit from hypoxia-inducing therapies such as the VEGFA-targeting antibody bevacizumab in future clinical evaluations. © The Author (2017). Published by

  12. Mechanisms underlying KCNQ1channel cell volume sensitivity

    DEFF Research Database (Denmark)

    Hammami, Sofia

    volume alterations is not yet fully understood. The KCNQ1 channel belonging to the voltage gated KCNQ family is considered a precise sensor of volume changes. The goal of this thesis was to elucidate the mechanism that induces cell volume sensitivity. Until now, a number of investigators have implicitly......) osmotic cell swelling and (2) local membrane stretch on the highly volume sensitive KCNQ1 channel and the highly stretch sensitive BK channel. In this study we present evidence against this assumption by showing that activation of BK channels by local membrane stretch is not mimicked by cell swelling......, and activation of KCNQ1 channels by cell volume increase is not mimicked by stretch of the cell membrane. Thus, we conclude that stretch- and volume-sensitivity can be considered two independent regulatory mechanisms. Alternatively, volume-activation of ion channels could be mediated by an autocrine mechanism...

  13. PCTAIRE1-knockdown sensitizes cancer cells to TNF family cytokines.

    Directory of Open Access Journals (Sweden)

    Teruki Yanagi

    Full Text Available While PCTAIRE1/PCTK1/Cdk16 is overexpressed in malignant cells and is crucial in tumorigenesis, its function in apoptosis remains unclear. Here we investigated the role of PCTAIRE1 in apoptosis, especially in the extrinsic cell death pathway. Gene-knockdown of PCTAIRE1 sensitized prostate cancer PPC1 and Du145 cells, and breast cancer MDA-MB-468 cells to TNF-family cytokines, including TNF-related apoptosis-inducing ligand (TRAIL. Meanwhile, PCTAIRE1-knockdown did not sensitize non-malignant cells, including diploid fibroblasts IMR-90 and the immortalized prostate epithelial cell line 267B1. PCTAIRE1-knockdown did not up-regulate death receptor expression on the cell surface or affect caspase-8, FADD and FLIP expression levels. PCTAIRE1-knockdown did promote caspase-8 cleavage and RIPK1 degradation, while RIPK1 mRNA knockdown sensitized PPC1 cells to TNF-family cytokines. Furthermore, the kinase inhibitor SNS-032, which inhibits PCTAIRE1 kinase activity, sensitized PPC1 cells to TRAIL-induced apoptosis. Together these results suggest that PCTAIRE1 contributes to the resistance of cancer cell lines to apoptosis induced by TNF-family cytokines, which implies that PCTAIRE1 inhibitors could have synergistic effects with TNF-family cytokines for cytodestruction of cancer cells.

  14. Research Progress of Photoanodes for Quantum Dot Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    LI Zhi-min

    2017-08-01

    Full Text Available This paper presents the development status and tendency of quantum dot sensitized solar cells. Photoanode research progress and its related technologies are analyzed in detail from the three ways of semiconductor thin films, quantum dot co-sensitization and quantum dot doping, deriving from the approach that the conversion efficiency can be improved by photoanode modification for quantum dot sensitized solar cells. According to the key factors which restrict the cell efficiency, the promising future development of quantum dot sensitized solar cells is proposed,for example,optimizing further the compositions and structures of semiconductor thin films for the photoanodes, exploring new quantum dots with broadband absorption and developing high efficient techniques of interface modification.

  15. Dye-sensitized solar cell and photocatalytic performance of ...

    Indian Academy of Sciences (India)

    s12034-016-1280-1. Dye-sensitized solar cell and photocatalytic performance of nanocomposite photocatalyst prepared by electrochemical anodization. MOHAMAD MOHSEN MOMENI. Department of Chemistry, Isfahan University of Technology ...

  16. Cell-sensitive phase contrast microscopy imaging by multiple exposures.

    Science.gov (United States)

    Yin, Zhaozheng; Su, Hang; Ker, Elmer; Li, Mingzhong; Li, Haohan

    2015-10-01

    We propose a novel way of imaging live cells in a Petri dish by the phase contrast microscope. By taking multiple exposures of phase contrast microscopy images on the same cell dish, we estimate a cell-sensitive camera response function which responds to cells' irradiance signals but generates a constant on non-cell background signal. The result of this new microscopy imaging is visually superior quality, which reveals the appearance details of cells and suppresses background noise near zero. Using the cell-sensitive microscopy imaging, cells' original irradiance signals are restored from all exposures and the irradiance signals on non-cell background regions are restored as a uniform constant (i.e., the imaging system is sensitive to cells only but insensitive to non-cell background). The restored irradiance signals greatly facilitate the cell segmentation by simple thresholding. The experimental results validate that high quality cell segmentation can be achieved by our approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Hypoxic tumor environments exhibit disrupted collagen I fibers and low macromolecular transport.

    Directory of Open Access Journals (Sweden)

    Samata M Kakkad

    Full Text Available Hypoxic tumor microenvironments result in an aggressive phenotype and resistance to therapy that lead to tumor progression, recurrence, and metastasis. While poor vascularization and the resultant inadequate drug delivery are known to contribute to drug resistance, the effect of hypoxia on molecular transport through the interstitium, and the role of the extracellular matrix (ECM in mediating this transport are unexplored. The dense mesh of fibers present in the ECM can especially influence the movement of macromolecules. Collagen 1 (Col1 fibers form a key component of the ECM in breast cancers. Here we characterized the influence of hypoxia on macromolecular transport in tumors, and the role of Col1 fibers in mediating this transport using an MDA-MB-231 breast cancer xenograft model engineered to express red fluorescent protein under hypoxia. Magnetic resonance imaging of macromolecular transport was combined with second harmonic generation microscopy of Col1 fibers. Hypoxic tumor regions displayed significantly decreased Col1 fiber density and volume, as well as significantly lower macromolecular draining and pooling rates, than normoxic regions. Regions adjacent to severely hypoxic areas revealed higher deposition of Col1 fibers and increased macromolecular transport. These data suggest that Col1 fibers may facilitate macromolecular transport in tumors, and their reduction in hypoxic regions may reduce this transport. Decreased macromolecular transport in hypoxic regions may also contribute to poor drug delivery and tumor recurrence in hypoxic regions. High Col1 fiber density observed around hypoxic regions may facilitate the escape of aggressive cancer cells from hypoxic regions.

  18. Hypoxic tumor environments exhibit disrupted collagen I fibers and low macromolecular transport.

    Science.gov (United States)

    Kakkad, Samata M; Penet, Marie-France; Akhbardeh, Alireza; Pathak, Arvind P; Solaiyappan, Meiyappan; Raman, Venu; Leibfritz, Dieter; Glunde, Kristine; Bhujwalla, Zaver M

    2013-01-01

    Hypoxic tumor microenvironments result in an aggressive phenotype and resistance to therapy that lead to tumor progression, recurrence, and metastasis. While poor vascularization and the resultant inadequate drug delivery are known to contribute to drug resistance, the effect of hypoxia on molecular transport through the interstitium, and the role of the extracellular matrix (ECM) in mediating this transport are unexplored. The dense mesh of fibers present in the ECM can especially influence the movement of macromolecules. Collagen 1 (Col1) fibers form a key component of the ECM in breast cancers. Here we characterized the influence of hypoxia on macromolecular transport in tumors, and the role of Col1 fibers in mediating this transport using an MDA-MB-231 breast cancer xenograft model engineered to express red fluorescent protein under hypoxia. Magnetic resonance imaging of macromolecular transport was combined with second harmonic generation microscopy of Col1 fibers. Hypoxic tumor regions displayed significantly decreased Col1 fiber density and volume, as well as significantly lower macromolecular draining and pooling rates, than normoxic regions. Regions adjacent to severely hypoxic areas revealed higher deposition of Col1 fibers and increased macromolecular transport. These data suggest that Col1 fibers may facilitate macromolecular transport in tumors, and their reduction in hypoxic regions may reduce this transport. Decreased macromolecular transport in hypoxic regions may also contribute to poor drug delivery and tumor recurrence in hypoxic regions. High Col1 fiber density observed around hypoxic regions may facilitate the escape of aggressive cancer cells from hypoxic regions.

  19. Sparging - shear sensitivity of animal cells

    NARCIS (Netherlands)

    Pol, van der L.A.

    1998-01-01

    Biopharmaceuticals are increasingly produced by modern biotechnological techniques. The in-vitro culture of animal cells in stirred tanks is one of the feasible systems, especially for proteins that require specific post-tanslational modifications to evoke a desired respons in patients.

  20. Modification of the hypoxic fraction of a xenografted human colon tumor by differentiation-inducing agents

    Energy Technology Data Exchange (ETDEWEB)

    Leith, J.T.

    1988-05-18

    Xenografted tumors were produced in nude mice by injection of HCT-15 human colon tumor cells. The hypoxic fractions of control tumors as determined from x-ray survival curves were approximately 18%. Other tumors were treated (every day X 9) with daily injections of N-methylformamide (150 mg/kg) or sodium butyrate (2,000 mg/kg). For both agents, it was found that the hypoxic fractions were less than 0.05% and less than 1.7%, respectively. These data indicate that selected differentiation-inducing agents could be of value for treatment of human solid tumors that contain hypoxic cells.

  1. Solid-State Sensitized Heterojunction Solar Cells: Effect of Sensitizing Systems on Performance and Stability

    OpenAIRE

    Moon, Soo-Jin

    2011-01-01

    Dye-sensitized solar cells (DSCs) are considered as an emerging technology in order to replace conventional silicon solar cells or thin film solar cells such as amorphous silicon, CIGS, and CdTe. Liquid electrolytes containing iodide/triiodide redox couple have a durability problem due to the corrosion of metal contacts. In order to improve the long-term stability of DSC device it is important to find an alternate efficient redox couple. In search of ...

  2. Performance of Caesalpinia sappan heartwood extract as photo sensitizer for dye sensitized solar cells.

    Science.gov (United States)

    Ananth, S; Vivek, P; Saravana Kumar, G; Murugakoothan, P

    2015-02-25

    A natural dye extracted from Caesalpinia sappan heartwood was used as photo sensitizer for the first time to fabricate titanium dioxide (TiO2) nanoparticles based dye sensitized solar cells. Brazilin and brazilein are the major pigments present in the natural dye and their optimized molecular structure were calculated using Density functional theory (DFT) at 6-31G (d) level. The HOMO-LUMO were performed to reveal the energy gap using optimized structure. Pure TiO2 nanoparticles in anatase phase were synthesized by sol-gel technique. The pure and natural dye sensitized TiO2 nanoparticles were subjected to structural, optical, spectral and morphological studies. Low cost and environment friendly dye sensitized solar cells were fabricated using natural dye sensitized TiO2 based photo anode. The solar light to electron conversion efficiency of Caesalpinia sappan heartwood extract sensitized dye sensitized solar cell is 1.1%. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Genistein attenuates hypoxic pulmonary hypertension via enhanced nitric oxide signaling and the erythropoietin system.

    Science.gov (United States)

    Kuriyama, Sachiko; Morio, Yoshiteru; Toba, Michie; Nagaoka, Tetsutaro; Takahashi, Fumiyuki; Iwakami, Shin-Ichiro; Seyama, Kuniaki; Takahashi, Kazuhisa

    2014-06-01

    Upregulation of the erythropoietin (EPO)/EPO receptor (EPOR) system plays a protective role against chronic hypoxia-induced pulmonary hypertension (hypoxic PH) through enhancement of endothelial nitric oxide (NO)-mediated signaling. Genistein (Gen), a phytoestrogen, is considered to ameliorate NO-mediated signaling. We hypothesized that Gen attenuates and prevents hypoxic PH. In vivo, Sprague-Dawley rats raised in a hypobaric chamber were treated with Gen (60 mkg/kg) for 21 days. Pulmonary hemodynamics and vascular remodeling were ameliorated in Gen-treated hypoxic PH rats. Gen also restored cGMP levels and phosphorylated endothelial NO synthase (p-eNOS) at Ser(1177) and p-Akt at Ser(473) expression in the lungs. Additionally, Gen potentiated plasma EPO concentration and EPOR-positive endothelial cell counts. In experiments with hypoxic PH rats' isolated perfused lungs, Gen caused NO- and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent vasodilation that reversed abnormal vasoconstriction. In vitro, a combination of EPO and Gen increased the p-eNOS and the EPOR expression in human umbilical vein endothelial cells under a hypoxic environment. Moreover, Gen potentiated the hypoxic increase in EPO production from human hepatoma cells. We conclude that Gen may be effective for the prevention of hypoxic PH through the improvement of PI3K/Akt-dependent, NO-mediated signaling in association with enhancement of the EPO/EPOR system. Copyright © 2014 the American Physiological Society.

  4. Large pi-aromatic molecules as potential sensitizers for highly efficient dye-sensitized solar cells.

    Science.gov (United States)

    Imahori, Hiroshi; Umeyama, Tomokazu; Ito, Seigo

    2009-11-17

    Recently, dye-sensitized solar cells have attracted much attention relevant to global environmental issues. Thus far, ruthenium(II) bipyridyl complexes have proven to be the most efficient TiO(2) sensitizers in dye-sensitized solar cells. However, a gradual increment in the highest power conversion efficiency has been recognized in the past decade. More importantly, considering that ruthenium is a rare metal, novel dyes without metal or using inexpensive metal are desirable for highly efficient dye-sensitized solar cells. Large pi-aromatic molecules, such as porphyrins, phthalocyanines, and perylenes, are important classes of potential sensitizers for highly efficient dye-sensitized solar cells, owing to their photostability and high light-harvesting capabilities that can allow applications in thinner, low-cost dye-sensitized solar cells. Porphyrins possess an intense Soret band at 400 nm and moderate Q bands at 600 nm. Nevertheless, the poor light-harvesting properties relative to the ruthenium complexes have limited the cell performance of porphyrin-sensitized TiO(2) cells. Elongation of the pi conjugation and loss of symmetry in porphyrins cause broadening and a red shift of the absorption bands together with an increasing intensity of the Q bands relative to that of the Soret band. On the basis of the strategy, the cell performance of porphyrin-sensitized solar cells has been improved intensively by the enhanced light absorption. Actually, some push-pull-type porphyrins have disclosed a remarkably high power conversion efficiency (6-7%) that was close to that of the ruthenium complexes. Phthalocyanines exhibit strong absorption around 300 and 700 nm and redox features that are similar to porphyrins. Moreover, phthalocyanines are transparent over a large region of the visible spectrum, thereby enabling the possibility of using them as "photovoltaic windows". However, the cell performance was poor, owing to strong aggregation and lack of directionality in the

  5. Sensitizing Cancer Cells: Is It Really All about U?

    OpenAIRE

    Stover, Patrick J.; Weiss, Robert S.

    2012-01-01

    In this issue of Cancer Cell, Hu et al. report that TMPK and RNR, two key enzymes in deoxyribonucleotide biosynthesis, co-localize to damaged DNA and produce nucleotides necessary for DNA repair while suppressing uracil incorporation. TMPK inhibition disrupts this balance and selectively sensitizes cancer cells to low-dose chemotherapy.

  6. Constitutively activated ERK sensitizes cancer cells to doxorubicin ...

    Indian Academy of Sciences (India)

    2017-02-03

    Feb 3, 2017 ... Constitutively activated ERK sensitizes cancer cells to doxorubicin: Involvement of p53-EGFR-ERK pathway. RATNA KUMARI. 1,†. , SURBHI CHOUHAN. 1,†. , SNAHLATA SINGH. 1,†. , RISHI RAJ CHHIPA. 2. ,. AMRENDRA KUMAR AJAY. 3 and MANOJ KUMAR BHAT*. National Centre for Cell Science, ...

  7. Osmotically sensitive renin release from permeabilized juxtaglomerular cells

    DEFF Research Database (Denmark)

    Jensen, B L; Skøtt, O

    1993-01-01

    Renin secretion from juxtaglomerular (JG) cells is sensitive to external osmolality in a way that has been suggested to depend either on cellular volume or on effects on secretory granules. To distinguish between these possibilities, a technique for permeabilization of JG cell membranes was devel...

  8. Fabrication of dye-sensitized solar cells with multilayer photoanodes ...

    Indian Academy of Sciences (India)

    TiO2 NPs. This could show an increase of about 30% in the efficiency compared to the similar cell with a photoanode made of two layers of hydrothermally grown TiO2 NCs. Keywords. Dye-sensitized solar cells; hydrothermal method; TiO2 nanocrystals; multilayer photoanodes; energy conversion efficiency. 1. Introduction.

  9. Human Umbilical Cord-Derived Mesenchymal Stem Cells Improve Learning and Memory Function in Hypoxic-Ischemic Brain-Damaged Rats via an IL-8-Mediated Secretion Mechanism Rather than Differentiation Pattern Induction

    Directory of Open Access Journals (Sweden)

    Xiaoqin Zhou

    2015-04-01

    Full Text Available Background: MSCs are a promising therapeutic resource. Paracrine effects and the induction of differentiation patterns are thought to represent the two primary mechanisms underlying the therapeutic effects of mesenchymal stem cell (MSC transplantation in vivo. However, it is unclear which mechanism is involved in the therapeutic effects of human umbilical cord-derived MSC (hUC-MSC transplantation. Methods and Results: Based on flow cytometry analysis, hUC-MSCs exhibited the morphological characteristics and surface markers of MSCs. Following directed neural induction, these cells displayed a neuron-like morphology and expressed high levels of neural markers. All types of hUC-MSCs, including differentiated and redifferentiated cells, promoted learning and memory function recovery in hypoxic-ischemic brain damaged (HIBD rats. The hUC-MSCs secreted IL-8, which enhanced angiogenesis in the hippocampus via the JNK pathway. However, the differentiated and redifferentiated cells did not exert significantly greater therapeutic effects than the undifferentiated hUC-MSCs. Conclusion: hUC-MSCs display the biological properties and neural differentiation potential of MSCs and provide therapeutic advantages by secreting IL-8, which participates in angiogenesis in the rat HIBD model. These data suggest that hUC-MSC transplantation improves the recovery of neuronal function via an IL-8-mediated secretion mechanism, whereas differentiation pattern induction was limited.

  10. Marine Natural Products as Inhibitors of Hypoxic Signaling in Tumors.

    Science.gov (United States)

    Nagle, Dale G; Zhou, Yu-Dong

    2009-06-01

    Marine natural products have become a major source of new chemical entities in the discovery of potential anticancer agents that potently suppress various antitumor molecular targets. As a consequence of insufficient vascularization, hypoxic regions form within rapidly growing solid tumor masses. Specific alterations of gene expression in these hypoxic tumor cells help facilitate the survival and metastatic spread of solid tumors. The transcriptional response to cellular hypoxia is primarily mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1) that regulates the expression of more than 100 genes involved in cellular adaptation and survival under hypoxic stress. Clinical studies in cancer patients indicate that HIF-1 activation is directly correlated with advanced disease stages and treatment resistance. HIF-1 has emerged as an important tumor-selective molecular target for anticancer drug discovery. As a result, natural product-based inhibitors of HIF-1 activation have been identified from plants and microorganisms. Recently, structurally unique natural products from marine sponges, crinoids, and algae have been identified as HIF-1 activation inhibitors. The US National Cancer Institute's Open Repository of marine invertebrate and algae extracts has proven to be a valuable source of natural product HIF-1 inhibitors. Among the active compounds identified, certain marine natural products have also been shown to suppress the hypoxic induction of HIF-1 target genes such as vascular endothelial growth factor (VEGF). Some of these marine HIF-1 inhibitors act by interfering with the generation of mitochondrial signaling molecules in hypoxic cells. However, the precise mechanisms of action for many newly identified marine natural product HIF-1 inhibitors remain unresolved.

  11. Probenecid Sensitizes Neuroblastoma Cancer Stem Cells to Cisplatin.

    Science.gov (United States)

    Campos-Arroyo, Denise; Maldonado, Vilma; Bahena, Ivan; Quintanar, Valeria; Patiño, Nelly; Carlos Martinez-Lazcano, Juan; Melendez-Zajgla, Jorge

    2016-01-01

    We used both in vitro cultures of neuroblastoma cell lines and nude-mice xenotransplants to explore the effects of co-administration of cisplatin and probenecid. Probenecid sensitized neuroblastoma cells, including tumor cells with stem features, to the effects of cisplatin, both in vitro and in vivo. This effect was mediated by an increase in the apoptotic cell death and a concomitant decrease in cell proliferation. This effect is accompanied by modulation of the mRNA and protein of the drug efflux transporters MDR1, MRP2, and BCRP. The co-administration of probenecid with cisplatin should be explored as a possible therapeutic strategy.

  12. GREEN SEAWEEDS EXTRACT AS CO-SENSITIZER FOR DYE SENSITIZED SOLAR CELLS

    Directory of Open Access Journals (Sweden)

    ANCA DUMBRAVA

    2016-04-01

    Full Text Available The row extract of ethanol soluble compounds from the green alga Enteromorpha intestinalis was used as source for chlorophyll pigments in the sensitization and co-sensitization of TiO2-based Dye Sensitized Solar Cells (DSSCs. We used two techniques for co-sensitization (the successive adsorptions of dyes, respective the cocktails of dyes and the characteristics of DSSCs were studied having in view different pHs of the extracts. The results for DSSCs based on co-sensitized TiO2 photoanodes, obtained in diverse pH conditions, were compared with those for DSSCs based on substrates sensitized by a single source of pigments. The DSSCs fabricated using photoanodes sensitized with a cocktail of green seaweeds and red cabbage extracts, in basic medium, have higher value for efficiency, compared to green seaweeds, respective red cabbage extracts in the same conditions, and the fill factor was remarkable high (0.795. Thus, the co-sensitization by cocktail method may be a proper technique to enhance the light harvesting capability of natural dyes based DSSCs.

  13. CD40 stimulation sensitizes CLL cells to rituximab-induced cell death

    NARCIS (Netherlands)

    Jak, M.; van Bochove, G. G. W.; van Lier, R. A. W.; Eldering, E.; van Oers, M. H. J.

    2011-01-01

    In vitro CD40-stimulated chronic lymphocytic leukemia (CLL) cells are resistant to cytotoxic drugs. In sharp contrast, we here show that CD40 stimulation sensitizes CLL cells to rituximab-mediated cell death. This increased sensitivity is specific for anti-CD20 treatment. Rituximab-mediated death in

  14. Triazoloisoquinoline-Based/Ruthenium-Hybrid Sensitizer for Efficient Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Che-Lung Lee

    2013-01-01

    Full Text Available Triazoloisoquinoline-based organic dyestuffs were synthesized and used in the fabrication of dye-sensitized solar cells (DSSCs. After cosensitization with ruthenium complex, the triazoloisoquinoline-based organic dyestuffs overcame the deficiency of ruthenium dyestuff absorption in the blue part of the visible spectrum. This method also fills the blanks of ruthenium dyestuff sensitized TiO2 film and forms a compact insulating molecular layer due to the nature of small molecular organic dyestuffs. The incident photon-to-electron conversion efficiency of N719 at shorter wavelength regions is 49%. After addition of a triazoloisoquinoline-based dyestuff for co-sensitization, the IPCE at 350–500 nm increased significantly. This can be attributed to the increased photocurrent of the cells, which improves the dye-sensitized photoelectric conversion efficiency from 6.23% to 7.84%, and the overall conversion efficiency increased by about 26%. As a consequence, this low molecular weight organic dyestuff is a promising candidate as coadsorbent and cosensitizer for highly efficient dye-sensitized solar cells.

  15. Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed

    Science.gov (United States)

    Min, Sang Hee; Goldman, I. David; Zhao, Rongbao

    2013-01-01

    Pemetrexed is a new generation antifolate approved for the treatment of mesothelioma and non-small cell lung cancer. Caffeine is known to augment radiation or chemotherapeutic drug-induced cell killing. The current study addresses the impact of caffeine on the activity of pemetrexed in mesothelioma cell lines. Caffeine enhanced pemetrexed activity in all four mesothelioma cell lines tested (H2052, H2373, H28 and MSTO-211H). Caffeine sensitized H2052 cells in a dose- and schedule-dependent manner, and was associated with a markedly decreased clonogenic survival. Caffeine sensitization occurred only in cells subjected to pulse, but not continuous, exposure to pemetrexed. Similar pemetrexed sensitization was also observed with the clinically better tolerated caffeine analog, theobromine. Pemetrexed sensitization by caffeine was associated with an increase in pemetrexed-induced phosphorylation of ataxia-telangiectasia-mutated (ATM) and Chk1. These data indicate that caffeine and its analog, theobromine, may be a useful approach to enhance pemetrexed-based chemotherapy. PMID:17594092

  16. Recent Advances in Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    F. O. Lenzmann

    2007-01-01

    Full Text Available This review describes recent advances in the research on dye-sensitized solar cells. After a brief discussion of the general operation principles and a presentation of record efficiencies, stability data and key technology drivers, current trends will be reviewed. The focus of this review is on materials development (sensitizers, nanostructured oxide films, and electrolyte, but commercialization aspects will also be briefly addressed. The review describes the most relevant characteristics and major trends in a compact way.

  17. Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Yanyan; Verbiest, Tom; Devery, Aoife M.; Bokobza, Sivan M.; Weber, Anika M.; Leszczynska, Katarzyna B.; Hammond, Ester M.; Ryan, Anderson J., E-mail: anderson.ryan@oncology.ox.ac.uk

    2016-06-01

    Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors potentiate radiation therapy in preclinical models of human non-small cell lung cancer (NSCLC) and other types of cancer. However, the mechanisms underlying radiosensitization in vivo are incompletely understood. Herein, we investigated the impact of hypoxia on radiosensitization by the PARP inhibitor olaparib in human NSCLC xenograft models. Methods and Materials: NSCLC Calu-6 and Calu-3 cells were irradiated in the presence of olaparib or vehicle under normoxic (21% O{sub 2}) or hypoxic (1% O{sub 2}) conditions. In vitro radiosensitivity was assessed by clonogenic survival assay and γH2AX foci assay. Established Calu-6 and Calu-3 subcutaneous xenografts were treated with olaparib (50 mg/kg, daily for 3 days), radiation (10 Gy), or both. Tumors (n=3/group) were collected 24 or 72 hours after the first treatment. Immunohistochemistry was performed to assess hypoxia (carbonic anhydrase IX [CA9]), vessels (CD31), DNA double strand breaks (DSB) (γH2AX), and apoptosis (cleaved caspase 3 [CC3]). The remaining xenografts (n=6/group) were monitored for tumor growth. Results: In vitro, olaparib showed a greater radiation-sensitizing effect in Calu-3 and Calu-6 cells in hypoxic conditions (1% O{sub 2}). In vivo, Calu-3 tumors were well-oxygenated, whereas Calu-6 tumors had extensive regions of hypoxia associated with down-regulation of the homologous recombination protein RAD51. Olaparib treatment increased unrepaired DNA DSB (P<.001) and apoptosis (P<.001) in hypoxic cells of Calu-6 tumors following radiation, whereas it had no significant effect on radiation-induced DNA damage response in nonhypoxic cells of Calu-6 tumors or in the tumor cells of well-oxygenated Calu-3 tumors. Consequently, olaparib significantly increased radiation-induced growth inhibition in Calu-6 tumors (P<.001) but not in Calu-3 tumors. Conclusions: Our data suggest that hypoxia potentiates the radiation-sensitizing effects of

  18. A panchromatic anthracene-fused porphyrin sensitizer for dye-sensitized solar cells

    KAUST Repository

    Ball, James M.

    2012-01-01

    The development of ruthenium-free sensitizers which absorb light over a broad range of the solar spectrum is important for improving the power conversion efficiency of dye-sensitized solar cells. Here we study three chemically tailored porphyrin-based dyes. We show that by fusing the porphyrin core to an anthracene unit, we can extend the conjugation length and lower the optical gap, shifting the absorption spectrum into the near-infrared (NIR). All three dyes were tested in dye-sensitized solar cells, using both titanium dioxide and tin dioxide as the electron-transport material. Solar cells incorporating the anthracene-fused porphyrin dye exhibit photocurrent collection at wavelengths up to about 1100 nm, which is the longest reported for a porphyrin-based system. Despite extending the photon absorption bandwidth, device efficiency is found to be low, which is a common property of cells based on porphyrin dyes with NIR absorption. We show that in the present case the efficiency is reduced by inefficient electron injection into the oxide, as opposed to dye regeneration, and highlight some important design considerations for panchromatic sensitizers. © 2012 The Royal Society of Chemistry.

  19. Large scintillation cells for high sensitivity radon concentration measurements

    Science.gov (United States)

    Cohen, B. L.; El Ganayni, M.; Cohen, E. S.

    1983-07-01

    Methods for improving the sensitivity of scintillation cells for radon concentration measurements were studied with emphasis on improving light collection efficiency. This allows the length and hence the volume of the cell to be increased. Variables studied were choice of scintillator material, its method of application and thickness, length of cell, cell material, type and configuration of reflectors, choice of photomultipliers, and factors affecting background. Response from various areas of the cell surface was studied with an alpha source and with radon filling. Coating the window with phosphor was found to be counter-productive. The optimum results obtained were with the inside of the cell (other than the window) covered with a thick layer of ZnS(Ag), or with a thick layer of reflective material coated with a thin layer of phosphor. With it, a 10 cm diameter plexiglass cell can be extended to at least 50 cm length without difficulty from insufficient pulse height.

  20. Heterogeneity reduces sensitivity of cell death for TNF-Stimuli

    Directory of Open Access Journals (Sweden)

    Schliemann Monica

    2011-12-01

    Full Text Available Abstract Background Apoptosis is a form of programmed cell death essential for the maintenance of homeostasis and the removal of potentially damaged cells in multicellular organisms. By binding its cognate membrane receptor, TNF receptor type 1 (TNF-R1, the proinflammatory cytokine Tumor Necrosis Factor (TNF activates pro-apoptotic signaling via caspase activation, but at the same time also stimulates nuclear factor κB (NF-κB-mediated survival pathways. Differential dose-response relationships of these two major TNF signaling pathways have been described experimentally and using mathematical modeling. However, the quantitative analysis of the complex interplay between pro- and anti-apoptotic signaling pathways is an open question as it is challenging for several reasons: the overall signaling network is complex, various time scales are present, and cells respond quantitatively and qualitatively in a heterogeneous manner. Results This study analyzes the complex interplay of the crosstalk of TNF-R1 induced pro- and anti-apoptotic signaling pathways based on an experimentally validated mathematical model. The mathematical model describes the temporal responses on both the single cell level as well as the level of a heterogeneous cell population, as observed in the respective quantitative experiments using TNF-R1 stimuli of different strengths and durations. Global sensitivity of the heterogeneous population was quantified by measuring the average gradient of time of death versus each population parameter. This global sensitivity analysis uncovers the concentrations of Caspase-8 and Caspase-3, and their respective inhibitors BAR and XIAP, as key elements for deciding the cell's fate. A simulated knockout of the NF-κB-mediated anti-apoptotic signaling reveals the importance of this pathway for delaying the time of death, reducing the death rate in the case of pulse stimulation and significantly increasing cell-to-cell variability. Conclusions Cell

  1. Unsymmetrical Heptamethine Dyes for NIR Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Thomas Geiger

    2014-01-01

    Full Text Available Seven unsymmetrical heptamethine dyes with carboxylic acid functionality were synthesized and characterized. These near-infrared dyes exhibit outstanding photophysical properties depending on their heterocyclic moieties and molecular structure. As proof of principle, the dyes were used as photosensitizers in dye-sensitized solar cells. Using the most promising dye, an overall conversion efficiency of 1.22% and an almost colorless solar cell were achieved.

  2. Dye-sensitized solar cells: a successful combination of materials

    Directory of Open Access Journals (Sweden)

    Longo Claudia

    2003-01-01

    Full Text Available Dye-sensitized TiO2 solar cells, DSSC, are a promising alternative for the development of a new generation of photovoltaic devices. DSSC are a successful combination of materials, consisting of a transparent electrode coated with a dye-sensitized mesoporous film of nanocrystalline particles of TiO2, an electrolyte containing a suitable redox-couple and a Pt coated counter-electrode. In general, Ru bipyridyl complexes are used as the dye sensitizers. The light-to-energy conversion performance of the cell depends on the relative energy levels of the semiconductor and dye and on the kinetics of the electron-transfer processes at the sensitized semiconductor | electrolyte interface. The rate of these processes depends on the properties of its components. This contribution presents a discussion on the influence of each of the materials which constitute the DSSC of the overall process for energy conversion. An overview of the results obtained for solid-state dye-sensitized TiO2 solar cells assembled with polymer electrolytes is also presented.

  3. DNA methylation and sensitivity to antimetabolites in cancer cell lines.

    Science.gov (United States)

    Sasaki, Shin; Kobunai, Takashi; Kitayama, Joji; Nagawa, Hirokazu

    2008-02-01

    The prediction of the cellular direction of metabolic pathways toward either DNA synthesis or DNA methylation is crucial for determining the susceptibility of cancers to anti-metabolites such as fluorouracil (5-FU). We genotyped the methylenetetrahydrofolate reductase (MTHFR) gene in NCI-60 cancer cell lines, and identified the methylation status of 24 tumor suppressor genes using methylation-specific multiplex ligation-dependent probe amplification. The susceptibility of the cancer cell lines to seven antimetabolites was then determined. Cells homozygous for CC at MTHFR-A1298C were significantly more sensitive to cyclocytidine, cytarabine (AraC) and floxuridine than those with AA or AC (p=0.0215, p=0.0166, and p=0.0323, respectively), and carried more methylated tumor suppressor genes (p=0.0313). Among the 12 tumor suppressor genes which were methylated in >25% of cancer cell lines, the methylation status of TIMP3, APC and IGSF4 significantly correlated with sensitivity to pyrimidine synthesis inhibitors. In particular, cells with methylated TIMP3 had reduced mRNA levels and were significantly more sensitive to aphidicolin-glycinate, AraC and 5-FU than cells with unmethylated TIMP3. We speculate that MTHFR-A1298C homozygous CC might direct the methylation rather than the synthesis of DNA, and result in the methylation of several tumor suppressor genes such as TIMP3. These genes could be useful biological markers for predicting the efficacy of antimetabolites.

  4. Natural dyes as photosensitizers for dye-sensitized solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Sancun; Wu, Jihuai; Huang, Yunfang; Lin, Jianming [Institute of Materials Physical Chemistry, Huaqiao University, Quanzhou, Fujian 362021 (China)

    2006-02-15

    The dye-sensitized solar cells (DSC) were assembled by using natural dyes extracted from black rice, capsicum, erythrina variegata flower, rosa xanthina, and kelp as sensitizers. The I{sub SC} from 1.142mA to 0.225mA, the V{sub OC} from 0.551V to 0.412V, the fill factor from 0.52 to 0.63, and P{sub max} from 58{mu}W to 327{mu}W were obtained from the DSC sensitized with natural dye extracts. In the extracts of natural fruit, leaves and flower chosen, the black rice extract performed the best photosensitized effect, which was due to the better interaction between the carbonyl and hydroxyl groups of anthocyanin molecule on black rice extract and the surface of TiO{sub 2} porous film. The blue-shift of absorption wavelength of the black rice extract in ethanol solution on TiO{sub 2} film and the blue-shift phenomenon from absorption spectrum to photoaction spectrum of DSC sensitized with black rice extract are discussed in the paper. Because of the simple preparation technique, widely available and low cheap cost natural dye as an alternative sensitizer for dye-sensitized solar cell is promising. (author)

  5. Hypoxic Tumor Microenvironments Reduce Collagen I Fiber Density

    Directory of Open Access Journals (Sweden)

    Samata M. Kakkad

    2010-08-01

    Full Text Available Although the mechanisms through which hypoxia influences several phenotypic characteristics such as angiogenesis, selection for resistance to apoptosis, resistance to radiation and chemotherapy, and increased invasion and metastasis are well characterized, the relationship between tumor hypoxia and components of the extracellular matrix (ECM is relatively unexplored. The collagen I (Col1 fiber matrix of solid tumors is the major structural part of the ECM. Col1 fiber density can increase tumor initiation, progression, and metastasis, with cancer cell invasion occurringalong radially aligned Col1 fibers. Here we have investigated the influence of hypoxia on Col1 fiber density in solid breast and prostate tumor models. Second harmonic generation (SHG microscopy was used to detect differences in Col1 fiber density and volume between hypoxic and normoxic tumor regions. Hypoxic regions were detected by fluorescence microscopy, using tumors derived from human breast and prostate cancer cell lines stably expressing enhanced green fluorescent protein (EGFP under transcriptional control of the hypoxia response element. In-house fiber analysis software was used to quantitatively analyze Col1 fiber density and volume from the SHG microscopy images. Normoxic tumor regions exhibited a dense mesh of Col1 fibers. In contrast, fewer and structurally altered Col1 fibers were detected in hypoxic EGFP-expressing tumor regions. Microarray gene expression analyses identified increased expression of lysyl oxidase and reduced expression of some matrix metal loproteases in hypoxic compared with normoxic cancer cells. These results suggest that hypoxia mediates Col1 fiber restructuring in tumors, which may impact delivery of macromolecular agents as well as dissemination of cells.

  6. Transforming growth factor-beta1 upregulation triggers pulmonary artery smooth muscle cell proliferation and apoptosis imbalance in rats with hypoxic pulmonary hypertension via the PTEN/AKT pathways.

    Science.gov (United States)

    Liu, Yun; Cao, Yonggang; Sun, Shuyang; Zhu, Jinquan; Gao, Shan; Pang, Jie; Zhu, Daling; Sun, Zengxian

    2016-08-01

    Transforming growth factor-beta1 (TGFβ1) and Phosphatase and Tensin homolog deleted on chromosome ten (PTEN) are involved in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. In previous studies, we have shown that TGFβ1 and PTEN play an important role in the progression of pulmonary vascular remodeling induced by pulmonary artery smooth muscle cells (PASMCs). However, the mechanisms involved in the activation of PASMCs between TGFβ1 and PTEN pathways remain unknown. We found that pulmonary vascular walls in hypoxic pulmonary arterial hypertension (PAH) rats were thicker than the vessels from normal rats in vivo. Substantially higher levels of TGFβ1 and significant loss of PTEN expression were observed in the lungs of PAH rats when compared with normoxia. Meanwhile, AKT, a downstream proliferative signaling protein of the PTEN antagonist PI3K, was markedly activated in the lungs of PAH rats. In vitro studies using PASMCs showed that TGFβ1 increased cell proliferation in PTEN-dependent manner. Moreover, we found that TGFβ1 enhanced cell survival, up-regulated the expression of Bcl-2 and procaspase-3, decreased the number of TUNEL-positive cells and caspase-3 expression in PASMCs under serum-deprived (SD) condition via PI3K/AKT pathway. The results further establish that TGFβ1 promoted PAH by decreasing PTEN expression and increasing PI3K/AKT activation in the lung. In conclusion, TGFβ1 mediated PTEN inactivation and resistance to apoptosis seems to be key mediators of lung vascular remodeling associated with PAH. These findings further clarify molecular mechanisms that support targeting PTEN/AKT signaling pathway to attenuate pathogenic derangements in PAH. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Organic sensitizers for dye-sensitized solar cell (DSSC): Properties from computation, progress and future perspectives

    Science.gov (United States)

    Obotowo, I. N.; Obot, I. B.; Ekpe, U. J.

    2016-10-01

    The advent of the dye-sensitized solar cells (DSSCs) came at a time when the quest for alternative energy was high, replacing p-n junction photovoltaic devices. Its uniqueness arises from the fact that unlike the conventional systems where the semiconductor assumes the task of light absorption and charge transport, the two functions are separated in DSSC. Organic sensitizers have been used to harvest a large fraction of sunlight ranging from the UV region to the near infrared region of the spectrum leading to power conversion efficiencies of up to ∼ 10.65 % for metal-free organic sensitizers. Currently, experimental analysis of photo sensitizers utilized in DSSCs is often a trial and error process, often laborious and require extensive and expensive chemical synthesis. In most cases, disappointing results from late-stage of the dye synthesis indicate an urgent need to understand the properties of the dyes at a molecular level, before experiments take place. Fortunately, the use of quantum chemical calculations especially Density Functional Theory (DFT) to screen potential dyes has helped in developing efficient sensitizers and to reduce cost. In the present review article, we discuss the current state of the field, new concepts, design strategies, challenges facing the theoretical design and development of organic sensitizers for DSSCs and future perspectives.

  8. Metal Complex Dyes for Dye-Sensitized Solar Cells: Recent ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 15; Issue 9. Metal Complex Dyes for Dye-Sensitized Solar Cells: ... Author Affiliations. N Sekar1 Vishal Y Gehlot. Dyestuff Technology Department Institute of Chemical Technology (Formerly UDCT) Nathalal Parekh Marg Matunga Mumbai 400 019, India.

  9. Ionic Liquid Electrolytes for Flexible Dye-Sensitized Solar Cells

    Science.gov (United States)

    2014-09-01

    Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite...Gorlov, M. Ionic Liquid Electrolyte for Dye-Sensitized Solar Cells. RSC DaltonTrans. 2008, 20, 2655–2666. 7. Zakeeruddin, S. M.; Wang, P.; Humphry

  10. Parametric Sensitivity Tests- European PEM Fuel Cell Stack Test Procedures

    DEFF Research Database (Denmark)

    Araya, Samuel Simon; Andreasen, Søren Juhl; Kær, Søren Knudsen

    2014-01-01

    As fuel cells are increasingly commercialized for various applications, harmonized and industry-relevant test procedures are necessary to benchmark tests and to ensure comparability of stack performance results from different parties. This paper reports the results of parametric sensitivity tests...

  11. Efficient eco-friendly inverted quantum dot sensitized solar cells

    NARCIS (Netherlands)

    Park, Jinhyung; Sajjad, Muhammad T.; Jouneau, Pierre-Henri; Ruseckas, Arvydas; Faure-Vincent, Jérôme; Samuel, Ifor D. W.; Reiss, Peter; Aldakov, Dmitry

    2016-01-01

    Recent progress in quantum dot (QD) sensitized solar cells has demonstrated the possibility of low-cost and efficient photovoltaics. However, the standard device structure based on n-type materials often suffers from slow hole injection rate, which may lead to unbalanced charge transport. We have

  12. Dye-sensitized solar cell and photocatalytic performance of ...

    Indian Academy of Sciences (India)

    sensitized solar cells) and photocatalysis properties (decomposition of methomyl) was investigated. In all investigated cases, the sample C, which was formed by anodizing in a ethylene glycol electrolyte containing 9 mM K 3 Fe(CN) 6 , exhibited ...

  13. Fuel utilization and fuel sensitivity of solid oxide fuel cells

    Science.gov (United States)

    Huang, Kevin

    2011-03-01

    Fuel utilization and fuel sensitivity are two important process variables widely used in operation of SOFC cells, stacks, and generators. To illustrate the technical values, the definitions of these two variables as well as practical examples are particularly given in this paper. It is explicitly shown that the oxygen-leakage has a substantial effect on the actual fuel utilization, fuel sensitivity and V-I characteristics. An underestimation of the leakage flux could potentially results in overly consuming fuel and oxidizing Ni-based anode. A fuel sensitivity model is also proposed to help extract the leakage flux information from a fuel sensitivity curve. Finally, the "bending-over" phenomenon observed in the low-current range of a V-I curve measured at constant fuel-utilization is quantitatively coupled with leakage flux.

  14. Review of Polymer, Dye-Sensitized, and Hybrid Solar Cells

    Directory of Open Access Journals (Sweden)

    S. N. F. Mohd-Nasir

    2014-01-01

    Full Text Available The combination of inorganic nanoparticles semiconductor, conjugated polymer, and dye-sensitized in a layer of solar cell is now recognized as potential application in developing flexible, large area, and low cost photovoltaic devices. Several conjugated low bandgap polymers, dyes, and underlayer materials based on the previous studies are quoted in this paper, which can provide guidelines in designing low cost photovoltaic solar cells. All of these materials are designed to help harvest more sunlight in a wider range of the solar spectrum besides enhancing the rate of charge transfer in a device structure. This review focuses on developing solid-state dye-synthesized, polymer, and hybrid solar cells.

  15. Parametric Optimization of Dye-Sensitized Solar Cells Using Far red Sensitizing Dye with Cobalt Electrolyte

    Science.gov (United States)

    Pradhan, A.; Saikiran, M.; Kapil, G.; Pandey, S. S.; Hayase, S.

    2017-11-01

    A far-red sensitizing dye SQ-75 has been employed as a model sensitizer with Co(bpy)2+/3+ redox electrolytes to fabricate dye-sensitized solar cells (DSSCs) and optimize the various device parameters which influence the overall photoconversion efficiency (PCE). It has been found that the optimization of the TiO2 thickness, surface treatment with TiCl4, and an optimum amount of the chenodeoxycholic acid (CDCA) as coadsorber are necessary to attain the overall improved PCE. TiCl4 surface treatment on both FTO and TiO2 has been found to outperform as compared to their untreated counterparts owing to the suppression of the charge recombination. DSSCs with an optimized TiO2 thickness of 6 μm and CDCA concentration of 4 mM have exhibited best performance due to enhanced photon harvesting and reduced dye aggregation, respectively.

  16. Nature of a red cell sensitizing substance from streptococci.

    Science.gov (United States)

    Jackson, R W; Moskowitz, M

    1966-06-01

    Jackson, Robert W. (Purdue University, Lafayette, Ind.), and Merwin Moskowitz. Nature of a red cell sensitizing substance from streptococci. J. Bacteriol. 91:2205-2209. 1966.-A method for purifying a streptococcal antigen which sensitizes red cells to agglutination by antiserum is described. The antigen, when purified by this method, is almost exclusively composed of glycerophosphate and d-alanine. The ratio of alanine to glycerophosphate varies from 1:5 to 1:3. The glycerophosphate is polymerized and is thus a teichoic acid. The polyglycerophosphate appears to be the antigenic determinant for agglutination. d-Alanine is readily removed by mild base and appears to be necessary for the attachment of the teichoic acid to red cells. Quantitative removal of alanine does not affect the ability of the polymer to absorb antibody from serum.

  17. Decursin reduce radio-resistance of hypoxic regions under the proton beam therapy by induced HIF-1α degradation

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Myung Hwan; Kim, Kye Ryung [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-10-15

    Protons induce cancer-cell apoptosis in vitro and block blood vessel formation in vivo through the generation of reactive oxygen species (ROS). The fact that proton severely inhibits blood vessel development in zebrafish embryos suggests a higher sensitivity of vascular endothelial cells to proton beam. Decursin, a coumarin compound, was originally isolated from Angelica gigas Nakai (Dang Gui). A. gigas root has been traditionally used in Korean folk medicine for the treatment of anemia and other common diseases. In previous reports, decursin was reported to exhibit anti-tumor activity against various cancer cells and to inhibit the activities of the androgen and androgen-receptor (AR) signaling pathway in prostate cancer, induction of cell cycle arrest and apoptosis in various cancer cells, such as prostate, breast, bladder, and colon cancer cells. Decursin also inhibits VEGF-induced angiogenesis through the suppression of the VEGFR-2-signaling pathway. However, the mechanism of decursin mediates change of HIF-1α activities is not clear. In this research, we identified regulations of the HIF-1α and the anti-angiogenesis effects of decursin in proton-beam-irradiated human lung cancer, prostate cancer and Hepatic cancer cells. We investigated the underlying mechanisms of positive effects of protonbeam-induced anti-angiogenesis. Our data indicate that the groups co-treated with decursin and a proton-beam had significant reduced HIF-1α activity compared with the groups treated with only a proton beam under the hypoxic condition caused by DFX(desferrioxamine). Decursin was found to induced HIF-1α degradation. Therefore, we suggest that decursin may be a potential candidate for use as a sensitizer for proton-beaminduced cell apoptosis. Here we have shown that decursin successfully reduced HIF-1α stability under hypoxic condition by induced desferrioxamine. We showed novel candidates for anti-angiogenic compound, decursin, leading to complete inhibition of radio

  18. Dithiafulvene-based organic sensitizers using pyridine as the acceptor for dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jun; Cao, Yaxiong; Liang, Xiaozhong; Zheng, Jingxia; Zhang, Fang [Ministry of Education Key Laboratory of Interface Science and Engineering in Advanced Materials, Research Center of Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China); Wei, Shuxian; Lu, Xiaoqing [College of Science, China University of Petroleum, Qingdao, Shandong 266555 (China); Guo, Kunpeng, E-mail: guokunpeng@tyut.edu.cn [Ministry of Education Key Laboratory of Interface Science and Engineering in Advanced Materials, Research Center of Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China); Yang, Shihe, E-mail: chsyang@ust.hk [Ministry of Education Key Laboratory of Interface Science and Engineering in Advanced Materials, Research Center of Advanced Materials Science and Technology, Taiyuan University of Technology, Taiyuan 030024 (China); Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong (China)

    2017-05-01

    Three dithiafulvene-based metal-free organic sensitizers all using pyridine as the acceptor but with different π-bridges of phenyl (DTF-Py1), thienyl (DTF-Py2) and phenyl-thienyl (DTF-Py3) have been designed, synthesized and used as photosensitizers for dye-sensitized solar cells (DSCs). Introducing thienyl unit into the π-bridge, as well as extension of the π-bridge can dramatically improve their light harvesting ability and suppress the electron recombination, thus uplifting the performance of DSCs. The overall power conversion efficiency of DSC based on DTF-Py3 shows the highest efficiency of 2.61% with a short-circuit photocurrent density of 7.99 mA cm{sup -2}, an open-circuit photovoltage of 630 mV, and a fill factor of 0.52, under standard global AM 1.5 solar light condition. More importantly, the long-term stability of the DTF-Py3 based DSCs under 500 h light-soaking has been demonstrated. - Highlights: • Dithiafulvene sensitizers using pyridine ring as the acceptor were synthesized for the first time. • The power conversion efficiency of 2.61% was obtained for DTF-Py3 sensitized cell. • DTF-Py3 loaded TiO{sub 2} film shows improved light harvesting ability and suppressed electron recombination.

  19. Perylene anhydride fused porphyrins as near-infrared sensitizers for dye-sensitized solar cells

    KAUST Repository

    Jiao, Chongjun

    2011-07-15

    Two perylene anhydride fused porphyrins 1 and 2 have been synthesized and employed successfully in dye-sensitized solar cells (DSCs). Both compounds showed broad incident monochromatic photon-to-current conversion efficiency spectra covering the entire visible spectral region and even extending into the near-infrared (NIR) region up to 1000 nm, which is impressive for ruthenium-free dyes in DSCs. © 2011 American Chemical Society.

  20. Modulating cell-to-cell variability and sensitivity to death ligands by co-drugging

    Science.gov (United States)

    Flusberg, Deborah A.; Sorger, Peter K.

    2013-06-01

    TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) holds promise as an anti-cancer therapeutic but efficiently induces apoptosis in only a subset of tumor cell lines. Moreover, even in clonal populations of responsive lines, only a fraction of cells dies in response to TRAIL and individual cells exhibit cell-to-cell variability in the timing of cell death. Fractional killing in these cell populations appears to arise not from genetic differences among cells but rather from differences in gene expression states, fluctuations in protein levels and the extent to which TRAIL-induced death or survival pathways become activated. In this study, we ask how cell-to-cell variability manifests in cell types with different sensitivities to TRAIL, as well as how it changes when cells are exposed to combinations of drugs. We show that individual cells that survive treatment with TRAIL can regenerate the sensitivity and death-time distribution of the parental population, demonstrating that fractional killing is a stable property of cell populations. We also show that cell-to-cell variability in the timing and probability of apoptosis in response to treatment can be tuned using combinations of drugs that together increase apoptotic sensitivity compared to treatment with one drug alone. In the case of TRAIL, modulation of cell-to-cell variability by co-drugging appears to involve a reduction in the threshold for mitochondrial outer membrane permeabilization.

  1. Game performance and intermittent hypoxic training

    OpenAIRE

    Hinckson, E A; Hamlin, M J; Wood, M R; Hopkins, W G

    2007-01-01

    Live high‐train low altitude exposure simulated by hypoxic devices may improve athletic performance. In this study, intermittent normobaric hypoxia was achieved with the GO2altitude® hypoxicator to determine its effects on sea level performance in rugby players. Ten players were randomly assigned to two groups. Players in each group received 14 sessions of either hypoxic (10–15% O2) or normoxic (21% O2) exposure at rest over 14 consecutive days in a single blind fashion. Various performance m...

  2. Knockdown of OCT4 may sensitize NSCLC cells to cisplatin.

    Science.gov (United States)

    Liu, X; Ma, M; Duan, X; Zhang, H; Yang, M

    2017-05-01

    Cisplatin is commonly used in non-small-cell lung cancer (NSCLC) chemotherapy; however, chemoresistance to cisplatin remains a great clinical challenge. Octamer-binding protein 4 (OCT4) has been reported to be overexpressed in NSCLC. In this study, we aimed to investigate the potential role of OCT4 in NSCLC with chemoresistance to cisplatin. Expressions of OCT4 was detected in NSCLC tissues and cell lines. We utilized siRNA to knock down OCT4 expression in human NSCLC cells and analyzed their phenotypic changes. We found that the difference of OCT4 expression between NSCLC and the adjacent non-tumourous tissues was statistically significant. Knockdown of OCT4 in NSCLC cells could decrease cell proliferation, and potentiate apoptosis induced by cisplatin, suggesting OCT4 may contribute to cisplatin resistance in NSCLC. Our findings indicate that targeting OCT4 could improve cisplatin effect in NSCLC, confirming their role in modulating cisplatin sensitivity.

  3. Hypoxic-Ischemic Neonatal Encephalopathy: Animal Experiments for Neuroprotective Therapies

    Directory of Open Access Journals (Sweden)

    Hiroshi Sameshima

    2013-01-01

    Full Text Available Hypoxic-ischemic neonatal encephalopathy and ensuing brain damage is still an important problem in modern perinatal medicine. In this paper, we would like to share some of the results of our recent studies on neuroprotective therapies in animal experiments, as well as some literature reviews. From the basic animal studies, we have now obtained some possible candidates for therapeutic measures against hypoxic-ischemic neonatal encephalopathy. For example, they are hypothermia, rehabilitation, free radical scavenger, neurotrophic factors and growth factors, steroid, calcium channel blocker, vagal stimulation, some anti apoptotic agents, pre- and post conditioning, antioxidants, cell therapy with stem cells, modulators of K(+-ATP channels, and so on. Whether combination of these therapies may be more beneficial than any single therapy needs to be clarified. Hypoxia-ischemia is a complicated condition, in which the cause, severity, and time-course are different in each case. Likewise, each fetus has its own inherent potentials such as adaptation, preconditioning-tolerance, and intolerance. Therefore, further extensive studies are required to establish an individualized strategy for neuroprotection against perinatal hypoxic-ischemic insult.

  4. Low-dose radiation suppresses Pokemon expression under hypoxic conditions.

    Science.gov (United States)

    Kim, Seung-Whan; Yu, Kweon; Shin, Kee-Sun; Kwon, Kisang; Hwang, Tae-Sik; Kwon, O-Yu

    2014-01-01

    Our previous data demonstrated that CoCl2-induced hypoxia controls endoplasmic reticulum (ER) stress-associated and other intracellular factors. One of them, the transcription factor Pokemon, was differentially regulated by low-dose radiation (LDR). There are limited data regarding how this transcription factor is involved in expression of the unfolded protein response (UPR) under hypoxic conditions. The purpose of this study was to obtain clues on how Pokemon is involved in the UPR. Pokemon was selected as a differentially expressed gene under hypoxic conditions; however, its regulation was clearly repressed by LDR. It was also demonstrated that both expression of ER chaperones and ER stress sensors were affected by hypoxic conditions, and the same results were obtained when cells in which Pokemon was up- or down-regulated were used. The current state of UPR and LDR research associated with the Pokemon pathway offers an important opportunity to understand the oncogenesis, senescence, and differentiation of cells, as well as to facilitate introduction of new therapeutic radiopharmaceuticals.

  5. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells.

    Science.gov (United States)

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-12

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na⁺/H⁺ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal-regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors.

  6. Expression of N-methyl D-aspartate receptor subunits in amoeboid microglia mediates production of nitric oxide via NF-κB signaling pathway and oligodendrocyte cell death in hypoxic postnatal rats.

    Science.gov (United States)

    Murugan, Madhuvika; Sivakumar, Viswanathan; Lu, Jia; Ling, Eng-Ang; Kaur, Charanjit

    2011-04-01

    The present study was focused on identifying the expression of N-methyl D-aspartate receptor (NMDAR) subunits on activated microglia and to determine their role in the pathogenesis of periventricular white matter damage (PWMD) in neonatal rats following hypoxia. One day old wistar rats were subjected to hypoxia (5% O(2) ; 95% N(2) ) and the mRNA and protein expression of NMDAR subunits (NR1, NR2A-D, and NR3A) in the periventricular white matter (PWM) was determined at different time points (3,24 h, 3, 7, and 14 days) following hypoxic exposure. Immunoexpression of NR1 and NR2A-D was localized in amoeboid microglial cells (AMC) suggesting the presence of functional NMDARs in them. The expression of NMDAR in primary microglial cultures was ascertained by RT-PCR analysis and double immunofluorescence studies. The functionality of the microglial NMDAR in cultured microglial cells was examined by monitoring calcium movements in cells with fura-2. In primary microglial cultures, hypoxia induced the nuclear translocation of NF-κB which was suppressed by administration of MK801, an NMDAR antagonist. MK801 also down regulated the hypoxia-induced expression of tumor necrosis factor-α, interleukin-1β, inducible nitric oxide synthase (iNOS), and nitric oxide (NO) production by microglia which may be mediated by the NF-κB signaling pathway. NO produced by microglia is known to cause death of oligodendrocytes in the developing PWM. In this connection, pharmacological agents such as MK801, BAY (NF-κB inhibitor), and 1400w (iNOS inhibitor) proved to be beneficial since they reduced the hypoxia-induced iNOS expression, NO production, and a corresponding reduction in the death of oligodendrocytes following hypoxia. Copyright © 2011 Wiley-Liss, Inc.

  7. Co-sensitization of organic dyes for efficient dye-sensitized solar cells.

    Science.gov (United States)

    Cheng, Ming; Yang, Xichuan; Li, Jiajia; Zhang, Fuguo; Sun, Licheng

    2013-01-01

    Novel cyanine dyes, in which a tetrahydroquinoline derivative is used as an electron donor and 1-butyl-5-carboxy-3, 3-dimethyl-indol-1-ium moiety is used as an electron acceptor and anchoring group, were designed and synthesized for application in dye-sensitized solar cells. The photovoltaic performance of these solar cells depends markedly on the molecular structure of the dyes in terms of the n-hexyl chains and the methoxyl unit. Retardation of charge recombination caused by the introduction of n-hexyl chains resulted in an increase in electron lifetime. As a consequence, an improvement of open-circuit photovoltage (V(oc)) was achieved. Also, the electron injection efficiencies were improved by the introduction of methoxyl moiety, which led to a higher short-circuit photocurrent density (J(sc)). The highest average efficiency of the sensitized devices (η) was 5.6% (J(sc)=13.3 mA cm(-2), V(oc)=606 mV, and fill factor FF=69.1%) under 100 mW cm(-2) (AM 1.5G) solar irradiation. All of these dyes have very high absorption extinction coefficients and strong absorption in a relatively narrow spectrum range (500-650 nm), so one of our organic dyes was explored as a sensitizer in co-sensitized solar cells in combination with the other two other existing organic dyes. Interestingly, a considerably improved photovoltaic performance of 8.2% (J(sc)=20.1 mA cm(-2), V(oc)=597 mV, and FF=68.3%) was achieved and the device showed a panchromatic response with a high incident photon-to-current conversion efficiency exceeding 85% in the range of 400-700 nm. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Differential responsiveness in VEGF receptor subtypes to hypoxic stress in various tissues of plateau animals.

    Science.gov (United States)

    Xie, Hui-Chun; Li, Jin-Gang; He, Jian-Ping

    2017-05-04

    With hypoxic stress, hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are elevated and their responses are altered in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (Ochotona curzoniae)] as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. The results indicate that HIF-1alpha and VEGF are engaged in physiological functions under hypoxic environment. The purpose of the current study was to examine the protein levels of VEGF receptor subtypes (VEGFRs: VEGFR-1, VEGFR-2 and VEGFR-3) in the end organs, namely skeletal muscle, heart and lung in response to hypoxic stress. ELISA and Western blot analysis were employed to determine HIF-1alpha and the protein expression of VEGFRs in control animals and plateau pikas. We further blocked HIF-1alpha signal to determine if HIF-1alpha regulates alternations in VEGFRs in those tissues. We hypothesized that responsiveness of VEGFRs in the major end organs of plateau animals is differential with insult of hypoxic stress and is modulated by low oxygen sensitive HIF-1alpha. Our results show that hypoxic stress induced by exposure of lower O(2) for 6 h significantly increased the levels of VEGFR-2 in skeletal muscle, heart and lung and the increases were amplified in plateau pikas. Our results also demonstrate that hypoxic stress enhanced VEGFR-3 in lungs of plateau animals. Nonetheless, no significant alternations in VEGFR-1 were observed in those tissues with hypoxic stress. Moreover, we observed decreases of VEGFR-2 in skeletal muscle, heart and lung; and decreases of VEGFR-3 in lung following HIF-1alpha inhibition. Overall, our findings suggest that in plateau animals 1) responsiveness of VEGFRs is different under hypoxic environment; 2) amplified VEGFR-2 response appears in skeletal muscle, heart and lung, and enhanced VEGFR-3 response is mainly observed in lung; 3) HIF-1alpha plays a regulatory role in the levels of VEGFRs. Our results

  9. Outcome Factors in Hypoxic Ischemic Encephalopathy

    OpenAIRE

    J Gordon Millichap

    2002-01-01

    The predictive value of history, examination, Glasgow Coma Scale (GCS) scores, EEG and sensory evoked potentials (SEP) in the prognosis of children with acute hypoxic-ischemic encephalopathy (HIE) was evaluated at the University Hospital of Lille, France.

  10. Red Sicilian orange and purple eggplant fruits as natural sensitizers for dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Calogero, Giuseppe; Marco, Gaetano Di [CNR, Istituto per i Processi Chimico-Fisici (Sede di Messina) Salita Sperone, C. da Papardo, I-98158 Faro Superiore Messina (Italy)

    2008-11-15

    Dye-sensitized solar cells (DSSCs) were assembled by using red Sicilian orange juice (Citrus Sinensis) and the purple extract of eggplant peels (Solanum melongena, L.) as natural sensitizers of TiO{sub 2} films. Conversion of solar light into electricity was successfully accomplished with both fruit-based solar cells. The best solar energy conversion efficiency ({eta}=0.66%) was obtained by red orange juice dye that, under AM 1.5 illumination, achieved up to J{sub sc}=3.84 mA/cm{sup 2}, V{sub oc}=0.340 V and fill factor=0.50. In the case of the extract of eggplant peels, the values determined were up to J{sub sc}=3.40 mA/cm{sup 2}, V{sub oc}=0.350 V and fill factor=0.40. Cyanidine-3-glucoside (cyanine) and delphinidin 3-[4-(p-coumaroyl)-L-rhamnosyl(1-6)-glucopyranoside]-5-glucopyranoside (nasunin) are the main pigments of cocktail dyes for red orange and eggplant, respectively. Actually, their application is far below the industrial requirements. Nevertheless, their study is an interesting multidisciplinary exercise useful for dissemination of knowledge and to educate people on renewable energy sources. Here, we report and discuss the role of the structure, the absorption spectra and the sensitization activity of the mentioned compounds. (author)

  11. Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

    DEFF Research Database (Denmark)

    Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E

    2007-01-01

    with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment....... for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells...

  12. DNA repair and radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Stackhouse, M. [Los Alamos National Lab., NM (United States); Chen, D.S. [Rochester Univ., NY (United States). Dept. of Radiation Oncology

    1993-02-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  13. DNA repair and radiation sensitivity in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, D.J.C.; Stackhouse, M. (Los Alamos National Lab., NM (United States)); Chen, D.S. (Rochester Univ., NY (United States). Dept. of Radiation Oncology)

    1993-01-01

    Ionizing radiation induces various types of damage in mammalian cells including DNA single-strand breaks, DNA double-strand breaks (DSB), DNA-protein cross links, and altered DNA bases. Although human cells can repair many of these lesions there is little detailed knowledge of the nature of the genes and the encoded enzymes that control these repair processes. We report here on the cellular and genetic analyses of DNA double-strand break repair deficient mammalian cells. It has been well established that the DNA double-strand break is one of the major lesions induced by ionizing radiation. Utilizing rodent repair-deficient mutant, we have shown that the genes responsible for DNA double-strand break repair are also responsible for the cellular expression of radiation sensitivity. The molecular genetic analysis of DSB repair in rodent/human hybrid cells indicate that at least 6 different genes in mammalian cells are responsible for the repair of radiation-induced DNA double-strand breaks. Mapping and the prospect of cloning of human radiation repair genes are reviewed. Understanding the molecular and genetic basis of radiation sensitivity and DNA repair in man will provide a rational foundation to predict the individual risk associated with radiation exposure and to prevent radiation-induced genetic damage in the human population.

  14. Dye-sensitized back-contact solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Dongchuan; Zhang, Xiao Li [ARC Centre of Excellence for Electromaterials Science, Department of Materials Engineering, Monash University, Clayton Victoria, 3800, 3168 (Australia); Barber, Richard L [MiniFAB (Aust) Pty Ltd, 1 Dalmore Drive, Scoresby Victoria 3179 (Australia); Bach, Udo [ARC Centre of Excellence for Electromaterials Science, Department of Materials Engineering and School of Chemistry, Monash University, Clayton Victoria, 3800 (Australia)

    2010-10-08

    Dye-sensitized back-contact solar cells are fabricated on back plates comprising a patterned FTO glass substrate, a selectively deposited Pt coating, a protective ZrO{sub 2} coating covering the Pt layers and a screen printed TiO{sub 2} film. Such devices show a solar energy conversion efficiency of 3.64% under AM 1.5 sunlight and a peak incident photon to electron conversion efficiency of 54%. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  15. Involvement of SIRT1 in hypoxic down-regulation of c-Myc and β-catenin and hypoxic preconditioning effect of polyphenols

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Kyung-Soo [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Park, Jun-Ik [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Mi-Ju; Kim, Hak-Bong; Lee, Jae-Won [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Dao, Trong Tuan; Oh, Won Keun [BK21 Project Team, College of Pharmacy, Chosun University, Gwangju (Korea, Republic of); Kang, Chi-Dug, E-mail: kcdshbw@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Kim, Sun-Hee, E-mail: ksh7738@pusan.ac.kr [Department of Biochemistry, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Research Center for Ischemic Tissue regeneration, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2012-03-01

    SIRT1 has been found to function as a Class III deacetylase that affects the acetylation status of histones and other important cellular nonhistone proteins involved in various cellular pathways including stress responses and apoptosis. In this study, we investigated the role of SIRT1 signaling in the hypoxic down-regulations of c-Myc and β-catenin and hypoxic preconditioning effect of the red wine polyphenols such as piceatannol, myricetin, quercetin and resveratrol. We found that the expression of SIRT1 was significantly increased in hypoxia-exposed or hypoxic preconditioned HepG2 cells, which was closely associated with the up-regulation of HIF-1α and down-regulation of c-Myc and β-catenin expression via deacetylation of these proteins. In addition, blockade of SIRT1 activation using siRNA or amurensin G, a new potent SIRT1 inhibitor, abolished hypoxia-induced HIF-1α expression but increased c-Myc and β-catenin expression. SIRT1 was also found to stabilize HIF-1α protein and destabilize c-Myc, β-catenin and PHD2 under hypoxia. We also found that myricetin, quercetin, piceatannol and resveratrol up-regulated HIF-1α and down-regulated c-Myc, PHD2 and β-catenin expressions via SIRT1 activation, in a manner that mimics hypoxic preconditioning. This study provides new insights of the molecular mechanisms of hypoxic preconditioning and suggests that polyphenolic SIRT1 activators could be used to mimic hypoxic/ischemic preconditioning. -- Graphical abstract: Polyphenols mimicked hypoxic preconditioning by up-regulating HIF-1α and SIRT1 and down-regulating c-Myc, PHD2, and β-catenin. HepG2 cells were pretreated with the indicated doses of myricetin (MYR; A), quercetin (QUR; B), or piceatannol (PIC; C) for 4 h and then exposed to hypoxia for 4 h. Levels of HIF-1α, SIRT1, c-Myc, β-catenin, and PHD2 were determined by western blot analysis. The data are representative of three individual experiments. Highlights: ► SIRT1 expression is increased in hypoxia

  16. Game performance and intermittent hypoxic training

    Science.gov (United States)

    Hinckson, E A; Hamlin, M J; Wood, M R; Hopkins, W G

    2007-01-01

    Live high‐train low altitude exposure simulated by hypoxic devices may improve athletic performance. In this study, intermittent normobaric hypoxia was achieved with the GO2altitude® hypoxicator to determine its effects on sea level performance in rugby players. Ten players were randomly assigned to two groups. Players in each group received 14 sessions of either hypoxic (10–15% O2) or normoxic (21% O2) exposure at rest over 14 consecutive days in a single blind fashion. Various performance measures were obtained consecutively in a single testing session pre‐ and post‐exposure. Effects of hypoxic exposure on maximum speed and sprint times were trivial (<1.0%) but unclear (90% likely range, ±5% to ±9%). In rugby simulation, hypoxic exposure produced impairments of peak power in two scrums (15%, ±8%; 9%, ±7%) and impairments of time in offensive sprints (7%, ±8%) and tackle sprints (11%, ±9%). Pending further research, rugby players would be unwise to use normobaric intermittent hypoxic exposure to prepare for games at sea level. PMID:17311807

  17. File list: DNS.Adl.05.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adl.05.AllAg.Temperature_sensitive_cells dm3 DNase-seq Adult Temperature sensit...ive cells http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/DNS.Adl.05.AllAg.Temperature_sensitive_cells.bed ...

  18. File list: DNS.Adl.10.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adl.10.AllAg.Temperature_sensitive_cells dm3 DNase-seq Adult Temperature sensit...ive cells http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/DNS.Adl.10.AllAg.Temperature_sensitive_cells.bed ...

  19. File list: DNS.Adl.20.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Adl.20.AllAg.Temperature_sensitive_cells dm3 DNase-seq Adult Temperature sensit...ive cells http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/DNS.Adl.20.AllAg.Temperature_sensitive_cells.bed ...

  20. Inhibition of Skp2 sensitizes lung cancer cells to paclitaxel

    Directory of Open Access Journals (Sweden)

    Huang T

    2017-01-01

    Full Text Available Tonghai Huang, Lin Yang, Guangsuo Wang, Guanggui Ding, Bin Peng, Yuxin Wen, Zheng Wang Department of Thoracic Surgery, Shenzhen People’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China Abstract: S-phase kinase-associated protein 2 (Skp2 is an E3 ubiquitin ligase and plays an important role in the control of cell cycle progression. Skp2 is upregulated in several cancers, including lung cancers, but the role of Skp2 in the tumorigenesis and anticancer drug resistance in human lung cancer remains to be determined. We report here that Skp2 positively regulated mitotic arrest deficient 2 (MAD2 expression and that inhibition of Skp2 sensitizes human lung cancer cells to paclitaxel. Knockdown of Skp2 by small interfering RNA (siRNA decreased Mad2 messenger RNA (mRNA and protein levels in A549 and NCI-H1975 cells, accompanied with upregulation of p27 but decrease of the phosphorylation of retinoblastoma (Rb. In contrast, ectopic overexpression of Skp2 increased Mad2 mRNA and protein levels and phosphorylation of Rb, while it decreased p27. Pharmacological inhibition of CDK1/2 by flavopiridol or E2F1 with HLM006474 led to downregulation of Mad2 expression and prevented the increase of Mad2 expression by Skp2. Most importantly, pharmacological inhibition of Skp2 sensitized A549 and NCI-H1299 cells to paclitaxel. Our results demonstrated that SKP2 positively regulates the gene expression of MAD2 through p27-CDKs-E2F1 signaling pathway and that inhibition of Skp2 sensitizes A549 and NCI-H1299 cells to paclitaxel, suggesting that small molecule inhibitors of Skp2 are potential agents for the treatment of lung cancer with upregulation of Skp2. Keywords: SKP2, MAD2, spindle assembly checkpoint, lung cancer, paclitaxel

  1. Counter electrodes in dye-sensitized solar cells.

    Science.gov (United States)

    Wu, Jihuai; Lan, Zhang; Lin, Jianming; Huang, Miaoliang; Huang, Yunfang; Fan, Leqing; Luo, Genggeng; Lin, Yu; Xie, Yimin; Wei, Yuelin

    2017-10-02

    Dye-sensitized solar cells (DSSCs) are regarded as prospective solar cells for the next generation of photovoltaic technologies and have become research hotspots in the PV field. The counter electrode, as a crucial component of DSSCs, collects electrons from the external circuit and catalyzes the redox reduction in the electrolyte, which has a significant influence on the photovoltaic performance, long-term stability and cost of the devices. Solar cells, dye-sensitized solar cells, as well as the structure, principle, preparation and characterization of counter electrodes are mentioned in the introduction section. The next six sections discuss the counter electrodes based on transparency and flexibility, metals and alloys, carbon materials, conductive polymers, transition metal compounds, and hybrids, respectively. The special features and performance, advantages and disadvantages, preparation, characterization, mechanisms, important events and development histories of various counter electrodes are presented. In the eighth section, the development of counter electrodes is summarized with an outlook. This article panoramically reviews the counter electrodes in DSSCs, which is of great significance for enhancing the development levels of DSSCs and other photoelectrochemical devices.

  2. Voltage sensitive calcium channels (VSCC) in cultured neuronal hybrid cells

    Energy Technology Data Exchange (ETDEWEB)

    Richard, C.L.; U' Prichard, D.C.; Noronha-Blob, L.

    1986-03-01

    Calcium entry via VSCC has been identified in selected, neuronal clonal cell lines using /sup 45/Ca uptake and the fluorescent calcium indicator, quin 2. VSCC in NG108-15 hybrid cells, differentiated with dibutyryl cyclic AMP (1 mM, 4 days) have been further characterized. Depolarization (50 mM K/sup +/, dp) resulted in a rapid (15 sec) influx of Ca/sup 2 +/. Intracellular calcium concentrations were elevated approx. 3 fold from 223 +- 68 nM to 666 +- 74 nM. Dp-sensitive calcium entry was voltage dependent, independent of Na/sup +/, stimulated (40%) by the agonist Bay K 8644 (1..mu..M) and blocked by divalent cations (..mu..M range) and organic calcium channel antagonists (nM range) Bay K 8644, in the absence of KCl, failed to stimulate Ca/sup 2 +/ influx. Tetrodotoxin (TTX) and tetraethylammonium had no effect on VSCC activity. Blockage of VSCC by nimodipine was reversed by increasing Ca/sup 2 +/ ions. IC/sub 50/ values were right shifted from 6.5 nM (1mM/sup 0/Ca/sup 2 +/) to 840 nM (10 mM Ca/sup 2 +/). Ca/sup 2 +/ entry was also stimulated by veratridine (VE), in a Na/sup +//sub 0/-sensitive manner. VE-induced Ca/sup 2 +/ entry was voltage-independent, TTX-sensitive, and was only 25% of dp-sensitive Ca/sup 2 +/ entry. These results together indicate that VSCC in neuronal cells offer a useful system for studying ion channel regulation.

  3. A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy- first investigations of single biological cells.

    Science.gov (United States)

    Alrifaiy, Ahmed; Borg, Johan; Lindahl, Olof A; Ramser, Kerstin

    2015-04-18

    The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively.

  4. Neural progenitors generated from the mesenchymal stem cells of first-trimester human placenta matured in the hypoxic-ischemic rat brain and mediated restoration of locomotor activity.

    Science.gov (United States)

    Park, S; Koh, S-E; Maeng, S; Lee, W-D; Lim, J; Lee, Y-J

    2011-03-01

    Term placenta is a great reservoir of mesenchymal stem cells (MSCs), however, the potential of the earlier placenta is largely unknown. In this report, we established 17 MSC lines from 19 first-trimester human placenta (fPMSC). fPMSC proliferated for 90-150 days in vitro and by enhanced cellular interaction, fPMSC differentiated into nestin-expressing neural progenitor cells (fPMSC-NP), accompanied by inductions of immature neuron-specific genes. Therapeutic effect of the fPMSC-NP was tested in the animal model of hypoxia-ischemia (HI) which was devastating to dopaminergic neurons and to locomotor activity. Improvement of motor activity was evident as early as 2 weeks after transplantation of the fPMSC-NP into bilateral striatum and became indistinguishable from that of the age-matched normal animals by 8 weeks but no spontaneous recovery was observed in the control-grafted animals. Immunohistochemical analyses revealed that the implanted fPMSC-NP matured into ectodermal cells including the tyrosine hydroxylase (TH)-expressing neurons in the recipient striatum. So, the improved motor behavior was likely due to the dopaminergic differentiation of the implanted fPMSC-NP in the dopaminergic-denervated host brain. Based on this result, we propose that progenitors may be more advantageous than the terminally differentiated cells for the purpose of cell replacement therapies since the progenitors are easily obtainable and are expected to be more pliable to the new environment. Copyright © 2011. Published by Elsevier Ltd.

  5. Review on Metallic and Plastic Flexible Dye Sensitized Solar Cell

    Science.gov (United States)

    Yugis, A. R.; Mansa, R. F.; Sipaut, C. S.

    2015-04-01

    Dye sensitized solar cells (DSSCs) are a promising alternative for the development of a new generation of photovoltaic devices. DSSCs have promoted intense research due to their low cost and eco-friendly advantage over conventional silicon-based crystalline solar cells. In recent years, lightweight flexible types of DSSCs have attracted much intention because of drastic reduction in production cost and more extensive application. The substrate that used as electrode of the DSSCs has a dominant impact on the methods and materials that can be applied to the cell and consequently on the resulting performance of DSSCs. Furthermore, the substrates influence significantly the stability of the device. Although the power conversion efficiency still low compared to traditional glass based DSSCs, flexible DSSCs still have potential to be the most efficient and easily implemented technology.

  6. Synthetic Cell-Based Sensors with Programmed Selectivity and Sensitivity.

    Science.gov (United States)

    Bernard, Elvis; Wang, Baojun

    2017-01-01

    Bacteria live in an ever changing environment and, to adapt their physiology, they have to sense the changes. Our current understanding of the mechanisms and elements involved in the detection and processing of these environmental signals grant us access to an array of genetic components able to process such information. As engineers can use different electronic components to build a circuit, we can rewire the cellular components to create digital logic and analogue gene circuits that will program cell behaviour in a designed manner in response to a specific stimulus. Here we present the methods and protocols for designing and implementing synthetic cell-based biosensors that use engineered genetic logic and analogue amplifying circuits to significantly increase selectivity and sensitivity, for example, for heavy metal ions in an aqueous environment. The approach is modular and can be readily applied to improving the sensing limit and performance of a range of microbial cell-based sensors to meet their real world detection requirement.

  7. Research progress of triphenylamine dye sensitizers of solar cells

    Directory of Open Access Journals (Sweden)

    Yifeng YU

    2015-04-01

    Full Text Available Dye-sensitized solar cells (DSSC attracted widespread attention for its low cost, being easy to manufacture, large-scale production and environmentally friendly features. Sensitizer is a core component of the DSSC which plays a role in collecting sunlight and injecting excited state electron into the conduction band of the semiconductor, which is crucial to the photo-electric conversion efficiency. Organic dyes have a number of advantages such as easy synthesizing and tuning of photo-physical and electrochemical properties through molecular design. Triphenylamine is a strong electron donating group, and its non-planar spatial structure makes the degree of the dye molecules aggregation to be decreased. These properties are conducive to improve the absorption properties of the dye and the electron transport efficiency. In recent years, triphenylamine or substituted triphenylamine as electron donor of organic sensitizers becomes the research focus for improving the photoelectric conversion efficiency of solar cells. In this paper, the progress of triphenylamine photosensitive dyes is described.

  8. Hypoxic induction of AKAP12 variant 2 shifts PKA-mediated protein phosphorylation to enhance migration and metastasis of melanoma cells.

    Science.gov (United States)

    Finger, Elizabeth C; Castellini, Laura; Rankin, Erinn B; Vilalta, Marta; Krieg, Adam J; Jiang, Dadi; Banh, Alice; Zundel, Wayne; Powell, Marianne Broome; Giaccia, Amato J

    2015-04-07

    Scaffold proteins are critical hubs within cells that have the ability to modulate upstream signaling molecules and their downstream effectors to fine-tune biological responses. Although they can serve as focal points for association of signaling molecules and downstream pathways that regulate tumorigenesis, little is known about how the tumor microenvironment affects the expression and activity of scaffold proteins. This study demonstrates that hypoxia, a common element of solid tumors harboring low oxygen levels, regulates expression of a specific variant of the scaffold protein AKAP12 (A-kinase anchor protein 12), AKAP12v2, in metastatic melanoma. In turn, through a kinome-wide phosphoproteomic and MS study, we demonstrate that this scaffolding protein regulates a shift in protein kinase A (PKA)-mediated phosphorylation events under hypoxia, causing alterations in tumor cell invasion and migration in vitro, as well as metastasis in an in vivo orthotopic model of melanoma. Mechanistically, the shift in AKAP12-dependent PKA-mediated phosphorylations under hypoxia is due to changes in AKAP12 localization vs. structural differences between its two variants. Importantly, our work defines a mechanism through which a scaffold protein can be regulated by the tumor microenvironment and further explains how a tumor cell can coordinate many critical signaling pathways that are essential for tumor growth through one individual scaffolding protein.

  9. Diluent sensitivity in thermally stressed cells of pseudomonas fluorescens.

    Science.gov (United States)

    Gray, R J; Ordal, Z J; Witter, L D

    1977-01-01

    Thermally injured cells of Pseudomonas fluorescens were unable to produce colonies on Trypticase soy agar (TSA) after dilution with 0.1% peptone. Nutritional exigency could not be used as the criterion for this injury, since varying the composition of the plating medium had little effect on the number of colonies that developed. The injured cells had no requirement for compounds known to leak out during the heat treatment in order to recover. The cells did not exhibit injury if dilution preceded heat treatment on the plating medium, demonstrating that the heat treatment sensitized the cells to the trauma of dilution. Substitution of 0.1% peptone with growth medium as the diluent largely offset the previously observed drop in TSA count. Little difference in survival was observed when monosodium glutamate or the balance of the defined medium was used as the diluent. The diluent effect was ionic rather than osmotic. The presence of cations was important in maintaining the integrity of the injured cell, and divalent cations enhanced this protective effect. The role of these cations at the level of the cell envelope is discussed. PMID:406839

  10. Rose Bengal sensitized niobium pentaoxide photoanode for dye sensitized solar cell application

    Science.gov (United States)

    Beedri, Niyamat I.; Sayyed, Suhail A. A. R.; Jadkar, Sandesh R.; Pathan, Habib M.

    2017-05-01

    The present work deals with the study of Nb2O5 photoanode with low cost rose Bengal dye for dye sensitized solar cell (DSSC) application. Chemical route was used for preparation of nano-crystalline niobium pentaoxide (Nb2O5) and doctor blade method was employed for deposition of Nb2O5 films. The morphological and structural analysis of Nb2O5 photoanodes were carried out by scanning electron microscopy (SEM) and X-ray diffraction (XRD) respectively. The SEM micrograph shows spherical granular grains with porous structure useful for dye adsorption. The XRD analysis shows the formation of pure orthorhombic phase of Nb2O5. The band gap value for Nb2O5 photoanode was calculated as 3.2 eV using diffused reflectance spectroscopy (DRS). As an alternative to conventional ruthenium dye, we used rose Bengal (4, 5, 6, 7-tetrachloro- 20, 40, 50, 70 tetra-iodo-fluorescein) dye, which acts as a photo-sensitizer for DSSCs. The absorbance spectra of the rose Bengal dye was investigated by UV-visible spectrophotometer. The cell shows open circuit voltage (Voc), short circuit photocurrent (Jsc) and fill factor around 0.53V, 0.13mA /cm2 and 22% respectively.

  11. Sensitization of Xanthophylls-Chlorophyllin Mixtures on Titania Solar Cells

    Directory of Open Access Journals (Sweden)

    Indriana Kartini

    2015-03-01

    Full Text Available Co-sensitization of natural dyes on TiO2 for dye-sensitized solar cell (DSSC was proposed between chlorophyllin (C and xanthophylls (X at various volume ratios of C/X. Chlorophyllin is chlorophyll derivative providing -COOH groups essential for binding to TiO2. The chlorophyll was extracted from dried spinach (amaranthus viridis leaves in a mixture of methanol-acetone (70%:30%. Chlorophyll extract dye was obtained after partition of the crude extracts in diethyl ether solution. Then, it was hydrolyzed under alkaline condition to get chlorophyllin. Xanthophyll was extracted from fresh petal of chrysanthemum (chrysanthemum indicum flowers. Blending of chlorophyllin and xanthophyll was carried out at various volume ratios of C to X (1:0, 5:1, 1:1, 1:5, 0:1. Titania solar cells were constructed in sandwich system of conducting glass-titania/dyes as the photoanode and conducting glass-platinum as the photocathode. Electrolyte solution containing I-/I3- was inserted between the electrodes by capillary action. All dye extracts and blending solutions were analyzed by UV-Vis spectrophotometer. It is shown that the absorption spectra of blending dyes are complimentary in the visible region resulted in a panchromatic response of the dyes. From the cyclic voltammogram of the dyes and blended-dyes, it is found that the energy level of xanthophyll is the lowest. The I-V test at 100 mw/cm2 irradiation confirmed that the energy conversion efficiency (h of the blended dyes of xanthophyll and chlorophyllin-sensitized solar cell resulted in significant improvement than those of the single dye. Beneficially, the mixed dyes can be adsorbed from solution blend using single dipping step.

  12. Progress in nanostructured photoanodes for dye-sensitized solar cells

    Science.gov (United States)

    Liu, Xueyang; Fang, Jian; Liu, Yong; Lin, Tong

    2016-09-01

    Solar cells represent a principal energy technology to convert light into electricity. Commercial solar cells are at present predominately produced by single- or multi-crystalline silicon wafers. The main drawback to silicon-based solar cells, however, is high material and manufacturing costs. Dye-sensitized solar cells (DSSCs) have attracted much attention during recent years because of the low production cost and other advantages. The photoanode (working electrode) plays a key role in determining the performance of DSSCs. In particular, nanostructured photoanodes with a large surface area, high electron transfer efficiency, and low electron recombination facilitate to prepare DSSCs with high energy conversion efficiency. In this review article, we summarize recent progress in the development of novel photoanodes for DSSCs. Effect of semiconductor material (e.g. TiO2, ZnO, SnO2, N2O5, and nano carbon), preparation, morphology and structure (e.g. nanoparticles, nanorods, nanofibers, nanotubes, fiber/particle composites, and hierarchical structure) on photovoltaic performance of DSSCs is described. The possibility of replacing silicon-based solar cells with DSSCs is discussed.

  13. Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Ui Seok; Koh, Won Gun [Dept. of Chemical and Biomolecular Engineering, Yonsei University, Seoul (Korea, Republic of)

    2016-09-15

    Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

  14. Novel nanostructures for next generation dye-sensitized solar cells

    KAUST Repository

    Tétreault, Nicolas

    2012-01-01

    Herein, we review our latest advancements in nanostructured photoanodes for next generation photovoltaics in general and dye-sensitized solar cells in particular. Bottom-up self-assembly techniques are developed to fabricate large-area 3D nanostructures that enable enhanced charge extraction and light harvesting through optical scattering or photonic crystal effects to improve photocurrent, photovoltage and fill factor. Using generalized techniques to fabricate specialized nanostructures enables specific optoelectronic and physical characteristics like conduction, charge extraction, injection, recombination and light harvesting but also helps improve mechanical flexibility and long-term stability in low cost materials. © 2012 The Royal Society of Chemistry.

  15. New Components for Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Stefano Caramori

    2010-01-01

    Full Text Available Dye-Sensitized Solar Cells (DSSCs are among the most promising solar energy conversion devices of new generation, since coupling ease of fabrication and low cost offer the possibility of building integration in photovoltaic windows and facades. Although in their earliest configuration these systems are close to commercialization, fundamental studies are still required for developing new molecules and materials with more desirable properties as well as improving our understanding of the fundamental processes at the basis of the functioning of photoactive heterogeneous interfaces. In this contribution, some recent advances, made in the effort of improving DSSC devices by finding alternative materials and configurations, are reviewed.

  16. Microbeam PIXE analysis of platinum resistant and sensitive ovarian cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Jeynes, J.C.G., E-mail: J.C.Jeynes@surrey.ac.u [Ion Beam Centre, University of Surrey, Guildford GU2 7XH (United Kingdom); Bailey, M.J. [Ion Beam Centre, University of Surrey, Guildford GU2 7XH (United Kingdom); Coley, H. [Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH (United Kingdom); Kirkby, K.J.; Jeynes, C. [Ion Beam Centre, University of Surrey, Guildford GU2 7XH (United Kingdom)

    2010-06-15

    Microbeam PIXE was used to analyse platinum in single ovarian cancer cells. Carboplatin sensitive and resistant cells were grown as a monolayer on polypropylene and treated with either carboplatin or cisplatin. Pt from the carboplatin could not be detected. The Pt from cisplatin in the cells could be detected, and significantly more Zn was found in the resistant cells compared to the sensitive cells. The sensitive cells probably accumulated more cisplatin than the resistant ones.

  17. File list: His.Adl.20.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  18. File list: His.Adl.05.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  19. File list: His.Adl.50.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: His.Adl.10.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. Epimorphin-induced MET sensitizes ovarian cancer cells to platinum.

    Directory of Open Access Journals (Sweden)

    Kok-Hooi Yew

    Full Text Available Distinctive genotypic and phenotypic features of ovarian cancer via epithelial-mesenchymal transition (EMT have been correlated with drug resistance and disease recurrence. We investigated whether therapeutic reversal of EMT could re-sensitize ovarian cancer cells (OCCs to existing chemotherapy. We report that epimorphin, a morphogenic protein, has pivotal control over mesenchymal versus epithelial cell lineage decision of the putative OCCs. Exposure to epimorphin induced morphological changes reminiscent of mesenchymal-to-epithelial transition (MET, but in a dose dependent manner, i.e., at 10 µg/mL of epimorphin cells obtain a more mesenchymal-like morphology while at 20 µg/mL of epimorphin cells display an epithelial morphology. The latter changes were accompanied by suppression of mesenchymal markers, such as vimentin (∼8-fold↓, p<0.02, Twist1 (∼7-fold↓, p<0.03, dystroglycan (∼4-fold↓, p<0.01 and palladin (∼3-fold↓, p<0.01. Conversely, significant elevations of KLF4 (∼28-fold↑, p<0.002, β-catenin (∼6-fold↑, p<0.004, EpCAM (∼6-fold↑, p<0.0002 and occludin (∼15-fold↑, p<0.004 mRNAs as part of the commitment to the epithelial cell lineage were detected in response to 20 µg/mL of exogenous epimorphin. Changes in occludin mRNA levels were accompanied by a parallel, albeit weaker expression at the protein level (∼5-fold↑, p<0.001. Likewise, acquisition of epithelial-like properties, including mucin1, CK19, and β-catenin gene expression, was also obtained following epimorphin treatment. Further, MMP3 production was found to be reduced whereas laminin secretion was strongly amplified upon epimorphin-induced MET. These results suggest there is a dosage window for actions of epimorphin on cellular differentiation, wherein it can either suppress or enhance epithelial differentiation of OCCs. Importantly, induction of epithelial-like phenotypes by epimorphin led to an enhanced sensitivity to carboplatin. Overall

  2. Stable aneuploid tumors cells are more sensitive to TTK inhibition than chromosomally unstable cell lines.

    Science.gov (United States)

    Libouban, Marion A A; de Roos, Jeroen A D M; Uitdehaag, Joost C M; Willemsen-Seegers, Nicole; Mainardi, Sara; Dylus, Jelle; de Man, Jos; Tops, Bastiaan; Meijerink, Jules P P; Storchová, Zuzana; Buijsman, Rogier C; Medema, René H; Zaman, Guido J R

    2017-06-13

    Inhibition of the spindle assembly checkpoint kinase TTK causes chromosome mis-segregation and tumor cell death. However, high levels of TTK correlate with chromosomal instability (CIN), which can lead to aneuploidy. We show that treatment of tumor cells with the selective small molecule TTK inhibitor NTRC 0066-0 overrides the mitotic checkpoint, irrespective of cell line sensitivity. In stable aneuploid cells NTRC 0066-0 induced acute CIN, whereas in cells with high levels of pre-existing CIN there was only a small additional fraction of cells mis-segregating their chromosomes. In proliferation assays stable aneuploid cells were more sensitive than cell lines with pre-existing CIN. Tetraploids are thought to be an intermediate between diploid and unstable aneuploid cells. TTK inhibitors had the same potency on post-tetraploid and parental diploid cells, which is remarkable because the post-tetraploids are more resistant to mitotic drugs. Finally, we confirm that the reference compound reversine is a TTK inhibitor and like NTRC 0066-0, inhibits the proliferation of patient-derived colorectal cancer organoids. In contrast, treatment with TTK inhibitor did not reduce the viability of non-proliferating T cell acute lymphoblastic leukemia cells samples. Consequently, TTK inhibitor therapy is expected to spare non-dividing cells, and may be used to target stable aneuploid tumors.

  3. 53BP1 sensitizes breast cancer cells to 5-fluorouracil.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Li

    Full Text Available Chemoresistance of breast cancer is a worldwide problem for breast cancer and the resistance to chemotherapeutic agents frequently led to the subsequent recurrence and metastasis. In our previous study, we have found that 53BP1 showed a gradual decrease during the progression of breast cancer and loss of 53BP1 was associated with metastasis and poor prognosis in breast cancer. Here we aimed to reveal whether 53BP1 could sensitize breast cancer to 5-Fu. We found that ectopic expression of 53BP1 can significantly sensitize breast cancer cells to 5-Fu while knockdown of 53BP1 conferred the resistance. The in vivo experiments confirmed that overexpression of 53BP1 in combination with 5-Fu markedly inhibited growth of xenotransplanted tumors in nude mice when compared to either agent alone. Furthermore, we demonstrated that 53BP1 regulated the sensitivity to 5-Fu through thymidylate synthase (TS and dihydropyrimidine dehydrogenase (DPYD. The present studies provide a new clue that combination of 5-Fu and 53BP1 could be a potential novel targeted strategy for overcoming breast cancer chemoresistance.

  4. PCM1 Depletion Inhibits Glioblastoma Cell Ciliogenesis and Increases Cell Death and Sensitivity to Temozolomide

    Directory of Open Access Journals (Sweden)

    Lan B. Hoang-Minh

    2016-10-01

    Full Text Available A better understanding of the molecules implicated in the growth and survival of glioblastoma (GBM cells and their response to temozolomide (TMZ, the standard-of-care chemotherapeutic agent, is necessary for the development of new therapies that would improve the outcome of current GBM treatments. In this study, we characterize the role of pericentriolar material 1 (PCM1, a component of centriolar satellites surrounding centrosomes, in GBM cell proliferation and sensitivity to genotoxic agents such as TMZ. We show that PCM1 is expressed around centrioles and ciliary basal bodies in patient GBM biopsies and derived cell lines and that its localization is dynamic throughout the cell cycle. To test whether PCM1 mediates GBM cell proliferation and/or response to TMZ, we used CRISPR/Cas9 genome editing to generate primary GBM cell lines depleted of PCM1. These PCM1-depleted cells displayed reduced AZI1 satellite protein localization and significantly decreased proliferation, which was attributable to increased apoptotic cell death. Furthermore, PCM1-depleted lines were more sensitive to TMZ toxicity than control lines. The increase in TMZ sensitivity may be partly due to the reduced ability of PCM1-depleted cells to form primary cilia, as depletion of KIF3A also ablated GBM cells' ciliogenesis and increased their sensitivity to TMZ while preserving PCM1 localization. In addition, the co-depletion of KIF3A and PCM1 did not have any additive effect on TMZ sensitivity. Together, our data suggest that PCM1 plays multiple roles in GBM pathogenesis and that associated pathways could be targeted to augment current or future anti-GBM therapies.

  5. Sirtuin 6 protects the heart from hypoxic damage

    Energy Technology Data Exchange (ETDEWEB)

    Maksin-Matveev, Anna; Kanfi, Yariv [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel); Hochhauser, Edith [The Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva (Israel); Isak, Ahuva; Cohen, Haim Y. [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel); Shainberg, Asher, E-mail: asher.shainberg@gmail.com [The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900 (Israel)

    2015-01-01

    Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension. - Highlights: • Sirtuin 6 is a protein associated with prolonged life expectancy. • Over-expression of sirtuin 6 protects cardiocytes from hypoxia and oxidative stress. • Over-expression of sirtuin 6 activates the pAMPKα pathway and the Bcl2 expression. • Over-expression of sirtuin 6 decreases ROS formation and pAkt level during hypoxia. • These pathways protect cardiocytes from hypoxia and might explain lifespan extension.

  6. Analysis of Natural Sensitizers to Enhance the Efficiency in Dye Sensitized Solar Cell

    Directory of Open Access Journals (Sweden)

    S.Rajkumar

    2016-05-01

    Full Text Available Three vegetable dyes are used for the study: anthocyanin dye from pomegranate arils extract, betalain dye from beet root extract and chlorophyll dye from tridax procumbens leaf. The anthocyanin and betalain, anthocyanin and chlorophyll, betalain and chlorophyll dyes are blended in cocktail in equal proportions, by volume. This study determines the effect of different extraction concentrations and different vegetable dyes on energy gap using dye sensitized solar cells. The experimental results show that the cocktail dye blended using extracts of pomegranate arils, beet root and tridax procumbens leaf, in the volumetric proportion 1:1, using an extraction at room temperature the greatest energy gap (eg of up to 1.87eV.

  7. Dye-sensitized solar cells using Aloe Vera and Cladode of Cactus extracts as natural sensitizers

    Science.gov (United States)

    Ganta, D.; Jara, J.; Villanueva, R.

    2017-07-01

    The purpose of this study is to develop dye-sensitized solar cells (DSSCs) from natural plant-based dyes, extracted from the Cladode (nopal) of the Thornless Prickly Pear Cactus (Opuntia ficus-indica), the gel of Aloe Vera (Aloe barbadensis miller), and the combination of Cladode and Aloe Vera extracts on side-by-side configuration. Optical properties were analyzed using UV-Vis Absorption and Fourier Transform Infrared Spectroscopy. Open circuit voltages (Voc) varied from 0.440 to 0.676 V, fill factors (FF) were greater than 40%, short-circuit photocurrent densities (Jsc) ranged from 0.112 to 0.290 mA/cm2 and highest conversion efficiency of 0.740% was reported for the Cladode DSSC.

  8. Cycloruthenated sensitizers: improving the dye-sensitized solar cell with classical inorganic chemistry principles.

    Science.gov (United States)

    Robson, Kiyoshi C D; Bomben, Paolo G; Berlinguette, Curtis P

    2012-07-14

    A divergence from the conventional approach to chromophore design has led to the establishment of many exciting new benchmarks for the dye-sensitized solar cell (DSSC), including the first documented power conversion efficiency in excess of 12% at 1 sun illumination [Yella et al., Science 2011, 334, 629]. Paramount to these advances is the deviation from polypyridyl ruthenium dyes bearing NCS(-) ligands, such as [Ru(dcbpy)(2)(NCS)(2)] (N3; dcbpy = 4,4'-dicarboxy-2,2'-bipyridine). While metal-free and porphyrin dyes have demonstrated much promise, the discovery that the NCS(-) ligands of N3 can be replaced by anionic, chelating cyclometalating ligands without compromising device efficiencies has ushered in a new era of ruthenium dye development. A particularly appealing feature of this class of dyestuff is that they offer acute control of the frontier molecular orbitals to enable the precise attenuation of both the ground and excited state redox potentials through judicious chemical modification of the aryl ring. This Perspective summarizes very recent developments in the field, and demonstrates how the new and rapidly expanding class of Ru-based sensitizers provides a conduit for enhancing the performance (and potentially the stability) of the DSSC.

  9. Infrasound sensitizes human glioblastoma cells to cisplatin-induced apoptosis.

    Science.gov (United States)

    Rachlin, Kenneth; Moore, Dan H; Yount, Garret

    2013-11-01

    The development of nontoxic agents that can selectively enhance the cytotoxicity of chemotherapy is an important aim in oncology. This study evaluates the ability of infrasound exposure to sensitize glioblastoma cells to cisplatin-induced apoptosis. The infrasound was delivered using a device designed to replicate the unique infrasound emissions measured during external Qigong treatments. Human glioblastoma cell lines harboring wild-type p53 (U87) or mutant p53 (U251, SF210, and SF188) were treated in culture with cisplatin, infrasound emissions, or the combination of the 2 agents. Induction of apoptosis was quantified after 24 hours by flow cytometry following annexin V/propidium iodide staining. Infrasound emissions alone, delivered at moderate levels (~10 mPa) with dynamic frequency content (7-13 Hz), did not induce apoptosis, yet combining infrasound with cisplatin augmented the induction of apoptosis by cisplatin in all the 4 cell lines (P < .05). Increased cellular uptake of the fluorophore calcein associated with infrasound exposure was quantified by fluorescence microscopy as well as flow cytometry, demonstrating increased cell membrane permeability. The 4 cell lines differed in the degree to which infrasound exposure increased calcein uptake, and these differences were predictive of the extent to which infrasound enhanced cisplatin-induced apoptosis. When exposed to specific frequencies, membrane permeabilization also appeared to be differentially responsive for each cell line, suggesting the potential for selective targeting of tissue types using isolated infrasonic frequencies. Additionally, the pressure amplitudes used in this study were several orders of magnitude less than those used in similar studies involving ultrasound and shock waves. The results of this study provide support for using infrasound to enhance the chemotherapeutic effects of cisplatin in a clinical setting.

  10. File list: Unc.Adl.20.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

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  1. File list: Unc.Adl.05.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

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  2. Synthesis and Characterization of Natural Sensitizers for Dye Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Mohammed Isah Kimpa

    2017-10-01

    Full Text Available Natural dyes of anthocyanin extract from flame tree flower (Delonix regia and chlorophyll extract from pawpaw leaf (Carica papaya were used as sensitizer to fabricate dye sensitized solar cell (DSSC. The photoelectrode were subjected to UV/Vis spectrophotometer to view their absorbability. The photo electrochemical performances of DSSCs obtained from I.V characteristics showed conversion efficiency, (ɳ of 0.80 % for the dye extracts from flame tree flower (anthocyanine, with open-circuit voltage (VOC of 0.5249 mV, short-circuit current density (Isc of 44.6191 mA/m2 and Fill factor (FF of 0.5837. Chlorophyll dyes extract from pawpaw leaf has VOC, Isc, FF and conversion efficiency, (ɳ of 0.5249 mV, 16.5283 mA/m2, 0.5585 and 0.27 % respectively. The conversion efficiency for the mixed dyes (anthocyanin and chlorophyll at ratio 1:2 is 0.23 % with VOC, Isc and FF of 0.5500 mV, 14.2750 mA/m2 and 0.5451 respectively, while the dye mixture at ratio 1:4 achieved VOC of 0.5249 mV, Isc of 18.4941 mA/m2, FF of 0.5206 and conversion efficiency (ɳ of 0.26 %. Anthocyanine from flame tree flower dye extract had the higher conversion efficiency of 0.8 % which could be better in term of application in dye solar cell.

  3. Effects of the differentiating agents sodium butyrate and N-methylformamide on the oxygen enhancement ratio of human colon tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Hallows, K.R.; Bliven, S.F.; Leith, J.T.

    1988-01-01

    We have previously shown that chronic adaptation of human tumor cells to the differentiation-inducing agents N-methylformamide (NMF) and sodium butyrate (NAB) increases the sensitivity of oxic cells to graded single doses of X rays. These studies were carried out to define the sensitivity of hypoxic cells after adaptation. Clone A colon tumor cells were grown for three passages in medium containing 170 mM NMF or 2 mM NAB and irradiated in suspension culture, after gassing with either oxygen (60 min) or ultrapure nitrogen (90 min), and complete survival curves were generated. Using the linear-quadratic equation to describe the data, it was found that NMF and NAB produced increased X-ray killing of hypoxic cells. At the 10% level of survival, the dose-modifying factors were about 1.20 and 1.25 for NMF- and NAB-adapted hypoxic cells, respectively, as compared to hypoxic control cells. However, since both oxic and hypoxic cells exhibited increased sensitivity after NMF and NAB adaptation, there was no major change in the oxygen enhancement ratio.

  4. Sensitivity of neoplastic cells to senescence unveiled under standard cell culture conditions.

    Science.gov (United States)

    Zieba, Jolanta; Ksiazkiewcz, Magdalena; Janik, Karolina; Banaszczyk, Mateusz; Peciak, Joanna; Piaskowski, Sylwester; Lipinski, Marek; Olczak, Michal; Stoczynska-Fidelus, Ewelina; Rieske, Piotr

    2015-05-01

    Cancer cells are typically defined as infinitely proliferating, whereas normal cells (except stem cells) are considered as being programmed to become senescent. Our data show that this characterization is misleading. Multiplex Ligation-dependent Probe Amplification, TP53 sequencing, real-time polymerase chain reaction (PCR) for MUC1 and SCGB2A2 and immunocytochemistry, together with senescence detection assay and real-time microscopic observations were used to analyze primary neoplastic cells isolated from prostate, breast and colorectal tumors, as well as stable cancer cell lines (MCF7, MDA-MB-468, SW962, SK-MEL28, NCI-H1975 and NCI-H469). In all cases of primary cancer cell cultures, in vitro conditions rapidly revealed senescence in the majority of cells. Two out of six stable cancer cell lines did not exhibit any senescence-associated-β-Galactosidase-positive cells. Interestingly, four cell lines had small sub-populations of senescent cells (single SA-β-Gal-positive cells). Primary neoplastic cells from different types of cancer (prostate, breast, colon cancer) appear to be senescent in vitro. Apparently, cancer cell lines that have been used for many years in drug-testing analyses have constantly been misleading researchers in terms of the general sensitivity of cancer cells to senescence. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Photovoltaic characteristics of natural light harvesting dye sensitized solar cells.

    Science.gov (United States)

    Hafez, H S; Shenouda, S S; Fadel, M

    2018-03-05

    In this work of research, anthocyanin as a natural dye obtained from raspberry fruits, was used and tested as a photon harvesting/electron donating dye in titanium dioxide nanoparticle-based DSSCs. A working photoelectrode made from TiO 2 nanoparticles with an average particle size (10-40nm) that is coated on Florine doped tin-oxide substrate, was prepared via a simple and low cost hydrothermal method. A detailed structural and morphological analysis of the TiO 2 photoactive electrode was investigated by X-ray diffraction (XRD), diffuse reflectance spectrometer, transmission electron microscope (TEM) and scanning electron microscope (SEM). Complete photovoltaic characteristics including (current, voltage, outpower, and responsivity) of the natural anthocyanin based dye sensitized solar cell have been investigated under different illumination intensity ranging from 10 to 100mW.cm -2 . The cell responsivity and efficiency of the fabricated solar cell under different illumination intensity were found to be in the range (R=15.6-23.8mA.W -1 and η=0.13-0.25) at AM=1.5 conditions. This study is important for enhancing the future applications of the promising DSSC technology. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Solution Processed Silver Nanoparticles in Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Marko Berginc

    2014-01-01

    Full Text Available A plasmonic effect of silver nanoparticles (Ag NPs in dye-sensitized solar cells (DSSCs is studied. The solutions of silver nitrate in isopropanol, ethylene glycol, or in TiO2 sol were examined as possible precursors for Ag NPs formation. The solutions were dip-coated on the top of the porous TiO2 layer. The results of optical measurements confirmed the formation of Ag NPs throughout the porous TiO2 layer after the heat treatment of the layers above 100°C. Heat treatment at 220°C was found to be optimal regarding the formation of the Ag NPs. The porous TiO2 layers with Ag NPs have been evaluated also in DSSC by measuring current-voltage characteristics and the external quantum efficiency of the cells. In addition, the amount of adsorbed dye has been determined to prove the plasmonic effect in the cells. The I-V characterization of the DSSCs revealed an increase of the short circuit current in the presence of Ag NPs although the amount of the attached dye molecules decreased. These results confirm that the performance enhancement is related to the plasmonic effect. However, neither a thin sol-gel TiO2 layer nor poly(4-vinylpyridine shells provide effective protection for the long term stability of the Ag NPs against the corrosion of I3-/I- based electrolyte.

  7. Photovoltaic characteristics of natural light harvesting dye sensitized solar cells

    Science.gov (United States)

    Hafez, H. S.; Shenouda, S. S.; Fadel, M.

    2018-03-01

    In this work of research, anthocyanin as a natural dye obtained from raspberry fruits, was used and tested as a photon harvesting/electron donating dye in titanium dioxide nanoparticle-based DSSCs. A working photoelectrode made from TiO2 nanoparticles with an average particle size (10-40 nm) that is coated on Florine doped tin-oxide substrate, was prepared via a simple and low cost hydrothermal method. A detailed structural and morphological analysis of the TiO2 photoactive electrode was investigated by X-ray diffraction (XRD), diffuse reflectance spectrometer, transmission electron microscope (TEM) and scanning electron microscope (SEM). Complete photovoltaic characteristics including (current, voltage, outpower, and responsivity) of the natural anthocyanin based dye sensitized solar cell have been investigated under different illumination intensity ranging from 10 to 100 mW.cm- 2. The cell responsivity and efficiency of the fabricated solar cell under different illumination intensity were found to be in the range (R = 15.6-23.8 mA.W- 1 and η = 0.13-0.25) at AM = 1.5 conditions. This study is important for enhancing the future applications of the promising DSSC technology.

  8. On the hypoxic tumor targeting ability of two chitosan micelles loaded with oil-soluble CdSe quantum dots.

    Science.gov (United States)

    Zhang, Shengyu; Zhao, Liuwan; Qiu, Nanqin; Liu, Yanjun; Xu, Bohui; Zhu, Hongyan

    2018-01-01

    Hypoxia, an outstanding characteristic of various solid tumors, has been considered a critical factor of aggressive tumor phenotypes, poor clinical prognosis, and increased expression of the multidrug-resistant gene. Therefore, it is critical to develop a drug delivery system to enhance the delivery effect of the antitumor drug in the hypoxic tumor. We constructed two types of tumor targeting micelles based on chitosan and evaluated their properties in targeting hypoxic tumors. Chitosan-based micelles consisted of a hydrophobic group octyl group, a hydrophilic polyethylene glycol, tumor targeting ligands glucosamine or folic acid, and a transmembrane peptide 9-d-arginine. The molecular structure, morphology, size distribution, zeta potential, and biosafety of two micelles were characterized. Oil-soluble CdSe quantum dots were used as a fluorescent probe to evaluate the hypoxic tumor cell targeting properties of the micelles. Moreover, HepG2 human hepatocellular carcinoma cells and HeLa human cervical carcinoma cells were used as in vitro models. We demonstrated that, under hypoxic conditions, two chitosan micelles showed better targeting ability to HepG2 and HeLa cells, which enhanced the effect of antitumor drugs by specifically targeting transport in hypoxic tumors. Therefore, chitosan micelles may be a potential drug delivery system that can be used to deliver antitumor drugs to hypoxic tumors.

  9. A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death.

    Science.gov (United States)

    Wood, Tabitha E; Dalili, Shadi; Simpson, Craig D; Hurren, Rose; Mao, Xinliang; Saiz, Fernando Suarez; Gronda, Marcela; Eberhard, Yanina; Minden, Mark D; Bilan, Philip J; Klip, Amira; Batey, Robert A; Schimmer, Aaron D

    2008-11-01

    Evasion of death receptor ligand-induced apoptosis is an important contributor to cancer development and progression. Therefore, molecules that restore sensitivity to death receptor stimuli would be important tools to better understand this biological pathway and potential leads for therapeutic adjuncts. Previously, the small-molecule N-[4-chloro-3-(trifluoromethyl)phenyl]-3-oxobutanamide (fasentin) was identified as a chemical sensitizer to the death receptor stimuli FAS and tumor necrosis factor apoptosis-inducing ligand, but its mechanism of action was unknown. Here, we determined that fasentin alters expression of genes associated with nutrient and glucose deprivation. Consistent with this finding, culturing cells in low-glucose medium recapitulated the effects of fasentin and sensitized cells to FAS. Moreover, we showed that fasentin inhibited glucose uptake. Using virtual docking studies with a homology model of the glucose transport protein GLUT1, fasentin interacted with a unique site in the intracellular channel of this protein. Additional chemical studies with other GLUT inhibitors and analogues of fasentin supported a role for partial inhibition of glucose transport as a mechanism to sensitize cells to death receptor stimuli. Thus, fasentin is a novel inhibitor of glucose transport that blocks glucose uptake and highlights a new mechanism to sensitize cells to death ligands.

  10. PlanHab: the combined and separate effects of 16 days of bed rest and normobaric hypoxic confinement on circulating lipids and indices of insulin sensitivity in healthy men.

    Science.gov (United States)

    Simpson, Elizabeth J; Debevec, Tadej; Eiken, Ola; Mekjavic, Igor; Macdonald, Ian A

    2016-04-15

    PlanHab is a planetary habitat simulation study. The atmosphere within future space habitats is anticipated to have reduced Po2, but information is scarce as to how physiological systems may respond to combined exposure to moderate hypoxia and reduced gravity. This study investigated, using a randomized-crossover design, how insulin sensitivity, glucose tolerance, and circulating lipids were affected by 16 days of horizontal bed rest in normobaric normoxia [NBR: FiO2 = 0.209; PiO2 = 133.1 (0.3) mmHg], horizontal bed rest in normobaric hypoxia [HBR: FiO2 = 0.141 (0.004); PiO2 = 90.0 (0.4) mmHg], and confinement in normobaric hypoxia combined with daily moderate intensity exercise (HAMB). A mixed-meal tolerance test, with arterialized-venous blood sampling, was performed in 11 healthy, nonobese men (25-45 yr) before (V1) and on the morning ofday 17of each intervention (V2). Postprandial glucose and c-peptide response were increased at V2 of both bed rest interventions (Peffects of bed rest on insulin sensitivity and glucose tolerance but appeared to increase insulin clearance. The negative effect of bed rest on HDL was compounded in hypoxia, which may have implications for long-term health of those living in future space habitats. Copyright © 2016 the American Physiological Society.

  11. Exploiting quantum interference in dye sensitized solar cells.

    Science.gov (United States)

    Maggio, Emanuele; Solomon, Gemma C; Troisi, Alessandro

    2014-01-28

    A strategy to hinder the charge recombination process in dye sensitized solar cells is developed in analogy with similar approaches to modulate charge transport across nanostructures. The system studied is a TiO2 (anatase)-chromophore interface, with an unsaturated carbon bridge connecting the two subunits. A theory for nonadiabatic electron transfer is employed in order to take explicitly into account the contribution from the bridge states mediating the process. If a cross-conjugated fragment is present in the bridge, it is possible to suppress the charge recombination by negative interference of the possible tunnelling path. Calculations carried out on realistic molecules at the DFT level of theory show how the recombination lifetime can be modulated by changes in the electron-withdrawing (donating) character of the groups connected to the cross-conjugated bridge. Tight binding calculations are employed to support the interpretation of the atomistic simulations.

  12. Exploiting quantum interference in dye sensitized solar cells

    DEFF Research Database (Denmark)

    Maggio, Emanuele; Solomon, Gemma C.; Troisi, Alessandro

    2014-01-01

    A strategy to hinder the charge recombination process in dye sensitized solar cells is developed in analogy with similar approaches to modulate charge transport across nanostructures. The system studied is a TiO2 (anatase)-chromophore interface, with an unsaturated carbon bridge connecting the two...... subunits. A theory for nonadiabatic electron transfer is employed in order to take explicitly into account the contribution from the bridge states mediating the process. If a cross-conjugated fragment is present in the bridge, it is possible to suppress the charge recombination by negative interference...... of the possible tunnelling path. Calculations carried out on realistic molecules at the DFT level of theory show how the recombination lifetime can be modulated by changes in the electron-withdrawing (donating) character of the groups connected to the cross-conjugated bridge. Tight binding calculations...

  13. Propranolol sensitizes thyroid cancer cells to cytotoxic effect of vemurafenib.

    Science.gov (United States)

    Wei, Wei-Jun; Shen, Chen-Tian; Song, Hong-Jun; Qiu, Zhong-Ling; Luo, Quan-Yong

    2016-09-01

    Treatment options for advanced metastatic or progressive thyroid cancers are limited. Although targeted therapy specifically inhibiting intracellular kinase signaling pathways has markedly changed the therapeutic landscape, side-effects and resistance of single agent targeted therapy often leads to termination of the treatment. The objective of the present study was to identify the antitumor property of the non-selective β-adrenergic receptor antagonist propranolol for thyroid cancers. Human thyroid cancer cell lines 8505C, K1, BCPAP and BHP27 were used in the present study. Broad β-blocker propranolol and β2-specific antagonist ICI118551, but not β1-specific antagonist atenolol, inhibited the growth of 8505C and K1 cells. Propranolol treatment inhibited growth and induced apoptosis of 8505C cells in vitro and in vivo, which are closely associated with decreased expressions of cyclin D1 and anti-apoptotic Bcl-2. Expression of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) also decreased following propranolol intervention. 18F-FDG PET/CT imaging of the 8505C xenografts validated shrinkage of the tumors in the propranolol-treated group when compared to the phosphate‑buffered saline treated group. Finally, we found that propranolol can amplify the cytotoxicity of vemurafenib and sensitize thyroid cancer cells to cytotoxic effect of vemurafenib. Our present results suggest that propranolol has potential activity against thyroid cancers and investigation of the combination with targeted molecular therapy for progressive thyroid cancers could be beneficial.

  14. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.

    Directory of Open Access Journals (Sweden)

    Yiyu Deng

    Full Text Available Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD, a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC(+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC(+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

  15. Galectin-3 inhibition sensitizes human renal cell carcinoma cells to arsenic trioxide treatment.

    Science.gov (United States)

    Xu, Yangyang; Gu, Xin; Gong, Mancheng; Guo, Guiying; Han, Kaiyu; An, Ruihua

    2013-10-01

    The anti-tumor effects of arsenic trioxide (ATO) were well established in acute promyelocytic leukemia, but not in renal cell carcinoma (RCC). Recent evidences indicate that galectin-3 (Gal-3) plays an anti-apoptotic role in chemotherapy induced tumor cell death. This study was intended to clarify the exact roles of Gal-3 performed in ATO-induced apoptosis in RCC cells. Weak apoptosis was observed in Gal-3-positive RCC cells (Caki-1, Caki-2, 786-0, and ACHN) following ATO treatment. However, ATO treatment upregulated Gal-3 expression concurrently caused a Synexin-cooperated translocation of Gal-3 from the nucleus to the cytoplasm. Gal-3-knockdown cells were more sensitive to ATO treatment as indicated by a strong mitochondria-dependent apoptosis following ATO treatment. Meanwhile, Gal-3 was found to inhibit ATO-induced apoptosis through enhancing Bcl-2 expression and stabilizing mitochondria. To confirm the results obtained from genetic method, we employed a Gal-3 inhibitor, modified citrus prectin (MCP), and co-treated the RCC cells with ATO. The cells showed an increased apoptosis in the syngeneic application of Gal-3 inhibition and ATO compared with ATO application alone. Based on these results, we conclude that Gal-3 inhibition sensitizes human renal cell carcinoma cells to ATO treatment through increasing mitochondria-dependent apoptosis. Our studies implicate synergetic application of ATO and Gal-3 inhibition as a potential strategy for RCC treatment.

  16. Let-7 Sensitizes KRAS Mutant Tumor Cells to Chemotherapy.

    Directory of Open Access Journals (Sweden)

    Xin Dai

    Full Text Available KRAS is the most commonly mutated oncogene in human cancers and is associated with poor prognosis and drug resistance. Let-7 is a family of tumor suppressor microRNAs that are frequently suppressed in solid tumors, where KRAS mutations are highly prevalent. In this study, we investigated the potential use of let-7 as a chemosensitizer. We found that let-7b repletion selectively sensitized KRAS mutant tumor cells to the cytotoxicity of paclitaxel and gemcitabine. Transfection of let-7b mimic downregulated the expression of mutant but not wild-type KRAS. Combination of let-7b mimic with paclitaxel or gemcitabine diminished MEK/ERK and PI3K/AKT signaling concurrently, triggered the onset of apoptosis, and reverted the epithelial-mesenchymal transition in KRAS mutant tumor cells. In addition, let-7b repletion downregulated the expression of β-tubulin III and ribonucleotide reductase subunit M2, two proteins known to mediate tumor resistance to paclitaxel and gemcitabine, respectively. Let-7 may represent a new class of chemosensitizer for the treatment of KRAS mutant tumors.

  17. Differential uptake and metabolism of nitrite in normoxic and hypoxic goldfish

    DEFF Research Database (Denmark)

    Jensen, Frank Bo; Hansen, Marie N.

    2011-01-01

    cells (RBCs) and muscle tissue of normoxic than hypoxic goldfish, suggesting that nitrite uptake was augmented by normoxia in spite of a predictable lower gill surface area. Elevation of nitrite was associated with increased concentrations of S-nitroso, N-nitroso and Fe-nitrosyl compounds in both......Nitrite is a physiological important nitric oxide donor at low concentrations but becomes toxic at high concentrations, as develops in freshwater fish exposed to environmental nitrite. We hypothesized that nitrite uptake across the gills differs between normoxic and hypoxic fish and that nitrite...... was converted to non-toxic nitrate. The generation of methemoglobin and nitrosylhemoglobin (assessed by spectral deconvolution) was more pronounced during normoxic nitrite exposure than during hypoxic nitrite exposure, in agreement with the higher nitrite load in normoxic fish. However, at any given nitrite...

  18. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury.

    Science.gov (United States)

    Rocha-Ferreira, Eridan; Hristova, Mariya

    2016-01-01

    Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI) of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity.

  19. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury

    Directory of Open Access Journals (Sweden)

    Eridan Rocha-Ferreira

    2016-01-01

    Full Text Available Hypoxic-ischaemic damage to the developing brain is a leading cause of child death, with high mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The developmental stage of the brain and the severity of the insult influence the selective regional vulnerability and the subsequent clinical manifestations. The increased susceptibility to hypoxia-ischaemia (HI of periventricular white matter in preterm infants predisposes the immature brain to motor, cognitive, and sensory deficits, with cognitive impairment associated with earlier gestational age. In term infants HI causes selective damage to sensorimotor cortex, basal ganglia, thalamus, and brain stem. Even though the immature brain is more malleable to external stimuli compared to the adult one, a hypoxic-ischaemic event to the neonate interrupts the shaping of central motor pathways and can affect normal developmental plasticity through altering neurotransmission, changes in cellular signalling, neural connectivity and function, wrong targeted innervation, and interruption of developmental apoptosis. Models of neonatal HI demonstrate three morphologically different types of cell death, that is, apoptosis, necrosis, and autophagy, which crosstalk and can exist as a continuum in the same cell. In the present review we discuss the mechanisms of HI injury to the immature brain and the way they affect plasticity.

  20. Collateral sensitivity to cisplatin in KB-8-5-11 drug-resistant cancer cells.

    LENUS (Irish Health Repository)

    Doherty, Ben

    2014-01-01

    KB-8-5-11 cells are a drug-resistant cervical cell model that overexpresses ABCB1 (P-glycoprotein). KB-8-5-11 has become sensitive to non-ABCB1 substrate cisplatin. Understanding the mechanism of collateral sensitivity to cisplatin may lead to biomarker discovery for platinum sensitivity in patients with cancer.

  1. Combining hypoxic methods for peak performance.

    Science.gov (United States)

    Millet, Gregoire P; Roels, B; Schmitt, L; Woorons, X; Richalet, J P

    2010-01-01

    New methods and devices for pursuing performance enhancement through altitude training were developed in Scandinavia and the USA in the early 1990s. At present, several forms of hypoxic training and/or altitude exposure exist: traditional 'live high-train high' (LHTH), contemporary 'live high-train low' (LHTL), intermittent hypoxic exposure during rest (IHE) and intermittent hypoxic exposure during continuous session (IHT). Although substantial differences exist between these methods of hypoxic training and/or exposure, all have the same goal: to induce an improvement in athletic performance at sea level. They are also used for preparation for competition at altitude and/or for the acclimatization of mountaineers. The underlying mechanisms behind the effects of hypoxic training are widely debated. Although the popular view is that altitude training may lead to an increase in haematological capacity, this may not be the main, or the only, factor involved in the improvement of performance. Other central (such as ventilatory, haemodynamic or neural adaptation) or peripheral (such as muscle buffering capacity or economy) factors play an important role. LHTL was shown to be an efficient method. The optimal altitude for living high has been defined as being 2200-2500 m to provide an optimal erythropoietic effect and up to 3100 m for non-haematological parameters. The optimal duration at altitude appears to be 4 weeks for inducing accelerated erythropoiesis whereas training) appears sufficient to increase erythropoiesis and improve sea-level performance. 'Longer is better' as regards haematological changes since additional benefits have been shown as hypoxic exposure increases beyond 16 h/day. The minimum daily dose for stimulating erythropoiesis seems to be 12 h/day. For non-haematological changes, the implementation of a much shorter duration of exposure seems possible. Athletes could take advantage of IHT, which seems more beneficial than IHE in performance enhancement

  2. Isoflurane provides neuroprotection in neonatal hypoxic ischemic brain injury by suppressing apoptosis.

    Science.gov (United States)

    Zhao, De-An; Bi, Ling-Yun; Huang, Qian; Zhang, Fang-Min; Han, Zi-Ming

    Isoflurane is halogenated volatile ether used for inhalational anesthesia. It is widely used in clinics as an inhalational anesthetic. Neonatal hypoxic ischemia injury ensues in the immature brain that results in delayed cell death via excitotoxicity and oxidative stress. Isoflurane has shown neuroprotective properties that make a beneficial basis of using isoflurane in both cell culture and animal models, including various models of brain injury. We aimed to determine the neuroprotective effect of isoflurane on hypoxic brain injury and elucidated the underlying mechanism. A hippocampal slice, in artificial cerebrospinal fluid with glucose and oxygen deprivation, was used as an in vitro model for brain hypoxia. The orthodromic population spike and hypoxic injury potential were recorded in the CA1 and CA3 regions. Amino acid neurotransmitters concentration in perfusion solution of hippocampal slices was measured. Isoflurane treatment caused delayed elimination of population spike and improved the recovery of population spike; decreased frequency of hypoxic injury potential, postponed the onset of hypoxic injury potential and increased the duration of hypoxic injury potential. Isoflurane treatment also decreased the hypoxia-induced release of amino acid neurotransmitters such as aspartate, glutamate and glycine induced by hypoxia, but the levels of γ-aminobutyric acid were elevated. Morphological studies showed that isoflurane treatment attenuated edema of pyramid neurons in the CA1 region. It also reduced apoptosis as evident by lowered expression of caspase-3 and PARP genes. Isoflurane showed a neuro-protective effect on hippocampal neuron injury induced by hypoxia through suppression of apoptosis. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

  3. Oxidative Stress in Hypoxic-Ischemic Encephalopathy: Molecular Mechanisms and Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Mingyi Zhao

    2016-12-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is one of the leading causes of morbidity and mortality in neonates. Because of high concentrations of sensitive immature cells, metal-catalyzed free radicals, non-saturated fatty acids, and low concentrations of antioxidant enzymes, the brain requires high levels of oxygen supply and is, thus, extremely sensitive to hypoxia. Strong evidence indicates that oxidative stress plays an important role in pathogenesis and progression. Following hypoxia and ischemia, reactive oxygen species (ROS production rapidly increases and overwhelms antioxidant defenses. A large excess of ROS will directly modify or degenerate cellular macromolecules, such as membranes, proteins, lipids, and DNA, and lead to a cascading inflammatory response, and protease secretion. These derivatives are involved in a complex interplay of multiple pathways (e.g., inflammation, apoptosis, autophagy, and necrosis which finally lead to brain injury. In this review, we highlight the molecular mechanism for oxidative stress in HIE, summarize current research on therapeutic strategies utilized in combating oxidative stress, and try to explore novel potential clinical approaches.

  4. Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dae-Hee, E-mail: leedneo@gmail.com [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Dong-Wook [Department of Microbiology, Immunology, and Cancer Biology, University of VA (United States); Jung, Chang-Hwa [Division of Metabolism and Functionality Research, Korea Food Research Institute (Korea, Republic of); Lee, Yong J. [Departments of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA (United States); Park, Daeho, E-mail: daehopark@gist.ac.kr [School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of)

    2014-09-15

    Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. - Highlights: • Most GBM cells have been reported to be resistant to TRAIL-induced apoptosis. • Gingerol enhances the expression level of anti-apoptotic proteins by ROS. • Gingerol enhances TRAIL-induced apoptosis through actions on the ROS–Bcl2 pathway.

  5. Efficient dye-sensitized solar cells using red turnip and purple wild sicilian prickly pear fruits

    National Research Council Canada - National Science Library

    Calogero, Giuseppe; Di Marco, Gaetano; Cazzanti, Silvia; Caramori, Stefano; Argazzi, Roberto; Di Carlo, Aldo; Bignozzi, Carlo Alberto

    2010-01-01

    Dye-sensitized solar cells (DSSCs) were assembled by using the bougainvillea flowers, red turnip and the purple wild Sicilian prickly pear fruit juice extracts as natural sensitizers of TiO(2) films...

  6. CELLULAR BASIS FOR DIFFERENTIAL SENSITIVITY TO CISPLATIN IN HUMAN GERM-CELL TUMOR AND COLON-CARCINOMA CELL-LINES

    NARCIS (Netherlands)

    SARK, MWJ; TIMMERBOSSCHA, H; MEIJER, C; UGES, DRA; SLUITER, WJ; PETERS, WHM; MULDER, NH; DEVRIES, EGE

    Cisplatin (CDDP) resistance mechanisms were studied in a model of three germ cell tumour and three colon carcinoma cell lines representing intrinsically CDDP-sensitive and -resistant tumours respectively. The CDDP sensitivity of the cell lines mimicked the clinical situation. The glutathione levels

  7. Pomegranate leaves and mulberry fruit as natural sensitizers for dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Ho; Lo, Yu-Jen [Department of Mechanical Engineering, National Taipei University of Technology (China)

    2010-10-15

    This study employs chlorophyll extract from pomegranate leaf and anthocyanin extract from mulberry fruit as the natural dyes for a dye-sensitized solar cell (DSSC). A self-developed nanofluid synthesis system is employed to prepare TiO{sub 2} nanofluid with an average particle size of 25 nm. Electrophoresis deposition was performed to deposit TiO{sub 2} nanoparticles on the indium tin oxide (ITO) conductive glass, forming a TiO{sub 2} thin film with the thickness of 11 {mu}m. Furthermore, this TiO{sub 2} thin film was sintered at 450 C to enhance the thin film compactness. Sputtering was used to prepare counter electrode by depositing Pt thin film on FTO glass at a thickness of 20 nm. The electrodes, electrolyte (I{sub 3}{sup -}), and dyes were assembled into a cell module and illuminated by a light source simulating AM 1.5 with a light strength of 100 mW/cm{sup 2} to measure the photoelectric conversion efficiency of the prepared DSSCs. According to experimental results, the conversion efficiency of the DSSCs prepared by chlorophyll dyes from pomegranate leaf extract is 0.597%, with open-circuit voltage (V{sub OC}) of 0.56 V, short-circuit current density (J{sub SC}) of 2.05 mA/cm{sup 2}, and fill factor (FF) of 0.52. The conversion efficiency of the DSSCs prepared by anthocyanin dyes from mulberry extract is 0.548%, with V{sub OC} of 0.555 V and J{sub SC} of 1.89 mA/cm{sup 2} and FF of 0.53. The conversion efficiency is 0.722% for chlorophyll and anthocyanin as the dye mixture, with V{sub OC} of 0.53 V, J{sub SC} of 2.8 mA/cm{sup 2}, and FF of 0.49. (author)

  8. Sensitized solar cells with colloidal PbS-CdS core-shell quantum dots

    NARCIS (Netherlands)

    Lai, Lai-Hung; Protesescu, Loredana; Kovalenko, Maksym V.; Loi, Maria A.

    2014-01-01

    We report on the fabrication of PbS-CdS (core-shell) quantum dot (QD)-sensitized solar cells by direct adsorption of core-shell QDs on mesoporous TiO2 followed by 3-mercaptopropionic acid ligand exchange. PbS-CdS QD-sensitized solar cells show 4 times higher efficiency with respect to solar cells

  9. Toward interaction of sensitizer and functional moieties in hole-transporting materials for efficient semiconductor-sensitized solar cells.

    Science.gov (United States)

    Im, Sang Hyuk; Lim, Choong-Sun; Chang, Jeong Ah; Lee, Yong Hui; Maiti, Nilkamal; Kim, Hi-Jung; Nazeeruddin, Md K; Grätzel, Michael; Seok, Sang Il

    2011-11-09

    Sb(2)S(3)-sensitized mesoporous-TiO(2) solar cells using several conjugated polymers as hole-transporting materials (HTMs) are fabricated. We found that the cell performance was strongly correlated with the chemical interaction at the interface of Sb(2)S(3) as sensitizer and the HTMs through the thiophene moieties, which led to a higher fill factor (FF), open-circuit voltage (V(oc)), and short-circuit current density (J(sc)). With the application of PCPDTBT (poly(2,6-(4,4-bis-(2-ethylhexyl)-4H-cyclopenta[2,1-b;3,4-b']dithiophene)-alt-4,7(2,1,3-benzothiadiazole)) as a HTM in a Sb(2)S(3)-sensitized solar cell, overall power conversion efficiencies of 6.18, 6.57, and 6.53% at 100, 50, and 10% solar irradiation, respectively, were achieved with a metal mask.

  10. Doped Heterojunction Used in Quantum Dot Sensitized Solar Cell

    Directory of Open Access Journals (Sweden)

    Yanyan Gao

    2014-01-01

    Full Text Available Incorporated foreign atoms into the quantum dots (QDs used in heterojunction have always been a challenge for solar energy conversion. A foreign atom indium atom was incorporated into PbS/CdS QDs to prepare In-PbS/In-CdS heterojunction by successive ionic layer adsorption and reaction method which is a chemical method. Experimental results indicate that PbS or CdS has been doped with In by SILAR method; the concentration of PbS and CdS which was doped In atoms has no significantly increase or decrease. In addition, incorporating of Indium atoms has resulted in the lattice distortions or changes of PbS or CdS and improved the light harvest of heterojunction. Using this heterojunction, Pt counter electrode and polysulfide electrolyte, to fabricate quantum dot sensitized solar cells, the short circuit current density ballooned to 27.01 mA/cm2 from 13.61 mA/cm2 and the open circuit voltage was improved to 0.43 V from 0.37 V at the same time.

  11. Nanostructured Semiconductor Materials for Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Carmen Cavallo

    2017-01-01

    Full Text Available Since O’Regan and Grätzel’s first report in 1991, dye-sensitized solar cells (DSSCs appeared immediately as a promising low-cost photovoltaic technology. In fact, though being far less efficient than conventional silicon-based photovoltaics (being the maximum, lab scale prototype reported efficiency around 13%, the simple design of the device and the absence of the strict and expensive manufacturing processes needed for conventional photovoltaics make them attractive in small-power applications especially in low-light conditions, where they outperform their silicon counterparts. Nanomaterials are at the very heart of DSSC, as the success of its design is due to the use of nanostructures at both the anode and the cathode. In this review, we present the state of the art for both n-type and p-type semiconductors used in the photoelectrodes of DSSCs, showing the evolution of the materials during the 25 years of history of this kind of devices. In the case of p-type semiconductors, also some other energy conversion applications are touched upon.

  12. Numerical Procedure for Optimizing Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Mihai Razvan Mitroi

    2014-01-01

    Full Text Available We propose a numerical procedure consisting of a simplified physical model and a numerical method with the aim of optimizing the performance parameters of dye-sensitized solar cells (DSSCs. We calculate the real rate of absorbed photons (in the dye spectral range Grealx by introducing a factor β<1 in order to simplify the light absorption and reflection on TCO electrode. We consider the electrical transport to be purely diffusive and the recombination process only to occur between electrons from the TiO2 conduction band and anions from the electrolyte. The used numerical method permits solving the system of differential equations resulting from the physical model. We apply the proposed numerical procedure on a classical DSSC based on Ruthenium dye in order to validate it. For this, we simulate the J-V characteristics and calculate the main parameters: short-circuit current density Jsc, open circuit voltage Voc, fill factor FF, and power conversion efficiency η. We analyze the influence of the nature of semiconductor (TiO2 and dye and also the influence of different technological parameters on the performance parameters of DSSCs. The obtained results show that the proposed numerical procedure is suitable for developing a numerical simulation platform for improving the DSSCs performance by choosing the optimal parameters.

  13. Sensitivity of bladder cancer cells to curcumin and its derivatives depends on the extracellular matrix.

    Science.gov (United States)

    Hauser, Paul J; Han, Zhiyong; Sindhwani, Puneet; Hurst, Robert E

    2007-01-01

    Because the response of cancer cells to chemotherapeutic agents depends upon the supporting extracellular matrix (ECM), the response in vivo may not be reproduced in 2-dimensional cell culture. The dose-response to curcumin and two derivatives by bladder cancer cells grown on both normal (SISgel) and cancer-derived ECM (Matrigel) and on plastic were contrasted. Cells grown on Matrigel were resistant to curcumins, but cells growing on SISgel, which mimic cancer cells suppressed by normal ECM, were nearly as sensitive as cells grown on plastic. SV40-immortalized urothelial cells, which are models for premalignant cells, were the most sensitive, but even aggressive cell lines were nearly as sensitive when grown on SISgel as on plastic. Curcumin response depends highly on the supporting ECM, and cells grown on plastic poorly models cells growing on natural ECM. Curcumin could prove an effective chemopreventive for bladder cancer recurrence when administered intravesically post-therapy.

  14. Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells.

    Science.gov (United States)

    Lee, Dae-Hee; Kim, Dong-Wook; Jung, Chang-Hwa; Lee, Yong J; Park, Daeho

    2014-09-15

    Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS). We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Molecular chaperones and hypoxic-ischemic encephalopathy

    Directory of Open Access Journals (Sweden)

    Cong Hua

    2017-01-01

    Full Text Available Hypoxic-ischemic encephalopathy (HIE is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway. Numerous treatments for hypoxic-ischemic brain injury caused by HIE have been developed over the last half century. Hypothermia, xenon gas treatment, the use of melatonin and erythropoietin, and hypoxic-ischemic preconditioning have proven effective in HIE patients. Molecular chaperones are proteins ubiquitously present in both prokaryotes and eukaryotes. A large number of molecular chaperones are induced after brain ischemia and hypoxia, among which the heat shock proteins are the most important. Heat shock proteins not only maintain protein homeostasis; they also exert anti-apoptotic effects. Heat shock proteins maintain protein homeostasis by helping to transport proteins to their target destinations, assisting in the proper folding of newly synthesized polypeptides, regulating the degradation of misfolded proteins, inhibiting the aggregation of proteins, and by controlling the refolding of misfolded proteins. In addition, heat shock proteins exert anti-apoptotic effects by interacting with various signaling pathways to block the activation of downstream effectors in numerous apoptotic pathways, including the intrinsic pathway, the endoplasmic reticulum-stress mediated pathway and the extrinsic Fas receptor pathway. Molecular chaperones play a key role in neuroprotection in HIE. In

  16. Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR.

    Science.gov (United States)

    Xu, Xue-Feng; Lv, Ying; Gu, Wei-Zhong; Tang, Li-Li; Wei, Jia-Kai; Zhang, Li-Yan; Du, Li-Zhong

    2013-02-14

    Accumulating evidence reveals that intrauterine growth retardation (IUGR) can cause varying degrees of pulmonary arterial hypertension (PAH) later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR. The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC) were isolated from the rat lungs by magnetic-activated cell sorting (MACS). We investigated epigenetic regulation of the endothelin-1 (ET-1) gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia. The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α) binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling. These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.

  17. Epigenetics of hypoxic pulmonary arterial hypertension following intrauterine growth retardation rat: epigenetics in PAH following IUGR

    Directory of Open Access Journals (Sweden)

    Xu Xue-Feng

    2013-02-01

    Full Text Available Abstract Background Accumulating evidence reveals that intrauterine growth retardation (IUGR can cause varying degrees of pulmonary arterial hypertension (PAH later in life. Moreover, epigenetics plays an important role in the fetal origin of adult disease. The goal of this study was to investigate the role of epigenetics in the development of PAH following IUGR. Methods The IUGR rats were established by maternal undernutrition during pregnancy. Pulmonary vascular endothelial cells (PVEC were isolated from the rat lungs by magnetic-activated cell sorting (MACS. We investigated epigenetic regulation of the endothelin-1 (ET-1 gene in PVEC of 1-day and 6-week IUGR rats, and response of IUGR rats to hypoxia. Results The maternal nutrient restriction increased the histone acetylation and hypoxia inducible factor-1α (HIF-1α binding levels in the ET-1 gene promoter of PVEC in IUGR newborn rats, and continued up to 6 weeks after birth. These epigenetic changes could result in an IUGR rat being highly sensitive to hypoxia later in life, causing more significant PAH or pulmonary vascular remodeling. Conclusions These findings suggest that epigenetics is closely associated with the development of hypoxic PAH following IUGR, further providing a new insight for improved prevention and treatment of IUGR-related PAH.

  18. Aptamer-Functionalized Fluorescent Silica Nanoparticles for Highly Sensitive Detection of Leukemia Cells

    Science.gov (United States)

    Tan, Juntao; Yang, Nuo; Hu, Zixi; Su, Jing; Zhong, Jianhong; Yang, Yang; Yu, Yating; Zhu, Jianmeng; Xue, Dabin; Huang, Yingying; Lai, Zongqiang; Huang, Yong; Lu, Xiaoling; Zhao, Yongxiang

    2016-06-01

    A simple, highly sensitive method to detect leukemia cells has been developed based on aptamer-modified fluorescent silica nanoparticles (FSNPs). In this strategy, the amine-labeled Sgc8 aptamer was conjugated to carboxyl-modified FSNPs via amide coupling between amino and carboxyl groups. Sensitivity and specificity of Sgc8-FSNPs were assessed using flow cytometry and fluorescence microscopy. These results showed that Sgc8-FSNPs detected leukemia cells with high sensitivity and specificity. Aptamer-modified FSNPs hold promise for sensitive and specific detection of leukemia cells. Changing the aptamer may allow the FSNPs to detect other types of cancer cells.

  19. Ethnic Differences in Insulin Sensitivity, β-Cell Function, and Hepatic Extraction Between Japanese and Caucasians

    DEFF Research Database (Denmark)

    Møller, Jonas B; Dalla Man, Chiara; Overgaard, Rune V

    2014-01-01

    : This was a cross-sectional study with oral glucose tolerance tests to assess β-cell function, hepatic insulin extraction, and insulin sensitivity. PARTICIPANTS: PARTICIPANTS included 120 Japanese and 150 Caucasian subjects. MAIN OUTCOMES: Measures of β-cell function, hepatic extraction, and insulin sensitivity...... were assessed using C-peptide, glucose, and insulin minimal models. RESULTS: Basal β-cell function (Φ(b)) was lower in Japanese compared with Caucasians (P ... compared with Caucasians (P insulin action showed higher sensitivity in the Japanese IGT subjects. Hepatic extraction was similar in NGT and IGT groups but higher in Japanese type 2 diabetic subjects (P insulin sensitivity, β-cell function...

  20. Paris Saponin I Sensitizes Gastric Cancer Cell Lines to Cisplatin via Cell Cycle Arrest and Apoptosis

    OpenAIRE

    Song, Shuichuan; Du, Leiwen; Jiang, Hao; Zhu, Xinhai; Li, Jinhui; Xu, Ji

    2016-01-01

    Background Dose-related toxicity is the major restriction of cisplatin and cisplatin-combination chemotherapy, and is a challenge for advanced gastric cancer treatment. We explored the possibility of using Paris saponin I as an agent to sensitize gastric cancer cells to cisplatin, and examined the underlying mechanism. Material/Methods Growth inhibition was detected by MTT assay. The cell cycle and apoptosis were detected using flow cytometry and Annexin V/PI staining. The P21waf1/cip1, Bcl-2...

  1. Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin

    Directory of Open Access Journals (Sweden)

    Yiwen Jiang

    2017-01-01

    Full Text Available The identity of the glioblastoma (GBM cell of origin and its contributions to disease progression and treatment response remain largely unknown. We have analyzed how the phenotypic state of the initially transformed cell affects mouse GBM development and essential GBM cell (GC properties. We find that GBM induced in neural stem-cell-like glial fibrillary acidic protein (GFAP-expressing cells in the subventricular zone of adult mice shows accelerated tumor development and produces more malignant GCs (mGC1GFAP that are less resistant to cancer drugs, compared with those originating from more differentiated nestin- (mGC2NES or 2,′3′-cyclic nucleotide 3′-phosphodiesterase (mGC3CNP-expressing cells. Transcriptome analysis of mouse GCs identified a 196 mouse cell origin (MCO gene signature that was used to partition 61 patient-derived GC lines. Human GC lines that clustered with the mGC1GFAP cells were also significantly more self-renewing, tumorigenic, and sensitive to cancer drugs compared with those that clustered with mouse GCs of more differentiated origin.

  2. [Bortezomib enhances the sensitivity of prostate cancer cells to natural killer cell-mediated cytotoxicity].

    Science.gov (United States)

    Hu, Wei; Gao, Zhen-Yu; Wang, Wei

    2014-03-01

    To investigate whether bortezomib can enhance the sensitivity of human prostate cancer (PCa) cells to natural killer (NK) cell-mediated cytotoxicity, and whether it produces the same effect on different PCa cell lines. We treated androgen-dependent PCa LNCaP cells and androgen-independent PCa DU145 cells with bortezomib at the concentrations of 0, 5, 10, 15, 20 and 25 nmol/L for 24, 48 and 72 hours, and then detected the proliferation and apoptosis of the tumor cells by CCK-8 and Annexin V/PI, respectively. The proliferation rates of the DU145 cells treated with 15, 20 and 25 nmol/L bortezomib were (82.79 +/-2.04)%, (73.59+/- 2.95)% and (74.16+/- 6. 16)% at 48 hours and (71.24+/- 5.30)%, (51.20+/- 2.91)% and (38.02+/- 2.67)% at 72 hours, and those of the LNCaP cells were (77.04+/- 7.74)% , (42.61 +/- 6.62)% and (23.85 +/-6.04)% at 48 hours and (36.45 +/-7.02)%, (14.94 +/-5.76)% and (11.65 +/-5. 87)% at 72 hours, both significantly inhibited as compared with the control group (P cancer therapies, and it is more efficacious for androgen-independent prostate cancer.

  3. Cycloruthenated Chromophores for the Dye-Sensitized Solar Cell

    Science.gov (United States)

    Bomben, Paolo Giovanni

    A series of bidentate cyclometalated Ru(II) complexes of general formula [Ru(N. N)(N. N)(C. N)]+, where N. N = polypyridyl ligand and C. N = cyclometalating ligand, have been synthesized, characterized and tested in dye-sensitized solar cells (DSSCs). Cyclometalated Ru(II) complexes, in general, exhibited broader absorption profiles and cathodically shifted electrochemical potentials compared to their polypyridyl analogues. The prototypical cycloruthenated compound, [Ru(bpy)2(ppy)]+ (bpy = 2,2'-bipyridine; Hppy = 2-phenylpyridine), displayed comparable UV-vis spectral coverage to the standard DSSC dye, N3. Molar extinction coefficients were enhanced and the absorption profile was red-shifted through substitution of the molecular periphery. Molecules from the [Ru(bpy)2(ppy)] + family displayed HOMO and excited-state energy levels properly aligned for use in the DSSC. Anchoring -CO2H groups were ideally located on the bidentate polypyridyl ligands (e.g., H2dcbpy; H2dcbpy = 4,4'-dicarboxy-2,2'-bipyridine) because this arrangement localized excited-state electron density proximate to TiO 2. Increased molecular light absorption was accomplished by installing conjugated substituents (e.g., -NO2, -phenyl, -pyridyl, -2-thiophene-carbaldehyde) on the anionic ring of molecules with general formula [Ru(H2dcbpy)2(C. N)]+.Aromatic substituents were superior to -NO2 because of an ideally positioned lowest excited-state (i.e., localized to H2dcbpy instead of -NO2). Substitution of the anionic ring with 2-thiophene-5-carbaldehyde para to the Ru-C bond resulted in a superior absorption profile enabling a modest cell power conversion efficiency (PCE) of 3.3%. Replacement of one H2dcbpy ligand with bpy generated tris-heteroleptic cyclometalated Ru(II) dyes with general formula [Ru(H2dcbpy)(bpy)( C. N)]+. The use of electron-rich cyclometalating ligands,however, led to poor PCEs because of incompatible Ru electrochemical potentials for dye regeneration. Strong electron withdrawing

  4. Effect of dye extracting solvents and sensitization time on photovoltaic performance of natural dye sensitized solar cells

    Directory of Open Access Journals (Sweden)

    Md. Khalid Hossain

    Full Text Available In this study, natural dye sensitizer based solar cells were successfully fabricated and photovoltaic performance was measured. Sensitizer (turmeric sources, dye extraction process, and photoanode sensitization time of the fabricated cells were analyzed and optimized. Dry turmeric, verdant turmeric, and powder turmeric were used as dye sources. Five distinct types of solvents were used for extraction of natural dye from turmeric. Dyes were characterized by UV–Vis spectrophotometric analysis. The extracted turmeric dye was used as a sensitizer in the dye sensitized solar cell’s (DSSC photoanode assembly. Nano-crystalline TiO2 was used as a film coating semiconductor material of the photoanode. TiO2 films on ITO glass substrate were prepared by simple doctor blade technique. The influence of the different parameters VOC, JSC, power density, FF, and η% on the photovoltaic characteristics of DSSCs was analyzed. The best energy conversion performance was obtained for 2 h adsorption time of dye on TiO2 nano-porous surface with ethanol extracted dye from dry turmeric. Keywords: DSSC, Natural dye, TiO2 photoanode, Dye extracting solvent, Dye-adsorption time

  5. Interaction of Sensitizing Dyes with Nanostructured TiO2 Film in Dye-Sensitized Solar Cells Using Terahertz Spectroscopy.

    Science.gov (United States)

    Ghann, William; Rahman, Aunik; Rahman, Anis; Uddin, Jamal

    2016-07-22

    The objective of this investigation was to shed light on the nature of interaction of different organic dyes and an inorganic dye, Ruthenium (II) polypyridine complex, with TiO2 nanoparticles. TiO2 is commonly deployed as an efficient energy transfer electrode in dye sensitized solar cells. The efficiency of dye sensitized solar cells is a function of the interaction of a dye with the electrode material such as TiO2. To the best of our knowledge the present study is the first effort in the determination of terahertz absorbance signals, investigation of real-time dye permeation kinetics, and the surface profiling and 3D imaging of dye sensitized TiO2 films. Herein, we report that the terahertz spectra of the natural dye sensitized TiO2 films were distinctively different from that of the inorganic dye with prominent absorption of natural dyes occurring at approximately the same wavelength. It was observed that the permeation of the natural dyes were more uniform through the layers of the mesoporous TiO2 compared to the inorganic dye. Finally, defects and flaws on TiO2 film were easily recognized via surface profiling and 3D imaging of the films. The findings thus offer a new approach in characterization of dye sensitized solar cells.

  6. The influence of the number of cells scored on the sensitivity in the comet assay

    DEFF Research Database (Denmark)

    Sharma, Anoop Kumar; Soussaline, Françoise; Sallette, Jerome

    2012-01-01

    The impact on the sensitivity of the in vitro comet assay by increasing the number of cells scored has only been addressed in a few studies. The present study investigated whether the sensitivity of the assay could be improved by scoring more than 100 cells. Two cell lines and three different...... out by means of a fully automated scoring system and the results were analyzed by evaluating the % tail DNA of 100–700 randomly selected cells for each slide consisting of two gels. By increasing the number of cells scored, the coefficients of variance decreased, leading to an improved sensitivity...

  7. Inhibition of geranylgeranylation mediates sensitivity to CHOP-induced cell death of DLBCL cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Ageberg, Malin, E-mail: Malin.Ageberg@med.lu.se [Division of Hematology and Transfusion Medicine, Lund University, BMC C14, 221 84 Lund (Sweden); Rydstroem, Karin, E-mail: Karin.Rydstom@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Linden, Ola, E-mail: Ola.Linden@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Linderoth, Johan, E-mail: Johan.Linderoth@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Jerkeman, Mats, E-mail: Mats.Jerkeman@skane.se [Department of Oncology, Skanes University Hospital, Allmaenmott, Onkologiska kliniken i Lund, 221 85 Lund (Sweden); Drott, Kristina, E-mail: Kristina.Drott@med.lu.se [Division of Hematology and Transfusion Medicine, Lund University, BMC C14, 221 84 Lund (Sweden)

    2011-05-01

    Prenylation is a post-translational hydrophobic modification of proteins, important for their membrane localization and biological function. The use of inhibitors of prenylation has proven to be a useful tool in the activation of apoptotic pathways in tumor cell lines. Rab geranylgeranyl transferase (Rab GGT) is responsible for the prenylation of the Rab family. Overexpression of Rab GGTbeta has been identified in CHOP refractory diffuse large B cell lymphoma (DLBCL). Using a cell line-based model for CHOP resistant DLBCL, we show that treatment with simvastatin, which inhibits protein farnesylation and geranylgeranylation, sensitizes DLBCL cells to cytotoxic treatment. Treatment with the farnesyl transferase inhibitor FTI-277 or the geranylgeranyl transferase I inhibitor GGTI-298 indicates that the reduction in cell viability was restricted to inhibition of geranylgeranylation. In addition, treatment with BMS1, a combined inhibitor of farnesyl transferase and Rab GGT, resulted in a high cytostatic effect in WSU-NHL cells, demonstrated by reduced cell viability and decreased proliferation. Co-treatment of BMS1 or GGTI-298 with CHOP showed synergistic effects with regard to markers of apoptosis. We propose that inhibition of protein geranylgeranylation together with conventional cytostatic therapy is a potential novel strategy for treating patients with CHOP refractory DLBCL.

  8. From Cell to Module: Fabrication and Long-term Stability of Dye-sensitized Solar Cells

    Science.gov (United States)

    Nursam, N. M.; Hidayat, J.; Muliani, L.; Anggraeni, P. N.; Retnaningsih, L.; Idayanti, N.

    2017-07-01

    Dye-sensitized solar cell (DSSC), which has been firstly developed by Graetzel et al back in 1991, has attracted a considerable interest since its discovery. However, two of the main challenges that the DSSC technology will have to overcome towards commercialization involve device scale-up and long-term stability. In our group, the fabrication technology of DSSC has been developed from laboratory to module scale over the past few years, nevertheless, the long-term stability has still became a major concern. In this contribution, the long-term DSSC performance in relation to their scale-up from cell to module is investigated. The photoelectrode of the DSSCs were fabricated using nanocrystalline titanium dioxide materials that were subsequently sensitized using ruthenium-based dye. Additionally, TiCl4 pre- and post-treatment were carried out to enhance the overall device efficiency. When fabricated as cells, the DSSC prototypes showed relatively stable performance during repeated tests over three months. In order to increase the output power of the solar cells, the DSSCs were then connected in a Z-type series connection to obtain sub-module panels. The DSSC sub-modules exhibit poor stability, particularly as indicated by the significant decrease in the short circuit current (ISC ). Herein, the effect of photoelectrode and sealant materials as well as module design are investigated, highlighting their profound influence upon the DSSC efficiency and long-term stability.

  9. Metal oxide-encapsulated dye-sensitized photoanodes for dye-sensitized solar cells

    Science.gov (United States)

    Hupp, Joseph T.; Son, Ho-Jin

    2016-01-12

    Dye-sensitized semiconducting metal oxide films for photoanodes, photoanodes incorporating the films and DSCs incorporating the photoanodes are provided. Also provided are methods for making the dye sensitized semiconducting metal oxide films. The methods of making the films are based on the deposition of an encapsulating layer of a semiconducting metal oxide around the molecular anchoring groups of photosensitizing dye molecules adsorbed to a porous film of the semiconducting metal oxide. The encapsulating layer of semiconducting metal oxide is formed in such a way that it is not coated over the chromophores of the adsorbed dye molecules and, therefore, allows the dye molecules to remain electrochemically addressable.

  10. RasGRP1 confers the phorbol ester-sensitive phenotype to EL4 lymphoma cells.

    Science.gov (United States)

    Han, Shujie; Knoepp, Stewart M; Hallman, Mark A; Meier, Kathryn E

    2007-01-01

    The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to the tumor promoter phorbol 12-myristate 13-acetate (PMA). In sensitive EL4 cells, PMA causes robust Erk mitogen-activated protein kinase activation that results in growth arrest. In resistant cells, PMA induces minimal Erk activation, without growth arrest. PMA stimulates IL-2 production in sensitive, but not resistant, cells. The role of RasGRP1, a PMA-activated guanine nucleotide exchange factor for Ras, in EL4 phenotype was examined. Endogenous RasGRP1 protein is expressed at much higher levels in sensitive than in resistant cells. PMA-induced Ras activation is observed in sensitive cells but not in resistant cells lacking Ras-GRP1. PMA induces down-regulation of RasGRP1 protein in sensitive cells but increases RasGRP1 in resistant cells. Transfection of RasGRP1 into resistant cells enhances PMA-induced Erk activation. In the reverse experiment, introduction of small interfering RNA (siRNA) for RasGRP1 suppresses PMA-induced Ras and Erk activations in sensitive cells. Sensitive cells incubated with siRNA for RasGRP1 exhibit the PMA-resistant phenotype, in that they are able to proliferate in the presence of PMA and do not secrete IL-2 when stimulated with PMA. These studies indicate that the PMA-sensitive phenotype, as previously defined for the EL4 cell line, is conferred by endogenous expression of RasGRP1 protein.

  11. Resveratrol Sensitizes Selectively Thyroid Cancer Cell to 131-Iodine Toxicity

    Directory of Open Access Journals (Sweden)

    Seyed Jalal Hosseinimehr

    2014-01-01

    Full Text Available Background. In this study, the radiosensitizing effect of resveratrol as a natural product was investigated on cell toxicity induced by 131I in thyroid cancer cell. Methods. Human thyroid cancer cell and human nonmalignant fibroblast cell (HFFF2 were treated with 131I and/or resveratrol at different concentrations for 48 h. The cell proliferation was measured by determination of the percent of the survival cells using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Results. Findings of this study show that resveratrol enhanced the cell death induced by 131I on thyroid cancer cell. Also, resveratrol exhibited a protective effect on normal cells against 131I toxicity. Conclusion. This result indicates a promising effect of resveratrol on improvement of cellular toxicity during iodine therapy.

  12. Synthesis of dye-sensitized solar cells. Efficiency cells as a thickness of titanium dioxide

    Directory of Open Access Journals (Sweden)

    Szura Dominika

    2017-01-01

    Full Text Available Defying the influence of the thickness of TiO2 efficiency of dye-sensitized solar cell. It was confirmed that the compatibility of printed layers with the parameters closely related with the DSSC. It was found that the increase in thickness of the titanium dioxide layer, increases the distance between the electrodes, determined by the thickness of the Surlyn foil. With the rise of thickness of dyed layer of TiO2 established decrease in the value of its transmittance. Greatest transparency and aesthetic value obtained for photovoltaic modules with a single layer of titanium dioxide. The improved performance efficiency and preferred yields maximum power were noticed and exhibited by the cells covered with three layers of TiO2. It was established that the behaviour of economic efficiency in the production process, provides a range of cells with two layers of oxide, showing a similar performance and greater transparency.

  13. File list: ALL.Adl.10.AllAg.Temperature_sensitive_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. Liquid Redox Electrolytes for Dye-Sensitized Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Ze

    2012-07-01

    This thesis focuses on liquid redox electrolytes in dye-sensitized solar cells (DSCs). A liquid redox electrolyte, as one of the key constituents in DSCs, typically consists of a redox mediator, additives and a solvent. This thesis work concerns all these three aspects of liquid electrolytes, aiming through fundamental insights to enhance the photovoltaic performances of liquid DSCs. Initial attention has been paid to the iodine concentration effects in ionic liquid (IL)-based electrolytes. It has been revealed that the higher iodine concentration required in IL-based electrolytes can be attributed to both triiodide mobility associated with the high viscosity of the IL, and chemical availability of triiodide. The concept of incompletely solvated ionic liquids (ISILs) has been introduced as a new type of electrolyte solvent for DSCs. It has been found that the photovoltaic performance of ISIL-based electrolytes can even rival that of organic solvent-based electrolytes. And most strikingly, ISIL-based electrolytes provide highly stable DSC devices under light-soaking conditions, as a result of the substantially lower vapor pressure of the ISIL system. A significant synergistic effect has been observed when both guanidinium thiocyanate and N-methylbenzimidazole are employed together in an IL-based electrolyte, exhibiting an optimal overall conversion efficiency. Tetrathiafulvalene (TTF) has been investigated as an organic iodine-free redox couple in electrolytes for DSCs. An unexpected worse performance has been observed for the TTF system, albeit it possesses a particularly attractive positive redox potential. An organic, iodine-free thiolate/disulfide system has also been adopted as a redox couple in electrolytes for organic DSCs. An impressive efficiency of 6.0 % has successfully been achieved by using this thiolate/disulfide redox couple in combination with a poly (3, 4-ethylenedioxythiophene) (PEDOT) counter electrode material under full sunlight illumination (AM

  18. Multiple cyclin-dependent kinases signals are critical mediators of ischemia/hypoxic neuronal death in vitro and in vivo.

    Science.gov (United States)

    Rashidian, Juliet; Iyirhiaro, Grace; Aleyasin, Hossein; Rios, Mario; Vincent, Inez; Callaghan, Steven; Bland, Ross J; Slack, Ruth S; During, Matthew J; Park, David S

    2005-09-27

    The mechanisms involving neuronal death after ischemic/hypoxic insult are complex, involving both rapid (excitotoxic) and delayed (apoptotic-like) processes. Recent evidence suggests that cell cycle regulators such as cyclin-dependent kinases are abnormally activated in neuropathological conditions, including stroke. However, the function of this activation is unclear. Here, we provide evidence that inhibition of the cell cycle regulator, Cdk4, and its activator, cyclinD1, plays critical roles in the delayed death component of ischemic/hypoxic stress by regulating the tumor suppressor retinoblastoma protein. In contrast, the excitotoxic component of ischemia/hypoxia is predominately regulated by Cdk5 and its activator p35, components of a cyclin-dependent kinase complex associated with neuronal development. Hence, our data both characterize the functional significance of the cell cycle Cdk4 and neuronal Cdk5 signals as well as define the pathways and circumstances by which they act to control ischemic/hypoxic damage.

  19. Cinnamaldehyde derivative (CB-PIC) sensitizes chemo-resistant cancer cells to drug-induced apoptosis via suppression of MDR1 and its upstream STAT3 and AKT signalling.

    Science.gov (United States)

    Yun, Miyong; Lee, Duckgue; Park, Moon-Nyeo; Kim, Eun-Ok; Sohn, Eun Jung; Kwon, Byung-Mog; Kim, Sung-Hoon

    2015-01-01

    Our group reported that cinnamaldehyde derivative, (E)-4-((2-(3-oxopop-1-enyl)phenoxy)methyl)pyridinium malonic acid (CB-PIC) induced apoptosis in hypoxic SW620 colorectal cancer cells via activation of AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase (ERK). Herein, sensitizing effect of CB-PIC was investigated in resistant cancer cells such as paclitaxel (PT) resistant lung cancer cells (H460/PT), and Adriamycin (Adr) resistant breast cancer (MCF7/Adr) and colon cancer (HCT15/cos) cells. Various drug resistant cell lines were treated with CB-PIC, and the signalling pathway and functional assay were explored by Western blot, Rhodamine assay, FACS, RT-PCR and MTT assay. We found that CB-PIC effectively exerted cytotoxicity, increased sub G1 population and the cleaved form of poly (ADP-ribose) polymerase (PARP) and caspase 9 in drug resistant cancer cells. Furthermore, CB-PIC sensitized resistant cancer cells to adriamycin via downregulation of survival proteins such as survivin, Bcl-xL and Bcl-2, along with MDR1 suppression leading to accumulation of drug in the intracellular region. Of note, CB-PIC transcriptionally decreased MDR1 expression via suppression of STAT3 and AKT signalling in three resistant cancer cells with highly expressed P-glycoprotein. Nonetheless, CB-PIC did not affect transport activity of P-glycoprotein in a short time efflux assay, while epigallocatechin gallate (EGCG) accumulated Rhodamine 123 into intracellular region of cell by direct inhibition of MDR1 transport activity. These data demonstrate that CB-PIC suppresses the P-glycoprotein expression through inhibition of STAT3 and AKT signalling to overcome drug resistance in chemo-resistant cancer cells as a potent chemotherapeutic sensitizer. © 2015 S. Karger AG, Basel.

  20. Allergen immunotherapy modulates sensitivity of Treg cells to apoptosis in a rat model of allergic asthma.

    Science.gov (United States)

    Datta, Ankur; Moitra, Saibal; Das, Prasanta K; Mondal, Somnath; Omar Faruk, Sk Md; Hazra, Iman; Tripathi, Santanu K; Chaudhuri, Swapna

    2017-11-01

    To study the apoptosis of Foxp3+ Treg cells following Alstonia scholaris pollen sensitization-challenge and following allergen immunotherapy. Wistar rats were sensitized-challenged with Alstonia scholaris pollen and were further given intranasal immunotherapy. For the analysis of the apoptotic proteins on Treg cells by flow cytometry, multiple gating procedures were followed. Allergen sensitization-challenge increases Annexin-V, Fas, FasL, caspases-8, 9, 3 cytochrome-C, APAF-1, Bax, perforin-1 and granzyme-B on Treg cells which is decreased following intranasal immunotherapy. On the other hand, Bcl-2 expression is decreased in allergy and increased by immunotherapy. Apoptosis of Treg cells is increased following allergen sensitization-challenge via extrinsic, intrinsic and perforin/granzyme pathways and allergen immunotherapy decreased the sensitivity to apoptosis of Treg cells.

  1. Cells in fluidic environments are sensitive to flow frequency.

    Science.gov (United States)

    Balcells, Mercedes; Fernández Suárez, Marta; Vázquez, María; Edelman, Elazer R

    2005-07-01

    Virtually all cells accommodate to their mechanical environment. In particular, cells subject to flow respond to rapid changes in fluid shear stress (SS), cyclic stretch (CS), and pressure. Recent studies have focused on the effect of pulsatility on cellular behavior. Since cells of many different tissue beds are constantly exposed to fluid flows over a narrow range of frequencies, we hypothesized that an intrinsic flow frequency that is optimal for determining cell phenotype exists. We report here that cells from various tissue beds (bovine aortic endothelial cells (BAEC), rat small intestine epithelial cells (RSIEC), and rat lung epithelial cells (RLEC)) proliferate maximally when cultured in a perfusion bioreactor under pulsatile conditions at a specific frequency, independent of the applied SS. Vascular endothelial and pulmonary epithelial cell proliferation peaked under 1 Hz pulsatile flow. In contrast, proliferation of gastrointestinal cells, which in their physiological context are subject to no flow or higher wavelength signal, was maximum at 0.125 Hz or under no flow. Moreover, exposure of BAEC to pulsatile flow of varying frequency influenced their nitric oxide synthase activity and prostacyclin production, which reached maximum values at 1 Hz. Notably, the "optimal" frequencies for the cell types examined correspond to the physiologic operating range of the organs from where they were initially derived. These findings suggest that frequency, independent of shear, is an essential determinant of cell response in pulsatile environments. (c) 2004 Wiley-Liss, Inc.

  2. Enhancement of Bleomycin Sensitivity in Human Lung Cancer Cell ...

    African Journals Online (AJOL)

    Purpose: To demonstrate the effectiveness of Centella asiatica aqueous extract in augmenting the cytotoxic effect of bleomycin in the adenocarcinoma human alveolar basal epithelial A549 cell line. Methods: The inhibitory effect of bleomycin on A549 cells was determined by incubating the cells for 24 h in different ...

  3. Hypoxic challenge test applied to healthy children

    DEFF Research Database (Denmark)

    Kobbernagel, Helene Elgaard; Nielsen, Kim Gjerum; Hanel, Birgitte

    2013-01-01

    BACKGROUND: Commercial aircraft are pressurised to ~2438 m (8000 ft) above sea level that equates breathing 15% oxygen at sea level. A preflight hypoxic challenge test (HCT) is therefore recommended for children with cystic fibrosis or other chronic lung diseases and inflight oxygen is advised...... if pulse oximetric saturation (SpO2) decreases children during flight, with a view to challenge the evidence of the current cut-off. METHODS: Oxygenation...... cut-off of 90% for children with chronic lung disease reflects clinical oxygen dependence during flights....

  4. To probe the equivalence and opulence of nanocrystal and nanotube based dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Jyoti, Divya, E-mail: divyabathla17@gmail.com [Department of Physics, University College, Jaito, Distt. Faridkot, Punjab (India); Mohan, Devendra [Department of Applied Physics, Guru Jambheshwar University of Science and Technology, Hisar, Haryana (India)

    2016-05-06

    Dye-Sensitized solar cells based on TiO{sub 2} nanocrystal and TiO{sub 2} nanotubes have been fabricated by a simple sol-gel hydrothermal process and their performances have been compared. Current density and voltage (JV) characteristics and incident photon to current conversion efficiency (IPCE) plots have been set as criterion to check which one is better as a photoanode candidate in dye-sensitized solar cell. It has been observed that although open circuit voltage values for both type of cells do not differ much still, nanotube based dye-sensitized solar cells are more successful having an efficiency value of 7.28%.

  5. To probe the equivalence and opulence of nanocrystal and nanotube based dye-sensitized solar cells

    Science.gov (United States)

    Jyoti, Divya; Mohan, Devendra

    2016-05-01

    Dye-Sensitized solar cells based on TiO2 nanocrystal and TiO2 nanotubes have been fabricated by a simple sol-gel hydrothermal process and their performances have been compared. Current density and voltage (JV) characteristics and incident photon to current conversion efficiency (IPCE) plots have been set as criterion to check which one is better as a photoanode candidate in dye-sensitized solar cell. It has been observed that although open circuit voltage values for both type of cells do not differ much still, nanotube based dye-sensitized solar cells are more successful having an efficiency value of 7.28%.

  6. Sensitized solar cells with colloidal PbS-CdS core-shell quantum dots

    OpenAIRE

    Lai, Lai-Hung; Protesescu, Loredana; Kovalenko, Maksym V.; Loi, Maria A.

    2014-01-01

    We report on the fabrication of PbS-CdS (core-shell) quantum dot (QD)-sensitized solar cells by direct adsorption of core-shell QDs on mesoporous TiO2 followed by 3-mercaptopropionic acid ligand exchange. PbS-CdS QD-sensitized solar cells show 4 times higher efficiency with respect to solar cells sensitized with PbS QDs. The significantly enhanced mean electron lifetime and electron diffusion length provide crucial evidence for the higher efficiency of the cell. The average electron lifetime ...

  7. Non-endothelial endothelin counteracts hypoxic vasodilation in porcine large coronary arteries

    Directory of Open Access Journals (Sweden)

    Fröbert Ole

    2011-05-01

    Full Text Available Abstract Background The systemic vascular response to hypoxia is vasodilation. However, reports suggest that the potent vasoconstrictor endothelin-1 (ET-1 is released from the vasculature during hypoxia. ET-1 is reported to augment superoxide anion generation and may counteract nitric oxide (NO vasodilation. Moreover, ET-1 was proposed to contribute to increased vascular resistance in heart failure by increasing the production of asymmetric dimethylarginine (ADMA. We investigated the role of ET-1, the NO pathway, the potassium channels and radical oxygen species in hypoxia-induced vasodilation of large coronary arteries. Results In prostaglandin F2α (PGF2α, 10 μM-contracted segments with endothelium, gradual lowering of oxygen tension from 95 to 1% O2 resulted in vasodilation. The vasodilation to O2 lowering was rightward shifted in segments without endothelium at all O2 concentrations except at 1% O2. The endothelin receptor antagonist SB217242 (10 μM markedly increased hypoxic dilation despite the free tissue ET-1 concentration in the arterial wall was unchanged in 1% O2 versus 95% O2. Exogenous ET-1 reversed hypoxic dilation in segments with and without endothelium, and the hypoxic arteries showed an increased sensitivity towards ET-1 compared to the normoxic controls. Without affecting basal NO, hypoxia increased NO concentration in PGF2α-contracted arteries, and an NO synthase inhibitor, L-NOARG,(300 μM, NG-nitro-L-Arginine reduced hypoxic vasodilation. NO-induced vasodilation was reduced in endothelin-contracted preparations. Arterial wall ADMA concentrations were unchanged by hypoxia. Blocking of potassium channels with TEA (tetraethylammounium chloride(10 μM inhibited vasodilation to O2 lowering as well as to NO. The superoxide scavenger tiron (10 μM and the putative NADPH oxidase inhibitor apocynin (10 μM leftward shifted concentration-response curves for O2 lowering without changing vasodilation to 1% O2. PEG (polyethylene

  8. Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa

    Energy Technology Data Exchange (ETDEWEB)

    Vander Woude, D.L.; Wagner, P.D.; Shu, S.; Chang, A.E. (Univ. of Michigan, Ann Arbor (USA))

    1991-03-01

    Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy. Interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106 pulmonary metastases. This effect was evident in irradiated mice, indicating that a host response to the interferon alfa was not required. Interferon alfa treatment increased class I major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells. These results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer.

  9. Losartan sensitizes selectively prostate cancer cell to ionizing radiation.

    Science.gov (United States)

    Yazdannejat, H; Hosseinimehr, S J; Ghasemi, A; Pourfallah, T A; Rafiei, A

    2016-01-11

    Losartan is an angiotensin II receptor (AT-II-R) blocker that is widely used by human for blood pressure regulation. Also, it has antitumor property. In this study, we investigated the radiosensitizing effect of losartan on cellular toxicity induced by ionizing radiation on prostate cancer and non-malignant fibroblast cells. Human prostate cancer (DU-145) and human non-malignant fibroblast cells (HFFF2) were treated with losartan at different concentrations (0.5, 1, 10, 50 and 100 µM) and then these cells were exposed to ionizing radiation. The cell proliferation was determined using MTT assay. Our results showed that losartan exhibited antitumor effect on prostate cancer cells; it was reduced cell survival to 66% at concentration 1 µM. Losartan showed an additive killing effect in combination with ionizing radiation on prostate cancer cell. The cell proliferation was reduced to 54% in the prostate cancer cells treated with losartan at concentration 1 µM in combination with ionizing radiation. Losartan did not exhibit any toxicity on HFFF2 cell. This result shows a promising effect of losartan on enhancement of therapeutic effect of ionizing radiation in patients during therapy.

  10. Epigallocatechin-3-gallate Sensitizes Human 786-O Renal Cell Carcinoma Cells to TRAIL-Induced Apoptosis.

    Science.gov (United States)

    Wei, Ruojing; Zhu, Guodong; Jia, Ning; Yang, Wenzeng

    2015-05-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent. Epigallocatechin-3-gallate (EGCG) is a polyphenolic constituent of green tea. In this study, potentiating effect of EGCG on TRAIL-induced apoptosis human renal carcinoma cell line 786-O which is relatively resistant to TRAIL was examined, and the possible mechanism was investigated. Here, we show that co-treatment with EGCG and TRAIL induced significantly more profound apoptosis in 786-O cells. Treatment of 786-O cells with EGCG and TRAIL downregulated c-FLIP, Mcl-1, and Bcl-2 proteins in a caspase-dependent pathway. Moreover, we found that pretreatment with NAC markedly inhibited the expression levels of c-FLIP, Mcl-1, and Bcl-2 downregulated by the combinatory treatment, suggesting that the regulating effect of EGCG on these above apoptosis-relevant molecules was partially mediated by generation of ROS. Taken together, the present study demonstrates that EGCG sensitizes human 786-O renal cell carcinoma cells to TRAIL-induced apoptosis by downregulation of c-FLIP, Mcl-1, and Bcl-2.

  11. Mathematical models of cell phenotype regulation and reprogramming: Make cancer cells sensitive again!

    Science.gov (United States)

    Wooten, David J; Quaranta, Vito

    2017-04-01

    A cell's phenotype is the observable actualization of complex interactions between its genome, epigenome, and local environment. While traditional views in cancer have held that cellular and tumor phenotypes are largely functions of genomic instability, increasing attention has recently been given to epigenetic and microenvironmental influences. Such non-genetic factors allow cancer cells to experience intrinsic diversity and plasticity, and at the tumor level can result in phenotypic heterogeneity and treatment evasion. In 2006, Takahashi and Yamanaka exploited the epigenome's plasticity by "reprogramming" differentiated cells into a pluripotent state by inducing expression of a cocktail of four transcription factors. Recent advances in cancer biology have shown not only that cellular reprogramming is possible for malignant cells, but it may provide a foundation for future therapies. Nevertheless, cell reprogramming experiments are frequently plagued by low efficiency, activation of aberrant transcriptional programs, instability, and often rely on expertise gathered from systems which may not translate directly to cancer. Here, we review a theoretical framework tracing back to Waddington's epigenetic landscape which may be used to derive quantitative and qualitative understanding of cellular reprogramming. Implications for tumor heterogeneity, evolution and adaptation are discussed in the context of designing new treatments to re-sensitize recalcitrant tumors. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby. Copyright © 2017. Published by Elsevier B.V.

  12. Towards Rational Designing of Efficient Sensitizers Based on Thiophene and Infrared Dyes for Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Ahmad Irfan

    2014-01-01

    Full Text Available Geometries, electronic properties, and absorption spectra of the dyes which are a combination of thiophene based dye (THPD and IR dyes (covering IR region; TIRBD1-TIRBD3 were performed using density functional theory (DFT and time dependent density functional theory (TD-DFT, respectively. Different electron donating groups, electron withdrawing groups, and IR dyes have been substituted on THPD to enhance the efficiency. The bond lengths of new designed dyes are almost the same. The lowest unoccupied molecular orbital energies of designed dyes are above the conduction band of TiO2 and the highest occupied molecular orbital energies are below the redox couple revealing that TIRBD1-TIRBD3 would be better sensitizers for dye-sensitized solar cells. The broad spectra and low energy gap also showed that designed materials would be efficient sensitizers.

  13. Distinctions in sensitivity and repair of cells of children with some hereditary diseases

    Energy Technology Data Exchange (ETDEWEB)

    Zasukhina, G.D.; Barashnev, Yu.I.; Vasil' eva, I.M.; Sdirkova, N.I.; Semyachkina, A.N. (AN SSSR, Moscow. Inst. Obshchej Genetiki)

    A study was made of blood cell sensitivity of children with some hereditary diseases, to ..gamma..-radiation and 4-nitro-quinoline-1-oxide. Using the host cell reactivation and chromatographic methods we revealed the increase in the sensitivity to the above mentioned agents and inhibition of the repair function in cells of patients with the following diseases: Marfan's disease, histidinemia, osteogenesis imperfecta, Sylvere-Russelle, Laurence, Franchescetti, and Losch-Nychane syndromes.

  14. Increased sensitivity to interferon-alpha in psoriatic T cells

    DEFF Research Database (Denmark)

    Eriksen, Karsten Wessel; Lovato, Paola; Skov, Lone

    2005-01-01

    Psoriasis is a chronic inflammatory skin disease characterized by abnormal epidermal proliferation. Several studies have shown that skin-infiltrating activated T cells and cytokines play a pivotal role during the initiation and maintenance of the disease. Interferon (IFN)-alpha plays an important...... disease characterized by CD8(+)-infiltrating T cells. In this study, we therefore investigate IFN-alpha signaling in T cells isolated from involved skin of psoriatic patients. We show that psoriatic T cells have increased and prolonged responses to IFN-alpha, on the level of signal transducers...... and activators of transcription (STAT) activation, compared with infiltrating T cells from skin of non-psoriatic donors. Functionally, the increased IFN-alpha signaling leads to an increased binding of STAT4 to the IFN-gamma promotor, IFN-gamma production, and inhibition of T cell growth. In contrast, to STAT...

  15. Increased light harvesting in dye-sensitized solar cells with energy relay dyes

    KAUST Repository

    Hardin, Brian E.

    2009-06-21

    Conventional dye-sensitized solar cells have excellent charge collection efficiencies, high open-circuit voltages and good fill factors. However, dye-sensitized solar cells do not completely absorb all of the photons from the visible and near-infrared domain and consequently have lower short-circuit photocurrent densities than inorganic photovoltaic devices. Here, we present a new design where high-energy photons are absorbed by highly photoluminescent chromophores unattached to the titania and undergo Förster resonant energy transfer to the sensitizing dye. This novel architecture allows for broader spectral absorption, an increase in dye loading, and relaxes the design requirements for the sensitizing dye. We demonstrate a 26% increase in power conversion efficiency when using an energy relay dye (PTCDI) with an organic sensitizing dye (TT1). We estimate the average excitation transfer efficiency in this system to be at least 47%. This system offers a viable pathway to develop more efficient dye-sensitized solar cells.

  16. Klotho sensitive regulation of dendritic cell functions by vitamin E

    OpenAIRE

    Xuan, Nguyen Thi; Trang, Phi Thi Thu; Van Phong, Nguyen; Toan, Nguyen Linh; Trung, Do Minh; Bac, Nguyen Duy; Nguyen, Viet Linh; Hoang, Nguyen Huy; Van Hai, Nong

    2016-01-01

    Background Dendritic cells (DCs) are the most potent professional antigen-presenting cells for naive T cells to link innate and acquired immunity. Klotho, an anti-aging protein, participates in the regulation of Ca2+ dependent migration in DCs. Vitamin E (VitE) is an essential antioxidant to protect cells from damage and elicits its inhibitory effects on NF-?B-mediated inflammatory response. However, the roles of VitE on mouse DC functions and the contribution of klotho to those effects both ...

  17. UCP2 inhibits ROS-mediated apoptosis in A549 under hypoxic conditions.

    Directory of Open Access Journals (Sweden)

    Sanming Deng

    Full Text Available The Crosstalk between a tumor and its hypoxic microenvironment has become increasingly important. However, the exact role of UCP2 function in cancer cells under hypoxia remains unknown. In this study, UCP2 showed anti-apoptotic properties in A549 cells under hypoxic conditions. Over-expression of UCP2 in A549 cells inhibited reactive oxygen species (ROS accumulation (P<0.001 and apoptosis (P<0.001 compared to the controls when the cells were exposed to hypoxia. Moreover, over-expression of UCP2 inhibited the release of cytochrome C and reduced the activation of caspase-9. Conversely, suppression of UCP2 resulted in the ROS generation (P = 0.006, the induction of apoptosis (P<0.001, and the release of cytochrome C from mitochondria to the cytosolic fraction, thus activating caspase-9. These data suggest that over-expression of UCP2 has anti-apoptotic properties by inhibiting ROS-mediated apoptosis in A549 cells under hypoxic conditions.

  18. KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Lin Lin

    Full Text Available Molecular biomarkers to determine the effectiveness of targeted therapies in cancer treatment have been widely adopted in colorectal cancer (CRC, but those to predict chemotherapy sensitivity remain poorly defined. We tested our hypothesis that KRAS mutation may be a predictor of oxaliplatin sensitivity in CRC. KRAS was knocked-down in KRAS-mutant CRC cells (DLD-1(G13D and SW480(G12V by small interfering RNAs (siRNA and overexpressed in KRAS-wild-type CRC cells (COLO320DM by KRAS-mutant vectors to generate paired CRC cells. These paired CRC cells were tested by oxaliplatin, irinotecan and 5FU to determine the change in drug sensitivity by MTT assay and flow cytometry. Reasons for sensitivity alteration were further determined by western blot and real-time quantitative reverse transcriptase polymerase chain reaction (qRT -PCR. In KRAS-wild-type CRC cells (COLO320DM, KRAS overexpression by mutant vectors caused excision repair cross-complementation group 1 (ERCC1 downregulation in protein and mRNA levels, and enhanced oxaliplatin sensitivity. In contrast, in KRAS-mutant CRC cells (DLD-1(G13D and SW480(G12V, KRAS knocked-down by KRAS-siRNA led to ERCC1 upregulation and increased oxaliplatin resistance. The sensitivity of irinotecan and 5FU had not changed in the paired CRC cells. To validate ERCC1 as a predictor of sensitivity for oxaliplatin, ERCC1 was knocked-down by siRNA in KRAS-wild-type CRC cells, which restored oxaliplatin sensitivity. In contrast, ERCC1 was overexpressed by ERCC1-expressing vectors in KRAS-mutant CRC cells, and caused oxaliplatin resistance. Overall, our findings suggest that KRAS mutation is a predictor of oxaliplatin sensitivity in colon cancer cells by the mechanism of ERCC1 downregulation.

  19. Natural Pigments from Plants Used as Sensitizers for TiO2 Based Dye-Sensitized Solar Cells

    Directory of Open Access Journals (Sweden)

    Reena Kushwaha

    2013-01-01

    Full Text Available Four natural pigments, extracted from the leaves of teak (Tectona grandis, tamarind (Tamarindus indica, eucalyptus (Eucalyptus globulus, and the flower of crimson bottle brush (Callistemon citrinus, were used as sensitizers for TiO2 based dye-sensitized solar cells (DSSCs. The dyes have shown absorption in broad range of the visible region (400–700 nm of the solar spectrum and appreciable adsorption onto the semiconductor (TiO2 surface. The DSSCs made using the extracted dyes have shown that the open circuit voltages (Voc varied from 0.430 to 0.610 V and the short circuit photocurrent densities (Jsc ranged from 0.11 to 0.29 mA cm−2. The incident photon-to-current conversion efficiencies (IPCE varied from 12–37%. Among the four dyes studied, the extract obtained from teak has shown the best photosensitization effects in terms of the cell output.

  20. π-Conjugated Donor-Acceptor Systems as Metal-Free Sensitizers for Dye-Sensitized Solar Cell Applications

    Directory of Open Access Journals (Sweden)

    Zakeeruddin S. M.

    2013-03-01

    Full Text Available High extinction coefficients and easily tunable spectral properties of π- conjugated donor-acceptor dyes are of superior advantage for the design of new metalfree organic sensitizers for applications in dye-sensitized solar cells. Ultrafast transient absorption spectroscopy on the femtosecond and nanosecond time scales provided deep insights into the dependence of charge carrier dynamics in fully organic dye/TiO2 systems on i the donor-acceptor distance, ii the π-conjugation length, and iii the coupling to TiO2 by different anchoring groups. Importantly, the observed differences in charge transfer dynamics justify the variations of photovoltaic performances of the dyes as applied in solar cell devices. This leads to the conclusion that the photoconversion efficiencies strongly depend on a delicate interplay between the dyes’ building blocks, i.e. the donor, the π-conjugated spacer and the anchor/acceptor moieties, and may easily be tuned by molecular design.

  1. Natural dye extract of lawsonia inermis seed as photo sensitizer for titanium dioxide based dye sensitized solar cells

    Science.gov (United States)

    Ananth, S.; Vivek, P.; Arumanayagam, T.; Murugakoothan, P.

    2014-07-01

    Natural dye extract of lawsonia inermis seed were used as photo sensitizer to fabricate titanium dioxide nanoparticles based dye sensitized solar cells. Pure titanium dioxide (TiO2) nanoparticles in anatase phase were synthesized by sol-gel technique and pre dye treated TiO2 nanoparticles were synthesized using modified sol-gel technique by mixing lawsone pigment rich natural dye during the synthesis itself. This pre dye treatment with natural dye has yielded colored TiO2 nanoparticles with uniform adsorption of natural dye, reduced agglomeration, less dye aggregation and improved morphology. The pure and pre dye treated TiO2 nanoparticles were subjected to structural, optical, spectral and morphological studies. Dye sensitized solar cells (DSSC) fabricated using the pre dye treated and pure TiO2 nanoparticles sensitized by natural dye extract of lawsonia inermis seed showed a promising solar light to electron conversion efficiency of 1.47% and 1% respectively. The pre dye treated TiO2 based DSSC showed an improved efficiency of 47% when compared to that of conventional DSSC.

  2. β-Functionalized Push-Pull opp-Dibenzoporphyrins as Sensitizers for Dye-Sensitized Solar Cells.

    Science.gov (United States)

    Hu, Yi; Yellappa, Shivaraj; Thomas, Michael B; Jinadasa, R G Waruna; Matus, Alex; Shulman, Max; D'Souza, Francis; Wang, Hong

    2017-10-18

    A novel class of β-functionalized push-pull zinc opp-dibenzoporphyrins were designed, synthesized, and utilized as sensitizers for dye-sensitized solar cells. Spectral, electrochemical, and computational studies were systematically performed to evaluate their spectral coverage, redox behavior, and electronic structures. These porphyrins displayed much broader spectral coverage and more facile oxidation upon extension of the π conjugation. Free-energy calculations and femtosecond transient absorption studies (charge injection rate in the range of 1011  s-1 ) suggested efficient charge injection from the excited singlet state of the porphyrin to the conduction band of TiO2 . The power conversion efficiency (η) of YH3 bearing acrylic acid linkers (η=5.9 %) was close to that of the best ruthenium dye N719 (η=7.4 %) under similar conditions. The superior photovoltaic performance of YH3 was attributed to its higher light-harvesting ability and more favorable electron injection and collection, as supported by electrochemical impedance spectral studies. This work demonstrates the exceptional potential of benzoporphyrins as sensitizers for dye-sensitized solar cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Biomarkers of Hypoxic Ischemic Encephalopathy in Newborns

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2012-11-01

    Full Text Available As neonatal intensive care has evolved, the focus has shifted from improving mortality alone to an effort to improve both mortality and morbidity. The most frequent source of neonatal brain injury occurs as a result of hypoxic-ischemic injury. Hypoxic-ischemic injury occurs in about 2 of 1,000 full-term infants and severe injured infants will have lifetime disabilities and neurodevelopmental delays. Most recently, remarkable efforts toward neuroprotection have been started with the advent of therapeutic hypothermia and a key step in the evolution of neonatal neuroprotection is the discovery of biomarkers that enable the clinician-scientist to screen infants for brain injury, monitor progression of disease, identify injured brain regions, and assess efficacy of neuroprotective clinical trials. Lastly, biomarkers offer great hope identifying when an injury occurred shedding light on the potential pathophysiology and the most effective therapy. In this article, we will review biomarkers of HIE including S100b, neuron specific enolase, umbilical cord IL-6, CK-BB, GFAP, myelin basic protein, UCHL-1, and pNF-H. We hope to contribute to the awareness, validation and clinical use of established as well as novel neonatal brain injury biomarkers.

  4. Photobiological studies on sensitivity to ultraviolet radiation in human cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Moriwaki, K. (Mie Univ., Tsu (Japan). School of Medicine)

    1981-12-01

    The present study dealt with ultraviolet light (UV)-sensitivity and DNA repair or semiconservative DNA synthesis in Cockayne's syndrome (CS) cells in vitro. Homozygous CS cell lines were more UV-sensitive in colony-forming ability than normal human fibroblast cell lines. There was no difference between CS and normal cells in the activity of excision and postreplication repairs following UV-irradiation. The semi-conservative DNA synthesis of CS cells was depressed by UV-irradiation at a rate similar to that of normal cells, but subsequent recovery was reduced. The reduction of this recovery appears to be attributed to an inhibition of the replicon initiation following UV-irradiation. A heterozygous CS cell line was indistinguishable from normal cells. These findings support the possibility that UV-induced chromatin alteration not related to well-known DNA repair processes persists longer in CS cells than in normal cells and consequently prevents replicon initiation.

  5. NATURAL PIGMENT SENSITIZED SOLAR CELLS BASED ON ZnO ...

    African Journals Online (AJOL)

    dye sensitizers many kinds of organic synthetic dyes and natural pigments have been actively studied and tested as .... sintering. The electrode was withdrawn from the dye solution and dried using a stream of dry air by a hair dryer. Oxidized poly(3,4-ethylenedioxythiophene) coated onto ITO was used as a cathode oxidized.

  6. MHC-I modulation due to changes in tumor cell metabolism regulates tumor sensitivity to CTL and NK cells

    Science.gov (United States)

    Catalán, Elena; Charni, Seyma; Jaime, Paula; Aguiló, Juan Ignacio; Enríquez, José Antonio; Naval, Javier; Pardo, Julián; Villalba, Martín; Anel, Alberto

    2015-01-01

    Tumor cells have a tendency to use glucose fermentation to obtain energy instead of mitochondrial oxidative phosphorylation (OXPHOS). We demonstrated that this phenotype correlated with loss of ERK5 expression and with reduced MHC class I expression. Consequently, tumor cells could evade cytotoxic T lymphocyte (CTL)-mediated immune surveillance, but also increase their sensitivity to natural killer (NK) cells. These outcomes were evaluated using two cellular models: leukemic EL4 cells and L929 transformed fibroblasts and their derived ρ° cell lines, which lack mitochondrial DNA. We have also used a L929 cell sub-line that spontaneously lost matrix attachment (L929dt), reminiscent of metastasis generation, that also downregulated MHC-I and ERK5 expression. MHC-I expression is lower in ρ° cells than in the parental cell lines, but they were equally sensitive to CTL. On the contrary, ρ° cells were more sensitive to activated NK cells than parental cells. On the other hand, L929dt cells were resistant to CTL and NK cells, showed reduced viability when forced to perform OXPHOS, and surviving cells increased MHC-I expression and became sensitive to CTL. The present results suggest that when the reduction in MHC-I levels in tumor cells due to glycolytic metabolism is partial, the increase in sensitivity to NK cells seems to predominate. However, when tumor cells completely lose MHC-I expression, the combination of treatments that increase OXPHOS with CTL-mediated immunotherapy could be a promising therapeutic approach. PMID:25949869

  7. Interferon-gamma sensitizes colonic epithelial cell lines to physiological and therapeutic inducers of colonocyte apoptosis.

    LENUS (Irish Health Repository)

    O'Connell, J

    2012-02-03

    Homeostasis in the colonic epithelium is achieved by a continuous cycle of proliferation and apoptosis, in which imbalances are associated with disease. Inflammatory bowel disease (IBD) and colon cancer are associated with either excessive or insufficient apoptosis of colonic epithelial cells, respectively. By using two colonic epithelial cell lines, HT29 and SW620, we investigated how the epithelial cell\\'s sensitivity to apoptosis was regulated by the proinflammatory cytokine interferon-gamma (IFN-gamma). We found that IFN-gamma sensitized HT29 cells, and to a lesser extent SW620, to diverse inducers of apoptosis of physiologic or therapeutic relevance to the colon. These apoptosis inducers included Fas (CD95\\/APO-1) ligand (FasL), short-chain fatty acids, and chemotherapeutic drugs. The extent of IFN-gamma-mediated apoptosis sensitization in these two cell lines correlated well with the degree of IFN-gamma-mediated upregulation of the proapoptotic protease caspase-1. Although IFN-gamma alone effectively sensitized HT29 cells to apoptosis, inclusion of the protein synthesis inhibitor cyclohexamide (CHX) during apoptotic challenge was necessary for maximal sensitization of SW620. The requirement of CHX to sensitize SW620 cells to apoptosis implies a need to inhibit translation of antiapoptotic proteins absent from HT29. In particular, the antiapoptotic protein Bcl-2 was strongly expressed in SW620 cells but absent from HT29. Our results indicate that IFN-gamma increases the sensitivity of colonic epithelial cells to diverse apoptotic stimuli in concert, via upregulation of caspase-1. Our findings implicate caspase-1 and Bcl-2 as important central points of control determining the general sensitivity of colonic epithelial cells to apoptosis.

  8. Flavonoid-induced autophagy in hormone sensitive breast cancer cells.

    Science.gov (United States)

    Brunelli, Elisa; Pinton, Giulia; Bellini, Paolo; Minassi, Alberto; Appendino, Giovanni; Moro, Laura

    2009-09-01

    The activity of 8-prenylapigenin (8-PA) and its 3'-methoxylated analogue isocannflavin B (IsoB) was investigated in estrogen-dependent T47-D and estrogen-independent MDA-MB-231 human breast cancer cell lines. 8-PA showed a biphasic effect on T47-D cell proliferation, while no significant effect was observed on MDA-MB-231 cells. Conversely, IsoB exhibited only an inhibitory effect on T47-D cell proliferation, accompanied by the appearance of an intense intracytoplasmic vacuolization of autophagic origin. Moreover, biochemical analysis showed that IsoB reduced Akt phosphorylation and p21(Cip1) expression in T47-D cells. These data show that the prenylflavone moiety is a versatile platform for the induction and modulation of bioactivity.

  9. Cyanidin-Based Novel Organic Sensitizer for Efficient Dye-Sensitized Solar Cells: DFT/TDDFT Study

    Directory of Open Access Journals (Sweden)

    Kalpana Galappaththi

    2017-01-01

    Full Text Available Cyanidin is widely considered as a potential natural sensitizer in dye-sensitized solar cells due to its promising electron-donating and electron-accepting abilities and cheap availability. We consider modifications of cyanidin structure in order to obtain broader UV-Vis absorption and hence to achieve better performance in DSSC. The modified molecule consists of cyanidin and the benzothiadiazolylbenzoic acid group, where the benzothiadiazolylbenzoic acid group is attached to the cyanidin molecule by replacing one hydroxyl group. The resulting structure was then computationally simulated by using the Spartan’10 software package. The molecular geometries, electronic structures, absorption spectra, and electron injections of the newly designed organic sensitizer were investigated in this work through density functional theory (DFT and time-dependent density functional theory (TDDFT calculations using the Gaussian’09W software package. Furthermore, TDDFT computational calculations were performed on cyanadin and benzothiadiazolylbenzoic acid separately, as reference. The computational studies on the new sensitizer have shown a reduced HOMO-LUMO gap; bathochromic and hyperchromic shifts of absorption spectra range up to near-infrared region revealing its enhanced ability to sensitize DSSCs.

  10. Sensitivity of cancer cells to truncated diphtheria toxin.

    Directory of Open Access Journals (Sweden)

    Yi Zhang

    2010-05-01

    Full Text Available Diphtheria toxin (DT has been utilized as a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to otherwise untreatable neoplasia. DT is an extremely potent toxin for which the entry of a single molecule into a cell can be lethal. DT has been targeted to cancer cells by deleting the cell receptor-binding domain and combining the remaining catalytic portion with targeting proteins that selectively bind to the surface of cancer cells. It has been assumed that "receptorless" DT cannot bind to and kill cells. In the present study, we report that "receptorless" recombinant DT385 is in fact cytotoxic to a variety of cancer cell lines.In vitro cytotoxicity of DT385 was measured by cell proliferation, cell staining and apoptosis assays. For in vivo studies, the chick chorioallantoic membrane (CAM system was used to evaluate the effect of DT385 on angiogenesis. The CAM and mouse model system was used to evaluate the effect of DT385 on HEp3 and Lewis lung carcinoma (LLC tumor growth, respectively.Of 18 human cancer cell lines tested, 15 were affected by DT385 with IC(50 ranging from 0.12-2.8 microM. Furthermore, high concentrations of DT385 failed to affect growth arrested cells. The cellular toxicity of DT385 was due to the inhibition of protein synthesis and induction of apoptosis. In vivo, DT385 diminished angiogenesis and decreased tumor growth in the CAM system, and inhibited the subcutaneous growth of LLC tumors in mice.DT385 possesses anti-angiogenic and anti-tumor activity and may have potential as a therapeutic agent.

  11. Extreme hypoxic conditions induce selective molecular responses and metabolic reset in detached apple fruit

    Directory of Open Access Journals (Sweden)

    Dubravka eCukrov

    2016-02-01

    Full Text Available The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control and hypoxic (0.4 and 0.8 kPa oxygen conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1,000 genes differentially expressed when comparing 0.4 vs 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These

  12. Carbohydrate Supplementation Influences Serum Cytokines after Exercise under Hypoxic Conditions

    Directory of Open Access Journals (Sweden)

    Aline Venticinque Caris

    2016-11-01

    Full Text Available Introduction: Exercise performed at the hypoxia equivalent of an altitude of 4200 m is associated with elevated inflammatory mediators and changes in the Th1/Th2 response. By contrast, supplementation with carbohydrates has an anti-inflammatory effect when exercise is performed under normoxic conditions. The objective of this study was to evaluate the effect of carbohydrate supplementation on cytokines and cellular damage markers after exercise under hypoxic conditions at a simulated altitude of 4200 m. Methods: Seven adult male volunteers who exercised for 60 min at an intensity of 50% VO2Peak were randomly evaluated under three distinct conditions; normoxia, hypoxia and hypoxia + carbohydrate supplementation. Blood samples were collected at rest, at the end of exercise and after 60 min of recovery. To evaluate hypoxia + carbohydrate supplementation, volunteers received a solution of 6% carbohydrate (maltodextrin or a placebo (strawberry-flavored Crystal Light®; Kraft Foods, Northfield, IL, USA every 20 min during exercise and recovery. Statistical analyses comprised analysis of variance, with a one-way ANOVA followed by the Tukey post hoc test with a significance level of p < 0.05. Results: Under normoxic and hypoxic conditions, there was a significant increase in the concentration of IL-6 after exercise and after recovery compared to at rest (p < 0.05, while in the hypoxia + carbohydrate group, there was a significant increase in the concentration of IL-6 and TNF-α after exercise compared to at rest (p < 0.05. Furthermore, under this condition, TNF-α, IL-2 and the balance of IL-2/IL-4 were increased after recovery compared to at rest (p < 0.05. Conclusion: We conclude that carbohydrate supplementation modified the IL-6 and TNF-α serum concentrations and shifted the IL-2/IL-4 balance towards Th1 in response without glycemic, glutaminemia and cell damage effects.

  13. Pluripotent Stem Cell Protein Sox2 Confers Sensitivity to LSD1 Inhibition in Cancer Cells

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    2013-10-01

    Full Text Available Gene amplification of Sox2 at 3q26.33 is a common event in squamous cell carcinomas (SCCs of the lung and esophagus, as well as several other cancers. Here, we show that the expression of LSD1/KDM1 histone demethylase is significantly elevated in Sox2-expressing lung SCCs. LSD1-specific inhibitors selectively impair the growth of Sox2-expressing lung SCCs, but not that of Sox2-negative cells. Sox2 expression is associated with sensitivity to LSD1 inhibition in lung, breast, ovarian, and other carcinoma cells. Inactivation of LSD1 reduces Sox2 expression, promotes G1 cell-cycle arrest, and induces genes for differentiation by selectively modulating the methylation states of histone H3 at lysines 4 (H3K4 and 9 (H3K9. Reduction of Sox2 further suppresses Sox2-dependent lineage-survival oncogenic potential, elevates trimethylation of histone H3 at lysine 27 (H3K27 and enhances growth arrest and cellular differentiation. Our studies suggest that LSD1 serves as a selective epigenetic target for therapy in Sox2-expressing cancers.

  14. RC-IAL cell line: sensitivity of rubella virus grow

    Directory of Open Access Journals (Sweden)

    Figueiredo Cristina A

    2000-01-01

    Full Text Available OBJECTIVE: The rapid growth of the rubella virus in RC-IAL² with development of cytopathic effect, in response to rubella virus infection, is described. For purposes of comparison, the rubella virus RA-27/3 strain was titered simultaneously in the RC-IAL, Vero, SIRC and RK13 cell lines. METHODS: Rubella virus RA-27/3 strain are inoculated in the RC-IAL cell line (rabbit Kidney, Institute Adolfo Lutz. Plates containing 1.5x10(5 cells/ml of RC-IAL line were inoculated with 0.1ml s RA-27/3 strain virus containing 1x 10(4TCID50/0.1ml. A 25% cytopathic effect was observed after 48 hours and 100% after 96 hours. The results obtained were compared to those observed with the SIRC, Vero and RK13 cell lines. Rubella virus was detected by immunohistochemistry. RESULTS: With the results, it was possible to conclude that the RC-IAL cell line is a very good substrate for culturing rubella virus. The cells inoculated with rubella virus were examined by phase contrast microscopy and showed the characteristic rounded, bipolar and multipolar cells. The CPE in RC-IAL was observed in the first 48 hours and the curve of the increased infectivity was practically the same as observed in other cell lines. CONCLUSIONS: These findings are important since this is one the few cell lines described in the literature with a cytopathic effect. So it can be used for antigen preparation and serological testing for the diagnosis of specific rubella antibodies.

  15. Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes

    NARCIS (Netherlands)

    Hockman, D. (Dorit); A.J. Burns (Alan); Schlosser, G. (Gerhard); Gates, K.P. (Keith P.); Jevans, B. (Benjamin); Mongera, A. (Alessandro); S. Fisher (Shannon); Unlu, G. (Gokhan); Knapik, E.W. (Ela W.); Kaufman, C.K. (Charles K.); Mosimann, C. (Christian); L.I. Zon (Leonard); Lancman, J.J. (Joseph J.); Dong, P.D.S. (P. Duc S.); Lickert, H. (Heiko); Tucker, A.S. (Abigail S.); Baker, C.V.H. (Clare V. H.)

    2017-01-01

    textabstractThe evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes – carotid body glomus cells, and ‘pulmonary neuroendocrine cells’ (PNECs) -are obscure. Homology has been proposed between glomus cells, which are neural crest-derived, and the

  16. Synthesis and characterization of Allium cepa L. as photosensitizer of dye-sensitized solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Sutikno, E-mail: smadnasri@yahoo.com [Physics Department, Faculty of Mathematics and Natural Sciences, Semarang State University D7 Building, 2nd Floor, Unnes, Sekaran Campus, Semarang, Indonesia, 50229 (Indonesia); Afrian, Noverdi; Supriadi,; Putra, Ngurah Made Dharma [Faculty of Computer Science, Dian Nuswantoro University Jl. Nakula I No. 5, Semarang (Indonesia)

    2016-04-19

    The synthesis and characterization of Allium cepa L. used as natural pigment for natural dye sensitizer of solar cell has successfully done and anthocyanin is extracted. Anthocynin is color pigment of plant which has characteristic absorption spectrum of photon and excites electrons up to pigment molecules. As the anthocyanin absorbed light increases the excited electrons increase as well. The generated current also increases and it leads to the efficiency increase. The energy conversion efficiency of the cells sensitized with dye of Allium cepa L. was 3,045 x 10{sup −4}%. A simple technique was taken to fabricate dye sensitizer solar cell is spincoating.

  17. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

    Directory of Open Access Journals (Sweden)

    Emara Marwan

    2010-09-01

    Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

  18. Pineal photoreceptor cells are required for maintaining the circadian rhythms of behavioral visual sensitivity in zebrafish.

    Directory of Open Access Journals (Sweden)

    Xinle Li

    Full Text Available In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity.

  19. Pineal Photoreceptor Cells Are Required for Maintaining the Circadian Rhythms of Behavioral Visual Sensitivity in Zebrafish

    Science.gov (United States)

    Li, Xinle; Montgomery, Jake; Cheng, Wesley; Noh, Jung Hyun; Hyde, David R.; Li, Lei

    2012-01-01

    In non-mammalian vertebrates, the pineal gland functions as the central pacemaker that regulates the circadian rhythms of animal behavior and physiology. We generated a transgenic zebrafish line [Tg(Gnat2:gal4-VP16/UAS:nfsB-mCherry)] in which the E. coli nitroreductase is expressed in pineal photoreceptor cells. In developing embryos and young adults, the transgene is expressed in both retinal and pineal photoreceptor cells. During aging, the expression of the transgene in retinal photoreceptor cells gradually diminishes. By 8 months of age, the Gnat2 promoter-driven nitroreductase is no longer expressed in retinal photoreceptor cells, but its expression in pineal photoreceptor cells persists. This provides a tool for selective ablation of pineal photoreceptor cells, i.e., by treatments with metronidazole. In the absence of pineal photoreceptor cells, the behavioral visual sensitivity of the fish remains unchanged; however, the circadian rhythms of rod and cone sensitivity are diminished. Brief light exposures restore the circadian rhythms of behavioral visual sensitivity. Together, the data suggest that retinal photoreceptor cells respond to environmental cues and are capable of entraining the circadian rhythms of visual sensitivity; however, they are insufficient for maintaining the rhythms. Cellular signals from the pineal photoreceptor cells may be required for maintaining the circadian rhythms of visual sensitivity. PMID:22815753

  20. Changes in subcutaneous fat cell volume and insulin sensitivity after weight loss.

    Science.gov (United States)

    Andersson, Daniel P; Eriksson Hogling, Daniel; Thorell, Anders; Toft, Eva; Qvisth, Veronica; Näslund, Erik; Thörne, Anders; Wirén, Mikael; Löfgren, Patrik; Hoffstedt, Johan; Dahlman, Ingrid; Mejhert, Niklas; Rydén, Mikael; Arner, Erik; Arner, Peter

    2014-07-01

    Large subcutaneous fat cells associate with insulin resistance and high risk of developing type 2 diabetes. We investigated if changes in fat cell volume and fat mass correlate with improvements in the metabolic risk profile after bariatric surgery in obese patients. Fat cell volume and number were measured in abdominal subcutaneous adipose tissue in 62 obese women before and 2 years after Roux-en-Y gastric bypass (RYGB). Regional body fat mass by dual-energy X-ray absorptiometry; insulin sensitivity by hyperinsulinemic-euglycemic clamp; and plasma glucose, insulin, and lipid profile were assessed. RYGB decreased body weight by 33%, which was accompanied by decreased adipocyte volume but not number. Fat mass in the measured regions decreased and all metabolic parameters were improved after RYGB (P fat cell size correlated strongly with improved insulin sensitivity (P = 0.0057), regional changes in fat mass did not, except for a weak correlation between changes in visceral fat mass and insulin sensitivity and triglycerides. The curve-linear relationship between fat cell size and fat mass was altered after weight loss (P = 0.03). After bariatric surgery in obese women, a reduction in subcutaneous fat cell volume associates more strongly with improvement of insulin sensitivity than fat mass reduction per se. An altered relationship between adipocyte size and fat mass may be important for improving insulin sensitivity after weight loss. Fat cell size reduction could constitute a target to improve insulin sensitivity. © 2014 by the American Diabetes Association.

  1. Development of Gravity Sensitive Plant Cells (Ceratodon) in Microgravity

    Science.gov (United States)

    Sack, Fred D.

    1999-01-01

    Protonemata of the moss Ceratodon are tip-growing cells that grow up in the dark. This cell type is unique compared to cells in almost any other organism, since the growth of the plant cell itself is completely oriented by gravity. Thus, both the processes of gravity sensing and the gravity response occur in the same cell. Gravity sensing appears to rely upon amyloplasts (starch-filled plastids) that sediment. This sedimentation occurs in specific zones and plastid zonation is complex with respect to plastid morphology, distribution, and gravity. Microtubules restrict the extent of plastid sedimentation (i.e., they are load-bearing). Light also is important since apical cells have a phytochrome-based positive phototropism, light quality influences plastid zonation and sedimentation (photomorphogenesis), and red light suppresses gravitropism at higher but not lower light intensities. Many of these processes were examined in a 16 day spaceflight experiment, "SPM-A" space moss" or "SPAM)) on STS-87 that landed in December, 1997. The work described here involves the definition of a second flight experiment that builds upon the data and questions arising from STS-87. Effort was directed towards further definition of an experiment for the Shuttle (dubbed "SOS" for "Son of SPAM"). Our current target is STS 107 that is scheduled to fly in January 2001. This definition addressed two goals of the STS107 experiment. The goals of the current experiment were to determine whether the cytoskeleton plays a role in maintaining and generating an apical (non-random) plastid distribution in microgravity and to determine the development and extent of clockwise spiral tip-growth in microgravity.

  2. Quantum dots sensitized graphene: In situ growth and application in photoelectrochemical cells

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Haixin; Lv, Xiaojun; Zhang, Hao; Li, Jinghong [Department of Chemistry, Tsinghua University, Beijing 100084 (China)

    2010-03-15

    A novel photoelectrochemical cells (PEC) based on quantum dots (QDs) sensitized graphene for light harvesting and energy conversion was described in this work. QDs sensitized graphene was prepared by in situ growth of QDs on noncovalently functionalized graphene. QDs sensitized graphene photoelectrodes showed enhanced photocurrent generation capability and incident photon-to-electron conversion efficiency (IPCE) at visible light, and could also be an efficient platform for other optoelectronic applications. (author)

  3. Characterizations of natural dye from garcinia mangostana with graphene oxide (GO) as sensitizer in dye-sensitizer solar cells

    Science.gov (United States)

    Ismail, Mashasriyah; Ludin, Norasikin Ahmad; Hamid, Norul Hisham; Ibrahim, Mohd Adib; Zulfakar, Mohd Syafiq; Mohamed, Norani Muti; Sopian, Kamaruzzaman

    2017-05-01

    Usage of natural product in improvement of dye-sensitized solar cell (DSSC) have been look upon in research field. There is numerous different type of nature product was used as natural dye but the performance of DSSC with natural dye are low efficiency compare to DSSC with Ruthenium (II) dye due to low anchoring strength between dye molecule with TiO2 surface. This paper is about an experiment DSSC device with sensitizer of Mangosteen with Graphene Oxide as catalyst. The highest device efficiency with graphene oxide (GO) concentration of 0.50 mg/ml obtained in this experiment is 0.40% with short-circuit current density (Jsc) = 1.00 mA/cm2, open circuit voltage (Voc) = 0.61 V and fill factor(FF) = 65.72%. It shows that GO helped to increase device performance by increase the ability of sensitizer absorbed onto TiO2 and adding more passageway for carriers movement between TiO2 surface and dye sensitizer.

  4. The Role of Physical Techniques on the Preparation of Photoanodes for Dye Sensitized Solar Cells

    National Research Council Canada - National Science Library

    Ahmadi, Shideh; Asim, Nilofar; Alghoul, M. A; Hammadi, F. Y; Saeedfar, Kasra; Ludin, N. A; Zaidi, Saleem H; Sopian, K

    2014-01-01

      Dye sensitized solar cells (DSSCs) have attracted numerous research, especially in the context of enhancing their efficiency and durability, due to the low-cost and environmentally friendly nature of photovoltaic (PV) technology...

  5. Electrical characterization of dye sensitized nano solar cell using natural pomegranate juice as photosensitizer

    Science.gov (United States)

    Adithi, U.; Thomas, Sara; Uma, V.; Pradeep, N.

    2013-02-01

    This paper shows Electrical characterization of Dye Sensitized Solar Cell using natural dye, extracted from the pomegranate as a photo sensitizer and ZnO nanoparticles as semiconductor. The constituents of fabricated dye sensitized solar cell were working electrode, dye, electrolyte and counter electrode. ZnO nanoparticles were synthesized and used as semiconductor in working electrode. Carbon soot was used as counter electrode. The resistance of ZnO film on ITO film was found out. There was an increase in the resistance of the film and film changes from conducting to semiconducting. Photovoltaic parameters of the fabricated cell like Short circuit current, open circuit voltage, Fill factor and Efficiency were found out. This paper shows that usage of natural dyes like pomegranate juice as sensitizer enables faster and simpler production of cheaper and environmental friendly solar cell.

  6. Carbon Nanotubes Counter Electrode for Dye-Sensitized Solar Cells Application

    National Research Council Canada - National Science Library

    A. Drygała; L. A. Dobrzański; M. Szindler; M. Prokopiuk vel Prokopowicz; M. Pawlyta; K. Lukaszkowicz

    2016-01-01

    The influence of the carbon nanotubes counter electrode deposited on the FTO glass substrates on the structure and optoelectrical properties of dye-sensitized solar cells counter electrode (CE) was analysed...

  7. miR-200/ZEB axis regulates sensitivity to nintedanib in non-small cell lung cancer cells

    OpenAIRE

    Nishijima, Nobuhiko; SEIKE, MASAHIRO; Soeno, Chie; CHIBA, MIKA; Miyanaga, Akihiko; Noro, Rintaro; SUGANO, TEPPEI; Matsumoto , Masaru; Kubota, Kaoru; Gemma, Akihiko

    2016-01-01

    Nintedanib (BIBF1120) is a multi-targeted angiokinase inhibitor and has been evaluated in idiopathic pulmonary fibrosis and advanced non-small cell lung cancer (NSCLC) patients in clinical studies. In the present study, we evaluated the antitumor effects of nintedanib in 16 NSCLC cell lines and tried to identify microRNA (miRNA) associated with sensitivity to nintedanib. No correlations between FGFR, PDGFR and VEGFR family activation and sensitivity to nintedanib were found. The difference in...

  8. Hypoxic tolerance in air-breathing invertebrates.

    Science.gov (United States)

    Schmitz, Anke; Harrison, Jon F

    2004-08-12

    Terrestrial invertebrates experience hypoxia in many habitats and under a variety of physiological conditions. Some groups (at least insects) are much more capable of recovery from anoxia than most vertebrates, but there is still a tremendous unexplained variation in hypoxia/anoxia tolerance among terrestrial invertebrates. Crustaceans and arachnids may be less often confronted with hypoxic environments than insects and myriapods and also seem to be less hypoxia/anoxia tolerant. Tracheated groups, especially those that are able to ventilate their tracheal system like many insects, cope with lower critical PO2 than nontracheated groups. Modulation of oxygen carrier proteins is normally not important in hypoxia resistance. Recent application of genetic and cellular tools are revealing that many of the same pathways documented for mammals (e.g. HIF, nitric oxide) function to regulate morphological and biochemical responses to hypoxia/anoxia in insects.

  9. Heart rate response to hypoxic exercise

    DEFF Research Database (Denmark)

    Lundby, C; Møller, P; Kanstrup, I L

    2001-01-01

    This study examined the effects of dopamine D(2)-receptor blockade on the early decrease in maximal heart rate at high altitude (4559 m). We also attempted to clarify the time-dependent component of this reduction and the extent to which it is reversed by oxygen breathing. Twelve subjects performed...... progressively decreased the maximal heart rate from day 1 and onwards; also, hypoxia by itself increased plasma noradrenaline levels after maximal exercise. Domperidone further increased maximal noradrenaline concentrations, but had no effect on maximal heart rate. On each study day at altitude, oxygen...... breathing completely reversed the decrease in maximal heart rate to values not different from those at sea level. In conclusion, dopamine D(2)-receptor blockade with domperidone demonstrates that hypoxic exercise in humans activates D(2)-receptors, resulting in a decrease in circulating levels...

  10. Targeted Inhibition of the miR-199a/214 Cluster by CRISPR Interference Augments the Tumor Tropism of Human Induced Pluripotent Stem Cell-Derived Neural Stem Cells under Hypoxic Condition

    Directory of Open Access Journals (Sweden)

    Yumei Luo

    2016-01-01

    Full Text Available The human induced pluripotent stem cell (hiPSC provides a breakthrough approach that helps overcoming ethical and allergenic challenges posed in application of neural stem cells (NSCs in targeted cancer gene therapy. However, the tumor-tropic capacity of hiPSC-derived NSCs (hiPS-NSCs still has much room to improve. Here we attempted to promote the tumor tropism of hiPS-NSCs by manipulating the activity of endogenous miR-199a/214 cluster that is involved in regulation of hypoxia-stimulated cell migration. We first developed a baculovirus-delivered CRISPR interference (CRISPRi system that sterically blocked the E-box element in the promoter of the miR-199a/214 cluster with an RNA-guided catalytically dead Cas9 (dCas9. We then applied this CRISPRi system to hiPS-NSCs and successfully suppressed the expression of miR-199a-5p, miR-199a-3p, and miR-214 in the microRNA gene cluster. Meanwhile, the expression levels of their targets related to regulation of hypoxia-stimulated cell migration, such as HIF1A, MET, and MAPK1, were upregulated. Further migration assays demonstrated that the targeted inhibition of the miR-199a/214 cluster significantly enhanced the tumor tropism of hiPS-NSCs both in vitro and in vivo. These findings suggest a novel application of CRISPRi in NSC-based tumor-targeted gene therapy.

  11. Measuring beta-cell function relative to insulin sensitivity in youth: Does the hyperglycemic clamp suffice?

    Science.gov (United States)

    To compare beta-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcD...

  12. A novel diphenylphosphinic acid coadsorbent for dye-sensitized solar cell

    Energy Technology Data Exchange (ETDEWEB)

    Shen Heping [State Key Laboratory of New Ceramics and Fine Processing, Department of Material Science and Engineering, Tsinghua University, Beijing 100084 (China); Lin Hong, E-mail: hong-lin@tsinghua.edu.c [State Key Laboratory of New Ceramics and Fine Processing, Department of Material Science and Engineering, Tsinghua University, Beijing 100084 (China); Liu Yizhu [State Key Laboratory of New Ceramics and Fine Processing, Department of Material Science and Engineering, Tsinghua University, Beijing 100084 (China); Li Xin [Pen-Tung Sah Micro-Nano Technology Research Center, Xiamen University, Xiamen 361005, Fujian (China); Zhang Jing [State Key Laboratory of New Ceramics and Fine Processing, Department of Material Science and Engineering, Tsinghua University, Beijing 100084 (China); Wang Ning [State Key Lab of Electronic Thin Films and Integrated Devices, University of Electronic Science and Technology of China, Chengdu, 610054 (China); Li Jianbao [State Key Laboratory of New Ceramics and Fine Processing, Department of Material Science and Engineering, Tsinghua University, Beijing 100084 (China)

    2011-02-01

    Diphenylphosphinic acid (DPPA) was adopted as a novel coadsorbent in dye-sensitized solar cells (DSCs) based on nanocrystalline TiO{sub 2} sensitized with N719 dye [(Bu{sub 4}N){sub 2}[Ru(dcbpyH){sub 2}(NCS){sub 2}

  13. Titanium dioxide nanoparticles biosynthesis for dye sensitized solar cells application: review

    CSIR Research Space (South Africa)

    Mbonyiryivuze, A

    2015-08-01

    Full Text Available -sensitized solar cells, in air and water purification, due to their potential oxidation strength, high photo stability and non-toxicity. Till now, titanium dioxide (TiO2) is the cornerstone semiconductors for dye-sensitized (DSSC) nanostructured electrodes for dye...

  14. A plasmonic nanosensor with inverse sensitivity for circulating cell-free DNA quantification.

    Science.gov (United States)

    Pallares, Roger M; Kong, Say Li; Ru, Tan Hui; Thanh, Nguyên T K; Lu, Yi; Su, Xiaodi

    2015-10-04

    A plasmonic nanosensor (using gold nanorods) with inverse sensitivity is presented for circulating cell-free DNA quantification. The inverse sensitivity (i.e. the lower the analyte concentration, the higher the response intensity) is achieved by the unusual DNA concentration-dependent gold nanorod aggregation. This assay method can adjust the dynamic range by controlling the concentration of nanoparticles in solution.

  15. Pancreatic beta-cell lipotoxicity induced by overexpression of hormone-sensitive lipase

    DEFF Research Database (Denmark)

    Winzell, Maria Sörhede; Svensson, Håkan; Enerbäck, Sven

    2003-01-01

    Lipid perturbations associated with triglyceride overstorage in beta-cells impair insulin secretion, a process termed lipotoxicity. To assess the role of hormone-sensitive lipase, which is expressed and enzymatically active in beta-cells, in the development of lipotoxicity, we generated transgenic...... results highlight the importance of mobilization of the islet triglyceride pool in the development of beta-cell lipotoxicity. We propose that hormone-sensitive lipase is involved in mediating beta-cell lipotoxicity by providing ligands for peroxisome proliferator-activated receptors and other lipid...

  16. Fabrication of dye-sensitized solar cells with multilayer photoanodes ...

    Indian Academy of Sciences (India)

    The highest efficiency of 6.5% was achieved for a cell with a photoanodecomposed of one transparent sub-layer of hydrothermally grown TiO 2 NCs and two over-layers of P25 NPs. Higher energy conversion efficiencies were also attainable using two transparent sub-layers of hydrothermally grown TiO 2 NCs. In this case ...

  17. Photoelectrochemical solar cells based on dye-sensitization of ...

    African Journals Online (AJOL)

    Hence, we investigated the photoelectrochemical properties of mesoporous colloidal anatase films in connection with their potential application in liquid junction photovoltaic cells. A respectable light to electric energy conversion efficiency of about 9.5% in 9 mW/cm2 (∼ 1/10 Sun) was obtained. In comparison (a Isc = 2.2 ...

  18. Ag nanoparticles sensitize IR-induced killing of cancer cells

    National Research Council Canada - National Science Library

    Xu, Ruizhi; Ma, Jun; Sun, Xinchen; Chen, Zhongping; Jiang, Xiaoli; Guo, Zhirui; Huang, Lan; Li, Yang; Wang, Meng; Wang, Changling; Liu, Jiwei; Fan, Xu; Gu, Jiayu; Chen, Xi; Zhang, Yu; Gu, Ning

    2009-01-01

    ... often requires the administration of nanoparticles into a cell culture system or into living organisms . It should be noted, however, that under such conditions nanopaticles are known to adsorb proteins from the biological system, and the resulting heterogeneity in surface proteins may in turn affect the biological effects of nanomaterials . ...

  19. Sensitivity to fuel diesel oil and cell wall structure of some Scenedesmus (Chlorococcales strains

    Directory of Open Access Journals (Sweden)

    Zbigniew Tukaj

    2014-01-01

    Full Text Available Sensitivity of three Scenedesmus strains exposed to aqueous fuel-oil extract (AFOE is strongly strain-dependent S. quadricauda is the most resistant, S. armatus moderately tolerant whereas the most sensitive appears to be S. microspina. The sensitivity of tested species increases parallel with decreasing of cell size and cell number in coenobium. The values of the cell surface/cell volumes ratios only partly explain the above relationships. Electron microscope investigations reveal that the sensitivity may depend on cell wall structure of the strains. Cell wall of all here investigated strains is built of two layers: the inner so-called cellulosic layer and the outer one showing a three-laminar structure (TLS. The latter contains an acetolysis-resistant biopolymer (ARB. These two layers are similar in thickness in the three strains tested, but the surface of Scenedesmus is covered with various epistructures that are characteristic of strains. Some of them as the tightly fitting warty layer of S. armatus and especially the loosely fitting reticulate layer of S. quadricauda may contribute to lower permeability of cell wall. The structure of the rosettes also appears to be correlated with the sensitivity of strains. Presence of invaginations of plasmalemma in areas under rosettes indicates their role in transport processes inside/outside the cells.

  20. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

    Science.gov (United States)

    Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

    2014-04-01

    As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

  1. Telomerase antagonist imetelstat increases radiation sensitivity in esophageal squamous cell carcinoma.

    Science.gov (United States)

    Wu, Xuping; Zhang, Jing; Yang, Sijun; Kuang, Zhihui; Tan, Guolei; Yang, Gang; Wei, Qichun; Guo, Zhigang

    2017-02-21

    The morbidity and mortality of esophageal cancer is one of the highest around the world and the principal therapeutic method is radiation. Thus, searching for sensitizers with lower toxicity and higher efficiency to improve the efficacy of radiation therapy is critical essential. Our research group has previously reported that imetelstat, the thio-phosphoramidate oligonucleotide inhibitor of telomerase, can decrease cell proliferation and colony formation ability as well as increase DNA breaks induced by radiation in esophageal cancer cells. Further study in this project showed that imetelstat significantly sensitized esophageal cancer cells to radiation in vitro. Later study showed that imetelstat leads to increased cell apoptosis. We also measured the expression level of several DNA repair and apoptosis signaling proteins. pS345 CHK1, γ-H2AX, p53 and caspase3 expression were up-regulated in imetelstat treated cells, identifying these factors as molecular markers. Mouse in vivo model using imetelstat at clinically achievable concentrations and fractionated irradiation scheme yielded results demonstrating radiosensitization effect. Finally, TUNEL assay, caspase 3 and Ki67 staining in tumor tissue proved that imetelstat sensitized esophageal cancer to radiation in vivo through promoting cell apoptosis and inhibiting cell proliferation. Our study supported imetelstat increase radiation sensitivity of esophageal squamous cell carcinoma through inducing cell apoptosis and the specific inhibitor of telomerase might serve as a potential novel therapeutic tool for esophageal squamous cell carcinoma therapy.

  2. Natural Compounds Regulate Glycolysis in Hypoxic Tumor Microenvironment

    Directory of Open Access Journals (Sweden)

    Jian-Li Gao

    2015-01-01

    Full Text Available In the early twentieth century, Otto Heinrich Warburg described an elevated rate of glycolysis occurring in cancer cells, even in the presence of atmospheric oxygen (the Warburg effect. Recently it became a therapeutically interesting strategy and is considered as an emerging hallmark of cancer. Hypoxia inducible factor-1 (HIF-1 is one of the key transcription factors that play major roles in tumor glycolysis and could directly trigger Warburg effect. Thus, how to inhibit HIF-1-depended Warburg effect to assist the cancer therapy is becoming a hot issue in cancer research. In fact, HIF-1 upregulates the glucose transporters (GLUT and induces the expression of glycolytic enzymes, such as hexokinase, pyruvate kinase, and lactate dehydrogenase. So small molecules of natural origin used as GLUT, hexokinase, or pyruvate kinase isoform M2 inhibitors could represent a major challenge in the field of cancer treatment. These compounds aim to suppress tumor hypoxia induced glycolysis process to suppress the cell energy metabolism or enhance the susceptibility of tumor cells to radio- and chemotherapy. In this review, we highlight the role of natural compounds in regulating tumor glycolysis, with a main focus on the glycolysis under hypoxic tumor microenvironment.

  3. Global analysis of sensitivity of bioretention cell design elements to hydrologic performance

    Directory of Open Access Journals (Sweden)

    Yan-wei Sun

    2011-09-01

    Full Text Available Analysis of sensitivity of bioretention cell design elements to their hydrologic performances is meaningful in offering theoretical guidelines for proper design. Hydrologic performance of bioretention cells was facilitated with consideration of four metrics: the overflow ratio, groundwater recharge ratio, ponding time, and runoff coefficients. The storm water management model (SWMM and the bioretention infiltration model RECARGA were applied to generating runoff and outflow time series for calculation of hydrologic performance metrics. Using a parking lot to build a bioretention cell, as an example, the Morris method was used to conduct global sensitivity analysis for two groups of bioretention samples, one without underdrain and the other with underdrain. Results show that the surface area is the most sensitive element to most of the hydrologic metrics, while the gravel depth is the least sensitive element whether bioretention cells are installed with underdrain or not. The saturated infiltration rate of planting soil and the saturated infiltration rate of native soil are the other two most sensitive elements for bioretention cells without underdrain, while the saturated infiltration rate of native soil and underdrain size are the two most sensitive design elements for bioretention cells with underdrain.

  4. Skin sensitizers differentially regulate signaling pathways in MUTZ-3 cells in relation to their individual potency.

    Science.gov (United States)

    Albrekt, Ann-Sofie; Johansson, Henrik; Börje, Anna; Borrebaeck, Carl; Lindstedt, Malin

    2014-02-11

    Due to the recent European legislations posing a ban of animal tests for safety assessment within the cosmetic industry, development of in vitro alternatives for assessment of skin sensitization is highly prioritized. To date, proposed in vitro assays are mainly based on single biomarkers, which so far have not been able to classify and stratify chemicals into subgroups, related to risk or potency. Recently, we presented the Genomic Allergen Rapid Detection (GARD) assay for assessment of chemical sensitizers. In this paper, we show how the genome wide readout of GARD can be expanded and used to identify differentially regulated pathways relating to individual chemical sensitizers. In this study, we investigated the mechanisms of action of a range of skin sensitizers through pathway identification, pathway classification and transcription factor analysis and related this to the reactive mechanisms and potency of the sensitizing agents. By transcriptional profiling of chemically stimulated MUTZ-3 cells, 33 canonical pathways intimately involved in sensitization to chemical substances were identified. The results showed that metabolic processes, cell cycling and oxidative stress responses are the key events activated during skin sensitization, and that these functions are engaged differently depending on the reactivity mechanisms of the sensitizing agent. Furthermore, the results indicate that the chemical reactivity groups seem to gradually engage more pathways and more molecules in each pathway with increasing sensitizing potency of the chemical used for stimulation. Also, a switch in gene regulation from up to down regulation, with increasing potency, was seen both in genes involved in metabolic functions and cell cycling. These observed pathway patterns were clearly reflected in the regulatory elements identified to drive these processes, where 33 regulatory elements have been proposed for further analysis. This study demonstrates that functional analysis of

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  12. Novel hydrophobic ionic liquids electrolyte based on cyclic sulfonium used in dye-sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Lei; Pan, Xu; Wang, Meng; Zhang, Changneng; Fang, Xiaqin; Chen, Shuanghong; Dai, Songyuan [Key Lab of Novel Thin Film Solar Cells, Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei, Anhui 230031 (China)

    2011-01-15

    A novel series of hydrophobic room temperature ionic liquids based on six cyclic sulfonium cations were first time synthesized and applied in dye-sensitized solar cells as pure solvents for electrolyte system. The chronoamperograms result showed that the length of substituent on sulfonium cations could inhibit the I{sub 3}{sup -} diffusion and the five-ring structure of sulfonium was benefit for fast triiodide ion diffusion. The electrochemical impendence spectra measurement of dye-sensitized solar cells with these ionic liquid electrolytes was carried out and the result indicated that the cations' structure had indeed influence on the cells' performance especially for the fill factor, which was further proved by the measurement result of I-V curves of these dye-sensitized solar cells. The conclusion was obtained that the electron exchange reaction on Pt counter electrode/electrolyte interface dominated the cells' performance for these ionic liquid electrolyte-based DSCs. (author)

  13. Post-hypoxic Myoclonus: Current Concepts, Neurophysiology, and Treatment.

    Science.gov (United States)

    Gupta, Harsh V; Caviness, John N

    2016-01-01

    Myoclonus may occur after hypoxia. In 1963, Lance and Adams described persistent myoclonus with other features after hypoxia. However, myoclonus occurring immediately after hypoxia may demonstrate different syndromic features from classic Lance-Adams syndrome (LAS). The aim of this review is to provide up-to-date information about the spectrum of myoclonus occurring after hypoxia with emphasis on neurophysiological features. A literature search was performed on PubMed database from 1960 to 2015. The following search terms were used: "myoclonus," "post anoxic myoclonus," "post hypoxic myoclonus," and "Lance Adams syndrome." The articles describing clinical features, neurophysiology, management, and prognosis of post-hypoxic myoclonus cases were included for review. Several reports in the literature were separated clinically into "acute post-hypoxic myoclonus," which occurred within hours of severe hypoxia, and "chronic post-hypoxic myoclonus," which occurred with some recovery of mental status as the LAS. Acute post-hypoxic myoclonus was generalized in the setting of coma. Chronic post-hypoxic myoclonus presented as multifocal cortical action myoclonus that was significantly disabling. There was overlap of neurophysiological findings for these two syndromes but also different features. Treatment options for these two distinct clinical-neurophysiologic post-hypoxic myoclonus syndromes were approached differently. The review of clinical and neurophysiological findings suggests that myoclonus after hypoxia manifests in one or a combination of distinct syndromes: acute and/or chronic myoclonus. The mechanism of post-hypoxic myoclonus may arise either from cortical and/or subcortical structures. More research is needed to clarify mechanisms and treatment of post-hypoxic myoclonus.

  14. Efficiency Investigation of Dye-Sensitized Solar Cells Based on the Zinc Oxide Nanowires

    OpenAIRE

    Ahmad Afifi; Mohammad Kazem Tabatabaei

    2014-01-01

    In this paper, we synthesized ZnO nanowires in dye sensitized solar cells. The nanowires have been fabricated using fast-microwave-hydrothermal process.We verify the effects of different lengths of ZnO nanowires on efficiency and absorptionofdye sensitized solar cells. J–V curves of the fabricated ZnO nanowire-based mercurochrome-sensitized solar cellsindicated that the short-circuit current density wouldincrease with increasing the length of nanowires.We also fabricate more efficient N719-se...

  15. Scintigraphic imaging of focal hypoxic tissue: development and clinical applications of 123I-IAZA

    Directory of Open Access Journals (Sweden)

    Leonard I. Wiebe

    2002-09-01

    Full Text Available Affected tissues in a number of diseases, including cancer, stroke, cardiac infarction and diabetes, develop focal tissue hypoxia during their progression. The presence of hypoxic tissue may make the disease refractory to therapy, as in the case of solid tumor therapy using low LET ionizing radiation. In other pathologies, the detection of viable but hypoxic tissues may serve as a prodromal indicator of developing disease (e.g. diabetes,or as a prognostic indicator for management of the disease (e.g. stroke. Over the past two decades, a number of hypoxia radioimaging agents have been developed and tested clinically. Of these, 18F-Fmiso and 123I-IAZA are the most widely used radiotracers for PET and SPECT/planar imaging, respectively. IAZA and Fmiso are a 2-nitroimidazoles that chemically bind to subcellular components of viable hypoxic tissues. They sensitize hypoxic tumour to the killing effects of ionizing radiation via mechanisms that mimic the radiosensitizing effects of oxygen, and are therefore called oxygen mimetics. The oxygen mimetic effect is attributable in large part to the covalent binding of reductively-activated nitroimidazole intermediates to critical cellular macromolecules. Nitroimidazoles labelled with gamma-emitting radionuclides (e.g. 18F-Fmiso and 123I-IAZA have been used as scintigraphic markers of tumour hypoxia, based on the need to identify radioresistant hypoxic tumour cells as part of the radiotherapy planning process. Broader interest in non-invasive, imaging-based identification of focal hypoxia in a number of diseases has extended hypoxia studies to include peripheral vascular disease associated with diabetes, rheumatoid arthritis, stroke, myocardial ischaemia, brain trauma and oxidative stress. In this review, the current status of hypoxia-selective studies with 123I-IAZA , an experimental diagnostic radiopharmaceutical, is reviewed with respect to its pre-clinical development and clinical applications.Os tecidos

  16. HPV-associated p16-expression and response to hypoxic modification of radiotherapy in head and neck cancer

    DEFF Research Database (Denmark)

    Lassen, Pernille; Eriksen, Jesper Grau; Hamilton-Dutoit, Stephen

    2010-01-01

    BACKGROUND: HPV/p16-positive head and neck cancers (HNSCC) show superior response to radiotherapy, compared with virus-negative tumours. Tumour hypoxia induces radioresistance and the randomised DAHANCA 5 trial found that the hypoxic cell radiosensitiser nimorazole significantly improved...

  17. High sensitivity plasmonic biosensor based on nanoimprinted quasi 3D nanosquares for cell detection.

    Science.gov (United States)

    Zhu, Shuyan; Li, Hualin; Yang, Mengsu; Pang, Stella W

    2016-07-22

    Quasi three-dimensional (3D) plasmonic nanostructures consisting of Au nanosquares on top of SU-8 nanopillars and Au nanoholes on the bottom were developed and fabricated using nanoimprint lithography with simultaneous thermal and UV exposure. These 3D plasmonic nanostructures were used to detect cell concentration of lung cancer A549 cells, retinal pigment epithelial (RPE) cells, and breast cancer MCF-7 cells. Nanoimprint technology has the advantage of producing high uniformity plasmonic nanostructures for such biosensors. Multiple resonance modes were observed in these quasi 3D plasmonic nanostructures. The hybrid coupling of localized surface plasmon resonances and Fabry-Perot cavity modes in the quasi 3D nanostructures resulted in high sensitivity of 496 nm/refractive index unit. The plasmonic resonance peak wavelength and sensitivity could be tuned by varying the Au thickness. Resonance peak shifts for different cells at the same concentration were distinct due to their different cell area and confluency. The cell concentration detection limit covered a large range of 5 × 10(2) to 1 × 10(7) cells ml(-1) with these new plasmonic nanostructures. They also provide a large resonance peak shift of 51 nm for as little as 0.08 cells mm(-2) of RPE cells for high sensitivity cell detection.

  18. Identification of a novel temperature sensitive promoter in cho cells

    Directory of Open Access Journals (Sweden)

    Hesse Friedemann

    2011-05-01

    Full Text Available Abstract Background The Chinese hamster ovary (CHO expression system is the leading production platform for manufacturing biopharmaceuticals for the treatment of numerous human diseases. Efforts to optimize the production process also include the genetic construct encoding the therapeutic gene. Here we report about the successful identification of an endogenous highly active gene promoter obtained from CHO cells which shows conditionally inducible gene expression at reduced temperature. Results Based on CHO microarray expression data abundantly transcribed genes were selected as potential promoter candidates. The S100a6 (calcyclin and its flanking regions were identified from a genomic CHO-K1 lambda-phage library. Computational analyses showed a predicted TSS, a TATA-box and several TFBSs within the 1.5 kb region upstream the ATG start signal. Various constructs were investigated for promoter activity at 37°C and 33°C in transient luciferase reporter gene assays. Most constructs showed expression levels even higher than the SV40 control and on average a more than two-fold increase at lower temperature. We identified the core promoter sequence (222 bp comprising two SP1 sites and could show a further increase in activity by duplication of this minimal sequence. Conclusions This novel CHO promoter permits conditionally high-level gene expression. Upon a shift to 33°C, a two to three-fold increase of basal productivity (already higher than SV40 promoter is achieved. This property is of particular advantage for a process with reduced expression during initial cell growth followed by the production phase at low temperature with a boost in expression. Additionally, production of toxic proteins becomes feasible, since cell metabolism and gene expression do not directly interfere. The CHO S100a6 promoter can be characterized as cold-shock responsive with the potential for improving process performance of mammalian expression systems.

  19. Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours

    DEFF Research Database (Denmark)

    Rudolph, Christiane; Melau, Cecilie; Nielsen, John E.

    2017-01-01

    BackgroundTesticular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype...... in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. MethodsThe expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2......, were investigated during testis development and in the pathogenesis of TGCT, including germ cell neoplasia in situ (GCNIS). The TGCT-derived cell line NTera2 was differentiated using retinoic acid (10 μM, 6 days) after which MMR protein expression and activity, as well as cisplatin sensitivity, were...

  20. ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib.

    Science.gov (United States)

    Wang, Chen; Jette, Nicholas; Moussienko, Daniel; Bebb, D Gwyn; Lees-Miller, Susan P

    2017-04-01

    The ataxia telangiectasia mutated (ATM) protein kinase plays a central role in the cellular response to DNA damage. Loss or inactivation of both copies of the ATM gene (ATM) leads to ataxia telangiectasia, a devastating childhood condition characterized by neurodegeneration, immune deficiencies, and cancer predisposition. ATM is also absent in approximately 40% of mantle cell lymphomas (MCLs), and we previously showed that MCL cell lines with loss of ATM are sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Next-generation sequencing of patient tumors has revealed that ATM is altered in many human cancers including colorectal, lung, prostate, and breast. Here, we show that the colorectal cancer cell line SK-CO-1 lacks detectable ATM protein expression and is sensitive to the PARP inhibitor olaparib. Similarly, HCT116 colorectal cancer cells with shRNA depletion of ATM are sensitive to olaparib, and depletion of p53 enhances this sensitivity. Moreover, HCT116 cells are sensitive to olaparib in combination with the ATM inhibitor KU55933, and sensitivity is enhanced by deletion of p53. Together our studies suggest that PARP inhibitors may have potential for treating colorectal cancer with ATM dysfunction and/or colorectal cancer with mutation of p53 when combined with an ATM kinase inhibitor. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. β-Functionalized Push-Pull Porphyrin Sensitizers in Dye-Sensitized Solar Cells: Effect of π-Conjugated Spacers.

    Science.gov (United States)

    Ishida, Masatoshi; Hwang, Daesub; Zhang, Zhan; Choi, Yung Ji; Oh, Juwon; Lynch, Vincent M; Kim, Dong Young; Sessler, Jonanthan L; Kim, Dongho

    2015-09-07

    A series of new β-functionalized push-pull-structured porphyrin dyes were synthesized so as to investigate the effect of the π-conjugated spacer on the performance of dye-sensitized solar cells (DSSCs). Suzuki- and Heck-type palladium-catalyzed coupling methodologies were used to obtain various β-functionalized porphyrins and β-benzoic acid (ZnPHn) and β-vinylbenzoic acid (ZnPVn) derivatives from β-borylated porphyrin precursors. Photophysical studies of the resulting porphyrins revealed a clear dependence on the nature of the β linker. In particular, it was found that a β-vinylene linkage perturbs the electronic structure of the porphyrin core; this is less true for a β-phenyl linkage. Theoretical analyses provided support for the intrinsic intramolecular charge-transfer character of the β-functionalized, push-pull porphyrins of this study. The extent of charge transfer depends on the nature of the β-conjugated linkage. The photovoltaic performances of the cells sensitized with β-phenylenevinylene ZnPVn exhibited higher power conversion efficiency values than those bearing β-phenyl linkages (ZnPHn). This was ascribed to differences in light-harvesting efficiency. Furthermore, compared to the use of a standard iodine-based electrolyte, the DSSC performance of cells made from the present porphyrins was improved by more than 1 % upon using a cobalt(II/III)-based electrolyte. Under standard AM 1.5 illumination, the highest efficiency, 8.2 %, was obtained by using cells made from the doubly β-butadiene-linked porphyrin. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Inactivation of SAG E3 ubiquitin ligase blocks embryonic stem cell differentiation and sensitizes leukemia cells to retinoid acid.

    Directory of Open Access Journals (Sweden)

    Mingjia Tan

    Full Text Available Sensitive to Apoptosis Gene (SAG, also known as RBX2 (RING box protein-2, is the RING component of SCF (SKP1, Cullin, and F-box protein E3 ubiquitin ligase. Our previous studies have demonstrated that SAG is an anti-apoptotic protein and an attractive anti-cancer target. We also found recently that Sag knockout sensitized mouse embryonic stem cells (mES to radiation and blocked mES cells to undergo endothelial differentiation. Here, we reported that compared to wild-type mES cells, the Sag(-/- mES cells were much more sensitive to all-trans retinoic acid (RA-induced suppression of cell proliferation and survival. While wild-type mES cells underwent differentiation upon exposure to RA, Sag(-/- mES cells were induced to death via apoptosis instead. The cell fate change, reflected by cellular stiffness, can be detected as early as 12 hrs post RA exposure by AFM (Atomic Force Microscopy. We then extended this novel finding to RA differentiation therapy of leukemia, in which the resistance often develops, by testing our hypothesis that SAG inhibition would sensitize leukemia to RA. Indeed, we found a direct correlation between SAG overexpression and RA resistance in multiple leukemia lines. By using MLN4924, a small molecule inhibitor of NEDD8-Activating Enzyme (NAE, that inactivates SAG-SCF E3 ligase by blocking cullin neddylation, we were able to sensitize two otherwise resistant leukemia cell lines, HL-60 and KG-1 to RA. Mechanistically, RA sensitization by MLN4924 was mediated via enhanced apoptosis, likely through accumulation of pro-apoptotic proteins NOXA and c-JUN, two well-known substrates of SAG-SCF E3 ligase. Taken together, our study provides the proof-of-concept evidence for effective treatment of leukemia patients by RA-MLN4924 combination.

  3. Post-hypoxic recovery of respiratory rhythm generation is gender dependent.

    Directory of Open Access Journals (Sweden)

    Alfredo J Garcia

    Full Text Available The preBötzinger complex (preBötC is a critical neuronal network for the generation of breathing. Lesioning the preBötC abolishes respiration, while when isolated in vitro, the preBötC continues to generate respiratory rhythmic activity. Although several factors influence rhythmogenesis from this network, little is known about how gender may affect preBötC function. This study examines the influence of gender on respiratory activity and in vitro rhythmogenesis from the preBötC. Recordings of respiratory activity from neonatal mice (P10-13 show that sustained post-hypoxic depression occurs with greater frequency in males compared to females. Moreover, extracellular population recordings from the preBötC in neonatal brainstem slices (P10-13 reveal that the time to the first inspiratory burst following reoxygenation (TTFB is significantly delayed in male rhythmogenesis when compared to the female rhythms. Altering activity of ATP sensitive potassium channels (KATP with either the agonist, diazoxide, or the antagonist, tolbutamide, eliminates differences in TTFB. By contrast, glucose supplementation improves post-hypoxic recovery of female but not male rhythmogenesis. We conclude that post-hypoxic recovery of respiration is gender dependent, which is, in part, centrally manifested at the level of the preBötC. Moreover, these findings provide potential insight into the basis of increased male vulnerability in a variety of conditions such as Sudden Infant Death Syndrome (SIDS.

  4. Physiological properties of eel haemoglobin: hypoxic acclimation, phosphate effects and multiplicity.

    Science.gov (United States)

    Weber, R E; Lykkeboe, G; Johansen, K

    1976-02-01

    Unlike the whole body oxygen affinity, which adapts readily to environmental oxygen tensions, haemoglobins, prepared from normoxic- and hypoxic-accimated eels (Anguilla anguilla) show no adaptive changes in oxygenation properties or in multiplicity. Hypoxic acclimation is, howeveer, accompanied by a strong decrease in red cell nucleoside triphosphates, particularly guanosine triphospphate (GTP), which depresses oxygen affinity of the composite and component haemoglobins more strongly than does the concurring ATP. The effects of pH, temperature and salts on the oxygenation properties of the (isolated) haemoglobins are reported, discussed in relation to the varying environmetal conditions encountered by eels, and compared with data on American and Japanese eels (A. rostrata and A. juponica, respectively.

  5. Extraction, preparation and application of pigments from Cordyline fruticosa and Hylocereus polyrhizus as sensitizers for dye-sensitized solar cells

    Science.gov (United States)

    Al-Alwani, Mahmoud A. M.; Ludin, Norasikin A.; Mohamad, Abu Bakar; Kadhum, Abd. Amir H.; Sopian, Kamaruzzaman

    2017-05-01

    Current study employs mixture of chlorophyll-anthocyanin dye extracted from leaves of Cordyline fruticosa as new sensitizers for dye-sensitized solar cell (DSSCs), as well as betalains dye obtained from fruit of Hylocereus polyrhizus. Among ten pigments solvents, the ethanol and methanol extracts revealed higher absorption spectra of pigments extracted from C. fruticosa and H. polyrhizus respectively. A major effect of temperature increase was studied to increase the extraction yield. The results indicated that extraction temperature between 70 and 80 °C exhibited a high dye concentration of each plant than other temperatures. The optimal temperature was around 80 °C and there was a sharp decrease of dye concentration at temperatures higher than this temperature. According to experimental results, the conversion efficiency of DSSC fabricated by mixture of chlorophyll and anthocyanin dyes from C. fruticosa leaves is 0.5% with short-circuit current (Isc) of 1.3 mA/cm- 2, open-circuit voltage (Voc) of 0.62 V and fill factor (FF) of 60.16%. The higher photoelectric conversion efficiency of the DSSC prepared from the extract of H. polyrhizus was 0.16%, with Voc of 0.5 V, Isc of 0.4 mA/cm- 2 and FF of 79.16%. The DSSC based betalain dye extracted from fruit of H. polyrhizus shows higher maximum IPCE of 44% than that of the DSSCs sensitized with mixed chlorophyll-anthocyanin dye from C. fruticosa (42%).

  6. THERMAL SENSITIVITY OF THE MURINE CFU-S-12 - ROLE OF ENVIRONMENTAL CELLS

    NARCIS (Netherlands)

    WIERENGA, PK; KONINGS, AWT

    1991-01-01

    The hyperthermic sensitivity of the CFU-S-12 in bone marrow from normal and anaemic mice was determined. The terminal slope of the survival curves, demonstrated by the T0 values, does not significantly differ in the resting and active cycling stem cells. In the active cycling stem cells the initial

  7. TIMP-1 gene deficiency increases tumour cell sensitivity to chemotherapy-induced apoptosis

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Würts, S.Ø.; Rømer, Maria Unni Koefoed

    2006-01-01

    this hypothesis, we have established TIMP-1 gene-deficient and TIMP-1 wild-type fibrosarcoma cells from mouse lung tissue. We have characterised these cells with regard to TIMP-1 genotype, TIMP-1 expression, malignant transformation and sensitivity to chemotherapy-induced apoptosis. We show that TIMP-1 gene...

  8. Sensitivity to ionizing radiation and chemotherapeutic agents in gemcitabine-resistant human tumor cell lines

    NARCIS (Netherlands)

    van Bree, Chris; Castro Kreder, Natasja; Loves, Willem J. P.; Franken, Nicolaas A. P.; Peters, Godefridus J.; Haveman, Jaap

    2002-01-01

    Purpose: To determine cross-resistance to anti-tumor treatments in 2',2'difluorodeoxycytidine (dFdC, gemcitabine)-resistant human tumor cells. Methods and Materials: Human lung carcinoma cells SW-1573 (SWp) were made resistant to dFdC (SWg). Sensitivity to cisplatin (cDDP), paclitaxel,

  9. First-Principles Modeling of Core/Shell Quantum Dot Sensitized Solar Cells

    NARCIS (Netherlands)

    Azpiroz, Jon Mikel; Infante, Ivan; De Angelis, Filippo

    2015-01-01

    We report on the density functional theory (DFT) modeling of core/shell quantum dot (QD) sensitized solar cells (QDSSCs), a device architecture that holds great potential in photovoltaics but has not been fully exploited so far. To understand the working mechanisms of this kind of solar cells, we

  10. [Oxidative stress in perinatal asphyxia and hypoxic-ischaemic encephalopathy].

    Science.gov (United States)

    Nuñez, Antonio; Benavente, Isabel; Blanco, Dorotea; Boix, Héctor; Cabañas, Fernando; Chaffanel, Mercedes; Fernández-Colomer, Belén; Fernández-Lorenzo, José Ramón; Loureiro, Begoña; Moral, María Teresa; Pavón, Antonio; Tofé, Inés; Valverde, Eva; Vento, Máximo

    2017-06-23

    Birth asphyxia is one of the principal causes of early neonatal death. In survivors it may evolve to hypoxic-ischaemic encephalopathy and major long-term neurological morbidity. Prolonged and intense asphyxia will lead to energy exhaustion in tissues exclusively dependent on aerobic metabolism, such as the central nervous system. Energy deficit leads to ATP-dependent pumps blockage, with the subsequent loss of neuronal transmembrane potential. The most sensitive areas of the brain will die due to necrosis. In more resistant areas, neuronal hyper-excitability, massive entrance of ionic calcium, activation of NO-synthase, free radical generation, and alteration in mitochondrial metabolism will lead to a secondary energy failure and programmed neuronal death by means of the activation of the caspase pathways. A third phase has recently been described that includes persistent inflammation and epigenetic changes that would lead to a blockage of oligodendrocyte maturation, alteration of neurogenesis, axonal maturation, and synaptogenesis. In this scenario, oxidative stress plays a critical role causing direct damage to the central nervous system and activating metabolic cascades leading to apoptosis and inflammation. Moderate whole body hypothermia to preserve energy stores and to reduce the formation of oxygen reactive species attenuates the mechanisms that lead to the amplification of cerebral damage upon resuscitation. The combination of hypothermia with coadjuvant therapies may contribute to improve the prognosis. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Degradation chemistry of RuLL´(NCS)2 complexes in the Dye-sensitized solar cell

    DEFF Research Database (Denmark)

    Lund, Torben

    In the last decade dye-sensitized solar cells (DSCs) have extensively been studied. From an economical point of view DSCs are of high interest because the manufacturing costs of DSCs devices are significantly lower in contrast to the costs of other solar devices such as silicon cells. One...... on the surface of a semiconductor anode (TiO2). In order to be able to predict the life time of the dye during solar cell operation it is essential to map all the possible side reactions and their rates initiated from the excited (S*), oxidized (S+) and ground state of the sensitizer (S). In my lecture I...

  12. Lessons learned: from dye-sensitized solar cells to all-solid-state hybrid devices.

    Science.gov (United States)

    Docampo, Pablo; Guldin, Stefan; Leijtens, Tomas; Noel, Nakita K; Steiner, Ullrich; Snaith, Henry J

    2014-06-25

    The field of solution-processed photovoltaic cells is currently in its second spring. The dye-sensitized solar cell is a widely studied and longstanding candidate for future energy generation. Recently, inorganic absorber-based devices have reached new record efficiencies, with the benefits of all-solid-state devices. In this rapidly changing environment, this review sheds light on recent developments in all-solid-state solar cells in terms of electrode architecture, alternative sensitizers, and hole-transporting materials. These concepts are of general applicability to many next-generation device platforms. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. ENHANCING THE EFFICIENCY OF AZO-BASED DYE SENSITIZED SOLAR CELLS BY SURFACE TREATMENTS

    OpenAIRE

    JEANINA LUNGU; ADRIAN GEORGESCU; ANCA DUMBRAVA

    2015-01-01

    We studied the conductive glass and/or the semiconductor surface treatments with aluminum ions as a technique to enhance the characteristics of dye sensitized solar cells (DSSCs) based on Al-doped ZnO. The aluminum ions were deposited on the surfaces using aluminum isopropoxide as precursor, by an easy and efficient method. We measured the characteristics of the dye sensitized solar cells based on pre- and/or post-treated electrodes. Our study showed a clear enhancement of cells efficiencies ...

  14. Novel zinc porphyrin sensitizers for dye-sensitized solar cells: synthesis and spectral, electrochemical, and photovoltaic properties.

    Science.gov (United States)

    Lee, Cheng-Wei; Lu, Hsueh-Pei; Lan, Chi-Ming; Huang, Yi-Lin; Liang, You-Ren; Yen, Wei-Nan; Liu, Yen-Chun; Lin, You-Shiang; Diau, Eric Wei-Guang; Yeh, Chen-Yu

    2009-01-01

    Novel meso- or beta-derivatized porphyrins with a carboxyl group have been designed and synthesized for use as sensitizers in dye-sensitized solar cells (DSSCs). The position and nature of a bridge connecting the porphyrin ring and carboxylic acid group show significant influences on the spectral, electrochemical, and photovoltaic properties of these sensitizers. Absorption spectra of porphyrins with a phenylethynyl bridge show that both Soret and Q bands are red-shifted with respect to those of porphyrin 6. This phenomenon is more pronounced for porphyrins 3 and 4, which have a pi-conjugated electron-donating group at the meso position opposite the anchoring group. Upon introduction of an ethynylene group at the meso position, the potential at the first oxidation alters only slightly whereas that for the first reduction is significantly shifted to the positive, thus indicating a decreased HOMO-LUMO gap. Quantum-chemical (DFT) results support the spectroelectrochemical data for a delocalization of charge between the porphyrin ring and the amino group in the first oxidative state of diarylamino-substituted porphyrin 5, which exhibits the best photovoltaic performance among all the porphyrins under investigation. From a comparison of the cell performance based on the same TiO(2) films, the devices made of porphyrin 5 coadsorbed with chenodeoxycholic acid (CDCA) on TiO(2) in ratios [5]/[CDCA] = 1:1 and 1:2 have efficiencies of power conversion similar to that of an N3-based DSSC, which makes this green dye a promising candidate for colorful DSSC applications.

  15. Photocurrent generation by dye-sensitized solar cells using natural pigments.

    Science.gov (United States)

    Armendáriz-Mireles, Eddie Nahúm; Rocha-Rangel, Enrique; Caballero-Rico, Frida; Ramírez-de-León, José Alberto; Vázquez, Manuel

    2017-01-01

    The development of photovoltaic panels has improved the conversion of solar radiation into electrical energy. This paper deals with the electrical and thermal characteristics (voltage, current, and temperature) of photovoltaic solar cells sensitized with natural pigments (dye-sensitized solar cell, DSSC) based on a titanium dioxide semiconductor. Several natural pigments (blackberry, beets, eggplant skin, spinach, flame tree flower, papaya leaf, and grass extracts) were evaluated to determine their sensitizing effect on titanium dioxide. The results showed the great potential of natural pigments for use in solar cells. The best results were obtained with the blackberry pigment, reaching a value of 7.1 mA current, open-circuit voltage (Voc ) of 0.72 V in 2 cm2 , and fill factor (ff) of 0.51 in the DSSC. This performance is well above than that currently offers by actual cells. © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  16. Metabolic reprogramming and apoptosis sensitivity: Defining the contours of a T cell response.

    Science.gov (United States)

    Voss, Kelsey; Larsen, Sasha E; Snow, Andrew L

    2017-11-01

    An effective adaptive immune response hinges on the rapid clonal expansion of T cells in response to antigen. The sensitivity of these T cells to programmed cell death (i.e. apoptosis) is carefully calibrated at various stages to ensure a robust yet measured reaction that resolves without inflicting unintended damage to host tissues. To meet bioenergetic demands associated with vigorous proliferation, acquisition of effector functions, and memory formation, T cells also undergo dynamic changes in their metabolism at every stage of this response. In this review, we focus on relatively recent studies that illuminate intimate links between metabolic programs and apoptosis sensitivity in T cells. We then examine how these connections ultimately influence T cell survival and function within the metabolically taxing environs of the tumor microenvironment. Published by Elsevier B.V.

  17. Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

    Science.gov (United States)

    He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

    2014-02-01

    Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

  18. miR-200/ZEB axis regulates sensitivity to nintedanib in non-small cell lung cancer cells.

    Science.gov (United States)

    Nishijima, Nobuhiko; Seike, Masahiro; Soeno, Chie; Chiba, Mika; Miyanaga, Akihiko; Noro, Rintaro; Sugano, Teppei; Matsumoto, Masaru; Kubota, Kaoru; Gemma, Akihiko

    2016-03-01

    Nintedanib (BIBF1120) is a multi-targeted angiokinase inhibitor and has been evaluated in idiopathic pulmonary fibrosis and advanced non-small cell lung cancer (NSCLC) patients in clinical studies. In the present study, we evaluated the antitumor effects of nintedanib in 16 NSCLC cell lines and tried to identify microRNA (miRNA) associated with sensitivity to nintedanib. No correlations between FGFR, PDGFR and VEGFR family activation and sensitivity to nintedanib were found. The difference in miRNA expression profiles between 5 nintedanib-sensitive and 5 nintedanib-resistant cell lines was evaluated by miRNA array and quantitative RT-PCR analysis (qRT-PCR). Expression of miR-200b, miR-200a and miR-141 belonging to the miR-200 family which contributes to epithelial-mesenchymal transition (EMT), was significantly lower in 5 nintedanib-resistant than in 5 nintedanib-sensitive cell lines. We examined the protein expression of EMT markers in these 10 NSCLC cell lines. E-cadherin expression was lower, and vimentin and ZEB1 expression were higher in 5 nintedanib-resistant cell lines. PC-1 was the most sensitive of the NSCLC cell lines to nintedanib. We established nintedanib-resistant PC-1 cells (PC-1R) by the stepwise method. PC-1R cells also showed decreased expression of miR-200b, miR-141 and miR-429 and increased expression of ZEB1 and ZEB2. We confirmed that induction of miR-200b or miR-141 enhanced sensitivity to nintedanib in nintedanib-resistant A549 and PC1-R cells. In addition, we evaluated the response to gefitinib in combination with nintedanib after TGF-β1 exposure of A549 cells. Nintedanib was able to reverse TGF-β1-induced EMT and resistance to gefitinib caused by miR-200b and miR-141 upregulation and ZEB1 downregulation. These results suggested that the miR-200/ZEB axis might be predictive biomarkers for sensitivity to nintedanib in NSCLC cells. Furthermore, nintedanib combined with gefitinib might be a novel therapeutic strategy for NSCLC cells with EMT

  19. Quantum Dot Sensitized Nanotubes for Full Solar Spectrum Photovoltaic Cell

    Science.gov (United States)

    Khanal, Sohana

    The demand for energy with limited non-renewable sources of energy has called researchers to find clean renewable energy sources. Solar light is considered good choice of the alternate energy. Our effort in this work was to investigate efficient photovoltaic (PV) systems by designing a hybrid photoelectrode with good absorption as well as charge transport properties. A coupled semiconductor material, one-dimensional TiO2 nanotubes (1D TiO2-NTs), filled with low band semiconductor quantum dots (QDs), PbS QDs, for better charge carrier transport was prepared and investigated. The vertically standing self assembled nanotubular array was attained by anodizing the Ti metal in two different solutions: (1) Ethylene Glycol with 0.5 wt% NH4F and 3 vol percent water and (2) 0.5M H3PO4 with 0.5 wt% NH4F. The anodized samples were annealed and then filled with the nanoparticles of other low band gap semiconductor materials. The CdS nanoparticles were used for the better understanding of the sensitizing process. The material was then switched to the PbS. As in the hypothesis, if PbS quantum dots are uniformly distributed in the 1D TiO2 Multiple Charge Carrier Generation can be created since PbS has a small band gap. A chemical bath deposition process in the presence of ultrasonic waves was adopted for the deposition of the QDs. Saturated lead sulfide solution was used as the lead source and the 0.2 M Na2S solution for the sulfur source. The process resulted in the successful uniform deposition of the PbS QDs onto the 1D TiO2 NTs. The deposited compound obeyed the stoichiometric ratio of 1:1 as desired. Photocurrent densities of 4.5 mA/cm2 was obtained, which is higher than the TiO2 alone in a polysulfide solution. PbS-TiO2 can be a suitable candidate for harvesting a broad solar spectrum as the UV-vis study proved that they absorb the light in the UV range.

  20. Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Holly A., E-mail: hport001@umaryland.edu [Center for Vascular and Inflammatory Diseases, 800 West Baltimore Street, Room 318, Baltimore, MD 21201 (United States); Molecular Medicine Program, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Carey, Gregory B., E-mail: gcarey@som.umaryland.edu [Center for Vascular and Inflammatory Diseases, 800 West Baltimore Street, Room 318, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Keegan, Achsah D., E-mail: akeegan@som.umaryland.edu [Center for Vascular and Inflammatory Diseases, 800 West Baltimore Street, Room 318, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Molecular Medicine Program, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201 (United States)

    2012-08-15

    The adapters IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2. -- Highlights: Black-Right-Pointing-Pointer IRS1 enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. Black-Right-Pointing-Pointer This sensitivity is abrogated by the expression of IRS2. Black-Right-Pointing-Pointer Expressing IRS1 in 32D cells increased levels of Annexin A2. Black-Right-Pointing-Pointer Both IRS1 and Annexin A2 were located in cytoplasmic and membrane fractions. Black-Right-Pointing-Pointer Decreasing Annexin A2 in 32D-IRS1 cells abated their sensitivity to chemotherapy.

  1. [Follow-up of newborns with hypoxic-ischaemic encephalopathy].

    Science.gov (United States)

    Martínez-Biarge, M; Blanco, D; García-Alix, A; Salas, S

    2014-07-01

    Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families. This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. Evaluación de metales redox-sensitivos como proxies de paleoxigenación en un ambiente marino hipóxico del norte de Chile Redox-sensitive metals evaluation as proxis of paleoxygenation in a hypoxic marine environment of northern Chile

    Directory of Open Access Journals (Sweden)

    JORGE VALDÉS

    2004-03-01

    metales registrada entre las muestras de la parte superior de los testigos (correspondientes a antes de 1996 y las muestras superficiales (correspondientes al año 2000 y tomadas en la misma zona de los testigos, pueden ser atribuidas al efecto de El Niño 1997-1998, el cual provocó un brusco descenso en el flujo de metales (principalmente Ni y Cd hacia los sedimentos, debido a una condición más oxigenada de la columna de agua. Este trabajo muestra que de los cinco metales analizados, solo en Ni y el Cd parecen tener un potencial como indicadores de paleoxigenación en la bahía Mejillones. Sin embargo, su uso está restringido para identificar cambios extremos desde una condición anóxica a una óxica en los sedimentos de fondo de esta bahía.The distribution of molybdenum, cadmium, zinc, vanadium and nickel, all redox-sensitive metals, was analyzed under a spatial (surface sediment samples and temporal (core samples perspective, in order to identify the potential of these metals for paleoxygenation interpretations in Mejillones bay, a hypoxic environment of northern Chile. Lithogenic supply (according to aluminum was discarded. Biogenic flux is not the unique factor that controls the mechanism of metals preservation in sediments of this bay. Spatial variation of metals concentration was investigated in relation to the bottom water oxygenation in each sampling station. Results showed that only Ni and Cd present a strong correlation with dissolved oxygen, increasing their concentration toward the deepest area of the bay were an oxygen minimum zone prevails with values around 0.02 mL L-1. The temporal variation in redox-sensitive metals, recorded in three sediments core covering the last 2,000 years, showed that bottom oxygenation of the bay changed from a more oxygenated environment in the past to a less oxygenated environment at present. A biogenic flux across a very well developed oxycline, associated to an anoxic sediment-water interface, are proposed to be the

  3. Fetal microchimerism persists at high levels in c-kit stem cells in sensitized mothers.

    Science.gov (United States)

    Dutta, Partha; Dart, Melanie L; Schumacher, Steve M; Burlingham, William J

    2010-10-01

    We previously showed that fetal and maternal exposure to non-inherited maternal antigens (NIMA) during gestation and nursing resulted in lifelong tolerance to NIMA in some offspring. This NIMA-specific tolerance was mediated by regulatory T cells (Tregs) and was correlated with the level of multi-lineage maternal microchimerism (Mc) indicating a causative link between Mc and Treg development. To determine if transfer of fetal cells into mothers resulted in a similar tolerance to fetal cells, we used qPCR to detect rare fetal derived cells and a delayed type hypersensitivity (DTH) assay to detect fetal alloantigen-specific effector and regulatory T cells in mothers. We found that 5/8 B6 mothers of H2(b/d) offspring were sensitized to the alloantigens H2(d) and HY, indicating a dominance of alloantigen-specific effector T cells. Though these sensitized mothers did not have detectable fetal Mc (FMc) in any of the organs tested, they had very high levels of fetus-derived c-kit(+) stem cells in their bone marrow. The remaining 3/8 B6 mothers that were not sensitized to the fetal antigens had detectable FMc found mostly in heart, lungs and liver, and in 2/3, we could detect alloantigen-specific regulatory T cells. This data indicates that, as in NIMA-specific tolerance, tolerance in multiparous females to inherited paternal antigens (IPA) expressed by the fetus is associated with the presence of fetal Mc in differentiated cell subsets. Surprisingly, robust lin(-)c-kit(+) bone marrow cell fetal Mc can occur in sensitized mothers. This suggests a continuous source of allospecific priming, coupled with active elimination of mature IPA-expressing lin(+) cells by effector T cells of the maternal host.

  4. Contact sensitizers trigger human CD1-autoreactive T-cell responses.

    Science.gov (United States)

    Betts, Richard J; Perkovic, Adrijana; Mahapatra, Subhashree; Del Bufalo, Aurélia; Camara, Kaddy; Howell, Amy R; Martinozzi Teissier, Silvia; De Libero, Gennaro; Mori, Lucia

    2017-07-01

    Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin disease induced by exposure to small molecular-weight haptens, which covalently bind to proteins. The abundance of cutaneous T cells that recognize CD1a antigen-presenting molecules raises the possibility that MHC-independent antigen presentation may be relevant in some hapten-driven immune responses. Here we examine the ability of contact sensitizers to influence CD1-restricted immunity. Exposure of human antigen-presenting cells such as monocyte-derived dendritic cells and THP-1 cells to the prototypical contact sensitizer dinitrochlorobenzene potentiated the response of CD1a- and CD1d-autoreactive T cells, which released a vast array of cytokines in a CD1- and TCR-dependent manner. The potentiating effects of dinitrochlorobenzene depended upon newly synthesized CD1 molecules and the presence of endogenous stimulatory lipids. Further examination of a broad panel of contact sensitizers revealed 1,4-benzoquinone, resorcinol, isoeugenol, and cinnamaldehyde to activate the same type of CD1-restricted responses. These findings provide a basis for the antigen-specific activation of skin-associated CD1-restricted T cells by small molecules and may have implications for contact sensitizer-induced inflammatory skin diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Aplysin Sensitizes Cancer Cells to TRAIL by Suppressing P38 MAPK/Survivin Pathway

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2014-09-01

    Full Text Available TNF-related apoptosis-inducing ligand (TRAIL is a tumor-selective apoptosis inducer and has been shown to be promising for treating various types of cancers. However, the application of TRAIL is greatly impeded by the resistance of cancer cells to its action. Studies show that overexpression of some critical pro-survival proteins, such as survivin, is responsible for TRAIL resistance. In this study, we found that Aplysin, a brominated compound from marine organisms, was able to restore the sensitivity of cancer cells to TRAIL both in vitro and in vivo. Aplysin was found to enhance the tumor-suppressing capacity of TRAIL on several TRAIL-resistant cancer cell lines. TRAIL-induced apoptosis was also potentiated in A549 and MCF7 cells treated with Aplysin. Survivin downregulation was identified as a mechanism by which Aplysin-mediated TRAIL sensitization of cancer cells. Furthermore, the activation of p38 MAPK was revealed in Aplysin-treated cancer cells, and its inhibitor SB203580 was able to abrogate the promoting effect of Aplysin on the response of cancer cells to TRAIL action, as evidenced by restored survivin expression, elevated cell survival and reduced apoptotic rates. In conclusion, we provided evidence that Aplysin acts as a sensitizer for TRAIL and its effect on p38 MAPK/survivin pathway may partially account for this activity. Considering its low cytotoxicity to normal cells, Aplysin may be a promising agent for cancer treatment in combination with TRAIL.

  6. MicroRNA-21 Increases Proliferation and Cisplatin Sensitivity of Osteosarcoma-Derived Cells.

    Directory of Open Access Journals (Sweden)

    Vanita Vanas

    Full Text Available Osteosarcoma is the most common primary bone tumor and poor prognosis for osteosarcoma patients is mainly due to chemotherapy resistance. MicroRNAs are important to maintain pathophysiological mechanisms of cancer and influence cell sensitivity to chemotherapy. In this study, we tested the functions of microRNA-21 for malignant features as well as for drug resistance of osteosarcoma. We used Northern blot to measure microRNA-21 levels in osteosarcoma-derived cell lines. MicroRNA-21 activity was modulated by either expressing a sponge to decrease its activity in an osteosarcoma-derived cell line expressing high levels of microRNA-21 or by introducing pri-microRNA-21 in a cell line with low endogenous levels. Cell migration was determined in a scratch assay and cell proliferation was measured by performing growth curve analysis. Sensitivity of the cells towards chemotherapeutics was investigated by performing cell viability assays and calculating the IC50 values. While cell migration was unaffected by modulated microRNA-21 levels, microRNA-21 inhibition slowed proliferation and exogenously expressed microRNA-21 promoted this process. Modulated microRNA-21 activity failed to effect sensitivity of osteosarcoma-derived cell lines to doxorubicin or methotrexate. Contrarily, reduction of microRNA-21 activity resulted in enhanced resistance towards cisplatin while ectopic expression of microRNA-21 showed the opposite effect. Increased microRNA-21 levels repressed the expression of Sprouty2 and ectopic expression of Sprouty2 was able to largely rescue the observed effects of microRNA-21 in osteosarcoma. In summary, our data indicate that in osteosarcoma microRNA-21 expression is an important component for regulation of cell proliferation and for determining sensitivity to cisplatin.

  7. Pulmonary hypoxic vasoconstriction: how strong? How fast?

    Science.gov (United States)

    Sheehan, D. W.; Klocke, R. A.; Farhi, L. E.

    1992-01-01

    We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

  8. Dataset for the proteomic inventory and quantitative analysis of the breast cancer hypoxic secretome associated with osteotropism

    Directory of Open Access Journals (Sweden)

    Thomas R. Cox

    2015-12-01

    Full Text Available The cancer secretome includes all of the macromolecules secreted by cells into their microenvironment. Cancer cell secretomes are significantly different to that of normal cells reflecting the changes that normal cells have undergone during their transition to malignancy. More importantly, cancer secretomes are known to be active mediators of both local and distant host cells and play an important role in the progression and dissemination of cancer. Here we have quantitatively profiled both the composition of breast cancer secretomes associated with osteotropism, and their modulation under normoxic and hypoxic conditions. We detect and quantify 162 secretome proteins across all conditions which show differential hypoxic induction and association with osteotropism. Mass Spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000397 and the complete proteomic, bioinformatic and biological analyses are reported in Cox et al. (2015 [1].

  9. Evaluation of cloned cells, animal model, and ATRA sensitivity of human testicular yolk sac tumor

    Directory of Open Access Journals (Sweden)

    Zhao Junfeng

    2012-03-01

    Full Text Available Abstract The testicular yolk sac tumor (TYST is the most common neoplasm originated from germ cells differentiated abnormally, a major part of pediatric malignant testicular tumors. The present study aimed at developing and validating the in vitro and vivo models of TYST and evaluating the sensitivity of TYST to treatments, by cloning human TYST cells and investigating the histology, ultra-structure, growth kinetics and expression of specific proteins of cloned cells. We found biological characteristics of cloned TYST cells were similar to the yolk sac tumor and differentiated from the columnar to glandular-like or goblet cells-like cells. Chromosomes for tumor identification in each passage met nature of the primary tumor. TYST cells were more sensitive to all-trans-retinoic acid which had significantly inhibitory effects on cell proliferation. Cisplatin induced apoptosis of TYST cells through the activation of p53 expression and down-regulation of Bcl- expression. Thus, we believe that cloned TYST cells and the animal model developed here are useful to understand the molecular mechanism of TYST cells and develop potential therapies for human TYST.

  10. Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ryota Domura

    2017-06-01

    Full Text Available The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments and different stiffness of the polymeric substrates (poly(l-lactic acid and poly(ε-caprolactone, PLLA and PCL, respectively as well as collagen substrates (coat and gel to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7. The morphological spreading parameter (nucleus/cytoplasm area ratio induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC50 of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.

  11. Henna (Lawsonia inermis L. Dye-Sensitized Nanocrystalline Titania Solar Cell

    Directory of Open Access Journals (Sweden)

    Khalil Ebrahim Jasim

    2012-01-01

    Full Text Available Low-cost solar cells have been the subject of intensive research activities for over half century ago. More recently, dye-sensitized solar cells (DSSCs emerged as a new class of low-cost solar cells that can be easily prepared. Natural-dye-sensitized solar cells (NDSSCs are shown to be excellent examples of mimicking photosynthesis. The NDSSC acts as a green energy generator in which dyes molecules adsorbed to nanocrystalline layer of wide bandgap semiconductor material harvest photons. In this paper we investigate the structural, optical, electrical, and photovoltaic characterization of two types of natural dyes, namely, the Bahraini Henna and the Yemeni Henna, extracted using the Soxhlet extractor. Solar cells from both materials were prepared and characterized. It was found that the levels of open-circuit voltage and short-circuit current are concentration dependent. Further suggestions to improve the efficiency of NDSSC are discussed.

  12. Measurement of cell respiration and oxygenation in standard multichannel biochips using phosphorescent O2-sensitive probes.

    Science.gov (United States)

    Kondrashina, Alina V; Papkovsky, Dmitri B; Dmitriev, Ruslan I

    2013-09-07

    Measurement of cell oxygenation and oxygen consumption is useful for studies of cell bioenergetics, metabolism, mitochondrial function, drug toxicity and common pathophysiological conditions. Here we present a new platform for such applications which uses commercial multichannel biochips (μ-slides, Ibidi) and phosphorescent O2 sensitive probes. This platform was evaluated with both extracellular and intracellular O2 probes, several different cell types and treatments including mitochondrial uncoupling and inhibition, depletion of extracellular Ca(2+) and inhibition of V-ATPase and histone deacetylases. The results show that compared to the standard microwell plates currently used, the μ-slide platform provides facile O2 measurements with both suspension and adherent cells, higher sensitivity and reproducibility, and faster measurement time. It also allows re-perfusion and multiple treatments of cells and multi-parametric analyses in conjunction with other probes. Optical measurements are conducted on standard fluorescence readers and microscopes.

  13. Loss of Atrx sensitizes cells to DNA damaging agents through p53-mediated death pathways.

    Directory of Open Access Journals (Sweden)

    Damiano Conte

    Full Text Available Prevalent cell death in forebrain- and Sertoli cell-specific Atrx knockout mice suggest that Atrx is important for cell survival. However, conditional ablation in other tissues is not associated with increased death indicating that diverse cell types respond differently to the loss of this chromatin remodeling protein. Here, primary macrophages isolated from Atrx(f/f mice were infected with adenovirus expressing Cre recombinase or β-galactosidase, and assayed for cell survival under different experimental conditions. Macrophages survive without Atrx but undergo rapid apoptosis upon lipopolysaccharide (LPS activation suggesting that chromatin reorganization in response to external stimuli is compromised. Using this system we next tested the effect of different apoptotic stimuli on cell survival. We observed that survival of Atrx-null cells were similar to wild type cells in response to serum withdrawal, anti-Fas antibody, C2 ceramide or dexamethasone treatment but were more sensitive to 5-fluorouracil (5-FU. Cell survival could be rescued by re-introducing Atrx or by removal of p53 demonstrating the cell autonomous nature of the effect and its p53-dependence. Finally, we demonstrate that multiple primary cell types (myoblasts, embryonic fibroblasts and neurospheres were sensitive to 5-FU, cisplatin, and UV light treatment. Together, our results suggest that cells lacking Atrx are more sensitive to DNA damaging agents and that this may result in enhanced death during development when cells are at their proliferative peak. Moreover, it identifies potential treatment options for cancers associated with ATRX mutations, including glioblastoma and pancreatic neuroendocrine tumors.

  14. A sensitive electrochemiluminescence cytosensor for quantitative evaluation of epidermal growth factor receptor expressed on cell surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yanjuan; Zhang, Shaolian; Wen, Qingqing; Huang, Hongxing; Yang, Peihui, E-mail: typh@jnu.edu.cn

    2015-06-30

    Highlights: • EGF-cytosensor was used for evaluating EGFR expression level on cell surfaces. • CdSQDs and EGF were coated on magnetic beads (MBs) for ECL-probe. • Good sensitivity was achieved due to the signal amplification of ECL-probe. - Abstract: A sensitive electrochemiluminescence (ECL) strategy for evaluating the epidermal growth factor receptor (EGFR) expression level on cell surfaces was designed by integrating the specific recognition of EGFR expressed on MCF-7 cell surfaces with an epidermal growth factor (EGF)-funtionalized CdS quantum dots (CdSQDs)-capped magnetic bead (MB) probe. The high sensitivity of ECL probe of EGF-funtionalized CdSQD-capped-MB was used for competitive recognition with EGFR expressed on cell surfaces with recombinant EGFR protein. The changes of ECL intensity depended on both the cell number and the expression level of EGFR receptor on cell surfaces. A wide linear response to cells ranging from 80 to 4 × 10{sup 6} cells mL{sup −1} with a detection limit of 40 cells mL{sup −1} was obtained. The EGF-cytosensor was used to evaluate EGFR expression levels on MCF-7 cells, and the average number of EGFR receptor on single MCF-7 cells was 1.35 × 10{sup 5} with the relative standard deviation of 4.3%. This strategy was further used for in-situ and real-time evaluating EGFR receptor expressed on cell surfaces in response to drugs stimulation at different concentration and incubation time. The proposed method provided potential applications in the detection of receptors on cancer cells and anticancer drugs screening.

  15. Raman spectroscopy differentiates between sensitive and resistant multiple myeloma cell lines

    Science.gov (United States)

    Franco, Domenico; Trusso, Sebastiano; Fazio, Enza; Allegra, Alessandro; Musolino, Caterina; Speciale, Antonio; Cimino, Francesco; Saija, Antonella; Neri, Fortunato; Nicolò, Marco S.; Guglielmino, Salvatore P. P.

    2017-12-01

    Current methods for identifying neoplastic cells and discerning them from their normal counterparts are often nonspecific and biologically perturbing. Here, we show that single-cell micro-Raman spectroscopy can be used to discriminate between resistant and sensitive multiple myeloma cell lines based on their highly reproducible biomolecular spectral signatures. In order to demonstrate robustness of the proposed approach, we used two different cell lines of multiple myeloma, namely MM.1S and U266B1, and their counterparts MM.1R and U266/BTZ-R subtypes, resistant to dexamethasone and bortezomib, respectively. Then, micro-Raman spectroscopy provides an easily accurate and noninvasive method for cancer detection for both research and clinical environments. Characteristic peaks, mostly due to different DNA/RNA ratio, nucleic acids, lipids and protein concentrations, allow for discerning the sensitive and resistant subtypes. We also explored principal component analysis (PCA) for resistant cell identification and classification. Sensitive and resistant cells form distinct clusters that can be defined using just two principal components. The identification of drug-resistant cells by confocal micro-Raman spectroscopy is thus proposed as a clinical tool to assess the development of resistance to glucocorticoids and proteasome inhibitors in myeloma cells.

  16. Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes.

    Science.gov (United States)

    Hockman, Dorit; Burns, Alan J; Schlosser, Gerhard; Gates, Keith P; Jevans, Benjamin; Mongera, Alessandro; Fisher, Shannon; Unlu, Gokhan; Knapik, Ela W; Kaufman, Charles K; Mosimann, Christian; Zon, Leonard I; Lancman, Joseph J; Dong, P Duc S; Lickert, Heiko; Tucker, Abigail S; Baker, Clare V H

    2017-04-07

    The evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes - carotid body glomus cells, and 'pulmonary neuroendocrine cells' (PNECs) - are obscure. Homology has been proposed between glomus cells, which are neural crest-derived, and the hypoxia-sensitive 'neuroepithelial cells' (NECs) of fish gills, whose embryonic origin is unknown. NECs have also been likened to PNECs, which differentiate in situ within lung airway epithelia. Using genetic lineage-tracing and neural crest-deficient mutants in zebrafish, and physical fate-mapping in frog and lamprey, we find that NECs are not neural crest-derived, but endoderm-derived, like PNECs, whose endodermal origin we confirm. We discover neural crest-derived catecholaminergic cells associated with zebrafish pharyngeal arch blood vessels, and propose a new model for amniote hypoxia-sensitive cell evolution: endoderm-derived NECs were retained as PNECs, while the carotid body evolved via the aggregation of neural crest-derived catecholaminergic (chromaffin) cells already associated with blood vessels in anamniote pharyngeal arches.

  17. Interferon-α reduces the gefitinib sensitivity of human non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Chi Pan

    2016-09-01

    Full Text Available Aim of the study : Many studies have shown that interferon-α(IFN-α enhances the antiproliferative effect of gefitinib in some solid tumours. We aimed to determine the effect of combining IFN-αwith gefitinib in human non-small cell lung cancer (NSCLC cell lines (A549, H1299, HCC827 with different EGFR and K-Ras gene statuses. Material and methods : An MTT assay was used to assess cell proliferation. Apoptosis was detected by an Annexin V/propidium iodide assay using flow cytometry, and western blotting was used to determine the expression of epidermal growth factor receptor/phosphorylated epidermal growth factor receptor (EGFR/p-EGFR and signal transducers and activators of transcription 3/phosphorylated signal transducers and activators of transcription 3 (STAT3/p-STAT3. Results : There was an additive interaction when gefitinib was combined with IFN-α in all cell lines; however, there was antagonism when gefitinib followed IFN-α pretreatment in three cell lines. Notably, IFN-α pretreatment significantly reduced the gefitinib sensitivity of HCC827 cells. Surprisingly, while IFN-α inhibited STAT3 phosphorylation in cell lines, gefitinib could do so. Conclusions : The results might confirm the hypothesis that IFN-α induces gefitinib sensitivity of NSCLC, and IFN-α inhibits phosphorylation of STAT3, which may be dependent on EGFR signal activation playing a role in the reduction of gefitinib sensitivity after IFN-α treatment in NSCLC cell lines.

  18. Differential sensitivities of bladder cancer cell lines to resveratol are unrelated to its metabolic profile

    Science.gov (United States)

    Li, Hong; Wu, Moli; Ren, Changle; Zhen, Yuhong; Ma, Xiaochi; Diao, Yunpeng; Ma, Xiaodong; Deng, Sa; Liu, Jia

    2017-01-01

    Resveratrol (RV) is a natural polyphenol compound with a wide range of activities, including inhibition of human bladder cancer (HBC) cell growth. Because RV is rapidly metabolized and has poor bioavailability, it is unclear whether the antitumor activity is due to RV or its metabolites. We therefore used liquid chromatography-mass spectroscopy, qRT-PCR, immunocytochemistry and western blotting to evaluate the metabolic profile and biotransformation of RV in the T24 and EJ HBC cell lines. Both T24 and EJ cells generated the same RV metabolite, RV monosulfate (RVS), and both exhibited upregulation of the RV-associated metabolic enzyme SULT1A1 (sulfotransferase). Despite these similarities, T24 cells were more sensitive to RV than EJ cells, yet T24 cells exhibited no sensitivity to an RVS mixture (84.13% RVS). Primary rat bladder epithelial cells showed no adverse effects when exposed to a therapeutic dose (100 μM) of RV. The differences in RV sensitivity between the two HBC cell lines did not reflect differences in the RV metabolic profile or SULT1A1 expression. Because RV exhibited stronger antitumor activity and better safety than RVS, we conclude that RV has significant therapeutic potential for HBC treatment, provided individual differences are considered during clinical research and application. PMID:28178690

  19. Hypoxic pulmonary vasoconstriction requires connexin 40–mediated endothelial signal conduction

    Science.gov (United States)

    Wang, Liming; Yin, Jun; Nickles, Hannah T.; Ranke, Hannes; Tabuchi, Arata; Hoffmann, Julia; Tabeling, Christoph; Barbosa-Sicard, Eduardo; Chanson, Marc; Kwak, Brenda R.; Shin, Hee-Sup; Wu, Songwei; Isakson, Brant E.; Witzenrath, Martin; de Wit, Cor; Fleming, Ingrid; Kuppe, Hermann; Kuebler, Wolfgang M.

    2012-01-01

    Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism by which pulmonary arteries constrict in hypoxic lung areas in order to redirect blood flow to areas with greater oxygen supply. Both oxygen sensing and the contractile response are thought to be intrinsic to pulmonary arterial smooth muscle cells. Here we speculated that the ideal site for oxygen sensing might instead be at the alveolocapillary level, with subsequent retrograde propagation to upstream arterioles via connexin 40 (Cx40) endothelial gap junctions. HPV was largely attenuated by Cx40-specific and nonspecific gap junction uncouplers in the lungs of wild-type mice and in lungs from mice lacking Cx40 (Cx40–/–). In vivo, hypoxemia was more severe in Cx40–/– mice than in wild-type mice. Real-time fluorescence imaging revealed that hypoxia caused endothelial membrane depolarization in alveolar capillaries that propagated to upstream arterioles in wild-type, but not Cx40–/–, mice. Transformation of endothelial depolarization into vasoconstriction involved endothelial voltage-dependent α1G subtype Ca2+ channels, cytosolic phospholipase A2, and epoxyeicosatrienoic acids. Based on these data, we propose that HPV originates at the alveolocapillary level, from which the hypoxic signal is propagated as endothelial membrane depolarization to upstream arterioles in a Cx40-dependent manner. PMID:23093775

  20. Reactive nitrogen species in mitochondria and their implications in plant energy status and hypoxic stress tolerance

    Directory of Open Access Journals (Sweden)

    Kapuganti Jagadis Gupta

    2016-03-01

    Full Text Available Hypoxic and anoxic conditions result in the energy crisis that leads to cell damage. Since mitochondria are the primary organelles for energy production, the support of these organelles in a functional state is an important task during oxygen deprivation. Plant mitochondria adapted the strategy to survive under hypoxia by keeping electron transport operative even without oxygen via the use of nitrite as a terminal electrons acceptor. The process of nitrite reduction to nitric oxide (NO in the mitochondrial electron transport chain recycles NADH and leads to a limited rate of ATP production. The produced ATP alongside with the ATP generated by fermentation supports the processes of transcription and translation required for hypoxic survival and recovery of plants. Non-symbiotic hemoglobins (called phytoglobins in plants scavenge NO and thus contribute to regeneration of NAD+ and nitrate required for the operation of anaerobic energy metabolism. This overall operation represents an important strategy of biochemical adaptation that results in the improvement of energy status and thereby in protection of plants in the conditions of hypoxic stress.

  1. Reactive Nitrogen Species in Mitochondria and Their Implications in Plant Energy Status and Hypoxic Stress Tolerance.

    Science.gov (United States)

    Gupta, Kapuganti Jagadis; Igamberdiev, Abir U

    2016-01-01

    Hypoxic and anoxic conditions result in the energy crisis that leads to cell damage. Since mitochondria are the primary organelles for energy production, the support of these organelles in a functional state is an important task during oxygen deprivation. Plant mitochondria adapted the strategy to survive under hypoxia by keeping electron transport operative even without oxygen via the use of nitrite as a terminal electrons acceptor. The process of nitrite reduction to nitric oxide (NO) in the mitochondrial electron transport chain recycles NADH and leads to a limited rate of ATP production. The produced ATP alongside with the ATP generated by fermentation supports the processes of transcription and translation required for hypoxic survival and recovery of plants. Non-symbiotic hemoglobins (called phytoglobins in plants) scavenge NO and thus contribute to regeneration of NAD(+) and nitrate required for the operation of anaerobic energy metabolism. This overall operation represents an important strategy of biochemical adaptation that results in the improvement of energy status and thereby in protection of plants in the conditions of hypoxic stress.

  2. TiO2 nanotube arrays for quantum dots sensitized solar cells

    Science.gov (United States)

    Wen, Xin; Tao, Junchao; Sun, Yingshui; Sun, Yan; Dai, Ning

    2009-07-01

    Vertically oriented, highly ordered TiO2 nanotube arrays have attracted considerable attention because of their impressive competence in a variety of applications including solar cells, chemical sensing, photocatalysis and biomedical industry. However, only a few papers reported on the solar cells prepared by combining TiO2 nanotubes and semiconductor quantum dots (QDs) based on composite structures. This paper presents the preparation of TiO2 nanotube arrays for the solar cells based on TiO2 nanotubes and CdSe QDs. The fabrication routes of highly organized TiO2 nanotube arrays synthesized by anodization of Ti foil in electrolyte were described, the performance of TiO2 nanotube arrays on the CdSe QDs sensitized TiO2 nanotube arrays photoelectrodes was investigated, too. The work herein details the effect of fabrication variables anodization time and examines the crystalline nature of the annealed (initially amorphous) samples. The nanotubes have an average inner diameter of 50 nm and a tube thickness of 12 nm. The maximum length of the TiO2 Nanotube we achieved is 9.75 μm. In QDs-sensitized TiO2 nanotube solar cells, CdSe QDs were used as the antenna layer (an absorber material) coating on the surface of titanium foil. Application of nanotube arrays to quantum dot solar cells under sunlight is discussed and compare to the dye sensitized solar cell. The quantum dots (QDs) sensitized solar cell's efficiencies can not match dye sensitized solar cell, but it will be a novel way to utilize solar energy in the future.

  3. Early cerebral hemodynamic, metabolic and histological changes in hypoxic-ischemic fetal lambs during postnatal life

    Directory of Open Access Journals (Sweden)

    Carmen eRey-Santano

    2011-09-01

    Full Text Available The hemodynamic, metabolic and biochemical changes produce during transition from fetal to neonatal life could be aggravated if asphyctic event occur during fetal life. The aim of the study was to examine the regional cerebral blood flow (RCBF, histological changes, and cerebral brain metabolism in preterm lambs, and to analyze the role of oxidative stress for the first hours of postnatal life following severe fetal asphyxia. 18 chronically instrumented fetal lambs were assigned to: hypoxic-ischemic group, following fetal asphyxia animals were delivered and maintained on intermittent-positive-pressure-ventilation for 3 hours, and non-injured animals that were managed similarly to the previous group and used as control group. During hypoxic-ischemic insult, injured group developed acidosis, hypoxia, hypercapnia, latacidaemia and tachycardia in comparison to control group, without hypotension. Intermittent-positive-pressure-ventilation transiently improved gas exchange and cardiovascular parameters. After HI injury and during ventilation-support, the increased RCBF in inner zones was maintained for hypoxic-ischemic group, but cortical flow did not exhibit differences compared to the control group. Also, the increase of TUNEL positive cells (apoptosis and antioxidant enzymes, and decrease of ATP reserves was significantly higher in the brain regions where the RCBF were not increased.In conclusion, early metabolic, histological and hemodynamic changes involved in brain damage have been intensively investigated and reported in premature asphyctic lambs for the first 3 hours of postnatal life. Those changes have been described in human neonates, so our model could be useful to test the security and the effectiveness of different neuroprotective or ventilatory strategies when are applied in the first hours after fetal hypoxic-ischemic injury.

  4. Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment

    DEFF Research Database (Denmark)

    Oplustilova, L.; Wolanin, K.; Bartkova, J.

    2012-01-01

    (ADp-ribose) polymerase-1 (PARP-1), an enzyme critical for repair pathways alternative to HR. While promising, treatment with PARP-1 inhibitors (PARP-1i) faces some hurdles, including (1) acquired resistance, (2) search for other sensitizing, non-BRCA1/2 cancer defects and (3) lack of biomarkers to predict response......Impaired DNA damage response pathways may create vulnerabilities of cancer cells that can be exploited therapeutically. One such selective vulnerability is the sensitivity of BRCA1- or BRCA2-defective tumors (hence defective in DNA repair by homologous recombination, HR) to inhibitors of the poly...... to PARP-1i. Here we addressed these issues using PARP-1i on 20 human cell lines from carcinomas of the breast, prostate, colon, pancreas and ovary. Aberrations of the Mre11-Rad50-Nbs1 (MRN) complex sensitized cancer cells to PARP-1i, while p53 status was less predictive, even in response to PARP-1i...

  5. Dye-sensitized solar cells with natural dyes extracted from achiote seeds

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Ortiz, N.M.; Vazquez-Maldonado, I.A.; Azamar-Barrios, J.A.; Oskam, G. [Departamento de Fisica Aplicada, CINVESTAV-IPN, Merida, Yuc. 97310 (Mexico); Perez-Espadas, A.R.; Mena-Rejon, G.J. [Laboratorio de Quimica Organica de Investigacion, Facultad de Quimica, Universidad Autonoma de Yucatan, Merida, Yuc. 97150 (Mexico)

    2010-01-15

    We have explored the application of natural dyes extracted from the seeds of the achiote shrub (Bixa orellana L.) in dye-sensitized solar cells (DSCs). The main pigments are bixin and norbixin, which were obtained by separation and purification from the dark-red extract (annatto). The dyes were characterized using {sup 1}H-NMR, FTIR spectroscopy, and UV-Vis spectrophotometry. Solar cells were prepared using TiO{sub 2} and ZnO nanostructured, mesoporous films and the annatto, bixin, and norbixin as sensitizers. The best results were obtained with bixin-sensitized TiO{sub 2} solar cells with efficiencies of up to 0.53%, illustrating the importance of purification of dyes from natural extracts. (author)

  6. PAX3-FKHR sensitizes human alveolar rhabdomyosarcoma cells to camptothecin-mediated growth inhibition and apoptosis

    Science.gov (United States)

    Zeng, Fu-Yue; Cui, Jimmy; Liu, Lingling; Chen, Taosheng

    2009-01-01

    Patients with alveolar rhabdomyosarcoma (ARMS) have poorer response to conventional chemotherapy and lower survival rates than those with embryonal RMS (ERMS). By high-throughput screening, we identified camptothecin as an ARMS-selective inhibitor. Camptothecin more efficiently inhibited proliferation and induced apoptosis in Rh30 (ARMS) than RD (ERMS) cells. Ectopic expression of the PAX3-FKHR (PF) fusion protein in RD cells significantly increased sensitivity, whereas siRNA knockdown of PF decreased sensitivity of Rh30 cells to camptothecin. The sensitization required a transcriptionally active PF, and camptothecin downregulated levels of PF protein. These findings suggest that it is feasible to develop agents that preferentially block the growth of ARMS. PMID:19442434

  7. Amiloride-sensitive channels in type I fungiform taste cells in mouse

    Directory of Open Access Journals (Sweden)

    Clapp Tod R

    2008-01-01

    Full Text Available Abstract Background Taste buds are the sensory organs of taste perception. Three types of taste cells have been described. Type I cells have voltage-gated outward currents, but lack voltage-gated inward currents. These cells have been presumed to play only a support role in the taste bud. Type II cells have voltage-gated Na+ and K+ current, and the receptors and transduction machinery for bitter, sweet, and umami taste stimuli. Type III cells have voltage-gated Na+, K+, and Ca2+ currents, and make prominent synapses with afferent nerve fibers. Na+ salt transduction in part involves amiloride-sensitive epithelial sodium channels (ENaCs. In rodents, these channels are located in taste cells of fungiform papillae on the anterior part of the tongue innervated by the chorda tympani nerve. However, the taste cell type that expresses ENaCs is not known. This study used whole cell recordings of single fungiform taste cells of transgenic mice expressing GFP in Type II taste cells to identify the taste cells responding to amiloride. We also used immunocytochemistry to further define and compare cell types in fungiform and circumvallate taste buds of these mice. Results Taste cell types were identified by their response to depolarizing voltage steps and their presence or absence of GFP fluorescence. TRPM5-GFP taste cells expressed large voltage-gated Na+ and K+ currents, but lacked voltage-gated Ca2+ currents, as expected from previous studies. Approximately half of the unlabeled cells had similar membrane properties, suggesting they comprise a separate population of Type II cells. The other half expressed voltage-gated outward currents only, typical of Type I cells. A single taste cell had voltage-gated Ca2+ current characteristic of Type III cells. Responses to amiloride occurred only in cells that lacked voltage-gated inward currents. Immunocytochemistry showed that fungiform taste buds have significantly fewer Type II cells expressing PLC signalling

  8. Intrapartum electronic fetal heart rate monitoring and the identification of metabolic acidosis and hypoxic-ischemic encephalopathy.

    Science.gov (United States)

    Larma, Joel D; Silva, Anadir M; Holcroft, Cynthia J; Thompson, Richard E; Donohue, Pamela K; Graham, Ernest M

    2007-09-01

    The purpose of this study was to determine whether electronic fetal monitoring can identify fetuses with metabolic acidosis and hypoxic-ischemic encephalopathy. The cases were 107 nonanomalous chromosomally normal fetuses with an umbilical arterial pH electronic fetal monitoring before delivery was evaluated by 3 obstetricians who were blinded to outcome. Cases had a significant increase in late and prolonged decelerations/hour and late decelerations/contractions. Those fetuses with hypoxic-ischemic encephalopathy had significant increases in bradycardia, decreased variability, and nonreactivity but no difference in late or variable decelerations/hour. For the identification of hypoxic-ischemic encephalopathy, the sensitivity, specificity, and positive and negative predictive values were 15.4%, 98.9%, 66.7%, and 89.4%, respectively, for bradycardia; 53.8%, 79.8%, 26.9%, and 92.6%, respectively, for decreased variability; 92.3%, 61.7%, 2.7%, and 82.9%, respectively, for nonreactivity; and 7.7%, 98.9%, 50.0%, and 88.6%, respectively, for all 3 abnormalities combined. Fetal metabolic acidosis and hypoxic-ischemic encephalopathy are associated with significant increases in electronic fetal monitoring abnormalities, but their predictive ability to identify these conditions is low.

  9. Quantum Dots Sensitized Solar Cell: Effect of CdSe Nanoparticles Purification Procedure of QD Sensitized Photoanodes

    Science.gov (United States)

    Yaacob, K. A.; Ishak, M. N.; Alias, N. N.

    2013-04-01

    In this research the effect of purification of CdSe nanoparticles for application in quantum dots sensitized solar cells (QDSSC) photoanodes are studied. The CdSe nanoparticles are attached to the titanium dioxide surface using a linker based approached (CdSe nanoparticles disperse in toluene) and direct mode attachment (CdSe re-disperse in dichloromethane (DCM)). Colloidal CdSe nanoparticles with estimated size of 3.0 nm were synthesized by hot injection method in trioctylphosphine oxide (TOPO) as stabilizing solvent. Prior to the sensitization, the CdSe nanoparticles were purified using a common purification step involving the alternate cycles of precipitation / redispersion in non-polar solvent and polar solvent. With increasing the number of purification, the concentrations of CdSe nanoparticles attached to the titanium dioxide were also increased; from 2.47 × 1015 dots/cc for 3 × wash CdSe nanoparticles to 3.70 × 1015 dots/cc for 4 × wash CdSe nanoparticles. Polysulfide electrolyte and Cu2S counterelectrodes were used to assemble a complete QDSSC. The highest efficiency of 0.05% was obtained from 4 × wash CdSe nanoparticles; Voc = 0.2V, Jsc = 0.34 mA/cm2 and FF = 0.07).

  10. A new era of semiconductor genetics using ion-sensitive field-effect transistors: the gene-sensitive integrated cell.

    Science.gov (United States)

    Toumazou, Christofer; Thay, Tan Sri Lim Kok; Georgiou, Pantelis

    2014-03-28

    Semiconductor genetics is now disrupting the field of healthcare owing to the rapid parallelization and scaling of DNA sensing using ion-sensitive field-effect transistors (ISFETs) fabricated using commercial complementary metal -oxide semiconductor technology. The enabling concept of DNA reaction monitoring introduced by Toumazou has made this a reality and we are now seeing relentless scaling with Moore's law ultimately achieving the $100 genome. In this paper, we present the next evolution of this technology through the creation of the gene-sensitive integrated cell (GSIC) for label-free real-time analysis based on ISFETs. This device is derived from the traditional metal-oxide semiconductor field-effect transistor (MOSFET) and has electrical performance identical to that of a MOSFET in a standard semiconductor process, yet is capable of incorporating DNA reaction chemistries for applications in single nucleotide polymorphism microarrays and DNA sequencing. Just as application-specific integrated circuits, which are developed in much the same way, have shaped our consumer electronics industry and modern communications and memory technology, so, too, do GSICs based on a single underlying technology principle have the capacity to transform the life science and healthcare industries.

  11. Efficient and stable solid-state dye-sensitized solar cells based on a high-molar-extinction-coefficient sensitizer.

    Science.gov (United States)

    Wang, Mingkui; Moon, Soo-Jin; Xu, Mingfei; Chittibabu, Kethineni; Wang, Peng; Cevey-Ha, Ngoc-Le; Humphry-Baker, Robin; Zakeeruddin, Shaik M; Grätzel, Michael

    2010-01-01

    The high-molar-extinction-coefficient heteroleptic ruthenium dye, cis-Ru (4,4'-bis(5-octylthieno[3,2-b] thiophen-2-yl)-2,2'-bipyridine) (4,4'-dicarboxyl-2,2'-bipyridine) (NCS)(2), exhibits an AM 1.5 solar (100 mW cm(-2))-to-electric power-conversion efficiency of 4.6% in a solid-state dye-sensitized solar cell (SSDSC) with 2,2', 7,7'-tetrakis-(N,N-di-p-methoxyphenylamine)9,9'-spirobifluorene (spiro-MeOTAD) as the organic hole-transporting material. These SSDSC devices exhibit good durability during accelerated tests under visible-light soaking for 1000 h at 60 degrees C. This demonstration elucidates a class of photovoltaic devices with potential for stable and low-cost power generation. The electron recombination dynamics and charge collection that take place at the dye-sensitized heterojunction are studied by means of impedance and transient photovoltage decay techniques.

  12. Carbohydrate Supplementation Influences Serum Cytokines after Exercise under Hypoxic Conditions.

    Science.gov (United States)

    Caris, Aline Venticinque; Da Silva, Edgar Tavares; Dos Santos, Samile Amorim; Lira, Fabio Santos; Oyama, Lila Missae; Tufik, Sergio; Dos Santos, Ronaldo Vagner Thomatieli

    2016-11-05

    Exercise performed at the hypoxia equivalent of an altitude of 4200 m is associated with elevated inflammatory mediators and changes in the Th1/Th2 response. By contrast, supplementation with carbohydrates has an anti-inflammatory effect when exercise is performed under normoxic conditions. The objective of this study was to evaluate the effect of carbohydrate supplementation on cytokines and cellular damage markers after exercise under hypoxic conditions at a simulated altitude of 4200 m. Seven adult male volunteers who exercised for 60 min at an intensity of 50% VO2Peak were randomly evaluated under three distinct conditions; normoxia, hypoxia and hypoxia + carbohydrate supplementation. Blood samples were collected at rest, at the end of exercise and after 60 min of recovery. To evaluate hypoxia + carbohydrate supplementation, volunteers received a solution of 6% carbohydrate (maltodextrin) or a placebo (strawberry-flavored Crystal Light(®); Kraft Foods, Northfield, IL, USA) every 20 min during exercise and recovery. Statistical analyses comprised analysis of variance, with a one-way ANOVA followed by the Tukey post hoc test with a significance level of p exercise and after recovery compared to at rest (p carbohydrate group, there was a significant increase in the concentration of IL-6 and TNF-α after exercise compared to at rest (p carbohydrate supplementation modified the IL-6 and TNF-α serum concentrations and shifted the IL-2/IL-4 balance towards Th1 in response without glycemic, glutaminemia and cell damage effects.

  13. Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

    Directory of Open Access Journals (Sweden)

    Huang Yen

    2011-09-01

    Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

  14. Oxygen sensing and signal transduction in hypoxic pulmonary vasoconstriction.

    Science.gov (United States)

    Sommer, Natascha; Strielkov, Ievgen; Pak, Oleg; Weissmann, Norbert

    2016-01-01

    Hypoxic pulmonary vasoconstriction (HPV), also known as the von Euler-Liljestrand mechanism, is an essential response of the pulmonary vasculature to acute and sustained alveolar hypoxia. During local alveolar hypoxia, HPV matches perfusion to ventilation to maintain optimal arterial oxygenation. In contrast, during global alveolar hypoxia, HPV leads to pulmonary hypertension. The oxygen sensing and signal transduction machinery is located in the pulmonary arterial smooth muscle cells (PASMCs) of the pre-capillary vessels, albeit the physiological response may be modulated in vivo by the endothelium. While factors such as nitric oxide modulate HPV, reactive oxygen species (ROS) have been suggested to act as essential mediators in HPV. ROS may originate from mitochondria and/or NADPH oxidases but the exact oxygen sensing mechanisms, as well as the question of whether increased or decreased ROS cause HPV, are under debate. ROS may induce intracellular calcium increase and subsequent contraction of PASMCs via direct or indirect interactions with protein kinases, phospholipases, sarcoplasmic calcium channels, transient receptor potential channels, voltage-dependent potassium channels and L-type calcium channels, whose relevance may vary under different experimental conditions. Successful identification of factors regulating HPV may allow development of novel therapeutic approaches for conditions of disturbed HPV. Copyright ©ERS 2016.

  15. Panchromatic Response in Solid-State Dye-Sensitized Solar Cells Containing Phosphorescent Energy Relay Dyes

    KAUST Repository

    Yum, Jun-Ho

    2009-11-23

    Running relay: Incorporating an energyrelay dye (ERD) into the hole transporter of a dye-sensitized solar cell increased power-conversion efficiency by 29% by extending light harvesting into the blue region. In the operating mechanism (see picture), absorption of red photons by the sensitizer transfers an electron into TiO2 and a hole into the electrolyte. Blue photons absorbed by the ERD are transferred by FRET to the sensitizer. Chemical Equitation Presentation © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

  16. Incorporating Multiple Energy Relay Dyes in Liquid Dye-Sensitized Solar Cells

    KAUST Repository

    Yum, Jun-Ho

    2011-01-05

    Panchromatic response is essential to increase the light-harvesting efficiency in solar conversion systems. Herein we show increased light harvesting from using multiple energy relay dyes inside dye-sensitized solar cells. Additional photoresponse from 400-590 nm matching the optical window of the zinc phthalocyanine sensitizer was observed due to Förster resonance energy transfer (FRET) from the two energy relay dyes to the sensitizing dye. The complementary absorption spectra of the energy relay dyes and high excitation transfer efficiencies result in a 35% increase in photovoltaic performance. © 2011 Wiley-VCH Verlag GmbH& Co. KGaA.

  17. Improved Diffuse Fluorescence Flow Cytometer Prototype for High Sensitivity Detection of Rare Circulating Cells In Vivo

    Science.gov (United States)

    Pestana, Noah Benjamin

    Accurate quantification of circulating cell populations is important in many areas of pre-clinical and clinical biomedical research, for example, in the study of cancer metastasis or the immune response following tissue and organ transplants. Normally this is done "ex-vivo" by drawing and purifying a small volume of blood and then analyzing it with flow cytometry, hemocytometry or microfludic devices, but the sensitivity of these techniques are poor and the process of handling samples has been shown to affect cell viability and behavior. More recently "in vivo flow cytometry" (IVFC) techniques have been developed where fluorescently-labeled cells flowing in a small blood vessel in the ear or retina are analyzed, but the sensitivity is generally poor due to the small sampling volume. To address this, our group recently developed a method known as "Diffuse Fluorescence Flow Cytometry" (DFFC) that allows detection and counting of rare circulating cells with diffuse photons, offering extremely high single cell counting sensitivity. In this thesis, an improved DFFC prototype was designed and validated. The chief improvements were three-fold, i) improved optical collection efficiency, ii) improved detection electronics, and iii) development of a method to mitigate motion artifacts during in vivo measurements. In combination, these improvements yielded an overall instrument detection sensitivity better than 1 cell/mL in vivo, which is the most sensitive IVFC system reported to date. Second, development and validation of a low-cost microfluidic device reader for analysis of ocular fluids is described. We demonstrate that this device has equivalent or better sensitivity and accuracy compared a fluorescence microscope, but at an order-of-magnitude reduced cost with simplified operation. Future improvements to both instruments are also discussed.

  18. Influence of Mesenchymal Stem Cells Conditioned Media on Proliferation of Urinary Tract Cancer Cell Lines and Their Sensitivity to Ciprofloxacin.

    Science.gov (United States)

    Maj, Malgorzata; Bajek, Anna; Nalejska, Ewelina; Porowinska, Dorota; Kloskowski, Tomasz; Gackowska, Lidia; Drewa, Tomasz

    2017-06-01

    Mesenchymal stem cells (MSCs) are known to interact with cancer cells through direct cell-to-cell contact and secretion of paracrine factors, although their exact influence on tumor progression in vivo remains unclear. To better understand how fetal and adult stem cells affect tumors, we analyzed viability of human renal (786-0) and bladder (T24) carcinoma cell lines cultured in conditioned media harvested from amniotic fluid-derived stem cells (AFSCs) and adipose-derived stem cells (ASCs). Both media reduced metabolic activity of 786-0 cells, however, decreased viability of T24 cells was noted only after incubation with conditioned medium from ASCs. To test the hypothesis that MSCs-secreted factors might be involved in chemoresistance acquisition, we further analyzed influence of mesenchymal stem cell conditioned media (MSC-CM) on cancer cells sensitivity to ciprofloxacin, that is considered as potential candidate agent for urinary tract cancers treatment. Significantly increased resistance to tested drug indicates that MSCs may protect cancer cells from chemotherapy. J. Cell. Biochem. 118: 1361-1368, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Advancing hypoxic training in team sports: from intermittent hypoxic training to repeated sprint training in hypoxia.

    Science.gov (United States)

    Faiss, Raphaël; Girard, Olivier; Millet, Grégoire P

    2013-12-01

    Over the past two decades, intermittent hypoxic training (IHT), that is, a method where athletes live at or near sea level but train under hypoxic conditions, has gained unprecedented popularity. By adding the stress of hypoxia during 'aerobic' or 'anaerobic' interval training, it is believed that IHT would potentiate greater performance improvements compared to similar training at sea level. A thorough analysis of studies including IHT, however, leads to strikingly poor benefits for sea-level performance improvement, compared to the same training method performed in normoxia. Despite the positive molecular adaptations observed after various IHT modalities, the characteristics of optimal training stimulus in hypoxia are still unclear and their functional translation in terms of whole-body performance enhancement is minimal. To overcome some of the inherent limitations of IHT (lower training stimulus due to hypoxia), recent studies have successfully investigated a new training method based on the repetition of short (<30 s) 'all-out' sprints with incomplete recoveries in hypoxia, the so-called repeated sprint training in hypoxia (RSH). The aims of the present review are therefore threefold: first, to summarise the main mechanisms for interval training and repeated sprint training in normoxia. Second, to critically analyse the results of the studies involving high-intensity exercises performed in hypoxia for sea-level performance enhancement by differentiating IHT and RSH. Third, to discuss the potential mechanisms underpinning the effectiveness of those methods, and their inherent limitations, along with the new research avenues surrounding this topic.

  20. Temperature-sensitive SV40-immortalized rat middle ear epithelial cells.

    Science.gov (United States)

    Toyama, Katsuhiro; Kim, Youngki; Paparella, Michael M; Lin, Jizhen

    2004-12-01

    The proliferation and differentiation of middle ear epithelial cells are essential in both normal and diseased middle ears. The normal situation involves physiologic growth and renewal of the epithelium, and the diseased situation involves pathological changes of the epithelium such as mucous cell metaplasia and ciliated cell proliferation in otitis media. In this study, we used a temperature-sensitive large T antigen (the SV40 mutant) to transduce and immortalize the primary culture of middle ear epithelial cells. SV40-immortalized middle ear epithelial cells have been cultured for more than 50 passages and are stable morphologically. Their nonimmortalized parent cells died at the second passage. Immortalized middle ear epithelial cells carrying the SV40 mutant show a monolayer, cobblestonelike morphology. The cell line expresses characteristic middle ear mucosal molecules such as mucins, keratins, and collagens. It also responds to temperature changes; namely, cells proliferate at 33 degrees C, when the SV40 antigen is active, and differentiate at 39 degrees C, when the SV40 antigen is inactive. Therefore, we conclude that a temperature-sensitive middle ear epithelial cell line has successfully been established.

  1. Exploring the contextual sensitivity of factors that determine cell-to-cell variability in receptor-mediated apoptosis.

    Directory of Open Access Journals (Sweden)

    Suzanne Gaudet

    Full Text Available Stochastic fluctuations in gene expression give rise to cell-to-cell variability in protein levels which can potentially cause variability in cellular phenotype. For TRAIL (TNF-related apoptosis-inducing ligand variability manifests itself as dramatic differences in the time between ligand exposure and the sudden activation of the effector caspases that kill cells. However, the contribution of individual proteins to phenotypic variability has not been explored in detail. In this paper we use feature-based sensitivity analysis as a means to estimate the impact of variation in key apoptosis regulators on variability in the dynamics of cell death. We use Monte Carlo sampling from measured protein concentration distributions in combination with a previously validated ordinary differential equation model of apoptosis to simulate the dynamics of receptor-mediated apoptosis. We find that variation in the concentrations of some proteins matters much more than variation in others and that precisely which proteins matter depends both on the concentrations of other proteins and on whether correlations in protein levels are taken into account. A prediction from simulation that we confirm experimentally is that variability in fate is sensitive to even small increases in the levels of Bcl-2. We also show that sensitivity to Bcl-2 levels is itself sensitive to the levels of interacting proteins. The contextual dependency is implicit in the mathematical formulation of sensitivity, but our data show that it is also important for biologically relevant parameter values. Our work provides a conceptual and practical means to study and understand the impact of cell-to-cell variability in protein expression levels on cell fate using deterministic models and sampling from parameter distributions.

  2. Potential development in dye-sensitized solar cells for renewable energy

    CERN Document Server

    Pandikumar, Alagarsamy

    2013-01-01

    The development of photovoltaic technology is expected to solve problems related to energy shortages and environmental pollution caused by the use of fossil fuels. Dye-sensitizedsolar cells (DSSCs) are promising next-generation alternatives to conventional silicon-based photovoltaic devices owing to their low manufacturing cost and potentially high conversion efficiency. This special topic volume addresses recent advances in the research on dye-sensitized solar cells. The focus of this special topic volume is on materials development (sensitizers, nanostructured oxide films, and electrolyte),

  3. The Arctic Alzheimer mutation enhances sensitivity to toxic stress in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Sennvik, Kristina; Nilsberth, Camilla; Stenh, Charlotte

    2002-01-01

    The E693G (Arctic) mutation of the amyloid precursor protein was recently found to lead to early-onset Alzheimer's disease in a Swedish family. In the present study, we report that the Arctic mutation decreases cell viability in human neuroblastoma cells. The cell viability, as measured by the MTT...... their secretion of beta-secretase cleaved amyloid precursor protein. The enhanced sensitivity to toxic stress in cells with the Arctic mutation most likely contributes to the pathogenic pathway leading to Alzheimer's disease....

  4. Imaging Lysosomal pH Alteration in Stressed Cells with a Sensitive Ratiometric Fluorescence Sensor.

    Science.gov (United States)

    Xue, Zhongwei; Zhao, Hu; Liu, Jian; Han, Jiahuai; Han, Shoufa

    2017-03-24

    The organelle-specific pH is crucial for cell homeostasis. Aberrant pH of lysosomes has been manifested in myriad diseases. To probe lysosome responses to cell stress, we herein report the detection of lysosomal pH changes with a dual colored probe (CM-ROX), featuring a coumarin domain with "always-on" blue fluorescence and a rhodamine-lactam domain activatable to lysosomal acidity to give red fluorescence. With sensitive ratiometric signals upon subtle pH changes, CM-ROX enables discernment of lysosomal pH changes in cells undergoing autophagy, cell death, and viral infection.

  5. [Establishment and characterization of human ovarian fibrosarcoma cell line and its sensitivity to anticancer agents].

    Science.gov (United States)

    Kiyozuka, Y; Nishimura, H; Iwanaga, S; Yakushiji, M; Ito, K; Nakano, S; Tamori, N; Adachi, S; Noda, T; Imai, S

    1992-04-01

    We succeeded in establishing a cell line (KEN-3) for subculture from a fibrosarcoma which originated in the ovary in a girl aged 17 years. Its characteristics and sensitivity to anticancer agents are reported in this paper. 1. Characteristics of established cell line. Lined cells consist of multinucleated giant cells mixed among many spindle-shaped cells. They grow in small colonies and have none of the pavement-like arrangement characteristic of epithelial tumor cells. The number of chromosomes ranged from 45 to 128 (mode: pseudo-triploidy region, 65). The doubling time, cellular density and plating efficiency were 76.9 hours, 5.4 x 10(5)/cm2 and 30.2%, respectively. Concerning tumor markers, CEA and sialyl SSEA-1 were only produced in small quantities. Subculture was possible subcutaneously in the nude mouse with no capacity for the production of ascites. 2. Susceptibility to anticancer agents and GP170 expression. The in vitro susceptibility to about 12 types of anticancer agents was investigated with the MTT assay. IC50/PPC was shown to be less than 1 for Adriamycin only. The sensitivity to CDDP (IC50/PPC: 4.8) was low, and no sensitivity was observed at all to DTIC, which is used frequently for mesenchymal tumors. GP170 (mdr-1 products) was positive in established cells in immunohistochemical stain.

  6. Cells bearing mutations causing Leber's hereditary optic neuropathy are sensitized to Fas-Induced apoptosis.

    Science.gov (United States)

    Danielson, Steven R; Wong, Alice; Carelli, Valerio; Martinuzzi, Andrea; Schapira, Anthony H V; Cortopassi, Gino A

    2002-02-22

    Three prevalent mitochondrial DNA pathogenic mutations at positions 11778, 3460, and 14484, which affect different subunits of Complex I, cause retinal ganglion cell death and optic nerve atrophy in Leber's hereditary optic neuropathy (LHON). The cell death is painless and without inflammation, consistent with an apoptotic mechanism. We have investigated the possibility that the LHON mutation confers a pro-apoptotic stimulus and have tested the sensitivity of osteosarcoma-derived cybrid cells carrying the most common and severe mutations (11778 and 3460) to cell death induced by Fas. We observed that LHON cybrids were sensitized to Fas-dependent death. Control cells that bear the same mitochondrial genetic background (the J haplogroup) without the pathogenic 11778 mutation are no more sensitive than other controls, indicating that increased Fas-dependent death in LHON cybrids was induced by the LHON pathogenic mutations. The type of death was apoptotic by several criteria, including induction by Fas, inhibition by the caspase inhibitor zVAD-fmk (zVal-Ala-Asp-fluoro-methyl ketone), activation of DEVDase activity (Asp-Glu-Val-Asp protease), specific cleavage of caspase-3, DNA fragmentation, and increased Annexin-V labeling. These data indicate that the most common and severe LHON pathogenic mutations 11778 and 3460 predispose cells to apoptosis, which may be relevant for the pathophysiology of cell death in LHON, and potential therapy.

  7. Refractory testicular germ cell tumors are highly sensitive to the second generation DNA methylation inhibitor guadecitabine.

    Science.gov (United States)

    Albany, Costantine; Hever-Jardine, Mary P; von Herrmann, Katherine M; Yim, Christina Y; Tam, Janice; Warzecha, Joshua M; Shin, Leah; Bock, Sarah E; Curran, Brian S; Chaudhry, Aneeq S; Kim, Fred; Sandusky, George E; Taverna, Pietro; Freemantle, Sarah J; Christensen, Brock C; Einhorn, Lawrence H; Spinella, Michael J

    2017-01-10

    Testicular germ cell tumors (TGCTs) are the most common cancers of young males. A substantial portion of TGCT patients are refractory to cisplatin. There are no effective therapies for these patients, many of whom die from progressive disease. Embryonal carcinoma (EC) are the stem cells of TGCTs. In prior in vitro studies we found that EC cells were highly sensitive to the DNA methyltransferase inhibitor, 5-aza deoxycytidine (5-aza). Here, as an initial step in bringing demethylation therapy to the clinic for TGCT patients, we evaluated the effects of the clinically optimized, second generation demethylating agent guadecitabine (SGI-110) on EC cells in an animal model of cisplatin refractory testicular cancer. EC cells were exquisitely sensitive to guadecitabine and the hypersensitivity was dependent on high levels of DNA methyltransferase 3B. Guadecitabine mediated transcriptional reprogramming of EC cells included induction of p53 targets and repression of pluripotency genes. As a single agent, guadecitabine completely abolished progression and induced complete regression of cisplatin resistant EC xenografts even at doses well below those required to impact somatic solid tumors. Low dose guadecitabine also sensitized refractory EC cells to cisplatin in vivo. Genome-wide analysis indicated that in vivo antitumor activity was associated with activation of p53 and immune-related pathways and the antitumor effects of guadecitabine were dependent on p53, a gene rarely mutated in TGCTs. These preclinical findings suggest that guadecitabine alone or in combination with cisplatin is a promising strategy to treat refractory TGCT patients.

  8. S100A10 protein expression is associated with oxaliplatin sensitivity in human colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Suzuki Sayo

    2011-12-01

    Full Text Available Abstract Background Individual responses to oxaliplatin (L-OHP-based chemotherapy remain unpredictable. The objective of our study was to find candidate protein markers for tumor sensitivity to L-OHP from intracellular proteins of human colorectal cancer (CRC cell lines. We performed expression difference mapping (EDM analysis of whole cell lysates from 11 human CRC cell lines with different sensitivities to L-OHP by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS, and identified a candidate protein by liquid chromatography/mass spectrometry ion trap time-of-flight (LCMS-IT-TOF. Results Of the qualified mass peaks obtained by EDM analysis, 41 proteins were differentially expressed in 11 human colorectal cancer cell lines. Among these proteins, the peak intensity of 11.1 kDa protein was strongly correlated with the L-OHP sensitivity (50% inhibitory concentrations (P R2 = 0.80. We identified this protein as Protein S100-A10 (S100A10 by MS/MS ion search using LCMS-IT-TOF. We verified its differential expression and the correlation between S100A10 protein expression levels in drug-untreated CRC cells and their L-OHP sensitivities by Western blot analyses. In addition, S100A10 protein expression levels were not correlated with sensitivity to 5-fluorouracil, suggesting that S100A10 is more specific to L-OHP than to 5-fluorouracil in CRC cells. S100A10 was detected in cell culture supernatant, suggesting secretion out of cells. Conclusions By proteomic approaches including SELDI technology, we have demonstrated that intracellular S100A10 protein expression levels in drug-untreated CRC cells differ according to cell lines and are significantly correlated with sensitivity of CRC cells to L-OHP exposure. Our findings provide a new clue to searching predictive markers of the response to L-OHP, suggesting that S100A10 is expected to be one of the candidate protein markers.

  9. Biochemical analysis of force-sensitive responses using a large-scale cell stretch device.

    Science.gov (United States)

    Renner, Derrick J; Ewald, Makena L; Kim, Timothy; Yamada, Soichiro

    2017-09-03

    Physical force has emerged as a key regulator of tissue homeostasis, and plays an important role in embryogenesis, tissue regeneration, and disease progression. Currently, the details of protein interactions under elevated physical stress are largely missing, therefore, preventing the fundamental, molecular understanding of mechano-transduction. This is in part due to the difficulty isolating large quantities of cell lysates exposed to force-bearing conditions for biochemical analysis. We designed a simple, easy-to-fabricate, large-scale cell stretch device for the analysis of force-sensitive cell responses. Using proximal biotinylation (BioID) analysis or phospho-specific antibodies, we detected force-sensitive biochemical changes in cells exposed to prolonged cyclic substrate stretch. For example, using promiscuous biotin ligase BirA* tagged α-catenin, the biotinylation of myosin IIA increased with stretch, suggesting the close proximity of myosin IIA to α-catenin under a force bearing condition. Furthermore, using phospho-specific antibodies, Akt phosphorylation was reduced upon stretch while Src phosphorylation was unchanged. Interestingly, phosphorylation of GSK3β, a downstream effector of Akt pathway, was also reduced with stretch, while the phosphorylation of other Akt effectors was unchanged. These data suggest that the Akt-GSK3β pathway is force-sensitive. This simple cell stretch device enables biochemical analysis of force-sensitive responses and has potential to uncover molecules underlying mechano-transduction.

  10. Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport

    Science.gov (United States)

    Velez, Juliana; Pan, Rongqing; Lee, Jason T.C.; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

    2016-01-01

    Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax. PMID:27283492

  11. Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats.

    Science.gov (United States)

    Zhang, Zhenwen; Fang, Penghua; He, Biao; Guo, Lili; Runesson, Johan; Langel, Ülo; Shi, Mingyi; Zhu, Yan; Bo, Ping

    2016-01-01

    Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebroventricular administration of M617 on insulin sensitivity and insulin signaling were evaluated in adipose tissues of type 2 diabetic rats. The results showed that central injection of M617 significantly increased plasma adiponectin contents, glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, GLUT4 mRNA expression levels, GLUT4 contents in plasma membranes, and total cell membranes of the adipose cells but reduced the plasma C-reactive protein concentration in nondiabetic and diabetic rats. The ratios of GLUT4 contents were higher in plasma membranes to total cell membranes in both nondiabetic and diabetic M617 groups than each control. In addition, the central administration of M617 enhanced the ratios of pAkt/Akt and pAS160/AS160, but not phosphorylative cAMP response element-binding protein (pCREB)/CREB in the adipose cells of nondiabetic and diabetic rats. These results suggest that excitation of central galanin receptor 1 facilitates insulin sensitivity via activation of the Akt/AS160 signaling pathway in the fat cells of type 2 diabetic rats.

  12. Co-sensitization of ZnO by CdS quantum dots in natural dye-sensitized solar cells with polymeric electrolytes to improve the cell stability

    Science.gov (United States)

    Junhom, W.; Magaraphan, R.

    2015-05-01

    The CdS quantum dots (QDs) were deposited on ZnO layer by chemical bath deposition method to absorb light in the shorter wavelength region and used as photoanode in the dye sensitized solar cell (DSSCs) with natural dye extracted from Noni leaves. Microstructures of CdS-ZnO from various dipping time were characterized by XRD, FE-SEM and EDX. The results showed that the CdS is hexagonal structure and the amount of CdS increases when the dipping time increases. The maximal conversion efficiency of 0.292% was achieved by the DSSCs based on CdS QDs-sensitized ZnO film obtained from 9 min-dipping time. Furthermore, the stability of DSSCs was improved by using polymeric electrolyte. Poly (acrylic acid) (PAA) and Polyacrylamide (PAM) were introduced to CdS QDs-sensitized ZnO film from 9 min-dipping time. Each polymeric electrolyte was prepared by swelling from 0.1-2.0 %w in H2O. The maximal conversion efficiency of 0.207% was achieved for DSSCs based on CdS QDs-sensitized ZnO film with PAM 1.0% and the conversion efficiency was decreased 25% when it was left for1 hr.

  13. Co-sensitization of ZnO by CdS quantum dots in natural dye-sensitized solar cells with polymeric electrolytes to improve the cell stability

    Energy Technology Data Exchange (ETDEWEB)

    Junhom, W.; Magaraphan, R. [Polymer Processing and Polymer Nanomaterials Research Unit, Petroleum and Petrochemical College, Chulalongkorn University, Bangkok (Thailand)

    2015-05-22

    The CdS quantum dots (QDs) were deposited on ZnO layer by chemical bath deposition method to absorb light in the shorter wavelength region and used as photoanode in the dye sensitized solar cell (DSSCs) with natural dye extracted from Noni leaves. Microstructures of CdS-ZnO from various dipping time were characterized by XRD, FE-SEM and EDX. The results showed that the CdS is hexagonal structure and the amount of CdS increases when the dipping time increases. The maximal conversion efficiency of 0.292% was achieved by the DSSCs based on CdS QDs-sensitized ZnO film obtained from 9 min-dipping time. Furthermore, the stability of DSSCs was improved by using polymeric electrolyte. Poly (acrylic acid) (PAA) and Polyacrylamide (PAM) were introduced to CdS QDs-sensitized ZnO film from 9 min-dipping time. Each polymeric electrolyte was prepared by swelling from 0.1-2.0 %w in H2O. The maximal conversion efficiency of 0.207% was achieved for DSSCs based on CdS QDs-sensitized ZnO film with PAM 1.0% and the conversion efficiency was decreased 25% when it was left for1 hr.

  14. Cutaneous sensitivity induced by immunization with irradiated Schistosoma mansoni cercariae. I. Induction, elicitation, and adoptive transfer analysis of cell-mediated cutaneous sensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Ch' ang, L.Y.; Colley, D.G.

    1986-06-01

    Exposure of C57BL/6 mice to highly irradiated (50 kR) cercariae of Schistosoma mansoni leads to the development of partial resistance against subsequent challenge with unattenuated cercariae. We have analyzed the cellular immune responses that occur during the afferent and efferent phases of this protective sensitization. Mice were immunized by exposure to irradiated S. mansoni cercariae. After challenge with irradiated cercariae, delayed-type (18-72 hr) cutaneous sensitivity reaction sites were rich in mononuclear cells and eosinophils. This reactivity was established by 4 days after sensitization, reached its maximum between 7 and 14 days after sensitization, and was maintained for over 20 weeks. These challenge reactions could be abrogated by treatment with either 200 mg/kg cyclophosphamide or 5 mg of hydrocortisone. Syngeneic adoptive transfer of cutaneous sensitivity was accomplished with lymphoid cells from the draining lymph nodes or spleens of mice sensitized 7-14 days previously. Negative selection studies of nylon-wool non-adherent cells from sensitized donors demonstrated that the cells responsible for transferring this eosinophil-rich, delayed-type cutaneous sensitivity to S. mansoni irradiated cercariae were Thy/sup -1 +/, Lyt/sup 1 +/, Lyt/sup 2 -/, surface Ig/sup -/ lymphocytes.

  15. Mycoplasma hyorhinis-Contaminated Cell Lines Activate Primary Innate Immune Cells via a Protease-Sensitive Factor.

    Directory of Open Access Journals (Sweden)

    Simon Heidegger

    Full Text Available Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments.

  16. [Apoptosis effects of drug sensitivity leukemia cells induced by nano-realgar].

    Science.gov (United States)

    Wang, Yong-Sheng; Zhou, Si-Tong; Wei, Hu-Lai

    2013-07-01

    To explore apoptosis-inducing effects of realgar nanoparticle (nano-realgar) on drug-sensitive leukemia cells. Preparation of nano-realgar was mechanical milled using a high-energy planetary ball mill. Using drug-sensitive leukemia cells (K562) as target cells, MTT assay was used to detect the proliferating activity of K562 cells, and the cellular apoptosis was investigated with double staining of FITC-Annexin V and propidium iodide (PI) by flow cytometry. Flow cytometry (FCM) was employed to detect expression of intracellular Bax, Bcl-2, P-53 protein and the activity of Caspase-3. The raw realgar was made to ultra-fine powder by ball milling, and the average diameter of the nanoparticle was (72.72 +/- 22.18) nm measured with electron microscopes. Nano-realgar significantly inhibited the proliferation of K562 cells, Treated for 24, 48 and 72 hours, the 50% inhibitory concentration (IC50) was 43.48, 20.52, 16.07 mg x L(-1). After exposure to 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 hours, the apoptosis of K562 cells detected by Annexin V/PI staining was increased, the apoptotic rate of K562 cells was 10. 52% and 73.25%. After the target cells were treated with 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 h, the expression of P-53, Bax, Bcl-2 markedly increased in a time and dose-dependent manner. After administration of 20 mg x L(-1) and 50 mg x L(-1) nano-realgar for 48 h, the percentage of BCRP+, P-gp+ and co-expressing P-gp and BCRP cell population in K562 cells incrased dramatically. Nano-Realgar significantly induced apoptosis of drug-sensitive leukemia cells.

  17. A rapid and sensitive method for measuring N-acetylglucosaminidase activity in cultured cells.

    Directory of Open Access Journals (Sweden)

    Victor Mauri

    Full Text Available A rapid and sensitive method to quantitatively assess N-acetylglucosaminidase (NAG activity in cultured cells is highly desirable for both basic research and clinical studies. NAG activity is deficient in cells from patients with Mucopolysaccharidosis type IIIB (MPS IIIB due to mutations in NAGLU, the gene that encodes NAG. Currently available techniques for measuring NAG activity in patient-derived cell lines include chromogenic and fluorogenic assays and provide a biochemical method for the diagnosis of MPS IIIB. However, standard protocols require large amounts of cells, cell disruption by sonication or freeze-thawing, and normalization to the cellular protein content, resulting in an error-prone procedure that is material- and time-consuming and that produces highly variable results. Here we report a new procedure for measuring NAG activity in cultured cells. This procedure is based on the use of the fluorogenic NAG substrate, 4-Methylumbelliferyl-2-acetamido-2-deoxy-alpha-D-glucopyranoside (MUG, in a one-step cell assay that does not require cell disruption or post-assay normalization and that employs a low number of cells in 96-well plate format. We show that the NAG one-step cell assay greatly discriminates between wild-type and MPS IIIB patient-derived fibroblasts, thus providing a rapid method for the detection of deficiencies in NAG activity. We also show that the assay is sensitive to changes in NAG activity due to increases in NAGLU expression achieved by either overexpressing the transcription factor EB (TFEB, a master regulator of lysosomal function, or by inducing TFEB activation chemically. Because of its small format, rapidity, sensitivity and reproducibility, the NAG one-step cell assay is suitable for multiple procedures, including the high-throughput screening of chemical libraries to identify modulators of NAG expression, folding and activity, and the investigation of candidate molecules and constructs for applications in

  18. Performance of natural-dye-sensitized solar cells by ZnO nanorod and nanowall enhanced photoelectrodes

    National Research Council Canada - National Science Library

    Saadaoui Saif; Ben Youssef Mohamed Aziz; Ben Karoui Moufida; Gharbi Rached; Smecca Emanuele; Strano Vincenzina; Mirabella Salvo; Alberti Alessandra; Puglisi Rosaria A

    2017-01-01

    In this work, two natural dyes extracted from henna and mallow plants with a maximum absorbance at 665 nm were studied and used as sensitizers in the fabrication of dye-sensitized solar cells (DSSCs...

  19. Elevation of circulating miR-210-3p in high-altitude hypoxic environment

    Directory of Open Access Journals (Sweden)

    Yan eYan

    2016-03-01

    Full Text Available Background: The induction of miR-210-3p, a master hypoxamir, is a consistent feature of the hypoxic response in both normal and malignant cells. However, whether miR-210-3p acts as a circulating factor in response to a hypoxic environment remains unknown. The current study aimed to examine the effect of a high-altitude hypoxic environment on circulating miR-210-3p.Methods: We examined and compared the levels of miR-210-3p using TaqMan-based qRT-PCR in both peripheral blood cells and plasma from 84 ethnic Chinese Tibetans residing at 3560 m, 46 newly arrived migrant Han Chinese (Tibet Han and 82 Han Chinese residing at 8.9 m (Nanjing Han. Furthermore, we analyzed the correlations of miR-210-3p with hematological indices. Results: The relative concentrations of miR-210-3p to internal reference U6 in blood cells were significantly higher in the Tibet Han group (1.01±0.11, P<0.001 and in the Tibetan group (1.17±0.09, P<0.001 than in the Nanjing Han group (0.51±0.04. The absolute concentrations of plasma miR-210-3p were also markedly elevated in the Tibet Han group (503.54±42.95 fmol/L, P=0.004 and in the Tibetan group (557.78±39.84 fmol/L, P<0.001 compared to the Nanjing Han group (358.39±16.16 fmol/L. However, in both blood cells and plasma, miR-210-3p levels were not significantly different between the Tibet Han group and the Tibetan group (P=0.280, P=0.620, respectively. Plasma miR-210-3p concentrations were positively correlated with miR-210-3p levels in blood cells (r=0.192, P=0.005. Furthermore, miR-210-3p levels in both blood cells and plasma showed strong positive correlations with red blood cell counts and hemoglobin and hematocrit values. Conclusion: These data demonstrated, for the first time, that miR-210-3p might act as a circulating factor in response to hypoxic environments and could be associated with human adaptation to life at high altitudes.

  20. Simplifying the construction of dye-sensitized solar cells to increase their accessibility for community education

    Energy Technology Data Exchange (ETDEWEB)

    Appleyard, Steve [Department of Environment and Conservation, PO Box K822, Perth, WA 6842 (Australia)

    2010-01-15

    Simple dye-sensitized solar cells were developed using blackboard chalk as a substrate for mixed ZnO and SnO{sub 2} films that were sensitized with Mercurochrome (Merbromine) dye. Graphite pencil 'leads' were used as counter electrodes for the cells and the electrolyte consisted of an aqueous solution of iodine and potassium iodide that was gelled with a disinfectant containing quaternary ammonium compounds and cyanoacrylate adhesive (Superglue {sup registered}). The open circuit potential of constructed cells was typically 0.50-0.64 V and the short circuit current varied between 0.5 and 2.0 mA cm{sup -2}. The cells were developed as an educational resource that could be simply and safely constructed in a home or school environment with readily accessible materials. (author)

  1. Dye ingredients and energy conversion efficiency at natural dye sensitized solar cells

    Science.gov (United States)

    Özbay Karakuş, Mücella; Koca, İrfan; Er, Orhan; Çetin, Hidayet

    2017-04-01

    In this work, natural dyes extracted from the same genus but different species flowers were used as sensitizer in Dye Sensitized Solar Cell (DSSC). To clearly show dye ingredients effect on electrical characteristics, the same genus flowers were selected. The dye ingredients were analyzed by Gas Chromatography Mass Spectrometer (GC-MS). The dyes were modified by a procedure that includes refluxing in acetone. All results indicate a relationship between gallic acid quantity in dyes and solar cell efficiency. To gain further insight, the solar cell parameters were obtained by using the single-diode and double-diode models and they were compared to each other. It was observed that the applied process causes a decrease in series resistance. How the modification process and gallic acid affect energy conversion efficiency were argued in detail in the frame of results that were obtained from solar cell models.

  2. Carbon Nanotubes Counter Electrode for Dye-Sensitized Solar Cells Application

    Directory of Open Access Journals (Sweden)

    Drygała A.

    2016-06-01

    Full Text Available The influence of the carbon nanotubes counter electrode deposited on the FTO glass substrates on the structure and optoelectrical properties of dye-sensitized solar cells counter electrode (CE was analysed. Carbon materials have been applied in DSSC s in order to produce low-cost solar cells with reasonable efficiency. Platinum is a preferred material for the counter electrode because of its high conductivity and catalytic activity. However, the costs of manufacturing of the platinum counter electrode limit its use to large-scale applications in solar cells. This paper presents the results of examining the structure and properties of the studied layers, defining optical properties of conductive layers and electrical properties of dye-sensitized solar cells manufactured with the use of carbon nanotubes.