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  • Open Access

    ARTICLE

    Inhibition of VEGF-A expression in hypoxia-exposed fetal retinal microvascular endothelial cells by exosomes derived from human umbilical cord mesenchymal stem cells

    JING LI1,2, WANWAN FAN4, LILI HAO1, YONGSHENG LI5, GUOCHENG YU1, WEI SUN6, XIANQIONG LUO2,*, JINGXIANG ZHONG1,3,*

    BIOCELL, Vol.47, No.11, pp. 2485-2494, 2023, DOI:10.32604/biocell.2023.044177

    Abstract Objective: This study aimed to investigate the potential of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes (hucMSC-Exos) in inhibiting hypoxia-induced cell hyper proliferation and overexpression of vascular endothelial growth factor A (VEGF-A) in immature human fetal retinal microvascular endothelial cells (hfRMECs). Methods: Exosomes were isolated from hucMSCs using cryogenic ultracentrifugation and characterized through various techniques, including transmission electron microscopy, nanoparticle tracking analysis, bicinchoninic acid assays, and western blotting. The hfRMECs were identified using von Willebrand factor (vWF) co-staining and divided into four groups: a control group cultured under normoxic condition, a hypoxic model group, a hypoxic group treated with… More > Graphic Abstract

    Inhibition of VEGF-A expression in hypoxia-exposed fetal retinal microvascular endothelial cells by exosomes derived from human umbilical cord mesenchymal stem cells

  • Open Access

    ARTICLE

    NR4A1 enhances glycolysis in hypoxia-exposed pulmonary artery smooth muscle cells by upregulating HIF-1α expression

    CHENYANG CHEN1,*, JUAN WEN1, WEI HUANG1, JIANG LI2,*

    BIOCELL, Vol.47, No.11, pp. 2423-2433, 2023, DOI:10.32604/biocell.2023.044459

    Abstract Background: Pulmonary arterial hypertension (PAH) is a chronic and progressive disease that is strongly associated with dysregulation of glucose metabolism. Alterations in nuclear receptor subfamily 4 group A member 1 (NR4A1) activity alter the outcome of PAH. This study aimed to investigate the effects of NR4A1 on glycolysis in PAH and its underlying mechanisms. Methods: This study included twenty healthy volunteers and twenty-three PAH patients, and plasma samples were collected from the participants. To mimic the conditions of PAH in vitro, a hypoxia-induced model of pulmonary artery smooth muscle cell (PASMC) model was established. The proliferation of PASMCs was assessed… More > Graphic Abstract

    NR4A1 enhances glycolysis in hypoxia-exposed pulmonary artery smooth muscle cells by upregulating HIF-1α expression

  • Open Access

    Anisodine hydrobromide alleviates oxidative stress caused by hypoxia/reoxygenation in human cerebral microvascular endothelial cells predominantly via inhibition of muscarinic acetylcholine receptor 4

    WENLI JIANG1,#, JUNYI SHEN1,#, XIAOQIANG DU1,#, YAN QIU1, JIAN ZHONG1, ZHI OUYANG1, BINGMEI M. FU2, YE ZENG1,*

    BIOCELL, Vol.47, No.10, pp. 2255-2263, 2023, DOI:10.32604/biocell.2023.030880

    Abstract Background: Anisodine hydrobromide (AT3), an anti-cholinergic agent, could be delivered to the brain across the blood-brain barrier and has been used clinically for the treatment of cerebral ischemia/reperfusion injury. Endothelial dysfunction can be caused by hypoxia/reoxygenation (H/R) via oxidative stress and metabolic alterations. The present study investigated whether AT3 regulates the production of nitric oxide (NO) and reactive oxygen species (ROS), and the HIF-1α pathway via regulation of muscarinic acetylcholine receptors (mAChRs) in brain microvascular endothelial cells after H/R exposure. Methods: Under H/R conditions, hCMEC/D3 cerebral microvascular endothelial cells were treated with AT3. Specific inhibitors of M2- and M4- mAChRs… More > Graphic Abstract

    Anisodine hydrobromide alleviates oxidative stress caused by hypoxia/reoxygenation in human cerebral microvascular endothelial cells predominantly via inhibition of muscarinic acetylcholine receptor 4

  • Open Access

    ARTICLE

    Reversal of maternal obesity attenuates hypoxia and improves placental development in the preeclamptic-like BPH/5 mouse model

    DANIELLA M. ADAMS1, KALIE F. BECKERS1, JULIET P. FLANAGAN1, VIVIANE C. L. GOMES1,#, CHIN-CHI LIU1, JENNY L. SONES1,2,*

    BIOCELL, Vol.47, No.9, pp. 2051-2058, 2023, DOI:10.32604/biocell.2023.029644

    Abstract Background: Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface. Methods: To test this hypothesis, BPH/5 mice were fed ad libitum (lib) and pair-fed (PF) to C57 ad lib controls beginning… More >

  • Open Access

    ARTICLE

    Mechanism of NURP1 in temozolomide resistance in hypoxia-treated glioma cells via the KDM3A/TFEB axis

    TAO LI#, XIN FU#, JIE WANG, WEI SHANG, XIAOTONG WANG, LINYUN ZHANG, JUN LI*

    Oncology Research, Vol.31, No.3, pp. 345-359, 2023, DOI:10.32604/or.2023.028724

    Abstract Temozolomide (TMZ) resistance is a major obstacle in glioma treatment. Nuclear protein-1 (NUPR1) is a regulator of glioma progression. This study investigated the mechanism of NUPR1 in TMZ resistance in hypoxia-treated glioma cells and its mechanism in modulating autophagy. We treated TMZ-resistant cells U251-TMZ and T98G-TMZ to normoxia or hypoxia and silenced NUPR1 in hypoxia-treated U251-TMZ and T98G-TMZ cells to assess cell viability, proliferation, apoptosis, LC3-II/LC3-I and p62 expressions, and autophagic flux under different concentrations of TMZ. We found that hypoxia upregulated NUPR1 expression and autophagy while NUPR1 silencing suppressed hypoxia-induced TMZ resistance and autophagy in glioma cells. We also… More > Graphic Abstract

    Mechanism of NURP1 in temozolomide resistance in hypoxia-treated glioma cells via the KDM3A/TFEB axis

  • Open Access

    REVIEW

    Hypoxia-induced reactive oxygen species in organ and tissue fibrosis

    LINSHEN XIE1, QIAOLAN WANG1, JINGXUAN MA1, YE ZENG2,*

    BIOCELL, Vol.47, No.2, pp. 261-267, 2023, DOI:10.32604/biocell.2023.024738

    Abstract Fibrosis is the end-stage change of damaged tissues in various human diseases, which can lead to permanent scarring or organ malfunction. Hypoxia leads to oxidative stress, mitochondrial dysfunction, and inflammation in dysfunctional organs and tissues. Oxidative stress resulting from the overproduction of reactive oxygen species plays a central role in the fibrosis of injured organs. This review addresses the updated knowledge of the relationship between hypoxia and tissue fibrosis mediated by the reactive oxygen species pathway. Moreover, novel anti-fibrotic strategies are discussed, which may suppress reactive oxygen species and organ fibrosis. More >

  • Open Access

    ARTICLE

    Silencing of NADPH Oxidase 4 Attenuates Hypoxia Resistance in Neuroblastoma Cells SH-SY5Y by Inhibiting PI3K/Akt-Dependent Glycolysis

    Ting Yu*1, Lei Li†1, Wenyan Liu*, Bailiu Ya*, Hongju Cheng*, Qing Xin*

    Oncology Research, Vol.27, No.5, pp. 525-532, 2019, DOI:10.3727/096504018X15179668157803

    Abstract Hypoxia-induced chemoresistance is a major obstacle in the development of effective cancer therapy. In our study, the reversal abilities of NADPH oxidase 4 (NOX4) silence on hypoxia resistance and the potential mechanism were investigated. Our data showed that the expression of NOX4 was upregulated in human neuroblastoma cells SH-SY5Y under hypoxia condition time dependently. Knockdown of NOX4 expression by siRNA inhibited glycolysis induced by hypoxia through decreasing the expression of glycolysis-related proteins (HIF-1 , LDHA, and PDK1), decreasing glucose uptake, lactate production, and ROS production, while increasing mitochondria membrane potential. Moreover, NOX4 silence inhibited cell growth under hypoxia condition through… More >

  • Open Access

    REVIEW

    Screening and evaluation of chilli (Capsicum annuum L.) genotypes for waterlogging tolerance at seedling stage

    MD. REZWAN MOLLA1,2,4, MD. MOTIAR ROHMAN2,*, MD. ROBYUL ISLAM1,2, MIRZA HASANUZZAMAN3,*, LUTFUL HASSAN4

    BIOCELL, Vol.46, No.7, pp. 1613-1627, 2022, DOI:10.32604/biocell.2022.019243

    Abstract Waterlogging is an illustrious abiotic stress and the constrictions it enforces on plant roots have negative effects on growth and development. This study was undertaken to investigate waterlogging stress tolerant potential in chilli (Capsicum annum L.) genotypes through evaluating morphological, physiological, biochemical and anatomical parameters. Thirty-five days old seedlings of 10 chilli genotypes were exposed to waterlogging stress maintaining water height 3–5 cm over the soil surface artificially for three days. This duration (36–38 DAE) was termed as waterlogging period, and subsequent withdrawal of waterlogging condition (39–45 DAE) was regarded as a recovery phase. Based on their survival performance, two… More >

  • Open Access

    ARTICLE

    Hypoxia induced apoptosis of rat gastric mucosal cells by activating autophagy through HIF-1α/TERT/mTORC1 pathway

    YAPING WANG1,2,#,*; XIAOHONG XUE2,#; ZHEN ZHAO1,#; XIAOLIN LI2; ZHIYONG ZHU1

    BIOCELL, Vol.46, No.7, pp. 1651-1659, 2022, DOI:10.32604/biocell.2022.018559

    Abstract The pathogenesis of high altitude-related gastric mucosal injury remains poorly understood, this study aimed to investigate the role of autophagy in hypoxia-induced apoptosis of rat gastric mucosal cells. Rats were randomized into four groups which were maintained at an altitude of 400 m (P) or received no treatment (H), autophagy inducer rapamycin (H+AI) or autophagy inhibitor 3-MA (H+AB) at an altitude of 4,300 m for 1, 7, 14 and 21 days, respectively, and the morphology, ultrastructure, autophagy, and apoptosis of gastric mucosal tissues were examined. Gastric mucosal epithelial cells CC-R039 were cultured under conditions of normoxia, 2% O2 (hypoxia), or… More >

  • Open Access

    ARTICLE

    Dihydropyrimidinase like 3 as a novel target of wild type p53 suppresses MAPK pathway in response to hypoxia

    YUANNA DU1,#, WENWEN GONG2,#, JING LIANG1,#, RUKUN ZANG1, JUNJUN MOU1

    BIOCELL, Vol.46, No.5, pp. 1181-1188, 2022, DOI:10.32604/biocell.2022.016148

    Abstract Endometrial cancer remains to be a major type of malignancy in threatening female life. Molecular insights in advancing our understanding of endometrial tumorigenesis are much needed. We here report that a less-studied protein Dihydropyrimidinase like 3 (DPYSL3) is a potent tumor suppressor. DPYSL3 is uniquely regulated by wild type p53 (wtp53), and its expression is at the highest level when cells carry wtp53 and are exposed to hypoxia. We reveal that wtp53 can bind DPYSL3 promoter to enhance DPYSL3 expression and in turn, the elevated DPYSL3 can restrain cancer cell proliferation and invasion in vitro and in vivo. Importantly, we… More >

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