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Hypoxia-inducible factor

A Archvadze, A Kistauri, N Gongadze, T Makharadze, K Chirakadze
Nowadays, chronic diseases are leading cause of death worldwide. One of popular chronic disease of 21 century is Diabetes Mellitus (DM) that affected 422 million people around the world in 2014; its prevalence is expected to increase to 592 million by the year 2035. Diabetic neuropathy (DN) seems to be the most common and least understood complication being present in over 50% of chronic diabetics. As the latest date explain the pathogenesis of DN is not fully understood. Therefore, considering the widespread of DN, severity of its consequences, it is vital to investigate details of its pathophysiology and find therapeutic strategies to improve patients' condition...
October 2018: Georgian Medical News
Ali Mahdi, Behrad Darvishi, Keivan Majidzadeh-A, Malihe Salehi, Leila Farahmand
It is now fully recognized that along with multiple physiological functions, angiogenesis is also involved in the fundamental process and pathobiology of several disorders including cancer. Recent studies have fully established the role of angiogenesis in cancer progression as well as invasion and metastasis. Consequently, many therapeutic agents such as monoclonal antibodies targeting angiogenesis pathway have been introduced in clinic with the hope for improving the outcomes of cancer therapy. Bevacizumab (Avastin®) was the first anti-vascular endothelial growth factor (VEGF) targeting monoclonal antibody developed with this purpose and soon received its accelerated US Food and Drug Administration (FDA) approval for treatment of patients with metastatic breast cancer in 2008...
December 4, 2018: Journal of Cellular Physiology
Effat Alizadeh, Parviz Mammadzada, Helder André
Ocular angiogenic diseases, such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, are associated with severe loss of vision. These pathologies originate from different vascular beds, retinal and choroidal microvasculatures, respectively. The activation of endothelial cells (EC) plays pivotal roles in angiogenesis, often triggered by oxygen deficiency. Hypoxia-inducible factors in ECs mediate the transcription of multiple angiogenic genes, including the canonical vascular endothelial growth factors...
December 3, 2018: International Journal of Molecular Sciences
Swetlana Rot, Helge Taubert, Matthias Bache, Thomas Greither, Peter Würl, Hans-Jürgen Holzhausen, Alexander W Eckert, Dirk Vordermark, Matthias Kappler
In various tumors, the hypoxia inducible factor-1α ( HIF-1α ) and the epidermal growth factor-receptor ( EGFR ) have an impact on survival. Nevertheless, the prognostic impact of both markers for soft tissue sarcoma (STS) is not well studied. We examined 114 frozen tumor samples from adult soft tissue sarcoma patients and 19 frozen normal tissue samples. The mRNA levels of HIF-1α, EGFR, and the reference gene hypoxanthine phosphoribosyltransferase (HPRT) were quantified using a multiplex qPCR technique. In addition, levels of EGFR or HIF-1α protein were determined from 74 corresponding protein samples using ELISA techniques...
December 3, 2018: International Journal of Molecular Sciences
Efseveia Frakolaki, Panagiota Kaimou, Maria Moraiti, Katerina I Kalliampakou, Kalliopi Karampetsou, Eleni Dotsika, Panagiotis Liakos, Dido Vassilacopoulou, Penelope Mavromara, Ralf Bartenschlager, Niki Vassilaki
Low oxygen tension exerts a profound effect on the replication of several DNA and RNA viruses. In vitro propagation of Dengue virus (DENV) has been conventionally studied under atmospheric oxygen levels despite that in vivo, the tissue microenvironment is hypoxic. Here, we compared the efficiency of DENV replication in liver cells, monocytes, and epithelial cells under hypoxic and normoxic conditions, investigated the ability of DENV to induce a hypoxia response and metabolic reprogramming and determined the underlying molecular mechanism...
December 1, 2018: Cells
Rohan Garje, Josiah J An, Kevin Sanchez, Austin Greco, Jeffrey Stolwijk, Eric Devor, Youcef Rustum, Yousef Zakharia
In the last two decades, the discovery of various pathways involved in renal cell carcinoma (RCC) has led to the development of biologically-driven targeted therapies. Hypoxia-inducible factors (HIFs), angiogenic growth factors, von Hippel⁻Lindau ( VHL ) gene mutations, and oncogenic microRNAs (miRNAs) play essential roles in the pathogenesis and drug resistance of clear cell renal cell carcinoma. These insights have led to the development of vascular endothelial growth factor (VEGF) inhibitors, Mechanistic target of rapamycin (mTOR) inhibitors, and immunotherapeutic agents, which have significantly improved the outcomes of patients with advanced RCC...
December 1, 2018: International Journal of Molecular Sciences
Weixiu Ji, Linjia Wang, Shiyi He, Lu Yan, Tieying Li, Jianxiong Wang, Ah-Ng Tony Kong, Siwang Yu, Ying Zhang
BACKGROUND: Hypoxia training enhances the endurance capacity of athletes. This response may in part be attributed to the hypoxia-induced increase in antioxidant capacity in skeletal muscles. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor which regulates the expression of genes via binding to the antioxidant-response element (ARE) of these genes, plays a crucial role in stimulating the body's defense system and potentially responds to hypoxia. Meanwhile, hypoxia-inducible factor-1α (HIF-1α) is an important player in protecting cells from hypoxic stress...
2018: PloS One
Guliang Yang, Chia-Che Chang, Yiwen Yang, Li Yuan, Leishiyuan Xu, Chi-Tang Ho, Shiming Li
Rheumatoid arthritis (RA) is a systemic autoimmune disease primarily affecting joints and is featured by chronic synovial inflammation and angiogenesis. We employed a bovine type-II collagen (BIIC)-induced Sprague-Dawley rat arthritis model and an in vitro RA model based on interleukin (IL)-1β-stimulated rat synovial cells (RSC-364) to explore the preventive effect of resveratrol on RA and the underlying mechanisms. We found that resveratrol ameliorated BIIC-elicited synovitis and RA-related pathological hallmarks such as inflammatory cell infiltration and angiogenesis in the synovial tissue...
December 4, 2018: Journal of Agricultural and Food Chemistry
Marco Papale, Elisabetta Ferretti, Giuseppe Battaglia, Diana Bellavia, Antonello Mai, Marco Tafani
During the past decades, several discoveries have established the role of epigenetic modifications and cellular microenvironment in tumor growth and progression. One of the main representatives concerning epigenetic modification is the polycomb group (PcG). It is composed of different highly conserved epigenetic effector proteins preserving, through several post-translational modifications of histones, the silenced state of the genes implicated in a wide range of central biological events such as development, stem cell formation, and tumor progression...
2018: Frontiers in Pediatrics
Jun Huang, Ciarán P Kelly, Kyriaki Bakirtzi, Javier A Villafuerte Gálvez, Dena Lyras, Steven J Mileto, Sarah Larcombe, Hua Xu, Xiaotong Yang, Kelsey S Shields, Weishu Zhu, Yi Zhang, Jeffrey D Goldsmith, Ishan J Patel, Joshua Hansen, Meijin Huang, Seppo Yla-Herttuala, Alan C Moss, Daniel Paredes-Sabja, Charalabos Pothoulakis, Yatrik M Shah, Jianping Wang, Xinhua Chen
Clostridium difficile infection (CDI) is mediated by two major exotoxins, toxin A (TcdA) and toxin B (TcdB), that damage the colonic epithelial barrier and induce inflammatory responses. The function of the colonic vascular barrier during CDI has been relatively understudied. Here we report increased colonic vascular permeability in CDI mice and elevated vascular endothelial growth factor A (VEGF-A), which was induced in vivo by infection with TcdA- and/or TcdB-producing C. difficile strains but not with a TcdA- TcdB- isogenic mutant...
December 3, 2018: Nature Microbiology
Romy R Schmidt, Martin Fulda, Melanie V Paul, Max Anders, Frederic Plum, Daniel A Weits, Monika Kosmacz, Tony R Larson, Ian A Graham, Gerrit T S Beemster, Francesco Licausi, Peter Geigenberger, Jos H Schippers, Joost T van Dongen
Plant response to environmental stimuli involves integration of multiple signals. Upon low-oxygen stress, plants initiate a set of adaptive responses to circumvent an energy crisis. Here, we reveal how these stress responses are induced by combining ( i ) energy-dependent changes in the composition of the acyl-CoA pool and ( ii ) the cellular oxygen concentration. A hypoxia-induced decline of cellular ATP levels reduces LONG-CHAIN ACYL-COA SYNTHETASE activity, which leads to a shift in the composition of the acyl-CoA pool...
December 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
Ilona Szabłowska-Gadomska, Magdalena Ducher, Magdalena Orzechowska, Joanna Bogusławska-Duch, Magdalena Kowalska, Helena Poławska, Maciej Małecki
Gynecological cancers constitute a serious problem in the world. Their advanced stages are often characterized by the accumulation of ascites, which leads to spreading of cancer cells outside their primary focus. Despite progress in the treatment, prognoses are still not satisfactory. The main causes of these failures are chemoresistance, metastases and recurrences of the disease, which is influenced by, among others, the microenvironment of cancer cells. This study investigated the effect of the microenvironment, which create ascites derived from patients with ovarian and endometrial cancer to non-gynecological HEK 293 cells...
2018: Polish Journal of Pathology: Official Journal of the Polish Society of Pathologists
Constantin Römmelt, Thomas Munsch, Andreas Drynda, Volkmar Lessmann, Christoph H Lohmann, Jessica Bertrand
The reasons for the high number of loosened metal-on-metal (MoM) hip implants are still not fully understood. Hypoxia-inducible factor 1 (HIF-1) mediated signaling pathways, which normally modulate tissue metabolism under hypoxic circumstances, could be triggered by metallic wear debris and influence bone metabolism favoring osteolysis. This may lead to early loosening of the orthopedic implants. Immunhistochemical staining of periprosthetic tissues of failed artificial hip implants showed that the concentration of HIF-1α in the surrounding tissues of failed MoM hip implants was significantly higher in comparison to failed metal-on-polyethylene (MoP) hip implants and osteoarthritic tissues...
December 3, 2018: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
Mariko Yamanoi, Kazuhiro Yamanoi, Chifumi Fujii, Michiko N Fukuda, Jun Nakayama
OBJECTIVES: To evaluate the expression of annexin A1 protein in patients with renal cell carcinoma. METHODS: Annexin A1 expression was examined in renal cell carcinoma specimens from 27 patients, and their disease-free survival was analyzed using the log-rank test. Annexin A1 knockdown in the human renal cell carcinoma cell line Caki-1 was carried out, and its proliferation, invasion, motility and adhesion were compared with those of control cells. RESULTS: In 13 out of 27 patients, annexin A1 was highly expressed in the membrane of renal cell carcinoma tumor cells, whereas in the rest of the patients, annexin A1 expression was weak or negligible in the membrane of those cells...
December 2, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
Xiaoli Niu, Siyuan Li, Simin Zheng, Hongfei Xiong, Junlin Lv, Huijuan Zhang, Hongtao Liu
The biochemical markers of rat under low oxygen concentration, including brain water level, lactic acid, necrosis and Na+-K+-ATPase, was detected to analyze the hypoxia-induced brain damage, and to analyze the mechanism of brain injury. Histopathological alteration in brain tissue induced by hypoxia were investigated through hematoxylin and eosin stain (HE). Hypoxia induced factor-1a (HIF-1a) expression level in the brain was carried out using immunohistochemistry. Lactic acid level was positively correlated with the level of hypoxia, while concentration-dependent decrease in total Na+-K+-ATPase activity was noted...
November 2018: Saudi Journal of Biological Sciences
Xinrui Zhao, Lidong Liu, Rui Li, Xuan Wei, Wenqing Luan, Peishu Liu, Jing Zhao
BACKGROUND Hypoxia induces cell apoptosis in the uterosacral ligaments of patients with pelvic organ prolapse by upregulation of hypoxia-inducible factor-1α (HIF-1α). This study aimed to investigate the effects of HIF-1α on human uterosacral ligament fibroblasts (hUSLFs) following treatment with the chemical inducer of hypoxia, cobalt chloride (CoCl2), and to explore the underlying mechanisms. MATERIAL AND METHODS Ten women who underwent hysterectomy for benign disease provided uterosacral ligament tissue for cell extraction...
December 3, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Sha Li, Shuren Li
OBJECTIVE: To evaluate the effects of transplantation of hypoxia-inducible factor-1α (HIF-1α) gene-modified cardiac stem cells (CSCs) on the cardiac function of heart failure rats after myocardial infarction (MI). METHODS: Twenty-four Sprague-Dawley rats were randomly divided into three groups: HIF-1α-modified CSCs group, single CSCs group, and model group. The model of heart failure after MI was established by thoracotomy-left anterior descending coronary artery ligation, followed by injection of modified CSCs, single CSCs, and PBS, respectively, 2 weeks later...
December 2018: Anatolian Journal of Cardiology
Lichan Tao, Long Wang, Xiaoyu Yang, Xiaohong Jiang, Fei Hua
BACKGROUND AND AIMS: Obstructive sleep apnea syndrome is a chronic disease associated with intermittent hypoxia (IH) and is an important risk factor for cardiovascular disease. Glucagon-like peptide (GLP-1) is a naturally occurring incretin used as a promising therapeutic agent in the treatment of acute myocardial infarction, dilated cardiomyopathy, and advanced heart failure. However, whether GLP-1 can protect against IH-induced cardiac injury is still unclear. Accordingly, in this study, we evaluated the effects of recombinant human GLP-1 (rhGLP-1) on cardiac health in mice...
November 29, 2018: Molecular and Cellular Endocrinology
M Mansour, J Degheili, I Khalifeh, H Tamim, R F Jaafar, Y El-Hout
BACKGROUND: Testicular torsion is a surgical emergency mainly affecting adolescent boys, with a relatively high rate of missed torsion and testicular loss secondary to delay in prompt diagnosis and surgical intervention. With ischemic reperfusion injury as its underlying culprit, testicular torsion may respond favorably to remote ischemic conditioning (RIC) where a non-privileged site (e.g. limb) is concurrently rendered ischemic to divert the cascade of reperfusion injury from the privileged organ (e...
September 24, 2018: Journal of Pediatric Urology
Faik Imeri, Karen A Nolan, Andreas M Bapst, Sara Santambrogio, Irene Abreu-Rodríguez, Patrick Spielmann, Svende Pfundstein, Silvana Libertini, Lisa Crowther, Ilaria M C Orlando, Sophie L Dahl, Anna Keodara, Willy Kuo, Vartan Kurtcuoglu, Carsten C Scholz, Weihong Qi, Edith Hummler, David Hoogewijs, Roland H Wenger
Erythropoietin (Epo) is essential for erythropoiesis and is mainly produced by the fetal liver and the adult kidney following hypoxic stimulation. Epo regulation is commonly studied in hepatoma cell lines, but differences in Epo regulation between kidney and liver limit the understanding of Epo dysregulation in polycythaemia and anaemia. To overcome this limitation, we have generated a novel transgenic mouse model expressing Cre recombinase specifically in the active fraction of renal Epo-producing (REP) cells...
November 23, 2018: Kidney International
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