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Hif-1 alpha

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https://www.readbyqxmd.com/read/29780805/stabilization-of-hypoxia-inducible-factor-1-alpha-augments-the-therapeutic-capacity-of-bone-marrow-derived-mesenchymal-stem-cells-in-experimental-pneumonia
#1
Naveen Gupta, Victor Nizet
Bone marrow-derived mesenchymal stem cells (MSCs) have therapeutic effects in experimental models of lung injury. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcriptional regulator that influences cellular metabolism, energetics, and survival under hypoxic conditions. The current study investigated the effects of stabilizing HIF-1α on the therapeutic capacity of MSCs in an experimental mouse model of bacterial pneumonia. HIF-1α stabilization was achieved by the small molecule prolyl-hydroxlase inhibitor, AKB-4924 (Aerpio Therapeutics, Inc...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29780505/macrophage-mediated-delivery-of-light-activated-nitric-oxide-prodrugs-with-spatial-temporal-and-concentration-control
#2
Michael A Evans, Po-Ju Huang, Yuji Iwamoto, Kelly N Ibsen, Emory M Chan, Yutaka Hitomi, Peter C Ford, Samir Mitragotri
Nitric oxide (NO) holds great promise as a treatment for cancer hypoxia, if its concentration and localization can be precisely controlled. Here, we report a "Trojan Horse" strategy to provide the necessary spatial, temporal, and dosage control of such drug-delivery therapies at targeted tissues. Described is a unique package consisting of (1) a manganese-nitrosyl complex, which is a photoactivated NO-releasing moiety (photoNORM), plus Nd3+ -doped upconverting nanoparticles (Nd-UCNPs) incorporated into (2) biodegradable polymer microparticles that are taken up by (3) bone-marrow derived murine macrophages...
April 21, 2018: Chemical Science
https://www.readbyqxmd.com/read/29771427/three-dimensional-echocardiography-in-the-diagnosis-of-myocardial-infarction-and-its-correlation-with-the-expressions-of-serum-hif-1%C3%AE-ho-1-and-vegf
#3
Q Yu, L Li, N Zhao
OBJECTIVE: To investigate the correlation between three-dimensional echocardiography and the expressions of hypoxia-inducible factor-1 alpha (HIF-1α), heme oxygenase 1 (HO-1) and vascular endothelial growth factor (VEGF) in patients with myocardial infarction. PATIENTS AND METHODS: A total of 40 patients with acute myocardial infarction treated with three-dimensional echocardiography and 40 patients receiving normal physical examination were selected. According to whether the disease occurred, they were divided into the myocardial infarction group and the normal group...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29763721/new-insights-into-hypoxia-related-mechanisms-involved-in-different-microvascular-patterns-of-bronchopulmonary-carcinoids-and-poorly-differentiated-neuroendocrine-carcinomas-role-of-ribonuclease-t2-rnaset2-and-hif-1-alpha
#4
Silvia Uccella, Stefano La Rosa, Debora Scaldaferri, Laura Monti, Roberta Maragliano, Elisa Sorrenti, Marzia Gariboldi, Roberto Taramelli, Fausto Sessa, Francesco Acquati
Ribonuclease T2 (RNASET2) is a pleiotropic and polyfunctional protein, which exerts several different activities in neoplastic cells since the early steps of tumor development. Besides having an antitumorigenic activity, RNASET2 inhibits both bFGF-induced and VEGF-induced angiogenesis and has a role as a stress-response, alarmin-like, protein. In this study, we investigated RNASET2 expression in well-differentiated and poorly differentiated neuroendocrine neoplasms of the lung (Lu-NENs), which are known to show clear-cut differences in morphology, biology and clinical behavior...
May 12, 2018: Human Pathology
https://www.readbyqxmd.com/read/29761922/fm19g11-inhibits-o-6-methylguanine-dna-methyltransferase-expression-under-both-hypoxic-and-normoxic-conditions
#5
Chao-Guo You, Han-Song Sheng, Chao-Ran Xie, Nu Zhang, Xue-Sheng Zheng
FM19G11 is a small molecular agent that inhibits hypoxia-inducible factor-1-alpha (HIF-1α) and other signaling pathways. In this study, we characterized the modulating effects of FM19G11 on O6 -methylguanine DNA-methyltransferase (MGMT), the main regulator of temozolomide (TMZ) resistance in glioblastomas. This study included 2 MGMT-positive cell lines (GBM-XD and T98G). MGMT promoter methylation status, mRNA abundance, and protein levels were determined before and after FM19G11 treatment, and the roles of various signaling pathways were characterized...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29756272/harnessing-human-decellularized-blood-vessel-matrices-and-cellular-construct-implants-to-promote-bone-healing-in-an-ex-vivo-organotypic-bone-defect-model
#6
Stefanie Inglis, Karl Heinrich Schneider, Janos M Kanczler, Heinz Redl, Richard O C Oreffo
Decellularized matrices offer a beneficial substitute for biomimetic scaffolds in tissue engineering. The current study examines the potential of decellularized placental vessel sleeves (PVS) as a periosteal protective sleeve to enhance bone regeneration in embryonic day 18 chick femurs contained within the PVS and cultured organotypically over a 10 day period. The femurs are inserted into decellularized biocompatibility-tested PVS and maintained in an organotypic culture for a period of 10 days. In femurs containing decellularized PVS, a significant increase in bone volume (p < 0...
May 14, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29748743/erythropoietin-and-nrf2-key-factors-in-the-neuroprotection-provided-by-apo-lactoferrin
#7
E T Zakharova, A V Sokolov, N N Pavlichenko, V A Kostevich, I N Abdurasulova, A V Chechushkov, I V Voynova, A Yu Elizarova, N N Kolmakov, M G Bass, I V Semak, A I Budevich, P M Kozhin, N K Zenkov, V M Klimenko, O V Kirik, D E Korzhevskii, E B Menshchikova, V B Vasilyev
Among the properties of lactoferrin (LF) are bactericidal, antianemic, immunomodulatory, antitumour, antiphlogistic effects. Previously we demonstrated its capacity to stabilize in vivo HIF-1-alpha and HIF-2-alpha, which are redox-sensitive multiaimed transcription factors. Various tissues of animals receiving recombinant human LF (rhLF) responded by expressing the HIF-1-alpha target genes, hence such proteins as erythropoietin (EPO), ceruloplasmin, etc. were synthesized in noticeable amounts. Among organs in which EPO synthesis occurred were brain, heart, spleen, liver, kidneys and lungs...
May 10, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/29747385/mithramycin-a-alleviates-osteoarthritic-cartilage-destruction-by-inhibiting-hif-2%C3%AE-expression
#8
Moon-Chang Choi, Woo Hee Choi
Osteoarthritis (OA) is the most common and increasing joint disease worldwide. Current treatment for OA is limited to control of symptoms. The purpose of this study was to determine the effect of specificity protein 1 (SP1) inhibitor Mithramycin A (MitA) on chondrocyte catabolism and OA pathogenesis and to explore the underlying molecular mechanisms involving SP1 and other key factors that are critical for OA. Here, we show that MitA markedly inhibited expressions of matrix-degrading enzymes induced by pro-inflammatory cytokine interleukin-1&beta; (IL-1&beta;) in mouse primary chondrocytes...
May 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29746587/metabolic-reprogramming-of-kaposi-s-sarcoma-associated-herpes-virus-infected-b-cells-in-hypoxia
#9
Rajnish Kumar Singh, Fengchao Lang, Yonggang Pei, Hem Chandra Jha, Erle S Robertson
Kaposi's sarcoma associated herpesvirus (KSHV) infection stabilizes hypoxia inducible factors (HIFs). The interaction between KSHV encoded factors and HIFs plays a critical role in KSHV latency, reactivation and associated disease phenotypes. Besides modulation of large-scale signaling, KSHV infection also reprograms the metabolic activity of infected cells. However, the mechanism and cellular pathways modulated during these changes are poorly understood. We performed comparative RNA sequencing analysis on cells with stabilized hypoxia inducible factor 1 alpha (HIF1α) of KSHV negative or positive background to identify changes in global and metabolic gene expression...
May 10, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29731777/the-hypoxia-mimetic-agent-cobalt-chloride-differently-affects-human-mesenchymal-stem-cells-in-their-chondrogenic-potential
#10
Gabriella Teti, Stefano Focaroli, Viviana Salvatore, Eleonora Mazzotti, Laura Ingra', Antonio Mazzotti, Mirella Falconi
Adult stem cells are a promising cell source for cartilage regeneration. They resided in a special microenvironment known as the stem-cell niche, characterized by the presence of low oxygen concentration. Cobalt chloride (CoCl2 ) imitates hypoxia in vitro by stabilizing hypoxia-inducible factor-alpha (HIF-1 α ), which is the master regulator in the cellular adaptive response to hypoxia. In this study, the influence of CoCl2 on the chondrogenic potential of human MSCs, isolated from dental pulp, umbilical cord, and adipose tissue, was investigated...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29716631/nherf1-and-tumor-microenvironment-a-new-scene-in-invasive-breast-carcinoma
#11
Concetta Saponaro, Alessandro Vagheggini, Emanuela Scarpi, Matteo Centonze, Ivana Catacchio, Ondina Popescu, Maria Irene Pastena, Francesco Giotta, Nicola Silvestris, Anita Mangia
BACKGROUND: Tumor microenvironment (TME) includes many factors such as tumor associated inflammatory cells, vessels, and lymphocytes, as well as different signaling molecules and extracellular matrix components. These aspects can be de-regulated and consequently lead to a worsening of cancer progression. In recent years an association between the scaffolding protein Na+ /H+ exchanger regulatory factor 1 (NHERF1) and tumor microenvironment changes in breast cancer (BC) has been reported...
May 2, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29698887/hypoxia-dependent-accumulation-of-hypoxia-inducible-factor-1-alpha-induces-transient-cell-cycle-arrest-in-porcine-trophectoderm-cells
#12
Wooyoung Jeong, Seoungo Jung, Fuller W Bazer, Jinyoung Kim
In the uterine environment, the pre-implantation embryo adapts to low oxygen concentrations through intracellular responses including modification of gene expression, progression via the cell cycle and metabolism. In this study, we determined mechanisms underlying the adaptation of pig embryos to oxygen deficiency in the maternal-conceptus microenvironment in in vitro experiments using our established porcine trophectoderm (pTr) cells in culture. The transition from G1 to S phase in pTr cells was reduced in response to 2% oxygen during a short period (<24 h), and the hypoxia-induced G1 arrest was reversible during prolonged hypoxia exposure...
April 14, 2018: Theriogenology
https://www.readbyqxmd.com/read/29690638/neurotensin-is-a-lipid-induced-gastrointestinal-peptide-associated-with-visceral-adipose-tissue-inflammation-in-obesity
#13
Ilaria Barchetta, Flavia Agata Cimini, Danila Capoccia, Laura Bertoccini, Valentina Ceccarelli, Caterina Chiappetta, Frida Leonetti, Claudio Di Cristofano, Gianfranco Silecchia, Marju Orho-Melander, Olle Melander, Maria Gisella Cavallo
Neurotensin (NT) is a 13-amino acid peptide localized in the neuroendocrine cells of the small intestine, which promotes fat absorption and fatty acids translocation in response to lipid ingestion. NT-knock-out mice fed with a high-fat diet are protected from obesity, fatty liver, and the development of insulin-resistance. In humans, higher plasma levels of pro-NT, which is the stable circulating precursor of NT, predict obesity, type 2 diabetes (T2D), and cardiovascular disease. In obesity, the presence of visceral adipose tissue (VAT) inflammation leads to unfavorable metabolic outcomes and is associated with the development of T2D and non-alcoholic fatty liver disease (NAFLD)...
April 23, 2018: Nutrients
https://www.readbyqxmd.com/read/29690507/hypoxia-induced-cisplatin-resistance-in-non-small-cell-lung-cancer-cells-is-mediated-by-hif-1%C3%AE-and-mutant-p53-and-can-be-overcome-by-induction-of-oxidative-stress
#14
Christophe Deben, Vanessa Deschoolmeester, Jorrit De Waele, Julie Jacobs, Jolien Van den Bossche, An Wouters, Marc Peeters, Christian Rolfo, Evelien Smits, Filip Lardon, Patrick Pauwels
The compound APR-246 (PRIMA-1MET ) is a known reactivator of (mutant) p53 and inducer of oxidative stress which can sensitize cancer cells to platinum-based chemotherapeutics. However, the effect of a hypoxic tumor environment has been largely overlooked in this interaction. This study focusses on the role of hypoxia-inducible factor-1&alpha; (HIF-1&alpha;) and the p53 tumor suppressor protein in hypoxia-induced cisplatin resistance in non-small cell lung cancer (NSCLC) cells and the potential of APR-246 to overcome this resistance...
April 21, 2018: Cancers
https://www.readbyqxmd.com/read/29671622/changes-in-kidney-tissue-and-effects-of-erythropoietin-after-acute-heart-failure
#15
A Güven Bağla, M Içkin Gülen, F Ercan, F Aşgün, E Ercan, C Bakar
Impairment of cardiac function causes renal damage. Renal failure after heart failure is attributed to hemodynamic derangement including reduced renal perfusion and increased venous pressure. One mechanism involves apoptosis and is defined as cardiorenal syndrome type 1. Erythropoietin (EPO) is a cytokine that induces erythropoiesis under hypoxic conditions. Hypoxia inducible factor 1 alpha (HIF-1α) plays a regulatory role in cellular response to hypoxia. Protective effects of EPO on heart, kidney and nervous system are unrelated to red blood cell production...
April 19, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29649529/mesoporous-silicate-nanoparticles-3d-nanofibrous-scaffold-mediated-dual-drug-delivery-for-bone-tissue-engineering
#16
Qingqing Yao, Yangxi Liu, Balaranjan Selvaratnam, Ranjit T Koodali, Hongli Sun
Controlled delivery systems play a critical role in the success of bone morphogenetic proteins (i.e., BMP2 and BMP7) for challenged bone repair. Instead of single-drug release that is currently and commonly prevalent, dual-drug delivery strategies are highly desired to achieve effective bone regeneration because natural bone repair process is driven by multiple factors. Particularly, angiogenesis is essential for osteogenesis and requires more than just one factor (e.g., Vascular Endothelial Growth Factor, VEGF)...
April 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29614494/deptor-deficiency-mediated-mtorc1-hyperactivation-in-vascular-endothelial-cells-promotes-angiogenesis
#17
Yan Ding, Lanlan Shan, Wenqing Nai, Xiaojun Lin, Ling Zhou, Xiaoying Dong, Hongyuan Wu, Min Xiao, Xuejuan Zhou, Linlin Wang, Ting Li, You Fu, Yijun Lin, Chunhong Jia, Meng Dai, Xiaochun Bai
BACKGROUND/AIMS: The mechanistic target of rapamycin (mTOR) signaling pathway is essential for angiogenesis and embryonic development. DEP domain-containing mTOR-interacting protein (DEPTOR) is an mTOR binding protein that functions to inhibit the mTOR pathway In vitro experiments suggest that DEPTOR is crucial for vascular endothelial cell (EC) activation and angiogenic responses. However, knowledge of the effects of DEPTOR on angiogenesis in vivo is limited. This study aimed to determine the role of DEPTOR in tissue angiogenesis and to elucidate the molecular mechanisms...
March 26, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29603404/a-review-of-the-mechanisms-of-action-of-dimethylfumarate-dmf-in-the-treatment-of-psoriasis
#18
REVIEW
J Brück, R Dringen, A Amasuno, I Pau-Charles, K Ghoreschi
Fumaric acid esters (FAEs) like dimethylfumarate (DMF) are used for the treatment of adults with moderate to severe psoriasis. The mode of action of FAEs is complex. Here we provide a comprehensive review of the literature to describe the molecular mechanisms by which DMF and its active metabolite monomethylfumarate (MMF) exert their anti-inflammatory and immune modulatory effects. MMF can bind to the hydroxy-carboxylic acid receptor 2 (HCA2) on the cell surface and both DMF and MMF react with intracellular glutathione following cell penetration...
March 30, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29525633/association-of-pd-l1-and-hif-1%C3%AE-coexpression-with-poor-prognosis-in-hepatocellular-carcinoma
#19
Xiaomeng Dai, Guoliang Pi, Sheng-Li Yang, George G Chen, Li-Ping Liu, Han-Hua Dong
OBJECTIVE: To investigate the correlation between the expression of PD-L1 and HIF-1α in hepatocellular carcinoma (HCC) tissue and further analyze the association with clinical parameters and the prognostic value of coexpression in HCC patients. METHODS: We assessed the expression of PD-L1 and HIF-1α by immunohistochemistry in tumor tissue from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients...
April 2018: Translational Oncology
https://www.readbyqxmd.com/read/29500923/regulation-of-hypoxia-inducible-factor-prolyl-hydroxylase-binding-domain-proteins-1-by-ppar%C3%AE-and-high-salt-diet
#20
Ezinne Ozurumba, Omana Mathew, Katsuri Ranganna, Myung Choi, Adebayo Oyekan
BACKGROUND: Hypoxia inducible factor (HIF)/prolyl hydroxylase domain (PHD)-containing proteins are involved in renal adaptive response to high salt (HS). Peroxisome proliferator activated receptor alpha (PPARα), a transcription factor involved in fatty acid oxidation is implicated in the regulation of renal function. As both HIF-1α/PHD and PPARα contribute to the adaptive changes to altered oxygen tension, this study tested the hypothesis that PHD-induced renal adaptive response to HS is PPARα-dependent...
March 28, 2018: Journal of Basic and Clinical Physiology and Pharmacology
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