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https://www.readbyqxmd.com/read/29778441/hypoxic-postconditioning-enhances-functional-recovery-following-endothelin-1-induced-middle-cerebral-artery-occlusion-in-conscious-rats
#1
Hong L Nguyen, Alexander M Ruhoff, Thomas Fath, Nicole M Jones
Stroke is a leading cause of death and a major contributor to neurological disability in adults. Tissue plasminogen activator is the only approved treatment. However, due to its narrow therapeutic window, <5% of patients receive treatment. Recently, hypoxic postconditioning (HPC) was shown to reduce stroke induced-injury in mice, but the mechanisms and functional outcomes are still unknown. In the current study, male Sprague Dawley rats were subjected to endothelin-1 induced stroke. HPC (8% O2 , 1 h/d for 5d) or normoxia treatments were started 24 h after stroke...
May 17, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29770329/aeg-1-contributes-to-metastasis-in-hypoxia-related-ovarian-cancer-by-modulating-the-hif-1alpha-nf-kappab-vegf-pathway
#2
Xiaoyu Yu, Yan Wang, Huilei Qiu, Hongtao Song, Di Feng, Yang Jiang, Shuzhe Deng, Hongxue Meng, Jingshu Geng
Objective: Ovarian carcinoma represents one of the deadliest malignancies among female cancer patients. Astrocyte-elevated gene-1 (AEG-1) participates in the ontogenesis of multiple human malignant diseases. Here we evaluated AEG-1, hypoxia-inducible factor- (HIF-) 1 α , nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κ B), and vascular endothelial growth factor (VEGF) amounts in hypoxia induced ovarian carcinoma cells. This study aimed to explore the mechanism by which AEG-1 regulates metastasis in hypoxia induced ovarian carcinoma...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29769561/transcriptome-analysis-of-circulating-pbmcs-to-understand-mechanism-of-high-altitude-adaptation-in-native-cattle-of-ladakh-region
#3
Preeti Verma, Ankita Sharma, Monika Sodhi, Kiran Thakur, Ranjit S Kataria, Saket K Niranjan, Vijay K Bharti, Prabhat Kumar, Arup Giri, Sahil Kalia, Manishi Mukesh
Ladakhi cattle is native population of Leh and Ladakh region and constantly exposed to hypobaric hypoxia over many generations. In present study, transcriptome signatures of cattle from Ladakh region (~5500 m) and Sahiwal cattle from tropical regions were evaluated using Agilent 44 K microarray chip. The top up-regulated genes in Ladakhi cows were INHBC, ITPRI, HECA, ABI3, GPR171, and HIF-1α involved in hypoxia and stress response. In Sahiwal cows, the top up-regulated genes eEF1A1, GRO1, CXCL2, DEFB3 and BOLA-DQA3 were associated with immune function and inflammatory response indicating their strong immune potential to combat the pathogens prevalent in the tropical conditions...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29765498/edaravone-improves-septic-cardiac-function-by-inducing-an-hif-1-%C3%AE-ho-1-pathway
#4
Chao He, Wei Zhang, Suobei Li, Wei Ruan, Junmei Xu, Feng Xiao
Septic myocardial dysfunction remains prevalent and raises mortality rate in patients with sepsis. During sepsis, tissues undergo tremendous oxidative stress which contributes critically to organ dysfunction. Edaravone, a potent radical scavenger, has been proved beneficial in ischemic injuries involving hypoxia-inducible factor- (HIF-) 1, a key regulator of a prominent antioxidative protein heme oxygenase- (HO-) 1. However, its effect in septic myocardial dysfunction remains unclarified. We hypothesized that edaravone may prevent septic myocardial dysfunction by inducing the HIF-1/HO-1 pathway...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29765155/genetic-transcriptional-and-post-translational-regulation-of-the-programmed-death-protein-ligand-1-in-cancer-biology-and-clinical-correlations
#5
REVIEW
Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z Rassidakis, Theodoros Foukakis
The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1...
May 16, 2018: Oncogene
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
#6
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/29761172/loss-of-hypoxia-inducible-factor-1%C3%AE-aggravates-%C3%AE-%C3%AE-t-cell-mediated-inflammation-during-acetaminophen-induced-liver-injury
#7
Tomohiro Suzuki, Shoko Minagawa, Takashi Yamazaki, Takatomo Arai, Mai Kanai, Satoko Shinjo, Nobuhito Goda
Acetaminophen (APAP)-induced liver injury is closely associated with acute hepatic inflammation. Hypoxia-inducible factor-1 (HIF-1) is activated during immunological processes and regulates gene expressions in various types of immune cells. Although HIF-1 controls the differentiation and functions of conventional T cells in chronic inflammation, the pathological importance of HIF-1 in innate-like T cells during acute inflammation remains unknown. Here, we investigated the role of HIF-1 in innate-like γδ T cells during APAP-induced acute liver injury...
May 2018: Hepatology Communications
https://www.readbyqxmd.com/read/29760417/ndrg3-lowers-the-metastatic-potential-in-prostate-cancer-as-a-feedback-controller-of-hypoxia-inducible-factors
#8
Ga Young Lee, Seung-Hyun Shin, Hyun-Woo Shin, Yang-Sook Chun, Jong-Wan Park
Expression of hypoxia-inducible factors (HIFs) and N-myc downstream-regulated gene 3 (NDRG3) are oxygen-dependently regulated by prolyl hydroxylase domain (PHD) enzymes. Little is known about the role of NDRG3 in the cellular adaptation to hypoxia, whereas the roles of HIFs are well understood. In this study, we investigated how NDRG3 affects the hypoxic response in prostate cancer cells. Compared with HIF-1α, hypoxic induction of NDRG3 was observed at a later phase. NDRG3 reduced hypoxic expression of HIF-1α by inhibiting AKT-driven translation of HIF1A mRNA...
May 14, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29755367/the-transcription-factor-hif-1-enhances-the-radio-resistance-of-mouse-mscs
#9
Irene Calvo-Asensio, Eugène T Dillon, Noel F Lowndes, Rhodri Ceredig
Mesenchymal stromal cells (MSCs) are multipotent progenitors supporting bone marrow hematopoiesis. MSCs have an efficient DNA damage response (DDR) and are consequently relatively radio-resistant cells. Therefore, MSCs are key to hematopoietic reconstitution following total body irradiation (TBI) and bone marrow transplantation (BMT). The bone marrow niche is hypoxic and via the heterodimeric transcription factor Hypoxia-inducible factor-1 (Hif-1), hypoxia enhances the DDR. Using gene knock-down, we have previously shown that the Hif-1α subunit of Hif-1 is involved in mouse MSC radio-resistance, however its exact mechanism of action remains unknown...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29748743/erythropoietin-and-nrf2-key-factors-in-the-neuroprotection-provided-by-apo-lactoferrin
#10
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/29748146/discovery-of-bicyclo-3-3-1-non-2-ene-as-a-novel-skeleton-for-hif-1-inhibitors
#11
Hiroki Ueda, Atsushi Yoshimori, Hiroyuki Nakamura
Bicyclo[3,3,1]non-2-ene was used as a novel three-dimensional skeleton for the design and synthesis of hypoxia-inducible factor (HIF)-1 inhibitors. Among the compounds synthesized, compound 4b was found to be a potent inhibitor of HIF-1α protein accumulation under hypoxia and inhibited HIF-1α transcriptional activity in HeLa (human cervical carcinoma) cells (half maximal inhibitory concentration [IC50 ] = 3.0 μM). The inhibition of HIF-1α accumulation induced by compound 4b was attenuated by treating the cells with MG132, a proteasome inhibitor, in a concentration-dependent manner, indicating that the compound 4b induces oxygen-independent proteasomal degradation of HIF-1α...
May 3, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29745343/indazoles-derivatives-promising-anti-tumor-agents
#12
Yichao Wan, Shengzhuo He, Wei Li, Zilong Tang
Currently, cancer continues being a dramatically increasing and serious threat to public health. Although many anti-tumor agents have been developed in recent years, the survival rate of patients is not satisfactory. The poor prognosis of cancer patients is closely related to the occurrence of drug resistance. Therefore, it is urgent to develop new anti-tumor agents to make up for the deficiency. Indazoles is an important class of heterocyclic compounds possessing a variety of biological activities, such as anti-tumor, anti-bacterial, anti-inflammatory, anti-depressant and anti-hypertensive...
May 9, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29742803/septin-9-isoform-1-sept9_i1-specifically-interacts-with-importin-%C3%AE-7-to-drive-hypoxia-inducible-factor-hif-1%C3%AE-nuclear-translocation
#13
Keren Tazat, Susanne Schindler, Reinhard Deppeing, Nicola J Mabjeesh
We have shown previously that septin 9 isoform 1 (SEPT9_i1) protein associates with hypoxia-inducible factor (HIF)-1α to augment HIF-1 transcriptional activity by driving its importin-α-mediated nuclear translocation. Using in vitro and in vivo binding assays we identified that HIF-1α interacts with importin-α5 and importin-α7 in prostate cancer cells but only importin-α7 interacts with SEPT9_i1. The interaction with importin-α7 was dependent on the first 25 amino acids of SEPT9_i1 that are unique compared to other members of the mammalian septin family...
May 9, 2018: Cytoskeleton
https://www.readbyqxmd.com/read/29742498/fg-4592-accelerates-cutaneous-wound-healing-by-epidermal-stem-cell-activation-via-hif-1%C3%AE-stabilization
#14
Di Tang, Junhui Zhang, Tiantian Yan, Jingyu Wei, Xupin Jiang, Dongxia Zhang, Qiong Zhang, Jiezhi Jia, Yuesheng Huang
BACKGROUND/AIMS: Regional hypoxia promptly develops after trauma because of microvascular injury and increased oxygen consumption. This acute hypoxia plays a positive role in early skin wound healing. One of the mechanisms underlying the beneficial effects of acute hypoxia on wound healing may be increased hypoxia-inducible factor-1 (HIF-1α) expression. HIF-1α may affect the wound-healing process through many aspects, including angiogenesis, metabolism, and extra-cellular matrix synthesis and remodelling...
May 5, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29739298/multicenter-prospective-study-of-angiogenesis-polymorphism-validation-in-hcc-patients-treated-with-sorafenib-an-innovate-study-protocol
#15
Andrea Casadei Gardini, Luca Faloppi, Giuseppe Aprile, Oronzo Brunetti, Chiara Caparello, Jody Corbelli, Luchino Chessa, Daniele Bruno, Giorgio Ercolani, Alessandro Leonetti, Giorgio de Stefano, Nunzia Farella, Francesco Giuseppe Foschi, Arianna Lanzi, Vincenzo Dadduzio, Giorgia Marisi, Gianluca Masi, Francesca V Negri, Flavia Pagan, Daniele Santini, Emanuela Scarpi, Marianna Silletta, Nicola Silvestris, Emiliano Tamburini, Davide Tassinari, Caterina Vivaldi, Umberto Vespasiani Gentilucci, Vittorina Zagonel, Lorenzo Calvetti, Stefano Cascinu, Giovanni Luca Frassineti, Mario Scartozzi
Introduction Although sorafenib is the upfront standard of care for advanced hepatocellular carcinoma (HCC), molecular predictors of efficacy have not been identified yet. In the ALICE-1 study, rs2010963 of VEGF-A and VEGF-C proved to be independent predictive factors for progression-free survival (PFS) and overall survival (OS) in multivariate analysis. The ALICE-1 study results were confirmed in the ALICE-2 study, in which VEGF and VEGFR SNPs were analyzed. In the ePHAS study we analyzed the SNPs of eNOS...
December 1, 2017: Tumori
https://www.readbyqxmd.com/read/29731777/the-hypoxia-mimetic-agent-cobalt-chloride-differently-affects-human-mesenchymal-stem-cells-in-their-chondrogenic-potential
#16
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/29719086/overexpression-of-genes-associated-with-hypoxia-in-cattle-adapted-to-trans-himalayan-region-of-ladakh
#17
Preeti Verma, Ankita Sharma, Monika Sodhi, Kiran Thakur, Vijay Bharti, Prabhat Kumar, Arup Giri, Sahil Kalia, Shelesh Kumar Swami, Manishi Mukesh
Ladakh is an important part of the Trans-Himalayan region located between the Kunlun mountain range in the north and the main Great Himalayas to the south in the state of Jammu and Kashmir of India. The local cattle from Leh and Ladakh region, known as "Ladakhi cattle" is a unique germplasm having excellent adaptation potential to high altitude hypobaric stress. In the present study, an effort was made to evaluate the transcriptional pattern of hypoxia inducing factor-1 (HIF-1) and several of its regulated genes in PBMCs of local Ladakhi cattle, Holstein Frisian crosses, Jersey (exotic) maintained at high altitude region and Sahiwal (Bos indicus) and Karan Fries (cross bred) cattle maintained in tropical environment...
May 2, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29717634/notch-signaling-enhances-stemness-by-regulating-metabolic-pathways-through-modifying-p53-nf-%C3%AE%C2%BAb-and-hif-1%C3%AE
#18
Hiroyuki Moriyama, Mariko Moriyama, Toshiyuki Ozawa, Daisuke Tsuruta, Taro Iguchi, Satoshi Tamada, Tatsuya Nakatani, Koichi Nakagawa, Takao Hayakawa
Human adipose-derived stromal cells (hASCs) are attractive for regenerative medicine, but their limited in vitro lifespan limits their therapeutic applicability. Recent data demonstrate that hypoxia may benefit the ex vivo culture of stem cells. Such cells exhibit a high level of glycolytic metabolism under hypoxic conditions. However, the physiological role of glycolytic activation and its underlying regulatory mechanism are incompletely understood. We have shown that when activated under conditions of 5% O<sub>2</sub>, Notch signaling dramatically increases the rate of glycolysis, improves proliferation efficiency, prevents senescence, and maintains the multipotency of hASCs...
May 2, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29716919/abemaciclib-a-selective-cdk4-6-inhibitor-enhances-the-radiosensitivity-of-non-small-cell-lung-cancer-in-vitro-and-in-vivo
#19
Sarwat Naz, Anastasia L Sowers, Rajani Choudhuri, Maria F Wissler, Janet Gamson, Askale Mathias, John A Cook, James B Mitchell
PURPOSE: To characterize the ionizing radiation (IR) enhancing effects and underlying mechanisms of CDK4/6 inhibitor, Abemaciclib in Non-Small Cell Lung Cancer cells (NSCLC) in vitro and in vivo Experimental Design: IR enhancement by Abemaciclib in a variety of NSCLC cell lines was assessed by in vitro clonogenic assay, flow cytometry, and target inhibition verified by immunoblotting. IR-induced DNA damage repair was evaluated by γ-H2AX analysis. Global metabolic alterations by Abemaciclib and IR combination was evaluated by LC/MS mass spectrometry and YSI-Bioanalyzer...
May 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29713350/sphingosine-1-phosphate-receptor-1-is-required-for-mmp-2-function-in-bone-marrow-mesenchymal-stromal-cells-implications-for-cytoskeleton-assembly-and-proliferation
#20
Chiara Sassoli, Federica Pierucci, Alessia Tani, Alessia Frati, Flaminia Chellini, Francesca Matteini, Ambra Vestri, Giulia Anderloni, Daniele Nosi, Sandra Zecchi-Orlandini, Elisabetta Meacci
Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling and proliferation and secretion ability, is played by matrix metalloproteinase- (MMP-) 2. Therefore, the identification of paracrine/autocrine regulators of MMP-2 function may be of great relevance for improving BM-MSC therapeutic potential. We recently reported that BM-MSCs release the bioactive lipid sphingosine 1-phosphate (S1P) and, here, we demonstrated an impairment of MMP-2 expression/release when the S1P receptor subtype S1PR1 is blocked...
2018: Stem Cells International
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