Anti-Androgen and Anti-Hypoxia Treatment for Severe COVID-19 Patients

2021 ◽  
Author(s):  
Siqi Wu ◽  
Binbin Guo ◽  
Chang Gao ◽  
Jieqiong Deng ◽  
Fang Li ◽  
...  
Keyword(s):  
Hypoxia Treatment

Prognostic Significance of [18F]-Misonidazole Positron Emission Tomography–Detected Tumor Hypoxia in Patients With Advanced Head and Neck Cancer Randomly Assigned to Chemoradiation With or Without Tirapazamine: A Substudy of Trans-Tasman Radiation Oncology Group Study 98.02

2006 ◽  
Vol 24 (13) ◽  
pp. 2098-2104 ◽  
Author(s):  
Danny Rischin ◽  
Rodney J. Hicks ◽  
Richard Fisher ◽  
David Binns ◽  
June Corry ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Head And Neck ◽  
Tumor Hypoxia ◽  
Prognostic Significance ◽  
Emission Tomography ◽  
Primary Tumors ◽  
Locoregional Failure ◽  
Positron Emission ◽  
Radiation Oncology Group ◽  
Hypoxia Treatment

Purpose To determine the association between tumor hypoxia, treatment regimen, and locoregional failure (LRF) in patients with stage III or IV squamous cell carcinoma of the head and neck randomly assigned to radiotherapy (70 Gy in 35 fractions over 7 weeks) plus either tirapazamine and cisplatin in weeks 1, 4, and 7 and tirapazamine alone in weeks 2 and 3 (TPZ/CIS) or cisplatin and infusional fluorouracil during weeks 6 and 7 (chemoboost). Patients and Methods Forty-five patients were enrolled onto a hypoxic imaging substudy of a larger randomized trial. Pretreatment and midtreatment [18F]-fluoromisonidazole positron emission tomography scans (FMISO-PET) were performed 2 hours after tracer administration, with qualitative scoring of uptake in both primary tumors and nodes. Results Thirty-two patients (71%) had detectable hypoxia in either or both primary and nodal disease. In patients who received chemoboost, one of 10 patients without hypoxia had LRF compared with eight of 13 patients with hypoxia; the risk of LRF was significantly higher in hypoxic patients (exact log-rank, P = .038; hazard ratio [HR] = 7.1). By contrast, in patients who received the TPZ/CIS regimen, only one of 19 patients with hypoxic tumors had LRF; risk of LRF was significantly higher in chemoboost patients (P = .001; HR = 15). Similarly, looking at the primary site alone, in patients with hypoxic primaries, zero of eight patients treated with TPZ/CIS experienced failure locally compared with six of nine patients treated with chemoboost (P = .011; HR = 0). Conclusion Hypoxia on FMISO-PET imaging, in patients receiving a nontirapazamine-containing chemoradiotherapy regimen, is associated with a high risk of LRF. Our data provide the first clinical evidence to support the experimental observation that tirapazamine acts by specifically targeting hypoxic tumor cells.

Lipid remodelling plays an important role in wheat (Triticum aestivum) hypoxia stress

2020 ◽  
Vol 47 (1) ◽  
pp. 58 ◽  
Author(s):  
Le Xu ◽  
Rui Pan ◽  
Meixue Zhou ◽  
Yanhao Xu ◽  
Wenying Zhang
Keyword(s):  
Triticum Aestivum ◽  
Oxygen Deficiency ◽  
Normal Growth ◽  
Triticum Aestivum L ◽  
Growth Conditions ◽  
Membrane Lipid ◽  
Hypoxia Stress ◽  
Phosphatidic Acids ◽  
Hypoxia Treatment ◽  
Lower Expression

Membrane lipid remodelling is one of the strategies that plants have developed to combat abiotic stress. In this study, physiological, lipidomic and proteome analyses were conducted to investigate the changes in glycerolipid and phospholipid concentrations in the wheat (Triticum aestivum L.) cultivars CIGM90.863 and Seri M82 under hypoxia treatment. The growth of CIGM90.863 remained unaffected, whereas Seri M82 was significantly stunted after 8 days of hypoxia treatment. The concentrations of all lipids except lysophosphatidylglycerol were significantly higher in the leaves of Seri M82 than in CIGM90.863 under normal growth conditions. The lipid profile changed significantly under hypoxia stress and varied between genotypes for some of the lipids. Phosphatidic acids remained unchanged in Seri M82 but they were gradually induced in CIGM90.863 in response to hypoxia stress because of the higher phospholipase D expression and lower expression of diglycerol kinase and phosphatidate phosphatases. In contrast, digalactosyldiacylglycerol content was highly stable in CIGM90.863 following hypoxia treatment, although it decreased significantly in Seri M82. Phosphatidylglycerol and lipoxygenase showed a stronger and faster response in CIGM90.863 than in Seri M82 under hypoxia stress. Different membrane lipid adjustments in wheat under oxygen deficiency conditions could be partly responsible for the differing tolerance of Seri M82 and CIGM90.863. This study will help us to better understand how wheat tolerates hypoxia stress by regulating lipid remodelling.

scholarly journals Hypoxia Suppresses TGF-B1-Induced Cardiac Myocyte Myofibroblast Transformation by Inhibiting Smad2/3 and Rhoa Signaling Pathways

2018 ◽  
Vol 45 (1) ◽  
pp. 250-257 ◽  
Author(s):  
Zhankui Yan ◽  
Daifei Shen ◽  
Jilin Liao ◽  
Yanmei Zhang ◽  
Yicun Chen ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Western Blotting ◽  
Intermittent Hypoxia ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Specific Cell ◽  
Dependent Manner ◽  
H9c2 Cells ◽  
Hypoxia Treatment ◽  
Tgf Β1

Background/Aims: Hypoxia modulation of transforming growth factor (TGF)- β-induced signaling during myofibroblast transformation is dependent on the specific cell type. The purpose of this study was to explore the effects of hypoxia on myofibroblast transformation of TGF-β1-induced cardiomyocyte H9c2 cells. Methods: H9c2 cells were cultured for intermittent hypoxia treatment and TGF-β1 treatment. α-Smooth muscle actin (α-SMA) expression was examined by western blotting and immunofluorescence after treatment. To further explore the possible mechanism for this effect, the effects of hypoxia on three early TGF-β-dependent signaling pathways, i.e. the Smad2/3, RhoA and mitogen-activated protein kinase (MAPK) pathways, were screened by western blotting. Results: Intermittent hypoxia induced TGF-β1 expression, but had no effect on α-SMA expression. Exogenous TGF-β1 alone upregulated α-SMA expression in H9c2 cells in a concentration- and time-dependent manner. α-SMA expression declined with the duration of hypoxia after intermittent hypoxia and exogenous TGF-β1 co-treatment. Phospho-JNK and phospho-p38 levels were not significantly altered after TGF-β1 and hypoxia treatment. However, levels of phospho-ERK increased after TGF-β1 treatment and continued to increase after hypoxia co-treatment. The activation of phospho-Smad2/3 and phospho-RhoA induced by TGFβ1 was significantly reduced after hypoxia co-treatment. Conclusion: Hypoxia can inhibit TGF-β1-induced H9c2 myofibroblast transformation, based on inhibition of α-SMA expression by suppressing signaling downstream of TGF-β1, Smad2/3 and RhoA. It suggested that TGF-β-mediated cardiomyocyte transformation is not involved in hypoxia-mediated fibrosis.

scholarly journals The Hypoxic Proteome and Metabolome of Barley (Hordeum vulgare L.) with and without Phytoglobin Priming

2020 ◽  
Vol 21 (4) ◽  
pp. 1546 ◽  
Author(s):  
Olga A. Andrzejczak ◽  
Jesper F. Havelund ◽  
Wei-Qing Wang ◽  
Sergey Kovalchuk ◽  
Christina E. Hagensen ◽  
...  
Keyword(s):  
Hordeum Vulgare ◽  
Metabolic Effects ◽  
Plant Tissues ◽  
Ros Production ◽  
Ion Transporters ◽  
Wild Type ◽  
Golden Promise ◽  
Hordeum Vulgare L ◽  
Plant Hemoglobins ◽  
Hypoxia Treatment

Overexpression of phytoglobins (formerly plant hemoglobins) increases the survival rate of plant tissues under hypoxia stress by the following two known mechanisms: (1) scavenging of nitric oxide (NO) in the phytoglobin/NO cycle and (2) mimicking ethylene priming to hypoxia when NO scavenging activates transcription factors that are regulated by levels of NO and O2 in the N-end rule pathway. To map the cellular and metabolic effects of hypoxia in barley (Hordeum vulgare L., cv. Golden Promise), with or without priming to hypoxia, we studied the proteome and metabolome of wild type (WT) and hemoglobin overexpressing (HO) plants in normoxia and after 24 h hypoxia (WT24, HO24). The WT plants were more susceptible to hypoxia than HO plants. The chlorophyll a + b content was lowered by 50% and biomass by 30% in WT24 compared to WT, while HO plants were unaffected. We observed an increase in ROS production during hypoxia treatment in WT seedlings that was not observed in HO seedlings. We identified and quantified 9694 proteins out of which 1107 changed significantly in abundance. Many proteins, such as ion transporters, Ca2+-signal transduction, and proteins related to protein degradation were downregulated in HO plants during hypoxia, but not in WT plants. Changes in the levels of histones indicates that chromatin restructuring plays a role in the priming of hypoxia. We also identified and quantified 1470 metabolites, of which the abundance of >500 changed significantly. In summary the data confirm known mechanisms of hypoxia priming by ethylene priming and N-end rule activation; however, the data also indicate the existence of other mechanisms for hypoxia priming in plants.

Inhaled nitric oxide for hypoxia treatment after open heart surgery

2004 ◽  
Vol 21 (Supplement 33) ◽  
pp. 32-33
Author(s):  
R. Mojasevic ◽  
Lj. Petrovic ◽  
N. Radovanovic
Keyword(s):  
Nitric Oxide ◽  
Heart Surgery ◽  
Open Heart Surgery ◽  
Inhaled Nitric Oxide ◽  
Open Heart ◽  
Hypoxia Treatment

scholarly journals PLGF Knockdown Attenuates Hypoxia-Induced Stimulation of Cell Proliferation and Glycolysis of Lung Adenocarcinoma Through Inhibiting Wnt/β-Catenin Pathway

2020 ◽  
Author(s):  
Wei Zhang ◽  
Yanwei Zhang ◽  
Wensheng Zhou ◽  
Fangfei Qian ◽  
Minjuan Hu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Lactate Dehydrogenase ◽  
Growth Factor ◽  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Placental Growth Factor ◽  
Tumor Xenografts ◽  
Hypoxia Treatment ◽  
Stimulation Of

Abstract Background: Angiogenic placental growth factor (PLGF) plays a role in hypoxia-induced angiogenesis. Here, we aimed to investigate the biological roles of PLGF in cell proliferation and glycolysis of lung adenocarcinoma (LUAD) and the underlying molecular mechanisms. Methods: PLGF was knocked down in H358 and H1975 cells by lentiviruses, which were then cultured under hypoxia (90% N2, 5%CO2 and 5%O2) for 24 h. PLGF was overexpressed in PC9 cells treated with XAV939, inhibitor of Wnt/β-catenin signaling pathway. PLGF-silencing H1975 cells were implanted into mice, and tumor xenografts were harvested and analyzed. Results: Hypoxia treatment led to up-regulation of PLGF, C-myc, lactate dehydrogenase A (LDHA), and β-catenin, promotion of cell proliferation and glycolysis inH358 and H1975 cells, which were obviously reversed by knocking down PLGF. In tumors, PLGF knockdown significantly prohibited cell proliferation and glycolysis, and decreased expression of C-myc, LDHA, and β-catenin. PLGF overexpression markedly strengthened cell proliferation and glycolysis, and increased β-catenin expressionin PC9 cells, which were abrogated by XAV939. Conclusion: PLGF knockdown inhibited the stimulatory effect of hypoxia on cell proliferation and glycolysis of LUAD through deactivating Wnt/β-catenin pathway.

scholarly journals Soluble (pro)renin receptor increased by hypoxia maintains oxidative metabolism in trophoblasts

2020 ◽  
Vol 64 (3) ◽  
pp. 145-154 ◽  
Author(s):  
Chikahito Suda ◽  
Junichi Yatabe ◽  
Midori Yatabe ◽  
Miki Yarita ◽  
Atsuhiro Ichihara
Keyword(s):  
Protease Inhibitor ◽  
Oxidative Metabolism ◽  
Culture Medium ◽  
Gestational Hypertension ◽  
Maternal Blood ◽  
And Function ◽  
Functional Analyses ◽  
Placental Ischemia ◽  
Hypoxia Treatment ◽  
Jar Cells

Elevated soluble (pro)renin receptor (s(P)RR) concentration in maternal blood is associated with gestational hypertension and preeclampsia. Placenta has abundant expression of (P)RR, and the binding of (P)RR with pyruvate dehydrogenase E1 beta subunit (PDHB) is reported to maintain oxidative metabolism. Thus, we hypothesized that placental hypoxia may increase (P)RR, and the increased (P)RR may preserve PDHB expression. Expression and functional analyses were performed using human placental trophoblast cells, mainly JAR cells. (P)RR co-immunoprecipitated and showed co-immunofluorescence with PDHB mainly in the mitochondria. Hypoxia treatment significantly increased intracellular s(P)RR protein expression, but secreted s(P)RR in the culture medium was decreased by hypoxia. Hypoxia treatment did not alter PDHB expression or activity in the basal condition, but when (P)RR was knocked down by siRNA, PDHB protein and activity were reduced by hypoxia. Acetyl-CoA, the product of PDH activity, was significantly reduced by hypoxia treatment with (P)RR siRNA. S(P)RR is generated from full-length PRR when cleaved by specific proteases. Protease inhibitor experiments suggested furin and site 1 protease as the enzymes generating s(P)RR in JAR cells, and only when treated by site 1 protease inhibitor, PF429242, PDHB protein showed a significant trend to decrease with hypoxia. In JAR cells, hypoxia increased intracellular s(P)RR, and (P)RR preserved the expression and function of PDHB during hypoxia. (P)RR may help maintain oxidative metabolism and efficient energy production during placental ischemia in hypertensive disorders of pregnancy.

scholarly journals The Effect of Acute Intermittent Hypercapnic Hypoxia Treatment on IL-6, TNF-α, and CRP Levels in Piglets

SLEEP ◽  
2007 ◽  
Vol 30 (6) ◽  
pp. 723-727 ◽  
Author(s):  
Charmaine S. Tam ◽  
Melanie Wong ◽  
Kimberley Tam ◽  
Leyla Aouad ◽  
Karen A. Waters
Keyword(s):  
Tnf Α ◽  
Hypercapnic Hypoxia ◽  
Hypoxia Treatment

Tissue-Specific HIF-1 and HIF-2 Regulatory Elements and Their Roles in Erythropoietin Gene Expression

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1303-1303
Author(s):  
Donghoon Yoon ◽  
Jihyun Song ◽  
Hyojin Kim ◽  
Bumjun Kim ◽  
Hyejin Shin ◽  
...  
Keyword(s):  
Regulatory Elements ◽  
Mouse Strains ◽  
Renal Tubules ◽  
Mrna Levels ◽  
Specific Element ◽  
Α Subunit ◽  
Tissue Specific ◽  
Hypoxic Induction ◽  
Hypoxia Treatment

Abstract Abstract 1303 Studies of the regulation of erythropoiesis by hypoxic induction of erythropoietin (EPO) transcription led to the discovery of oligonucleotide binding motifs, hypoxia responsive elements (HREs) essential for hypoxic upregulation of EPO. HREs bind hypoxia-inducible transcription factors (HIFs). HIFs are heterodimers of 3 α subunit isotypes; HIF-1α, HIF-2α, and HIF-3α, and a common β-subunit. EPO is expressed in diverse tissues, some regulated mainly by HIF-2 and others by HIF-1. Tissue-specific regulatory elements (i.e. Kidney Inducible Element KIE, Negative Regulatory Element NRE, and Negative Regulatory Liver specific Element NRLE) of the EPO gene spanning several kilobases were reported. Our in silico analysis of the human EPO genome found two additional canonical HIF-binding elements in the KIE and NRE regions, and comparative analysis of phylogenically conserved sequences of Epo genes refined these HIF-binding elements from several kbs to a few hundred nucleotides and further delineated them as mKIE, mNRE1, mNRE2, and mNRLE2. To further define the structure and function of these elements in vivo, we exposed mice to 8% O2 hypoxia and monitored hypoxic induction of Epo mRNA levels in the liver, kidney, brain, and spleen. Spleen, kidney, and brain had a peak induction of the Epo transcript at 3 hours of hypoxia treatment, while liver showed peak induction at 6 hours. At the end of the hypoxia treatment, the mice were sacrificed and organs were harvested, and in vivo chromatin immunoprecipitation (ChIPs) was performed with antibodies against HIF-1α and HIF-2α. The results from these studies are summarized below. “+” denotes presence and “−” absence of binding of HIF-1 and HIF-2. “Norm” - normoxia, “Hyp” - hypoxia. To further define the role of these elements in tissue-specific Epo expression, we cloned and mutated these elements with reporter constructs, and generated transgenic mouse strains. The reporter gene was expressed in renal tubules, the red pulp area of the spleen, and liver hepatocytes. By creating a designed point mutation to disrupt the function of KIE, we suppressed the hypoxia response in the kidney, while mutations of NRE1 and NRE2 abolished reporter expression in the liver. Studies of HREs in the brain are ongoing. In conclusion, we have refined the previously reported HREs to a few hundred bases (particularly, KIE is a 6 nucleotide bearing motif) and now demonstrate tissue-specific differential hypoxia-induced binding of HIF-1 and HIF-2 and their functional roles in EPO induction. This provides a background to examine the molecular basis of these elements in patients with aberrant EPO expression. Disclosures: Elliott: Amgen, Inc: Employment.

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