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International Journal of Molecular... Jul 2019Eukaryotes are often subjected to different kinds of stress. In order to adjust to such circumstances, eukaryotes activate stress-response pathways and regulate gene... (Review)
Review
Eukaryotes are often subjected to different kinds of stress. In order to adjust to such circumstances, eukaryotes activate stress-response pathways and regulate gene expression. Eukaryotic gene expression consists of many different steps, including transcription, RNA processing, RNA transport, and translation. In this review article, we focus on both transcriptional and post-transcriptional regulations of gene expression under hypoxic conditions. In the first part of the review, transcriptional regulations mediated by various transcription factors including Hypoxia-Inducible Factors (HIFs) are described. In the second part, we present RNA splicing regulations under hypoxic conditions, which are mediated by splicing factors and their kinases. This work summarizes and discusses the emerging studies of those two gene expression machineries under hypoxic conditions.
Topics: Animals; Gene Expression Regulation; Humans; Hypoxia; RNA Splicing; Transcription Factors; Transcription, Genetic
PubMed: 31277312
DOI: 10.3390/ijms20133278 -
Experimental Oncology Mar 2016Approximately 1.0-1.5% of the genome is transcriptionally regulated by hypoxia, and hypoxia-inducible factor (HIF)-1α is the transcription factor modulating many of... (Review)
Review
Approximately 1.0-1.5% of the genome is transcriptionally regulated by hypoxia, and hypoxia-inducible factor (HIF)-1α is the transcription factor modulating many of these genes. Cancer cells are able to survive hypoxic environments and hypoxia itself can activate adaptive cellular responses that contribute to tumor progression. Many HIF-1α-mediated biological effects are beneficial for tumor progression, including metabolic shift toward glycolysis, inhibition of fatty acid β-oxidation, production of cellular reactive oxygen species and altering expression of tumor suppressor genes. HIF-1 promotes selective mitochondrial autophagy, resistance to T cell mediated lysis of cancer cells, induction of pluripotent cancer stem cells, epithelial-mesenchymal and epithelial-mesenchymal-endothelial transitions beneficial for tumor growth and progression, loss of E-cadherin. HIF-1 also induces production of signal molecules and cytokines by carcinoma-associated fibroblasts and upregulation of certain microRNAs important for cancer progression. This minireview focuses on the HIF-1 promoting role in tumor initiation and progression and HIF-1 targeting. HIF-1 pathway downregulation seems to be promising in future cancer treatment.
Topics: Animals; Drug Discovery; Gene Expression Regulation, Neoplastic; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Molecular Targeted Therapy; Neoplasms; Neoplastic Stem Cells; Reactive Oxygen Species; Signal Transduction
PubMed: 27031712
DOI: No ID Found -
Acta Physiologica (Oxford, England) Jul 2022Hypoxic environments pose a severe challenge to vertebrates and even short periods of oxygen deprivation are often lethal as they constrain aerobic ATP production.... (Review)
Review
Hypoxic environments pose a severe challenge to vertebrates and even short periods of oxygen deprivation are often lethal as they constrain aerobic ATP production. However, a few ectotherm vertebrates are capable of surviving long-term hypoxia or even anoxia with little or no damage. Among these, freshwater turtles and crucian carp are the recognized champions of anoxia tolerance, capable of overwintering in complete oxygen deprivation for months at freezing temperatures by entering a stable hypometabolic state. While all steps of the oxygen cascade are adjusted in response to oxygen deprivation, this review draws from knowledge of freshwater turtles and crucian carp to highlight mechanisms regulating two of these steps, namely oxygen transport in the blood and oxygen utilization in mitochondria during three sequential phases: before anoxia, when hypoxia develops, during anoxia, and after anoxia at reoxygenation. In cold hypoxia, reduced red blood cell concentration of ATP plays a crucial role in increasing blood oxygen affinity and/or reducing oxygen unloading to tissues, to adjust aerobic metabolism to decrease ambient oxygen. In anoxia, metabolic rewiring of oxygen utilization keeps largely unaltered NADH/NAD ratios and limits ADP degradation and succinate buildup. These critical adjustments make it possible to restart mitochondrial respiration and energy production with little generation of reactive oxygen species at reoxygenation when oxygen is again available. Inhibition of key metabolic enzymes seems to play crucial roles in these responses, in particular mitochondrial complex V, although identifying the nature of such inhibition(s) in vivo remains a challenge for future studies.
Topics: Adenosine Triphosphate; Animals; Carps; Hypoxia; Oxygen; Turtles; Vertebrates
PubMed: 35548887
DOI: 10.1111/apha.13841 -
Expert Review of Respiratory Medicine Apr 2018Interstitial lung diseases (ILD) include a broad range of diffuse parenchymal lung disorders of known and unknown etiologies. Patients with ILD can experience acute... (Review)
Review
Interstitial lung diseases (ILD) include a broad range of diffuse parenchymal lung disorders of known and unknown etiologies. Patients with ILD can experience acute exacerbations (AE) which are associated with extremely high morbidity and mortality. Little is known about the etiology of AEs, and whether inciting triggers (such as infection) result in an aberrant inflammatory response in a predisposed host. Areas covered: The majority of data regarding AE-ILD comes from the idiopathic pulmonary fibrosis (IPF) population and is extrapolated to other forms of ILD. For the purposes of this review we have summarized the current literature regarding AE of IPF, and when available have included data from AE of other ILDs. Expert commentary: Therapeutic options for AE are limited without definitive treatments available, and the prognosis is often poor. Treatment is mainly based on correcting hypoxemia, looking for reversible etiologies of respiratory decline, and palliation of symptoms. Overall little is known about the pathogenesis of ILDs and AE-ILD, more research is needed in hopes of identifying better treatment options.
Topics: Humans; Hypoxia; Idiopathic Pulmonary Fibrosis; Lung; Lung Diseases, Interstitial; Prognosis
PubMed: 29486130
DOI: 10.1080/17476348.2018.1446831 -
Cellular Signalling Mar 2022DM (diabetic mellitus) and its common vascular complications VC (vascular calcification), are increasingly harmful to human health. In recent years, the research on the... (Review)
Review
DM (diabetic mellitus) and its common vascular complications VC (vascular calcification), are increasingly harmful to human health. In recent years, the research on the relationship between DM and VC is also deepening. Hypoxia, as one of the pathogenic factors of many disease models, is also closely related to the occurrence of DM and VC. There are some studies on the role of hypoxia in the pathogenesis of DM and VC respectively, but no one has made an in-depth summary of the systematic connection between hypoxia, DM and VC. Therefore, what we want to review in this article are the relationship between DM, VC and hypoxia, respectively, as well as the role of hypoxia in the development of DM and VC, which has little concern but is a novel and potentially target that may provide some new ideas for the prevention and treatment of DM, VC, especially diabetic VC.
Topics: Diabetes Mellitus; Humans; Hypoxia; Vascular Calcification
PubMed: 34921978
DOI: 10.1016/j.cellsig.2021.110219 -
Comparative Biochemistry and... Aug 2022Vertebrates need oxygen to survive. The central nervous system has an especially high energy demand, so brain and retinal neurons quickly die in anoxia. But fish of the...
Vertebrates need oxygen to survive. The central nervous system has an especially high energy demand, so brain and retinal neurons quickly die in anoxia. But fish of the genus Carassius are exceptionally anoxia-tolerant: the crucian carp (C. carassius) can survive months without oxygen in ice-covered ponds, and the common goldfish (C. auratus) can withstand hours of anoxia at room temperature. These fish previously offered insights into anoxia tolerance in the brain, heart, and liver. Here, we advance Carassius spp. as models to study anoxia tolerance in the retina. Electroretinogram and evoked potential recordings show that crucian carp reversibly downregulate their visual systems in anoxia, probably to save ATP. Notably, Carassius suppress their visual systems nearly twice as much as anoxia-tolerant turtles, Trachemys and Chrysemys spp., which are often promoted as the champions of anoxia tolerance. We summarize what is known about anoxia tolerance in the goldfish and crucian carp retinas, including cellular pathways which may protect retinal neurons from excitotoxic cell death. We compare the Carassius retina with two relevant models: natural anoxia tolerance in the turtle brain, and ischemic preconditioning in the rat retina. All three models include mitochondria as oxygen sensors: mitochondria depolarize due to mitochondrial ATP-dependent K channels, possibly to trigger neuroprotective second messenger cascades. The Carassius retina is an accessible and inexpensive model, with over 70 fruitful years of history in vision research. As a model for anoxia tolerance, it may provide new insights into diseases of the eye (like diabetes, macular degeneration, and eye stroke).
Topics: Adenosine Triphosphate; Animals; Carps; Goldfish; Hypoxia; Oxygen; Rats; Retina; Turtles
PubMed: 35618216
DOI: 10.1016/j.cbpa.2022.111244 -
Global Change Biology Aug 2022Oxygen availability is decreasing in many lakes and reservoirs worldwide, raising the urgency for understanding how anoxia (low oxygen) affects coupled biogeochemical...
Oxygen availability is decreasing in many lakes and reservoirs worldwide, raising the urgency for understanding how anoxia (low oxygen) affects coupled biogeochemical cycling, which has major implications for water quality, food webs, and ecosystem functioning. Although the increasing magnitude and prevalence of anoxia has been documented in freshwaters globally, the challenges of disentangling oxygen and temperature responses have hindered assessment of the effects of anoxia on carbon, nitrogen, and phosphorus concentrations, stoichiometry (chemical ratios), and retention in freshwaters. The consequences of anoxia are likely severe and may be irreversible, necessitating ecosystem-scale experimental investigation of decreasing freshwater oxygen availability. To address this gap, we devised and conducted REDOX (the Reservoir Ecosystem Dynamic Oxygenation eXperiment), an unprecedented, 7-year experiment in which we manipulated and modeled bottom-water (hypolimnetic) oxygen availability at the whole-ecosystem scale in a eutrophic reservoir. Seven years of data reveal that anoxia significantly increased hypolimnetic carbon, nitrogen, and phosphorus concentrations and altered elemental stoichiometry by factors of 2-5× relative to oxic periods. Importantly, prolonged summer anoxia increased nitrogen export from the reservoir by six-fold and changed the reservoir from a net sink to a net source of phosphorus and organic carbon downstream. While low oxygen in freshwaters is thought of as a response to land use and climate change, results from REDOX demonstrate that low oxygen can also be a driver of major changes to freshwater biogeochemical cycling, which may serve as an intensifying feedback that increases anoxia in downstream waterbodies. Consequently, as climate and land use change continue to increase the prevalence of anoxia in lakes and reservoirs globally, it is likely that anoxia will have major effects on freshwater carbon, nitrogen, and phosphorus budgets as well as water quality and ecosystem functioning.
Topics: Carbon; Ecosystem; Humans; Hypoxia; Lakes; Nitrogen; Oxygen; Phosphorus
PubMed: 35611634
DOI: 10.1111/gcb.16228 -
British Journal of Anaesthesia Oct 2022Peri-intubation oxygen administration to the pregnant patient during induction of general anaesthesia is critical to avoiding hypoxaemia and harm to the mother and...
Peri-intubation oxygen administration to the pregnant patient during induction of general anaesthesia is critical to avoiding hypoxaemia and harm to the mother and fetus. Recent modelling comparing low-flow with high-flow nasal oxygen in simulated term pregnant women of varying body habitus, taken together with previous work, suggests that face mask preoxygenation with the use of low-flow or high-flow nasal oxygen during the period of apnoea prolongs the safe apnoea period, with the benefit varying by body habitus. Low-flow compared with high-flow nasal oxygen may be easier to combine with face mask preoxygenation and is readily available in all operating theatres, although future improvements in high-flow nasal oxygen delivery systems may improve ease of use for this indication.
Topics: Apnea; Cesarean Section; Female; Humans; Hypoxia; Intubation, Intratracheal; Oxygen; Oxygen Inhalation Therapy; Pregnancy
PubMed: 35985842
DOI: 10.1016/j.bja.2022.07.014 -
Scientific Reports Oct 2022Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly...
Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly improved the survival and prognosis of patients with osteosarcoma, the survival rate is still very low due to frequent metastases in patients with osteosarcoma. In-depth exploration of the relationship between various influencing factors of osteosarcoma is very important for screening promising therapeutic targets. This study used multivariate COX regression analysis to select the hypoxia genes SLC2A1 and FBP1 in patients with osteosarcoma, and used the expression of these two genes to divide the patients with osteosarcoma into high-risk and low-risk groups. Then, we first constructed a prognostic model based on the patient's risk value and compared the survival difference between the high expression group and the low expression group. Second, in the high expression group and the low expression group, compare the differences in tumor invasion and inflammatory gene expression between the two groups of immune cells. Finally, the ferroptosis-related genes with differences between the high expression group and the low expression group were screened, and the correlation between these genes was analyzed. In the high-risk group, immune cells with higher tumor invasiveness, macrophages M0 and immune cells with lower invasiveness included: mast cell resting, regulatory T cells (Tregs) and monocytes. Finally, among genes related to ferroptosis, we found AKR1C2, AKR1C1 and ALOX15 that may be related to hypoxia. These ferroptosis-related genes were discovered for the first time in osteosarcoma. Among them, the hypoxia gene FBP1 is positively correlated with the ferroptosis genes AKR1C1 and ALOX15, and the hypoxia gene SLC2A1 is negatively correlated with the ferroptosis genes AKR1C2, AKR1C1 and ALOX15. This study constructed a prognostic model based on hypoxia-related genes SLC2A1 and FBP1 in patients with osteosarcoma, and explored their correlation with immune cells, inflammatory markers and ferroptosis-related genes. This indicates that SLC2A1 and FBP1 are promising targets for osteosarcoma research.
Topics: Female; Humans; Bone Neoplasms; Osteosarcoma; Prognosis; Neoplasm Invasiveness; Hypoxia; Fetal Hypoxia
PubMed: 36316355
DOI: 10.1038/s41598-022-17622-0 -
Chest Oct 2017Mortality related to severe-moderate and severe ARDS remains high. We searched the literature to update this topic. We defined severe hypoxemic respiratory failure as... (Review)
Review
Mortality related to severe-moderate and severe ARDS remains high. We searched the literature to update this topic. We defined severe hypoxemic respiratory failure as Pao/Fio < 150 mm Hg (ie, severe-moderate and severe ARDS). For these patients, we support setting the ventilator to a tidal volume of 4 to 8 mL/kg predicted body weight (PBW), with plateau pressure (Pplat) ≤ 30 cm HO, and initial positive end-expiratory pressure (PEEP) of 10 to 12 cm HO. To promote alveolar recruitment, we propose increasing PEEP in increments of 2 to 3 cm provided that Pplat remains ≤ 30 cm HO and driving pressure does not increase. A fluid-restricted strategy is recommended, and nonrespiratory causes of hypoxemia should be considered. For patients who remain hypoxemic after PEEP optimization, neuromuscular blockade and prone positioning should be considered. Profound refractory hypoxemia (Pao/Fio < 80 mm Hg) after PEEP titration is an indication to consider extracorporeal life support. This may necessitate early transfer to a center with expertise in these techniques. Inhaled vasodilators and nontraditional ventilator modes may improve oxygenation, but evidence for improved outcomes is weak.
Topics: Disease Management; Fluid Therapy; Humans; Hypoxia; Respiration, Artificial; Respiratory Insufficiency; Severity of Illness Index; Tidal Volume; Vasodilator Agents
PubMed: 28716645
DOI: 10.1016/j.chest.2017.06.039