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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 -
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 -
Occupational and Environmental Medicine Sep 2001
Review
Topics: Enzyme Inhibitors; Humans; Hypoxia; Methemoglobin; Methylene Blue; Occupational Diseases; Occupational Exposure; Oxidation-Reduction
PubMed: 11511749
DOI: 10.1136/oem.58.9.611 -
Oxidative Medicine and Cellular... 2010While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater... (Review)
Review
While mammals cannot survive oxygen deprivation for more than a few minutes without sustaining severe organ damage, some animals have mastered anaerobic life. Freshwater turtles belonging to the Trachemys and Chrysemys genera are the champion facultative anaerobes of the vertebrate world, often surviving without oxygen for many weeks at a time. The physiological and biochemical mechanisms that underlie anoxia tolerance in turtles include profound metabolic rate depression, post-translational modification of proteins, strong antioxidant defenses, activation of specific stress-responsive transcription factors, and enhanced expression of cytoprotective proteins. Turtles are also known for their incredible longevity and display characteristics of "negligible senescence". We propose that the robust stress-tolerance mechanisms that permit long term anaerobiosis by turtles may also support the longevity of these animals. Many of the mechanisms involved in natural anoxia tolerance, such as hypometabolism or the induction of various protective proteins/pathways, have been shown to play important roles in mammalian oxygen-related diseases and improved understanding of how cells survive without oxygen could aid in the understanding and treatment of various pathological conditions that involve hypoxia or oxidative stress. In the present review we discuss the recent advances made in understanding the molecular nature of anoxia tolerance in turtles and the potential links between this tolerance and longevity.
Topics: Anaerobiosis; Animals; Hypoxia; Longevity; Signal Transduction; Turtles
PubMed: 20716943
DOI: 10.4161/oxim.3.3.12356 -
International Journal of Molecular... Apr 2022Sucrose nonfermenting-1-related protein kinase 1 (SnRK1) is a central integrator of plant stress and energy starvation signalling pathways. We found that the...
Sucrose nonfermenting-1-related protein kinase 1 (SnRK1) is a central integrator of plant stress and energy starvation signalling pathways. We found that the -overexpression (OE) roots had a higher respiratory rate and tolerance to waterlogging than the -RNAi roots, suggesting that plays a positive role in the regulation of anaerobic respiration under waterlogging. upregulated the activity of anaerobic respiration-related enzymes including hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), pyruvate decarboxylase (PDC), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH). also enhanced the ability to quench reactive oxygen species (ROS) by increasing antioxidant enzyme activities. We sequenced the transcriptomes of the roots of both wild-type (WT) and -RNAi plants, and the differentially expressed genes (DEGs) were clearly enriched in the defence response, response to biotic stimuli, and cellular carbohydrate metabolic process. In addition, 42 genes involved in glycolysis and 30 genes involved in pyruvate metabolism were significantly regulated in -RNAi roots. We analysed the transcript levels of two anoxia-related genes and three , and the results showed that , , and were upregulated in response to , indicating that may be involved in the ethylene signalling pathway to improve waterlogging tolerance. In conclusion, increases the expression of and further activates anoxia response genes, thereby enhancing anaerobic respiration metabolism in response to low-oxygen conditions during waterlogging.
Topics: Anaerobiosis; Fragaria; Gene Expression Regulation, Plant; Hypoxia; Plant Roots; Respiratory Rate
PubMed: 35563305
DOI: 10.3390/ijms23094914 -
Medical Science Monitor : International... Nov 2021Hypoxia involves neoplastic cells. Unlike normal tissue, solid tumors are composed of aberrant vasculature, leading to a hypoxic microenvironment. Hypoxia is also known... (Review)
Review
Hypoxia involves neoplastic cells. Unlike normal tissue, solid tumors are composed of aberrant vasculature, leading to a hypoxic microenvironment. Hypoxia is also known to be involved in both metastasis initiation and therapy resistance. Radiotherapy is the appropriate treatment in about half of all cancers, but loco-regional control failure and a disease recurrence often occur due to clinical radioresistance. Hypoxia induces radioresistance through a number of molecular pathways, and numerous strategies have been developed to overcome this. Nevertheless, these strategies have resulted in disappointing results, including adverse effects and limited efficacy. Additional clinical studies are needed to achieve a better understanding of the complex hypoxia pathways. This review presents an update on the mechanisms of hypoxia in radioresistance in solid tumors and the potential therapeutic solutions.
Topics: Female; Humans; Hypoxia; Male; Neoplasms; Radiation Tolerance
PubMed: 34728593
DOI: 10.12659/MSM.934116 -
American Journal of Respiratory and... Apr 2023
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Bronchopulmonary Dysplasia; Hypertension, Pulmonary; Hypoxia; Oxygen; Respiration Disorders
PubMed: 36630576
DOI: 10.1164/rccm.202212-2290ED -
Angiogenesis May 2018The decline of oxygen tension in the tissues below the physiological demand leads to the hypoxic adaptive response. This physiological consequence enables cells to... (Review)
Review
The decline of oxygen tension in the tissues below the physiological demand leads to the hypoxic adaptive response. This physiological consequence enables cells to recover from this cellular insult. Understanding the cellular pathways that mediate recovery from hypoxia is therefore critical for developing novel therapeutic approaches for cardiovascular diseases and cancer. The master regulators of oxygen homeostasis that control angiogenesis during hypoxia are hypoxia-inducible factors (HIFs). HIF-1 and HIF-2 function as transcriptional regulators and have both unique and overlapping target genes, whereas the role of HIF-3 is less clear. HIF-1 governs the acute adaptation to hypoxia, whereas HIF-2 and HIF-3 expressions begin during chronic hypoxia in human endothelium. When HIF-1 levels decline, HIF-2 and HIF-3 increase. This switch from HIF-1 to HIF-2 and HIF-3 signaling is required in order to adapt the endothelium to prolonged hypoxia. During prolonged hypoxia, the HIF-1 levels and activity are reduced, despite the lack of oxygen-dependent protein degradation. Although numerous protein factors have been proposed to modulate the HIF pathways, their application for HIF-targeted therapy is rather limited. Recently, the miRNAs that endogenously regulate gene expression via the RNA interference (RNAi) pathway have been shown to play critical roles in the hypoxia response pathways. Furthermore, these classes of RNAs provide therapeutic possibilities to selectively target HIFs and thus modulate the HIF switch. Here, we review the significance of the microRNAs on the relationship between the HIFs under both physiological and pathophysiological conditions.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Gene Expression Regulation; Humans; Hypoxia; MicroRNAs; Signal Transduction; Transcription, Genetic
PubMed: 29383635
DOI: 10.1007/s10456-018-9600-2 -
International Journal of Medical... 2023Severe hypoxia can induce a range of systemic disorders; however, surprising resilience can be obtained through sublethal adaptation to hypoxia, a process termed as... (Review)
Review
Severe hypoxia can induce a range of systemic disorders; however, surprising resilience can be obtained through sublethal adaptation to hypoxia, a process termed as hypoxic conditioning. A particular form of this strategy, known as intermittent hypoxia conditioning hormesis, alternates exposure to hypoxic and normoxic conditions, facilitating adaptation to reduced oxygen availability. This technique, originally employed in sports and high-altitude medicine, has shown promise in multiple pathologies when applied with calibrated mild to moderate hypoxia and appropriate hypoxic cycles. Recent studies have extensively investigated the protective role of intermittent hypoxia conditioning and its underlying mechanisms using animal models, demonstrating its potential in organ protection. This involves a range of processes such as reduction of oxidative stress, inflammation, and apoptosis, along with enhancement of hypoxic gene expression, among others. Given that intermittent hypoxia conditioning fosters beneficial physiological responses across multiple organs and systems, this review presents a comprehensive analysis of existing studies on intermittent hypoxia and its potential advantages in various organs. It aims to draw attention to the possibility of clinically applying intermittent hypoxia conditioning as a multi-organ protective strategy. This review comprehensively discusses the protective effects of intermittent hypoxia across multiple systems, outlines potential procedures for implementing intermittent hypoxia, and provides a brief overview of the potential protective mechanisms of intermittent hypoxia.
Topics: Animals; Hypoxia; Oxygen; Oxidative Stress
PubMed: 37859700
DOI: 10.7150/ijms.86622 -
Molecular & Cellular Proteomics : MCP Jun 2013The separation between biological and technical variation without extensive use of technical replicates is often challenging, particularly in the context of different... (Review)
Review
The separation between biological and technical variation without extensive use of technical replicates is often challenging, particularly in the context of different forms of protein and peptide modifications. Biosampling procedures in the research laboratory are easier to conduct within a shorter time frame and under controlled conditions as compared with clinical sampling, with the latter often having issues of reproducibility. But is the research laboratory biosampling really less variable? Biosampling introduces within minutes rapid tissue-specific changes in the cellular microenvironment, thus inducing a range of different pathways associated with cell survival. Biosampling involves hypoxia and, depending on the circumstances, hypothermia, circumstances for which there are evolutionarily conserved defense strategies in the range of species and also are relevant for the range of biomedical conditions. It remains unclear to what extent such adaptive processes are reflected in different biosampling procedures or how important they are for the definition of sample quality. Lately, an increasing number of comparative studies on different biosampling approaches, post-mortem effects and pre-sampling biological state, have investigated such immediate early biosampling effects. Commonalities between biosampling effects and a range of ischemia/reperfusion- and hypometabolism/anoxia-associated biological phenomena indicate that even small variations in post-sampling time intervals are likely to introduce a set of nonrandom and tissue-specific effects of experimental importance (both in vivo and in vitro). This review integrates the information provided by these comparative studies and discusses how an adaptive biological perspective in biosampling procedures may be relevant for sample quality issues.
Topics: Adaptation, Physiological; Animals; Cellular Microenvironment; Gene Expression Regulation; Humans; Hypothermia; Hypoxia; Observer Variation; Organ Specificity; Proteins; Proteomics; Reproducibility of Results; Species Specificity; Specimen Handling; Time Factors
PubMed: 23382104
DOI: 10.1074/mcp.R112.024869