scholarly journals Is Hypoxic/Altitude Training an Important Topic in the Field of Hypoxia?

2021 ◽  
Author(s):  
Grégoire P. Millet ◽  
Martin Burtscher ◽  
Johannes Burtscher
Keyword(s):  
Biological Sciences ◽  
Molecular Mechanisms ◽  
Performance Enhancement ◽  
Hypoxia Inducible Factor ◽  
Altitude Training ◽  
Systemic Hypoxia ◽  
Biomedical Journals ◽  
And Performance ◽  
Number Of Citations ◽  
Hif Pathway

AbstractHypoxia is an essential topic in medical or biological sciences. The main aims of the present study were to examine the most important medical articles (i.e., the top 100 most cited) on hypoxia. We examine how the Nobel-prize awarded hypoxia inducible factor (HIF)-pathway discovery in the early 1990s has changed the thematic composition of this body of literature, with a special emphasis on the studies linking hypoxia and cancer. We searched Pubmed for articles with the terms #Hypox, #Altitude, or #Mountain in the title that have been published in biomedical journals and ranked the articles on their number of citations in Web of Science. A second search was performed in all journals for articles related to hypoxia and cancer. Strikingly, only 12 of the top-100 most-cited articles on hypoxia and only 3 articles of the top-100 articles related to cancer were published before 1995. Moreover, only 5 articles from prior 1995 reached 1000 citations, while 27 articles published in 1995 or later were cited more than 1000 times, most of them on the HIF-1 pathway. Eighty percent of the top-100 articles were related to the HIF pathway, while there were no articles on the application of hypoxia either for therapeutic use (i.e., hypoxic conditioning in patients) or for performance enhancement (i.e., altitude training in athletes). In conclusion, the early-1990s discovery of the HIF pathway and of its molecular regulation has shifted the focus of hypoxia research towards molecular mechanisms and consequences of tissue hypoxia, most notably in cancer. The importance of studies focusing on clinical and performance applications of systemic hypoxia is relatively lower.

scholarly journals The Hypoxia-Inducible Factor Pathway, Prolyl Hydroxylase Domain Protein Inhibitors, and Their Roles in Bone Repair and Regeneration

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Lihong Fan ◽  
Jia Li ◽  
Zefeng Yu ◽  
Xiaoqian Dang ◽  
Kunzheng Wang
Keyword(s):  
Cell Fate ◽  
Bone Repair ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Bone Tumours ◽  
Cell Fate Decisions ◽  
Tightly Coupled ◽  
Hif Pathway ◽  
Prolyl Hydroxylase Domain

Hypoxia-inducible factors (HIFs) are oxygen-dependent transcriptional activators that play crucial roles in angiogenesis, erythropoiesis, energy metabolism, and cell fate decisions. The group of enzymes that can catalyse the hydroxylation reaction of HIF-1 is prolyl hydroxylase domain proteins (PHDs). PHD inhibitors (PHIs) activate the HIF pathway by preventing degradation of HIF-αvia inhibiting PHDs. Osteogenesis and angiogenesis are tightly coupled during bone repair and regeneration. Numerous studies suggest that HIFs and their target gene, vascular endothelial growth factor (VEGF), are critical regulators of angiogenic-osteogenic coupling. In this brief perspective, we review current studies about the HIF pathway and its role in bone repair and regeneration, as well as the cellular and molecular mechanisms involved. Additionally, we briefly discuss the therapeutic manipulation of HIFs and VEGF in bone repair and bone tumours. This review will expand our knowledge of biology of HIFs, PHDs, PHD inhibitors, and bone regeneration, and it may also aid the design of novel therapies for accelerating bone repair and regeneration or inhibiting bone tumours.

Defining the “dose” of altitude training: how high to live for optimal sea level performance enhancement

2014 ◽  
Vol 116 (6) ◽  
pp. 595-603 ◽  
Author(s):  
Robert F. Chapman ◽  
Trine Karlsen ◽  
Geir K. Resaland ◽  
R.-L. Ge ◽  
Matthew P. Harber ◽  
...  
Keyword(s):  
Sea Level ◽  
Performance Enhancement ◽  
Cell Mass ◽  
Time Trial ◽  
Individual Variability ◽  
Altitude Training ◽  
Distance Runners ◽  
Before And After ◽  
And Performance ◽  
Level Performance

Chronic living at altitudes of ∼2,500 m causes consistent hematological acclimatization in most, but not all, groups of athletes; however, responses of erythropoietin (EPO) and red cell mass to a given altitude show substantial individual variability. We hypothesized that athletes living at higher altitudes would experience greater improvements in sea level performance, secondary to greater hematological acclimatization, compared with athletes living at lower altitudes. After 4 wk of group sea level training and testing, 48 collegiate distance runners (32 men, 16 women) were randomly assigned to one of four living altitudes (1,780, 2,085, 2,454, or 2,800 m). All athletes trained together daily at a common altitude from 1,250–3,000 m following a modified live high-train low model. Subjects completed hematological, metabolic, and performance measures at sea level, before and after altitude training; EPO was assessed at various time points while at altitude. On return from altitude, 3,000-m time trial performance was significantly improved in groups living at the middle two altitudes (2,085 and 2,454 m), but not in groups living at 1,780 and 2,800 m. EPO was significantly higher in all groups at 24 and 48 h, but returned to sea level baseline after 72 h in the 1,780-m group. Erythrocyte volume was significantly higher within all groups after return from altitude and was not different between groups. These data suggest that, when completing a 4-wk altitude camp following the live high-train low model, there is a target altitude between 2,000 and 2,500 m that produces an optimal acclimatization response for sea level performance.

scholarly journals Effects of genetic factors on high altitude training performance

2021 ◽  
Vol 5 (1) ◽  
pp. 2
Author(s):  
Havva Eda Cicavoğlu ◽  
Cansel Kaya ◽  
Mesut Cerit
Keyword(s):  
High Altitude ◽  
Hypoxia Inducible Factor ◽  
Circulatory System ◽  
Endurance Performance ◽  
Superior Performance ◽  
Metabolic Efficiency ◽  
Altitude Training ◽  
Monitoring And Control ◽  
Hypoxic Conditions ◽  
And Performance

High altitude is considered to be 1800-6000 meters. With the decrease of atmospheric pressure at this altitude, adequate oxygenation cannot be achieved in the tissues and hypoxia develops in the circulatory system. Athletes aim to provide superior performance by training in hypoxic conditions. Varying adaptations in hypobaric hypoxia environments by geographically separated populations represent well-trained specimens that may be relevant to endurance performance. While inhabitants of the Andes show higher levels of hemoglobin and saturation than Tibetans at similar altitude, Ethiopian climbers maintain oxygen delivery despite the hemoglobin levels and saturation typical in sea level ranges. It can also be predicted a significant relationship between the angiotensin converting enzyme (ACE) genotype, which affects metabolic efficiency and performance in hypoxic environments (high altitude). One of the genes that develop at high altitude and occur in response to hypoxia is the hypoxia inducible factor 1 alpha (HIF-1α) gene encoded by the hypoxia inducible factor (HIF-1A) gene. The vascular endothelial growth factor (VEGF-A) gene, which is another gene with angiogenetic factor produced in response to hypoxia, is revealed by the transcription of the HIF-1 alpha gene. Genetic heritage, environmental factors, and the character of exercise loads applied within the framework of lifestyle, neuromuscular development, balanced nutrition, and cultural differences that trigger athletic success may reveal individual changes or differences. Considering all these variables, monitoring and control of performance improvement and athletic achievement graph may become more predictable.

Hypoxia signalling manipulation for bone regeneration

2015 ◽  
Vol 17 ◽  
Author(s):  
Justin Drager ◽  
Edward J. Harvey ◽  
Jake Barralet
Keyword(s):  
Bone Regeneration ◽  
Bone Repair ◽  
Molecular Mechanisms ◽  
Bone Development ◽  
Hypoxia Inducible Factor ◽  
Cell Recruitment ◽  
Substantial Progress ◽  
Hif Pathway

Hypoxia-inducible factor (HIF) signalling is intricately involved in coupling angiogenesis and osteogenesis during bone development and repair. Activation of HIFs in response to a hypoxic bone micro-environment stimulates the transcription of multiple genes with effects on angiogenesis, precursor cell recruitment and differentiation. Substantial progress has been made in our understanding of the molecular mechanisms by which oxygen content regulates the levels and activity of HIFs. In particular, the discovery of the role of oxygen-dependent hydroxylase enzymes in modulating the activity of HIF-1α has sparked interest in potentially promising therapeutic strategies in multiple clinical fields and most recently bone healing. Several small molecules, termed hypoxia mimics, have been identified as activators of the HIF pathway and have demonstrated augmentation of both bone vascularity and bone regeneration in vivo. In this review we discuss key elements of the hypoxic signalling pathway and its role in bone regeneration. Current strategies for the manipulation of this pathway for enhancing bone repair are presented with an emphasis on recent pre-clinical in vivo investigations. These findings suggest promising approaches for the development of therapies to improve bone repair and tissue engineering strategies.

Artificial Intelligence for epigenetics: towards personalized medicine

2020 ◽  
Vol 27 ◽  
Author(s):  
Giulia De Riso ◽  
Sergio Cocozza
Keyword(s):  
Biological Sciences ◽  
Artificial Intelligence ◽  
Personalized Medicine ◽  
Molecular Mechanisms ◽  
Genomic Sequence ◽  
Health Care Interventions ◽  
Genome Wide ◽  
Genetic And Environmental Factors ◽  
Opening Up ◽  
Omic Data

: Epigenetics is a field of biological sciences focused on the study of reversible, heritable changes in gene function not due to modifications of the genomic sequence. These changes are the result of a complex cross-talk between several molecular mechanisms, that is in turn orchestrated by genetic and environmental factors. The epigenetic profile captures the unique regulatory landscape and the exposure to environmental stimuli of an individual. It thus constitutes a valuable reservoir of information for personalized medicine, which is aimed at customizing health-care interventions based on the unique characteristics of each individual. Nowadays, the complex milieu of epigenomic marks can be studied at the genome-wide level thanks to massive, highthroughput technologies. This new experimental approach is opening up new and interesting knowledge perspectives. However, the analysis of these complex omic data requires to face important analytic issues. Artificial Intelligence, and in particular Machine Learning, are emerging as powerful resources to decipher epigenomic data. In this review, we will first describe the most used ML approaches in epigenomics. We then will recapitulate some of the recent applications of ML to epigenomic analysis. Finally, we will provide some examples of how the ML approach to epigenetic data can be useful for personalized medicine.

scholarly journals Hypoxia, Metabolic Reprogramming, and Drug Resistance in Liver Cancer

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1715
Author(s):  
Macus Hao-Ran Bao ◽  
Carmen Chak-Lui Wong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Liver Cancer ◽  
Effective Treatment ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Metabolic Reprogramming ◽  
Combination Therapies ◽  
Low Oxygen ◽  
Treatment Regimens

Hypoxia, low oxygen (O2) level, is a hallmark of solid cancers, especially hepatocellular carcinoma (HCC), one of the most common and fatal cancers worldwide. Hypoxia contributes to drug resistance in cancer through various molecular mechanisms. In this review, we particularly focus on the roles of hypoxia-inducible factor (HIF)-mediated metabolic reprogramming in drug resistance in HCC. Combination therapies targeting hypoxia-induced metabolic enzymes to overcome drug resistance will also be summarized. Acquisition of drug resistance is the major cause of unsatisfactory clinical outcomes of existing HCC treatments. Extra efforts to identify novel mechanisms to combat refractory hypoxic HCC are warranted for the development of more effective treatment regimens for HCC patients.

scholarly journals Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Virginia Egea ◽  
Kai Kessenbrock ◽  
Devon Lawson ◽  
Alexander Bartelt ◽  
Christian Weber ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Human Mesenchymal Stem Cells ◽  
Target Cells ◽  
Autophagic Flux ◽  
Stromal Cell Derived Factor

AbstractBone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.

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