Normoxic Group Research Articles

Identification and validation of ferroptosis-related hub genes in obstructive sleep apnea syndrome.

By 2020, the prevalence of Obstructive Sleep Apnea Syndrome (OSAS) in the US has reached 26. 6-43.2% in men and 8.7-27.8% in women. OSAS promotes hypertension, diabetes, and tumor growth through unknown means. Chronic intermittent hypoxia (CIH), sleep fragmentation, and increased pleural pressure are central mechanisms of OSAS complications. CIH exacerbates ferroptosis, which is closely related to malignancies. The mechanism of ferroptosis in OSAS disease progression remains unknown. OSAS-related datasets (GSE135917 and GSE38792) were obtained from the GEO. Differentially expressed genes (DEGs) were screened using the R software and intersected with the ferroptosis database (FerrDb V2) to get ferroptosis-related DEGs (f-DEGs). GO, DO, KEGG, and GSEA enrichment were performed, a PPI network was constructed and hub genes were screened. The TCGA database was used to obtain the thyroid cancer (THCA) gene expression profile, and hub genes were analyzed for differential and survival analysis. The mechanism was investigated using GSEA and immune infiltration. The hub genes were validated with RT-qPCR, IHC, and other datasets. Sprague-Dawley rats were randomly separated into normoxia and CIH groups. ROS, MDA, and GSH methods were used to detect CIH-induced ferroptosis and oxidative stress. GSEA revealed a statistically significant difference in ferroptosis in OSAS (FDR < 0.05). HIF1A, ATM, HSPA5, MAPK8, MAPK14, TLR4, and CREB1 were identified as hub genes among 3,144 DEGs and 74 f-DEGs. HIF1A and ATM were the only two validated genes. F-DEGs were mainly enriched in THCA. HIF1A overexpression in THCA promotes its development. HIF1A is associated with CD8 T cells and macrophages, which may affect the immunological milieu. The result found CIH increased ROS and MDA while lowering GSH indicating that it could cause ferroptosis. In OSAS patients, non-invasive ventilation did not affect HIF1A and ATM expression. Carvedilol, hydralazine, and caffeine may be important in the treatment of OSAS since they suppress HIF1A and ATM. Our findings revealed that the genes HIF1A and ATM are highly expressed in OSAS, and can serve as biomarkers and targets for OSAS.

Insights into the pharmacodynamics and pharmacokinetics of meldonium after exposure to acute high altitude.

Objective: Meldonium, a well-known cardioprotective drug, has been reported to be protective against pulmonary injury at high altitudes; however, the pharmacodynamics of meldonium in other vital organs under acute high-altitude injury are less investigated and the related pharmacokinetics have not been fully elucidated. Methods and Results: The present study examined the basic pharmacodynamics and pharmacokinetics (PK) in rat exposure to acute high-altitude hypoxia after intragastrical and intravenous pre-administration of meldonium. The results indicate that meldonium can improve acute hypoxia-induced pathological damage in brain and lung tissues, and restore blood biochemistry and routine blood index of heart, liver and kidney tissues under a simulated acute high-altitude environment. Furthermore, compared to the normoxia group, rats exposed to simulated high-altitude hypoxia and premedicated with intragastrical meldonium showed linear kinetics in the dose range of 25-100mg/kg, with a significantly increase in the area under curve (AUC) and reduced clearance rate. No significant differences in these meldonium of PK parameters were observed with intravenous administration. Additionally, meldonium was involved in the regulation of succinic acid and 3-hydroxypropionic acid. Conclusion: These results will contribute to our understanding of the preclinical PK properties of meldonium and its acute high-altitude protective effects.

TRAP-induced PAR1 expression with its mechanism during AMI in a rat model

Background and objectiveProtease-activated receptor 1 (PAR1) is crucial in individuals with acute myocardial infarction (AMI). The continuous and prompt PAR1 activation mainly dependent on PAR1 trafficking is essential for the role of PAR1 during AMI in which cardiomyocytes are in hypoxia. However, the PAR1 trafficking in cardiomyocytes specially during the hypoxia is still unclear.Methods and resultA rat AMI model was created. PAR1 activation with thrombin-receptor activated peptide (TRAP) had a transient effect on cardiac function in normal rats but persistent improvement in rats with AMI. Cardiomyocytes from neonatal rats were cultured in a normal CO2 incubator and a hypoxic modular incubator chamber. The cells were then subjected to western blot for the total protein expression and staining with fluorescent reagent and antibody for PAR1 localization. No change in total PAR1 expression following TRAP stimulation was observed; however, it led to increased PAR1 expression in the early endosomes in normoxic cells and decreased expression in the early endosomes in hypoxic cells. Under hypoxic conditions, TRAP restored the PAR1 expression on both cell and endosomal surfaces within an hour by decreasing Rab11A (8.5-fold; 179.93 ± 9.82% of the normoxic control group, n = 5) and increasing Rab11B (15.5-fold) expression after 4 h of hypoxia. Similarly, Rab11A knockdown upregulated PAR1 expression under normoxia, and Rab11B knockdown downregulated PAR1 expression under both normoxic and hypoxic conditions. Cardiomyocytes knocked out of both Rab11A, and Rad11B lost the TRAP-induced PAR1 expression but still exhibited the early endosomal TRAP-induced PAR1 expression under hypoxia.ConclusionsTRAP-mediated activation of PAR1 in cardiomyocytes did not alter the total PAR1 expression under normoxic conditions. Instead, it triggers a redistribution of PAR1 levels under normoxic and hypoxic conditions. TRAP reverses the hypoxia-inhibited PAR1 expression in cardiomyocytes by downregulating Rab11A expression and upregulating Rab11B expression.

Identification of Novel Biomarkers for Abdominal Aortic Aneurysm Promoted by Obstructive Sleep Apnea

We sought to find new biomarkers for abdominal aortic aneurysms (AAA) caused by chronic intermittent hypoxia (CIH). The AAA mice model was created using Ang II. The mice were divided into normoxic and CIH groups. The structure of AAA was observed using abdominal ultrasonography, Elastica van Gieson (EVG), and hematoxylin and eosin (HE) staining. The expression of ɑ-SMA was investigated using immunohistochemistry. The novel biomarkers were screened using bioinformatics analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to verify the expression of novel genes in both normal oxygen and CIH. CIH appears to cause greater aortic dilation, higher AAA incidence, lower survival rate, thicker vessel wall, and more brittle elastic lamellae when compared to controls. The immunohistochemistry results showed that the expression of ɑ-SMA in the CIH group was reduced significantly. Four novel genes, including Homer2, Robo2, Ehf, and Asic1, were found to be differentially expressed between normal oxygen and CIH using qRT-PCR, indicating the same trend as bioinformatics analysis. We discovered that CIH could hasten the occurrence and progression of AAA. Four genes (Homer2, Robo2, Ehf, and Asic1) may be novel biomarkers for AAA, which could aid in the search for new therapies for patients with AAA caused by CIH.

Living high - training low model applied to C57BL/6J mice: Effects on physiological parameters related to aerobic fitness and acid-base balance

There is a scarcity of data regarding the acclimation to high altitude (hypoxic environment) accompanied by training at low altitude (normoxic conditions), the so-called “living high-training low” (LHTL) model in rodents. We aimed to investigate the effects of aerobic training on C57BL/6J mice living in normoxic (NOR) or hypoxic (HYP) environments on several parameters, including critical velocity (CV), a parameter regarded as a measure of aerobic capacity, on monocarboxylate transporters (MCTs) in muscles and hypothalamus, as well as on hematological parameters and body temperature. In each environment, mice were divided into non-trained (N) and trained (T). Forty rodents were distributed into the following experimental groups (N-NOR; T-NOR; N-HYP and T-HYP). HYP groups were in a normobaric tent where oxygen-depleted air was pumped from a hypoxia generator set an inspired oxygen fraction [FiO2] of 14.5 %. The HYP-groups were kept (18 h per day) in a normobaric tent for consecutive 8-weeks. Training sessions were conducted in normoxic conditions ([FiO2] = 19.5 %), 5 times per week (40 min per session) at intensity equivalent to 80 % of CV. In summary, eight weeks of LHTL did not promote a greater improvement in the CV, protein expression of MCTs in different tissues when compared to the application of training alone. The LHTL model increased red blood cells count, but reduced hemoglobin per erythrocyte was found in mice exposed to LHTL. Although the LHTL did not have a major effect on thermographic records, exercise-induced hyperthermia (in the head) was attenuated in HYP groups when compared to NOR groups.

The Effect of Oxygen Tension on the Differentiation of Outgrowth Cells from Embryoid Bodies Produced by Mouse Induced Pluripotent Stem Cells

The purpose of this study was to investigate the effects of oxygen tension on mouse induced pluripotent stem (iPS) cells by assessing differentiation in terms of embryoid body (EB) size and mRNA and protein expression levels of collagen type 1 and Runx2. EBs and outgrowth cells (OGCs) were cultured in conditions of hypoxia (2%), normoxia (21%) and hyperoxia (35%). Significantly larger EBs were observed in the hyperoxia and normoxia groups compared to the hypoxia group on Days 8 and 10. The hyperoxia group had significantly higher mRNA and protein expression levels of collagen type 1 and Runx2 compared to the hypoxia and normoxia groups on Days 10 and 26, and these expression levels in the hypoxia group were significantly lower than the normoxia group on Days 10 and 26. These results suggest that hyperoxia accelerates the enlargement in EBs and the differentiation of iPS cells.

Repair mechanism of radiation-induced salivary gland injury by hypoxia-pretreated human urine-derived stem cell exosomes.

To explore the protective effect of human urine-derived stem cell exosomes (hUSC-Exos) on radiation-induced salivary gland (SG) injuries in Sprague Dawley rats. Fresh adult urine was collected, and primary hUSCs were isolated and identified. The hUSCs were hypoxia-pretreated with 1% oxygen for 24 h and then transferred to a normoxic culture environment for 24 h. The hUSC-Exos were collected and identified for exosomes. A radiation-induced injury model was established in the rats, and exosomes were introduced by local injection in the SG and tail vein. The submandibular gland was excised for morphological observation 1 week later. Immunohistochemical detection of the glandular tissue was conducted by α-smooth muscle actin (a-SMA), stem cell growth factor receptor (c-Kit) staining, and periodic acid-Schiff staining. Qualitative polymerase chain reaction and western blot analysis were adopted to detect the gene and protein expression of Wnt3a, GSK3β, and Axin. In both the normoxic and hypoxic hUSC-Exo groups, microvesicular structures with bilayer membranes of approximately 80 nm in diameter were detected, and the expressions of CD9 and CD63 were detected by nanoflow cytometry. Compared with the control group, in the radiation-induced injury model group, the expression of a-SMA was significantly higher, the expression of c-Kit was significantly lower, and the expressions of Wnt3a, GSK3β, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). Compared with the model group, in the normoxic and hypoxic hUSC-Exo groups, the expression of a-SMA was significantly decreased, the expression of c-Kit was significantly increased, and the expressions of Wnt3a, GSK3β, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). Hypoxia-pretreated hUSC-Exos could repair radiation-induced SG injuries by activating the Wnt3a/GSK3β pathway to suppress the expressions of a-SMA and c-Kit.

An Update to a Comprehensive Assessment of the Methods and Effectiveness of Resistance Training in Normobaric Hypoxia for the Development of Strength and Muscular Hypertrophy

Background. Training muscle capacities in hypoxic conditions increases some manifestations, such as hypertrophy and muscle strength, due to a change in the muscle phenotype as a result of the activation of hypoxia-inducible factors (HIF). Despite the proven benefits of resistance training in hypoxic conditions that allow conjecture regarding the effectiveness in facilitating muscular capacities in different populations, there is still controversy regarding the difference between resistance training in hypoxia and normoxia. The objective of this review was to compile the present evidence and update the methods and effectiveness of resistance training in simulated hypoxia for the development of strength and muscle hypertrophy. Methodology. A systematic search for an integrative review was carried out based on the preferred reporting guidelines for systematic reviews and meta-analysis (PRISMA) in 4 stages: identification, data selection, data collection and extraction, and quality evolution. Results. Four studies (92 participants) reported benefits in strength when training in hypoxia, three (101 participants) benefits in hypertrophy, and twelve (327 participants) benefits in strength and hypertrophy. Conclusion. Based on the findings of this systematic review, it is concluded that there are positive effects on muscle size and ability to generate force after a hypoxic training programme. However, some studies did not show a statistically greater benefit than for the normoxia groups, but several methodologies have been identified that promote the benefits of hypoxia.

Expression profile of cytokines and chemokines in a mouse high-altitude cerebral edema model.

High-altitude cerebral edema (HACE) is considered to be the end-stage of acute mountain sickness (AMS); however, its pathophysiological mechanism remains unknown. Increasing evidences support that inflammation is an important risk factor for the occurrence of HACE. Including our published papers, previous studies demonstrated that the levels of IL-6, IL-1β, and TNF-α in both serum and hippocampus were increased in the mouse HACE model induced by LPS stimulation combined with hypobaric hypoxia exposure; however, the expression profile of other cytokines and chemokines remains unknown. This study was to analyze the expression profile of cytokines and chemokines in the HACE model. The mouse HACE model was established by LPS stimulation combined with hypobaric hypoxia exposure (LH). The mice were divided into the normoxic group, LH-6h group, LH-1d group, and LH-7d group. Brain water content (BWC) was determined using the wet/dry weight ratio. The levels of 30 cytokines and chemokines in the serum and hippocampal tissue were detected using LiquiChip. The mRNA expression of cytokines and chemokines in hippocampal tissue were determined by q-PCR. In the current study, we found that the brain water content was increased after the combinational treatment of LPS and hypobaric hypoxia. The results of LiquiChip showed that, in the serum and hippocampal tissue, most factors in all 30 cytokines and chemokines were dramatically upregulated at 6h, and then declined at the 1std and 7thd. Among these factors, G-CSF, M-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β were all increased in both serum and hippocampal tissue at 6h. In addition, the results of q-PCR showed the mRNA levels of G-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β in hippocampal tissue were dramatically upregulated at 6h. This study showed that the dynamic expression profile of 30 cytokines and chemokines in a mouse HACE model induced by LPS plus hypobaric hypoxia. The levels of G-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β in both serum and hippocampus were significantly increased at 6h, which may be involved in the occurrence and development of HACE.

The acute leukocyte and cytokine response of older adults to resistance exercise in normobaric hypoxia.

Ageing causes a decline in leukocyte function and blunted leukocyte responses to resistance exercise. Systemic hypoxia exposure augments the leukocyte response to resistance exercise in young adults, yet this response remains uncharacterised in older adults. This study characterised the effects of normobaric hypoxia on the acute leukocyte and inflammatory cytokine responses to resistance exercise in older adults. We recruited 20 adults aged 60-70 years to perform an acute bout of resistance exercise in normobaric hypoxia (FiO2 14.4%; n = 10) or normoxia (FiO2 20.93%; n = 10). Participants completed 4 × 10 repetitions of lower and upper body exercises at 70% of their predicted 1-repetition maximum. Venous blood was sampled before and up to 24 hours post-exercise to quantify neutrophils, lymphocytes, monocytes, eosinophils, basophils and cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, TNFα). Flow cytometry was used to classify lymphocytes as T (CD4+ helper and CD8+ cytotoxic), B and NK cells, in addition to the expression of the senescence marker CD45RA on T cells. The hypoxic group showed a larger lymphocyte response over the 24 hours post-exercise compared to the normoxic group (p = 0.035). Specifically, there were greater concentrations of CD4+ T helper cells following hypoxic exercise compared to normoxia (p = 0.046). There was also a greater proportion of CD45RA+ CD4+ T helper cells, suggesting that the cells were more senescent (p = 0.044). Hypoxia did not impact any other leukocyte population or cytokine following exercise. Normobaric hypoxia increases the lymphocyte response to an acute bout of resistance exercise in older adults.

Ssc-miR-141 Attenuates Hypoxia-Induced Alveolar Type II Epithelial Cell Injury in Tibetan Pigs by Targeting PDCD4.

The Tibetan pig is an endemic economic animal in the plateau region of China, and has a unique adaptation mechanism to the plateau hypoxic environment. Research into microRNAs (miRNAs) involved in the mechanism underlying hypoxia adaptation of Tibetan pig is very limited. Therefore, we isolated alveolar type II epithelial (ATII) cells from the lungs of the Tibetan pig, cultured them in normoxia/hypoxia (21% O2; 2% O2) for 48 h, and performed high-throughput sequencing analysis. We identified a hypoxic stress-related ssc-miR-141 and predicted its target genes. The target genes of ssc-miR-141 were mainly enriched in mitogen-activated protein kinase (MAPK), autophagy-animal, and Ras signaling pathways. Further, we confirmed that PDCD4 may serve as the target gene of ssc-miR-141. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis was performed to confirm the expression levels of ssc-miR-141 and PDCD4, and a dual-luciferase gene reporter system was used to verify the targeted linkage of ssc-miR-141 to PDCD4. The results showed that the expression level of ssc-miR-141 in the hypoxia group was higher than that in the normoxia group, while the expression level of PDCD4 tended to show the opposite trend and significantly decreased under hypoxia. These findings suggest that ssc-miR-141 is associated with hypoxia adaptation and provide a new insight into the role of miRNAs from ATII cells of Tibetan pig in hypoxia adaptation.

Preventive effects of antenatal CDP-choline in a rat model of neonatal hyperoxia-induced lung injury.

Antenatal steroid administration to pregnant women at risk of prematurity provides pulmonary maturation in infants, while it has limited effects on incidence of bronchopulmonary dysplasia (BPD), the clinical expression of hyperoxia-induced lung injury (HILI). Cytidine-5'-diphosphate choline (CDP-choline) was shown to alleviate HILI when administered to newborn rats. Therefore, we investigated effects of maternal administration of CDP-choline, alone or in combination with betamethasone, on lung maturation in neonatal rats subjected to HILI immediately after birth. Pregnant rats were randomly assigned to one of the four treatments: saline (1 mL/kg), CDP-choline (300 mg/kg), betamethasone (0.4 mg/kg), or CDP-choline plus betamethasone (combination therapy). From postnatal day 1 to 11, pups born to mothers in the same treatment group were pooled and randomly assigned to either normoxia or hyperoxia group. Biochemical an d histopathological effects of CDP-choline on neonatal lung tissue were evaluated. Antenatal CDP-choline treatment increased levels of phosphatidylcholine and total lung phospholipids, decreased apoptosis, and improved alveolarization. The outcomes were further improved with combination therapy compared to the administration of CDP-choline or betamethasone alone. These results demonstrate that antenatal CDP-choline treatment provides benefit in experimental HILI either alone or more intensively when administered along with a steroid, suggesting a possible utility for CDP-choline against BPD.

High Keratin Secretion of T47D Cell under Hypoxic Condition

BACKGROUND: Hypoxia adaptation in cancer cells is mediated by hypoxia inducible factor (HIF)-1 that induces the expression of various proteins. Up to date, the analysis of T47D breast cancer cells-secreted protein is still limited. The aim of this study was to compare the protein profile secreted by T47D breast cancer cells under hypoxic and to normoxic conditions and identify the proteins as candidate for hypoxia marker proteins in T47D breast cancer cells.METHODS: T47D breast cancer cells were cultured under standard conditions. Cells were subcultured in normoxic and hypoxic conditions. The normoxic group was incubated with 20% oxygen and the hypoxic groups were incubated in a hypoxic chamber with 0.5% and 5% oxygen for 6, 24, and 48 hours in serum free medium. Proteins in the culture media were isolated and precipitated. Protein concentrations released by the cells were then measured by bicinchoninic assay (BCA). Protein bands were visualized by the sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) method. The bands that had differences between the hypoxic and normoxic groups were further analyzed by liquid chromatography-mass spectrophotometer (LC-MS).RESULTS: Hypoxic groups showed higher secretory protein than normoxic group. Protein bands were found in the 0.5% hypoxic group with a size of 50-75 kDa. Secretory proteins identified by LC-MS were keratin 1, 2, 9, and 10.CONCLUSION: The T47D cell line under 0.5% hypoxic treatment showed higher secretory proteins that identified as keratin 1, 2, 9, and 10.KEYWORDS: hypoxia, secretory protein, liquid chromatography-mass spectrophotometer

Combined transcriptome and proteome analysis of yak PASMCs under hypoxic and normoxic conditions.

Yaks are animals that have lived in plateau environments for generations. Yaks can adapt to the hypoxic plateau environment and also pass this adaptability on to the next generation. The lungs are the most important respiratory organs for mammals to adapt to their environment. Pulmonary artery smooth muscle cells play an important role in vascular remodeling under hypoxia, but the genetic mechanism underpinning the yak's ability to adapt to challenging plateau conditions is still unknown. A tandem mass tag (TMT) proteomics study together with an RNA-seq transcriptome analysis were carried out on pulmonary artery smooth muscle cells (PASMCs) that had been grown for 72 hours in both normoxic (20% O2) and hypoxic (1% O2) environments. RNA and TP (total protein) were collected from the hypoxic and normoxic groups for RNA-seq transcriptome sequencing and TMT marker protein quantification, and RT-qPCR validation was performed. A total of 17,711 genes and 6,859 proteins were identified. Further, 5,969 differentially expressed genes (DEGs) and 531 differentially expressed proteins (DEPs) were identified in the comparison group, including 2,924 and 186 upregulated genes and proteins and 3,045 and 345 down-regulated genes and proteins, respectively. The transcriptomic and proteomic analyses revealed that 109 DEGs and DEPs were highly positively correlated, with 77 genes showing the same expression trend. Nine overlapping genes were identified in the HIF-1 signaling pathway, glycolysis / gluconeogenesis, central carbon metabolism in cancer, PPAR signaling pathway, AMPK signaling pathway, and cholesterol metabolism (PGAM1, PGK1, TPI1, HMOX1, IGF1R, OLR1, SCD, FABP4 and LDLR), suggesting that these differentially expressed genes and protein functional classifications are related to the hypoxia-adaptive pathways. Overall, our study offers abundant data for further analysis of the molecular mechanisms in yak PASMCs and their adaptability to different oxygen concentrations.

Endothelial cell‑derived connective tissue growth factor stimulates fibroblast differentiation into myofibroblasts through integrin αVβ3.

Connective tissue growth factor (CTGF) is expressed at high levels in blood vessels, where it functions as a regulator of a number of physiological processes, such as cell proliferation, angiogenesis and wound healing. In addition, CTGF has been reported to be involved in various pathological processes, such as tumor development and tissue fibrosis. However, one of the main roles of CTGF is to promote the differentiation of fibroblasts into myofibroblasts, a process that is involved in disease progression. Therefore, the present study aimed to investigate the possible mechanism by which pathological changes in the microvasculature can direct the activation of fibroblasts into myofibroblasts in the context of hypoxia/reoxygenation (H/R). Human umbilical vein endothelial cells (HUVECs) and normal human dermal fibroblasts were used in the present study. The expression levels of CTGF were determined by western blot analysis and reverse transcription-semi-quantitative PCR. To analyze the paracrine effect of HUVECs on fibroblasts, HUVECs were infected with CTGF-expressing adenovirus and then the culture supernatant of HUVECs was collected to treat fibroblasts. The formation of α-smooth muscle actin (α-SMA) stress fibers in fibroblasts were observed by immunofluorescence staining. It was found that H/R significantly increased CTGF expression in HUVECs. CTGF was also able to directly induce the differentiation of fibroblasts into myofibroblasts. In addition, the culture supernatant from CTGF-overexpressing HUVECs stimulated the formation of α-SMA stress fibers in fibroblasts, which was inhibited by treatment with a functional blocking antibody against integrin αVβ3 and to a lesser degree by a blocking antibody against α6 integrin. The mechanism of CTGF upregulation by H/R in HUVECs was then evaluated, where it was found that the CTGF protein was more stable in the H/R group compared with that in the normoxic control group. These findings suggest that CTGF expressed and secreted by vascular endothelial cells under ischemia/reperfusion conditions can exert a paracrine influence on neighboring fibroblasts, which may in turn promote myofibroblast-associated diseases. This association may hold potential as a therapeutic target.

ACUTE REPEATED WINGATE STYLE HIIT EXERCISE IN HYPOXIC CONDITIONS DOES NOT ALTER OXIDATIVE STATUS IN UNTRAINED MEN

Both high-intensity interval training and training in hypoxic conditions have gained popularity in recent years due to their cardiorespiratory and metabolic benefits. Recent studies focus on the combined effects of both factors in detail. But there is still a scientific gap in the literature on the effects caused and its magnitude in response to this type of training. Therefore, this study aims to investigate the acute effects of Repeated Wingate Style HIIT applied in hypoxic and normoxic conditions on oxidant and antioxidant indicators of recreationally active men. Sixteen participants were randomly assigned to normoxic or hypoxic groups and then they were completed a wingate style 30s*4rps*4 min (sprint time * repeats * recover between sprints) HIIT on normoxic and hypoxic conditions (2500m, FiO2: 0.130) in the normobaric environment. The normality assumption calculated using a Shapiro-Wilk test to ensure the normal distribution of the quantitative for all data (p &lt; 0.05). To analyze differences in baseline data between groups an Independent Sample t-test was performed. The Two-way analysis of variance was used in repeated measurements to reveal the effects of training under hypoxia and normoxia conditions (time, time × group interactions) oxidant and antioxidants. The activities of blood oxidant and antioxidant did not change significantly after training in the hypoxic and normoxic group. As a result, repeated Wingate style HIIT applied in hypoxic and normoxic conditions, did not change both MDA (p=0.79), which is an indicator of oxidant stress, and SOD (p=0.46), CAT (p=0.26), and GSHPX (p=0.17), which are general indicators of antioxidant defense.

Photoinduced Carbene for Effective Photodynamic Therapy Against Hypoxic Cancer Cells

Photoinduced Carbene for Effective Photodynamic Therapy Against Hypoxic Cancer Cells

RNA-seq and qRT-PCR analyses reveal the physiological response to acute hypoxia and reoxygenation in Epinephelus coioides.

Hypoxia is a critical problem in intensive Epinephelus coioides aquaculture systems. In the present study, the physiological responses of E. coioides muscle to acute hypoxic stress (DO = 0.6 ± 0.1mg/L) and reoxygenation (DO = 6.0 ± 0.1mg/L) were analyzed by transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR). RNA-seq was conducted on the muscle tissues of E. coioides in the hypoxia-tolerant (EMS), hypoxia-sensitive (EMW), and normoxic (CM) groups. Among the three groups, a total of 277 differentially expressed genes (DEGs) were identified. KEGG analysis revealed that the pathways significantly enriched after hypoxic stress are involved in the immune response, glycolysis/gluconeogenesis, energy metabolism, vasodilation and proliferation, cell proliferation, and apoptosis. qRT‒PCR verified that the differentially expressed genes FIH-1, PHD-2, PPARα, BCL-XL, LDH-A, and Flt-1 were significantly upregulated after hypoxic stress and returned to normal levels after reoxygenation, suggesting that these DEGs play important roles in responding to hypoxia treatment. In addition, the HIF-1 signaling pathway was also activated under hypoxic stress, and qRT‒PCR confirmed that the expression level of HIF-1α was significantly elevated under acute hypoxic stress, indicating that the HIF-1 signaling pathway is the central pathway in the E. coioides hypoxic response mechanism and activates other related pathways to adapt to hypoxic stress. These pathways jointly regulate energy metabolism, substance synthesis, blood vessel proliferation, cell proliferation, and differentiation and prolong survival time. These results provide ideas for understanding physiological regulation after hypoxic stress and reoxygenation and provide basic insights for the future breeding of hypoxia-tolerant E. coioides.

Effectiveness, implementation, and monitoring variables of intermittent hypoxic bicycle training in patients recovered from COVID-19: The AEROBICOVID study.

Hypoxic exposure is safely associated with exercise for many pathological conditions, providing additional effects on health outcomes. COVID-19 is a new disease, so the physiological repercussions caused by exercise in affected patients and the safety of exposure to hypoxia in these conditions are still unknown. Due to the effects of the disease on the respiratory system and following the sequence of AEROBICOVID research work, this study aimed to evaluate the effectiveness, tolerance and acute safety of 24 bicycle training sessions performed under intermittent hypoxic conditions through analysis of peripheral oxyhemoglobin saturation (SpO2), heart rate (HR), rate of perceived exertion (RPE), blood lactate concentration ([La-]) and symptoms of acute mountain sickness in patients recovered from COVID-19. Participants were allocated to three training groups: the normoxia group (GN) remained in normoxia (inspired fraction of O2 (FiO2) of ∼20.9%, a city with 526m altitude) for the entire session; the recovery hypoxia group (GHR) was exposed to hypoxia (FiO2 ∼13.5%, corresponding to 3,000m altitude) all the time except during the effort; the hypoxia group (GH) trained in hypoxia (FiO2 ∼13.5%) throughout the session. The altitude simulation effectively reduced SpO2 mean with significant differences between groups GN, GHR, and GH, being 96.9(1.6), 95.1(3.1), and 87.7(6.5), respectively. Additionally, the proposed exercise and hypoxic stimulus was well-tolerated, since 93% of participants showed no or moderate acute mountain sickness symptoms; maintained nearly 80% of sets at target heart rate; and most frequently reporting session intensity as an RPE of "3" (moderate). The internal load calculation, analyzed through training impulse (TRIMP), calculated using HR [TRIMPHR = HR * training volume (min)] and RPE [TRIMPRPE = RPE * training volume (min)], showed no significant difference between groups. The current strategy effectively promoted the altitude simulation and monitoring variables, being well-tolerated and safely acute exposure, as the low Lake Louise scores and the stable HR, SpO2, and RPE values showed during the sessions.

Effect of Intermittent Hypoxic Training on Selected Biochemical Indicators, Blood Rheological Properties, and Metabolic Activity of Erythrocytes in Rowers.

Simple SummaryRowing is among the oldest sports disciplines. Involving multiple muscle groups, it poses a considerable challenge to athletes and amateurs. To improve training efficiency, the hypoxic method (decreasing arterial oxygen concentration) is sometimes applied. The study determined the effect of 3-week hypoxic training on blood indicators in competitive rowers. The reported findings demonstrated that the phenomenon of hypoxia could be an extremely effective training measure in rowers as it exerted a beneficial impact on the athletes’ performance.The study assessed the effect of 3-week intermittent hypoxic training on blood biochemical indicators (blood morphology, fibrinogen), blood rheological properties (erythrocyte deformability, aggregation), erythrocyte enzymatic activity (acetylcholinesterase), and maximal oxygen uptake in competitive rowers. Fourteen male rowers were divided into two equal groups: experimental, training on ergometers under normobaric hypoxia (FiO2 = 16.0%), and control, training on ergometers under normoxia (FiO2 = 21%). Fasting blood was taken before and after training. A significant between-group difference in neutrophil levels before training was noted and a significant decrease in white blood cells in the hypoxia group. Both groups exhibited an increase in elongation index. In the normoxia group, a significant increase in erythrocyte aggregation amplitude was revealed. No significant changes occurred in the other biochemical indicators or those evaluating erythrocyte metabolic activity. Normobaric hypoxia increased erythrocyte deformability, improving blood rheological properties. Maximal oxygen uptake significantly increased only in the experimental group.