Search

Purpose: To investigate the effects of repeated-sprint training with voluntary hypoventilation at low (RSH-VHL) and high (RS-VHH) lung volume on repeated-sprint ability (RSA) in female athletes. Methods: Over a 6-week period, 24 female soccer players completed 12 sessions of repeated 30-m running sprints with end-expiratory breath holding (RSH-VHL, n = 8), end-inspiratory breath holding (RS-VHH, n = 8), or unrestricted breathing (RS-URB, n = 8). Before and after training, a running RSA test consisting of performing 30-m all-out sprints until exhaustion was implemented. Results: From before to after training, the number of sprints completed during the RSA test was increased in both RSH-VHL (19.3 [0.9] vs 22.6 [0.9]; P <.01) and RS-VHH (19.3 [1.5] vs 20.5 [1.7]; P <.01) but not in RS-URB (19.4 [1.3] vs 19.5 [1.7]; P =.67). The mean velocity and the percentage decrement score calculated over sprints 1 to 17 were, respectively, higher (82.2% [1.8%] vs 84.6% [2.1%] of maximal velocity) and lower (23.7% [3.1%] vs 19.4% [3.2%]) in RSH-VHL (P <.01), whereas they remained unchanged in RS-VHH and RS-URB. The mean arterial oxygen saturation recorded during training at the end of the sprints was lower in RSH-VHL (92.1% [0.4%]) than in RS-VHH (97.3% [0.1%]) and RS-URB (97.8% [0.1%]). Conclusions: This study shows that female athletes can benefit from the RSH-VHL intervention to improve RSA. The performance gains may have been limited by the short sprinting distance with end-expiratory breath holding, which provoked only moderate hypoxemia. The increase in the number of sprints in RS-VHH seems to show that factors other than hypoxia may have played a role in RSA improvement. [ABSTRACT FROM AUTHOR]

Background: Repeated exposure to heat (ie, plasma volume expansion) or altitude (ie, increase in total hemoglobin mass), in conjunction with exercise, induces hematological adaptations that enhance endurance performance in each respective environment. Recently, combining heat and altitude training has become increasingly common for athletes preparing to compete in temperate, sea-level conditions. Purpose: To review the physiological adaptations to training interventions combining thermal and hypoxic stimuli and summarize the implications for temperate, sea-level performance. Current Evidence: To date, research on combining heat and hypoxia has employed 2 main approaches: simultaneously combining the stressors during training or concurrently training in the heat and sleeping at altitude, sometimes with additional training in hypoxia. When environmental stimuli are combined in a training session, improvements in aerobic fitness and time-trial performance in temperate, sea-level conditions are generally similar in magnitude to those observed with heat, or altitude, training alone. Similarly, training in the heat and sleeping at altitude does not appear to provide any additional hematological or nonhematological benefits for temperate; sea-level performance relative to training in hot, hypoxic, or control conditions. Conclusions: Current research regarding combined heat and altitude interventions does not seem to indicate that it enhances temperate, sea-level performance to a greater extent than "traditional" (heat or hypoxia alone) training approaches. A major challenge in implementing combined-stressor approaches lies in the uncertainty surrounding the prescription of dosing regimens (ie, exercise and environmental stress). The potential benefits of conducting heat and altitude exposure sequentially (ie, one after the other) warrants further investigation. [ABSTRACT FROM AUTHOR]

Purpose: This study examined performance and physiological adaptations following 3 weeks of repeated-sprint training (RST) with blood-flow restriction (BFR) or without (non-BFR). Methods: Twenty-six semiprofessional and amateur adult male team-sport players were assessed for repeated-sprint ability, anaerobic capacity, leg lean mass, neuromuscular function, and maximal aerobic capacity before and after RST. Participants completed 9 cycling RST sessions (3 sets of 5–7 × 5-s sprints, 25-s passive recovery, 3-min rest) over a 3-week period with BFR or non-BFR. Results: During RST sessions, the BFR group demonstrated lower mean power output compared with non-BFR (−14.5%; g = 1.48; P =.001). Significant improvements (P <.05) in mean and peak power output during repeated-sprint ability (+4.1%; g = 0.42, and + 2.2%; g = 0.25, respectively) and anaerobic capacity (+4.8%; g = 0.47, and + 4.7%; g = 0.32, respectively) tests, leg lean mass (+2.0%; g = 0.16), and peak aerobic power (+3.3%; g = 0.25) were observed from pretesting to posttesting without any between-groups differences. No significant changes (P >.05) were observed for maximal isometric voluntary contraction and maximal aerobic capacity. Peak rate of force development decreased (P =.003) in both groups following RST (−14.6%; g = 0.65), without any between-groups differences. Conclusions: Repeated-sprint ability, anaerobic capacity, leg lean mass, and peak aerobic power improved following 3 weeks of RST; however, the addition of BFR did not further enhance adaptations. Interestingly, comparable improvements were achieved between groups despite lower external loads experienced during RST sessions with BFR. [ABSTRACT FROM AUTHOR]

Purpose: Total hemoglobin mass (tHbmass) and blood volume (BV) are important determinants of maximal oxygen uptake and endurance capacity. Higher-caliber endurance athletes usually possess higher tHbmass and BV values. This study aimed to compare tHbmass and BV among swimmers of diverse competitive calibers and distances. Methods: Thirty swimmers (16 female and 14 male) participated in the study: 3 were tier 5, world class (869 [59] FINA points); 15 were tier 4, elite/international (853 [38] points); and 12 were tier 3, highly trained/national (808 [35] points). They specialized in competition distances ranging from 200 m to open-water 10 km. Between February 2019 and February 2020, all swimmers had their tHbmass and BV measured by carbon monoxide rebreathing 1 to 6 times and participated in multiple competitions and race events. Results: Relative tHbmass and BV were not different (P >.05) between tiers among women or among men (pooled tHbmass values 14.5 [0.5], 12.5 [1.5], 12.6 [2.3] g/kg for tier 5, tier 4, and tier 3, respectively). No differences were observed in relative tHbmass (P =.215) and BV (P =.458) between pool and open-water swimmers or between 200-, 400-, and 1500-m specialists (P >.05). No significant correlations were found between the highest measured absolute or relative tHbmass and BV and the highest FINA points scored over the follow-up period (R = −.42–.17, P =.256–.833), irrespective of competition distance. Conclusion: tHbmass and BV values did not differ between swimmers of different calibers or among competition distances. Furthermore, these values did not correlate with FINA points, either in males or in females. The present results indicate that hematological characteristics may have a lesser impact on swimming performance than on land-based endurance sports. [ABSTRACT FROM AUTHOR]

Chronic fetal hypoxia is one of the most common complications of pregnancy and can programme cardiac abnormalities in adult offspring including ventricular remodelling, diastolic dysfunction and sympathetic dominance. However, the underlying mechanisms at the level of the cardiomyocyte are unknown, preventing the identification of targets for therapeutic intervention. Therefore, we aimed to link echocardiographic data with cardiomyocyte function to reveal cellular mechanism for cardiac dysfunction in rat offspring from hypoxic pregnancy. Further, we investigated the potential of maternal treatment with melatonin as antenatal antioxidant therapy. Wistar rats were randomly allocated into normoxic (21% O2) or hypoxic (13% O2) pregnancy with or without melatonin treatment (5 µg/ml; normoxic melatonin in the maternal drinking water from gestational day 6 to 20 (term = 22 days). After delivery, male and female offspring were maintained to adulthood (16 weeks). Cardiomyocytes were isolated from the left and right ventricles, and calcium (Ca2+) handling was investigated in field‐stimulated myocytes. Systolic and diastolic function was negatively impacted in male and female offspring of hypoxic pregnancy demonstrating biventricular systolic and diastolic dysfunction and compensatory increases in cardiac output. Ca2+ transients from isolated cardiomyocytes in offspring of both sexes in hypoxic pregnancy displayed diastolic dysfunction with a reduced rate of [Ca2+]i recovery. Cardiac and cardiomyocyte dysfunction in male and female adult offspring was ameliorated by maternal antenatal treatment with melatonin in hypoxic pregnancy. Therefore, cardiomyocyte Ca2+ mishandling provides a cellular mechanism explaining functional deficits in hearts of male and female offspring in pregnancies complicated by chronic fetal hypoxia. Key points: This study identified significant changes in Ca2+ handling within cardiomyocytes isolated from offspring of hypoxic pregnancy including reduced systolic Ca2+ transients, impaired diastolic recovery of [Ca2+]i and a greater increase in systolic [Ca2+]i amplitude to β‐adrenergic stimulation.These changes in cardiomyocyte Ca2+ handling help to explain dysregulation of biventricular systolic and diastolic dysfunction determined by echocardiography.The data show protection against maladaptive cardiomyocyte calcium handling and thereby improvement in cardiac function in adult offspring of hypoxic pregnancy treated with melatonin with doses lower than those recommended for overcoming jet lag in humans.Melatonin treatment alone in healthy pregnancy did cause some alterations in cardiac structure. Therefore, maternal treatment with melatonin should only be given to pregnancies affected by chronic fetal hypoxia. [ABSTRACT FROM AUTHOR]

Pallas' spadefoot toad is a Eurasian species of amphibian that winters for about half the year at a depth to 2 m below the level of soil freezing, since it does not survive negative temperatures. However, digging deep into the soil can cause oxygen deficiency. The minimum oxygen level sufficient for the long-term existence of Pelobates vespertinus and the lethal oxygen content in the air were revealed, and the metabolic pathways were evaluated under the conditions of normoxia and hypoxia in laboratory experiments. In addition, the seasonal dynamics of temperatures and oxygen concentrations in sandy loam soils at different depths were determined in a typical wintering biotope of the species (the Oka River valley). Animals have been found to be capable of withstanding a tenfold decrease in the oxygen content in soils compared to atmospheric oxygen for more than two months, thereby remaining quite active. When the concentration is decreased by 20 times (up to 1%), a state of coma occurs, which is reversible if it lasts no longer than a day. This shows a high degree of resistance of the species to stress resulting from reoxygenation and staying in an environment with variable oxygen levels. Thus, P. vespertinus is the second amphibian species, following the Siberian wood frog (Rana amurensis), that can tolerate the complete absence of oxygen for a long time (several months). Compared to its body weight, the spadefoot has small storage organs (fat bodies and liver) and a low content of reserve substances (lipids and glycogen) in its tissues, which are usually consumed at a low rate in normoxia at 3°C. During hypoxia, lipid utilization is suspended and glycogen consumption is increased, indicating a shift from aerobic to predominantly anaerobic metabolism. The cumulative effect of reduced metabolism due to low temperature (3°C) and the activation of glycolysis due to the lack of oxygen provides a high level of resistance to hypoxia, distinguishing Pallas' spadefoot toad from other swarming amphibian species studied. The oxygen content in the ground air of typical places at wintering depths (in sandy massifs) is shown to coincide with the atmospheric oxygen. The ubiquitous choice of wintering areas with loose soils by this species is assumed to be associated not with their excellent aeration, but rather with the ease of digging. The results obtained seem to be promising for using this spadefoot toad (and possibly other species of the spadefoot toad genus, as well as burrowing toads) as a model for exploring adaptations to air oxygen deficiency. [ABSTRACT FROM AUTHOR]

Red blood cells (RBCs) play a role in the regulation of vascular tone via release of adenosine triphosphate (ATP) into the vasculature in response to various stimuli. Interestingly, ApoE/LDLR double-deficient (ApoE/LDLR−/−) mice, a murine model of atherosclerosis, display a higher exercise capacity compared to the age-matched controls. However, it is not known whether increased exercise capacity in ApoE/LDLR−/− mice is linked to the altered ATP release from RBCs. In this work, we characterized the ATP release feature of RBCs from ApoE/LDLR−/− mice by exposing them to various stimuli in vitro. The results are linked to the previously reported mechanical and biochemical alterations in RBCs. 3V-induced ATP release from RBCs was at comparable levels for all groups, which indicated that the activity of adenylyl cyclase and the components of upstream signal-transduction pathway were intact. Moreover, hypoxia- and low pH-induced ATP release from RBCs was higher in ApoE/LDLR−/− mice compared to their age-matched controls, a potential contributing factor and a finding in line with the higher exercise capacity. Taken together, augmented hypoxia-induced ATP release from RBCs in ApoE/LDLR−/− mice indicates a possible deterioration in the ATP release pathway. This supports our previous reports on the role of the protein structure alterations of RBC cytosol in hypoxia-induced ATP release from RBCs in ApoE/LDLR−/− mice. Thus, we emphasize that the presented herein results are the first step to future pharmacological modification of pathologically impaired microcirculation. [ABSTRACT FROM AUTHOR]

Introduction: Hypoxia stress renders aquatic animals more susceptible to bacterial disease, yet the underlying mechanism remains elusive. Methods: We conducted an acute hypoxia stress experiment to investigate the impact of stress on the immune response of Litopenaeus vannamei via transcriptome analysis, RT-qPCR and Western blot. Results: Our results showed that acute hypoxia stress disrupted the tissue architecture, and significantly changed the gene expression profiles in the hepatopancreas of shrimp. More importantly, acute hypoxia stress significantly changed the expression levels of immune-related genes. Ladderlectin , GBP 1 , Caspase-1 , CLEC4F , MR1 and GBP 2 were significantly down-regulated, but HIF-1α , Cactus , TIPE , Akirin-2 , Ivns1abp and TLR3 were significantly up-regulated. We further demonstrated that acute hypoxia activated Yki via HIF-1α to enhance expression level of Cactus , and then Cactus inhibited the phosphorylation of Dorsal and its nuclear translocation, thereby suppressing antibacterial immunity. Subsequently, the challenge experiment following stress revealed that exposure to acute hypoxia stress amplified the infectivity and lethality of Vibrio parahaemolyticus to shrimp. The mechanism of HIF-1α-Yki-Cautus axis provided an explanation for this phenomenon. Discussion: This study offered new insights into interactions among environmental hypoxia stress, host immunity and pathogens, thereby providing practical guidelines for optimizing shrimp culture practices. [ABSTRACT FROM AUTHOR]

Cell-based assays are widely exploited for drug screening and biosensing, providing useful information about bioactivity of target analytes and complex biological samples. It is well recognized that 3D cell models are required to achieve highly valuable information, also from the perspective of replacing animal models. However, bioassays relying on 3D cell models are generally highly demanding in terms of facilities, equipment, and skilled personnel requirements. To reduce cost, increase sustainability, and provide a flexible 3D cell-based platform for bioassays, we here report a novel approach based on a 3D-printed microtissue device. To assess the suitability of this strategy for reporter gene technology, we selected to monitor two molecular pathways which were of interest in several applications, hypoxia signaling and the p53 pathway. The investigation of such pathways is highly relevant in fields spanning from drug screening to bioactivity monitoring for industrial by-product valorization. Microtissues of human hepatocarcinoma (HepG2) and human embryonic kidney (Hek293T) cell lines were obtained with a low-cost and sustainable chip platform and bioassays were developed to monitor the hypoxia-inducible factors (HIFs) and the p53 tumor suppressor pathway. HepG2 and Hek293T 3D cell models were genetically engineered to express the Luc2P from Photinus pyralis firefly either under the regulation of p53 or HIF response elements. The bioassays allowed quantitative assessment of hypoxia and tumoral activity with 1,10-phenanthroline for HIF and with doxorubicin for p53 pathway activation, respectively, showing good potential for applications of this sustainable and low-cost 3D-printed microfluidic platform for bioactivity analyses, drug screening, and precision medicine. [ABSTRACT FROM AUTHOR]

Copyright of Retos: Nuevas Perspectivas de Educación Física, Deporte y Recreación is the property of Federacion Espanola de Asociaciones de Docentes de Educacion Fisica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Hypoxia negatively affects the behavior, growth, reproduction and survival of fish, causing serious economic losses to aquaculture. Rainbow trout (Oncorhynchus mykiss), an important economic fish worldwide, belongs to a hypoxia-sensitive fish species, however, little is known about the regulatory mechanism of microRNAs (miRNAs) under hypoxia stress. Results: Rainbow trout were subjected to hypoxia stress for 3 h (H3h_L), 12 h (H12h_L), 24 h (H24h_L) and 3 h reoxygenation (R3h_L) to systemically evaluate the changes of miRNA expression profiles in liver, and functions of sha-miR-92a_L + 2R + 4 were investigated. We found 17, 144, 57 and 55 differentially expressed (DE) miRNAs in the H3h_L vs. control (N_L), H12h_L vs. N_L, H24h_L vs. N_L and R3h_L vs. N_L comparisons, respectively. Enrichment analysis revealed that the targets of DE miRNAs were significantly enriched in HIF signaling pathway, VEGF signaling pathway, FoxO signaling pathway and glycolysis/gluconeogenesis. Through miRNA-mRNA interaction and weighted gene co-expression network analysis (WGCNA), five key DE miRNAs (sha-miR-92a_L + 2R + 4, ssa-miR-128-3p, ssa-miR-101b-3p_R + 1, ola-miR-199a-5p_R + 2 and tni-miR-199_1ss18CG) were identified, which can target at least two hypoxia-responsive genes, such as vegfaa, ho, glut1a and junb. Functional analysis found that sha-miR-92a_L + 2R + 4 directly regulated vegfaa expression by targeting its 3′-UTR, overexpression of sha-miR-92a_L + 2R + 4 significantly decreased vegfaa expression in rainbow trout liver cells, while opposite results were obtained after transfection of sha-miR-92a_L + 2R + 4 inhibitor. Furthermore, overexpressed sha-miR-92a_L + 2R + 4 promoted rainbow trout liver cell proliferation and inhibited apoptosis. Conclusion: This study deepens our understanding of the crucial roles of miRNAs under hypoxia stress in rainbow trout. These results can contribute to devise strategies for improving rainbow trout survival rate and aquaculture production during hypoxia stress and help speeding up the selective breeding of hypoxia-tolerant rainbow trout. [ABSTRACT FROM AUTHOR]

Copyright of Shandong Medical Journal is the property of Shandong Medical Health Newspapers and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Hypoxia can drive tumor progression, suppress anti-tumor immunity, and reduce the effectiveness of radiotherapy and chemotherapy. This study aimed to assess the impact of remote ischemic conditioning (RIC) on tumor oxygenation (sO2) and the anti-tumor immune response. Material and methods: Fourteen B16-Ova tumor-bearing C57BL/6N mice received six 5-minute RIC cycles, while another fourteen underwent anesthesia only. Pimonidazole was administered 1.5 hours before sacrifice. Blood flow, sO2, and hemoglobin levels were measured in the non-ischemic hind limb and tumor. Tumor hypoxia was assessed using pimonidazole and CA IX immunohistochemistry, and T cell infiltration by CD3 and FoxP3 staining. Serum levels of 23 cytokines were analyzed using a multiplex immunoassay. Results: Isoflurane anesthesia caused a slight intraindividual increase in blood flow (p = 0.07) and sO2 (p = 0.06) of the hind limb and a sole increase in tumor sO2 (p = 0.035), whereas RIC improved sO2 of the tumor in relation to the hind limb (p=0.03). The median of the tumor oxygen saturation reached 51.4% in the control group and 62.7% in the RIC group (p = 0.09), exhibiting a slight tendency towards better oxygenation in the RIC group. Pimonidazole (p=0.24) and CA IX hypoxia score (p=0.48) did not reveal statistically significant differences between the two groups. In RIC-treated tumors, the number of CD3 (p=0.006), but not FoxP3- positive cells (p = 0.84), in the tumor core was significantly higher compared to the control group. In the RIC group, the mean fluorescence intensity (MFI) of IL-17 was significantly higher (p=0.035), and TNF-α was trend-wise higher (p=0.063) compared to the control group. Conclusion: Both isoflurane anesthesia and RIC have an impact on microcirculation. The application of RIC counteracted some of the effects of isoflurane, primarily in healthy tissue, and led to a significant improvement in relative tumor tissue oxygenation compared to the non-ischemic hind limb. RIC selectively enhanced immune infiltration within the tumor center, probably by previously activated tumor infiltrating T cells, while having no significant impact on T-regulatory cells. RIC appears to impact the cytokine profile, as indicated by elevated MFIs of TNF-α and IL-17. [ABSTRACT FROM AUTHOR]

Background: The hypoxic microenvironment is a key component of the gastric tumour niche. Carcinoembryonic antigen‐related cell adhesion molecule 6 (CEACAM6) is upregulated in gastric cancer and is considered a novel biomarker for the disease. However, no prior studies have elaborated on the status of CEACAM6 and its role in the hypoxic gastric cancer niche. Methods: In this short study, we evaluated the effect of hypoxia in modulating CEACAM6 level in gastric cancer cells (GCCs) through western blotting and determined the effect of CEACAM6 upregulation on gastric cancer progression through clonogenicity, cell proliferation and migration assays. The wound‐healing ability of GCCs was downregulated by siRNA‐mediated CEACAM6 silencing. Human gastric cancer biopsy samples were examined by immunofluorescence microscopy to assess the level of a hypoxia marker HIF1α and CEACAM6. The effect of empty vector or CEACAM6‐expression on peripheral blood‐derived mononuclear cell (PBMC)‐derived macrophage polarization under normoxia or hypoxia was studied by incubating macrophages in conditioned medium collected from GCC cultures. Macrophage polarization status was observed using flow cytometry and fluorescence microscopy. Reactive oxygen species (ROS) generation by macrophages was evaluated using fluorescence microscopy. Results: We identified that hypoxia promoted CEACAM6 in GCCs, and these cells acquired increased proliferative potential and migration ability. Moreover, the cell culture supernatant from hypoxia‐exposed CEACAM6‐overexpressing cells promoted an M2‐like macrophage population and discouraged the M1 phenotype. Conclusion: This study established that hypoxia increased CEACAM6 which promoted gastric cancer progression by influencing GCC proliferation and motility as well as macrophage polarization. [ABSTRACT FROM AUTHOR]

Background: Hypoxia-induced pulmonary hypertension (HPH) is a subgroup of type 3 pulmonary hypertension that may cause early right ventricular failure and eventual cardiac failure, which lacks potential therapeutic targets. Our previous research demonstrated that T follicular helper (TFH) cells that produce IL-21 were involved in HPH. However, the molecular mechanisms of TFH/IL-21-mediated pathogenesis of HPH have been elusive. Here we investigate the role of TFH cells and IL-21 in HPH. Methods: Studies were performed in C57BL/6 mice or IL-21 knockout mice exposed to chronic hypoxia to induce PH, and examined by hemodynamics. Molecular and cellular studies were performed in mouse lung and pulmonary arterial smooth muscle cells (PASMCs). M2 signature gene (Fizz1), M1 signature genes (iNos, IL-12β and MMP9), GC B cell and its marker GL-7, caspase-1, M2 macrophages, TFH cells, Bcl-6 and IL-21 level were measured. Proliferation rate of PASMCs was measured by EdU. Pyroptosis was assessed using Hoechst 33,342/PI double fluorescent staining. Results: In response to chronic hypoxia exposure-induced pulmonary hypertension, IL-21−/− mice or downregulation of TFH cells in WT mice developed blunted pulmonary hypertension, attenuated pulmonary vascular remodelling. Furthermore, chronic hypoxia exposure significantly increased the germinal center (GC) B cell responses, which were not present in IL-21−/− mice or downregulation of TFH cells in WT mice. Importantly, IL-21 promoted the polarization of primary alveolar macrophages toward the M2 phenotype. Consistently, significantly enhanced expression of M2 macrophage marker Fizz1 were detected in the bronchoalveolar lavage fluid of HPH mice. Moreover, alveolar macrophages that had been cultivated with IL-21 promoted PASMCs proliferation and pyroptosis in vitro, while a selective CX3CR1 antagonist, AZD8797 (AZD), significantly attenuated the proliferation and pyroptosis of the PASMCs. Finally, ECM1 knockdown promoted IL-2–STAT5 signaling and inhibited Bcl-6 signaling to inhibit TFH differentiation in HPH. Conclusions: TFH/IL-21 axis amplified pulmonary vascular remodelling in HPH. This involved M2 macrophage polarization, PASMCs proliferation and pyroptosis. These data suggested that TFH/IL-21 axis may be a novel therapeutic target for the treatment of HPH. [ABSTRACT FROM AUTHOR]

Background: To investigate the accuracy of quantitative blood oxygen level-dependent (qBOLD) magnetic resonance imaging (MRI) in identifying hypoxia within glioblastoma and explore dynamic changes in oxygenation status of glioblastoma with and without metformin administration. Methods: Three healthy and seven C6-bearing rats underwent 7-T qBOLD MRI. Oxygen extraction fraction (OEF) and cerebral metabolism rate of O2 (CMRO2) were calculated from qBOLD data. Tumor tissues were stained using hypoxia-inducible factor-1 α (HIF-1 α ) and pimonidazole. The correlation between the hypoxia markers and corresponding qBOLD-based parameters was analyzed. Six C6-bearing rats were divided into metformin-treated and control groups for a longitudinal study of qBOLD imaging changes, with scans conducted on the 12th, 15th, and 18th day post-tumor implantation. Results: In healthy rats, gray matter showed higher values than white matter in T2, T2*, cerebral blood volume (CBV), and cerebral blood flow (CBF), whereas OEF was lower. Glioblastoma tissues exhibited elevated T2, T2*, CBV, and CBF but decreased OEF and CMRO2 relative to normal-appearing white matter. No significant correlation was found between staining scores from HIF-1 α and pimonidazole. T2* and T2 values were negatively correlated with pimonidazole scores in tumor regions. As the tumor progressed, OEF values increased with intra-tissue variations, whereas CMRO2 decreased. Metformin delayed the reduction of T2 and T2* values, with significant differences in OEF and CMRO2 values compared to controls on day 18. Conclusion: T2* and T2 values were significantly associated with the hypoxia status in glioma. Metformin could potentially mitigate the progression of hypoxia in glioblastoma, which can be tracked by qBOLD parameters. Relevance statement: This study demonstrates the potential of qBOLD parameters in assessing glioma dynamic oxygen metabolism and the efficacy of metformin as an anti-hypoxic agent, providing insights into improving glioblastoma treatment strategies. Key Points: The study investigated qBOLD imaging's accuracy in identifying hypoxia status within glioblastoma. qBOLD effectively assesses hypoxia and its dynamic evolution in glioblastoma. qBOLD parameters assist in identifying a suitable patient demographic for metformin treatment. [ABSTRACT FROM AUTHOR]

The emergence of drug‐resistant strains of Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is on the rise and increasing antimicrobial resistance is a global threat. This phenomenon necessitates new drug design methods such as a prodrug strategy to develop novel antitubercular agents. The prodrug strategy is a viable and useful means to improve the absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles of pharmacologically active agents. Granulomas are a pathological hallmark of M.tb infection and bear a remarkable resemblance to the tumour microenvironment, including regions of hypoxia. The hypoxic environment observed in the two structures offer an exceptional opportunity to deliver antitubercular agents selectively in a similar manner to hypoxia activated prodrugs in cancer therapy. Nitroimidazoles have been studied extensively as bioactivated prodrugs of cancer, and their suitability as substrates for mammalian reductases highlight their huge potential. This review will discuss the mechanism of action and resistance mechanisms of the current prodrugs used for the treatment of tuberculosis. It will also highlight the potential advantages and challenges of using hypoxia activated prodrugs as a viable strategy to target latent M.tb in hypoxic regions of granulomas. [ABSTRACT FROM AUTHOR]

Coastal reservoirs (CRs) are important water resources worldwide, but environmental problems can arise due to limited material mixing caused by the blocked propagation of tidal waves. The Saemangeum Reservoir is a large brackish reservoir in South Korea; owing to its complex fluctuation characteristics, accurate reproduction of its three-dimensional (3D) circulation and material distribution characteristics remains a challenge. Here, we aimed to improve the reproducibility of the Delft3D model through long-term precision monitoring and analyze problems occurring in CRs. The model reproduced the hydraulic flow and stratification phenomena in CRs. The Richardson number ( $ {\textrm{R}_\textrm{i}} $ R i ) was higher than 100, and the Stratification Index ( $ \textrm{SI} $ SI ) was higher than 1 due to the density difference between the surface and bottom layers. The stratification strength of the Saemangeum Reservoir was, therefore, considered high. Moreover, a two-layer circulation occurred due to the strength of the eddy and the horizontal gradient of salinity. When the sluice gate was expanded, the area and number of days where hypoxia occurred decreased. It would also mitigate the retention of materials caused by the eddy and improve circulation. The findings of this study can be used as foundational data for solving and managing hydraulic problems within CRs. [ABSTRACT FROM AUTHOR]

The activation of hypoxia-inducible factors (HIF)-1α and 2α in the liver is closely linked to the progression of fatty liver diseases. Prior studies indicated that disrupting hepatocyte HIF-2α attenuates diet-induced hepatic steatosis, subsequently decreasing fibrosis. However, the direct role of hepatocyte HIF-2α in liver fibrosis has not been addressed. Hepatic HIF-2α expression was examined in mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. Conditional hepatocyte Hif-2α knockout mice were employed to investigate the role of hepatocyte HIF-2α in fibrosis. Markers of apoptosis, proliferation, inflammation, and fibrosis were assessed through biochemical, molecular, and histological analyses. We found an induction of HIF-2α in CCL4-injected liver injury and fibrosis mouse models. Hepatocyte-specific deletion of HIF-2α attenuated stellate cell activation and fibrosis, with no significant difference in inflammation. Disrupting hepatocyte HIF-2α led to reduced injury-mediated hepatocellular apoptosis. Surviving hepatocytes exhibited hypertrophy, which was strongly associated with the activation of c-JUN signaling. Our study demonstrates a direct role of hepatocyte HIF-2α in liver fibrosis by promoting hepatocyte apoptosis. The reduction in apoptosis and induction of hepatocyte hypertrophy following HIF-2α disruption is closely linked to enhanced c-JUN signaling, a survival mechanism in response to liver injury. These findings highlight HIF-2α as a potential therapeutic target for liver fibrosis. [ABSTRACT FROM AUTHOR]

As one of the most prevalent malignant neoplasms among women globally, the optimization of therapeutic strategies for breast cancer has perpetually been a research hotspot. The tumor microenvironment (TME) is of paramount importance in the progression of breast cancer, among which the extracellular matrix (ECM) and hypoxia are two crucial factors. The alterations of these two factors are predominantly regulated by the Hippo signaling pathway, which promotes tumor invasiveness, metastasis, therapeutic resistance, and susceptibility. Hence, this review focuses on the Hippo pathway in breast cancer, specifically, how the ECM and hypoxia impact the biological traits and therapeutic responses of breast cancer. Moreover, the role of miRNAs in modulating ECM constituents was investigated, and hsa-miR-33b-3p was identified as a potential therapeutic target for breast cancer. The review provides theoretical foundations and potential therapeutic direction for clinical treatment strategies in breast cancer, with the aspiration of attaining more precise and effective treatment alternatives in the future. [ABSTRACT FROM AUTHOR]

In hypoxic pulmonary hypertension (PH), pulmonary vascular remodeling is characterized by the emergence of activated adventitial fibroblasts, leading to medial smooth muscle hyperplasia. Previous studies have suggested that CD26/dipeptidyl peptidase-4 (DPP4) plays a crucial role in the pathobiological processes in lung diseases. However, its role in pulmonary fibroblasts in hypoxic PH remains unknown. Therefore, we aimed to clarify the mechanistic role of CD26/DPP4 in lung fibroblasts in hypoxic PH. Dpp4 knockout (Dpp4 KO) and wild-type (WT) mice were exposed to hypoxia for 4 weeks. The degree of PH severity and medial wall thickness was augmented in Dpp4 KO mice compared with that in WT mice, suggesting that CD26/DPP4 plays a suppressive role in the development of hypoxic PH. Transcriptome analysis of human lung fibroblasts cultured under hypoxic conditions revealed that TGFB2, TGFB3, and TGFA were all upregulated as differentially expressed genes after DPP4 knockdown with small interfering RNA treatment. These results suggest that CD26/DPP4 plays a suppressive role in TGFβ signal-regulated fibroblast activation under hypoxic conditions. Therefore, CD26/DPP4 may be a potential therapeutic target in patients with PH associated with chronic hypoxia. [ABSTRACT FROM AUTHOR]

Hypoxia-induced radioresistance limits therapeutic success in cancer. In addition, p53 mutations are widespread in tumors including non-small cell lung carcinomas (NSCLCs), and they might modify the radiation response of hypoxic tumor cells. We therefore analyzed the DNA damage and inflammatory response in chronically hypoxic (1% O2, 48 h) p53 null H358 NSCLC cells after X-ray exposure. We used the colony-forming ability assay to determine cell survival, γH2AX immunofluorescence microscopy to quantify DNA double-strand breaks (DSBs), flow cytometry of DAPI-stained cells to measure cell cycle distribution, ELISAs to quantify IL-6 and IL-8 secretion in cell culture supernatants, and RNA sequencing to determine gene expression. Chronic hypoxia increased the colony-forming ability and radioresistance of H358 cells. It did not affect the formation or resolution of X-ray-induced DSBs. It reduced the fraction of cells undergoing G2 arrest after X-ray exposure and delayed the onset of G2 arrest. Hypoxia led to an earlier enhancement in cytokines secretion rate after X-irradiation compared to normoxic controls. Gene expression changes were most pronounced after the combined exposure to hypoxia and X-rays and pertained to senescence and different cell death pathways. In conclusion, hypoxia-induced radioresistance is present despite the absence of functional p53. This resistance is related to differences in clonogenicity, cell cycle regulation, cytokine secretion, and gene expression under chronic hypoxia, but not to differences in DNA DSB repair kinetics. [ABSTRACT FROM AUTHOR]

Microglia, the brain-resident immune cells, orchestrate neuroinflammatory responses and are crucial in the progression of neurological diseases, including ischemic stroke (IS), which accounts for approximately 85% of all strokes worldwide. Initially deemed detrimental, microglial activation has been shown to perform protective functions in the ischemic brain. Besides their effects on neurons, microglia play a role in promoting post-ischemic angiogenesis, a pivotal step for restoring oxygen and nutrient supply. However, the molecular mechanisms underlying microglia–endothelial cell interactions remain largely unresolved, particularly in humans. Using both in vitro and in vivo models, we investigated the angiogenic signature and properties of extracellular vesicles (EVs) released by human microglia upon hypoxia–reperfusion stimulation. EVs were isolated and characterized in terms of their size, concentration, and protein content. Their angiogenic potential was evaluated using endothelial cell assays and a zebrafish xenograft model. The in vivo effects were further assessed in a mouse model of ischemic stroke. Our findings identified key proteins orchestrating the pro-angiogenic functions of human microglial EVs under hypoxic conditions. In vitro assays demonstrated that hypoxic EVs (hypEVs) promoted endothelial cell migration and tube formation. In vivo, hypEVs induced vessel sprouting in zebrafish and increased microvessel density in the perilesional area of mice following ischemic stroke. [ABSTRACT FROM AUTHOR]

Simple Summary: Fasciolosis is one of the parasitic diseases that exerts the greatest impact on sheep productive systems worldwide. Affected sheep generally show a decrease in their reproductive capacity, weight gain, meat and milk production, and wool quality. In the pathogenesis of Fasciola hepatica, the penetration and migration of parasitic stages through the liver provoke intense inflammatory immune responses and tissue damage. Following strong activation signals, polymorphonuclear neutrophils (PMNs) reportedly release chromatin and granular proteins into the extracellular space, forming DNA traps called neutrophil extracellular traps (NETs). It was recently demonstrated that F. hepatica induces NET formation in vivo in the liver parenchyma from naturally infected sheep. Thus, in this paper we investigated F. hepatica-mediated NET-derived cytotoxic effects in exposed hepatic cells in vitro as well as F. hepatica-triggered ovine NETs under hypoxic conditions (5% O2). Our results confirm the ability of ovine PMNs to form NETs in low-oxygen environments after F. hepatica antigen (FhAg) stimulation, as seen in many pathological and pro-inflammatory states, and their cytotoxic effects on exposed hepatic cells. In addition, we demonstrate that this defence mechanism is NADPH oxidase (NOX)-dependent and therefore a tightly regulated molecular process. Overall, we hypothesize that NET formation plays a role in the pathogenesis of fasciolosis, and NETs contribute to liver tissue damage if released in an uncontrolled manner. Fasciola hepatica is a parasitic trematode that causes fasciolosis in sheep, provoking a decrease in their reproductive capacity, weight gain, meat and milk production, and wool quality. In the pathogenesis of F. hepatica, the penetration and migration of parasitic stages through the liver provoke intense inflammatory immune responses and tissue damage. The aim of this study was to investigate the cytotoxic effects of Fascila hepatica-induced ovine NETs in exposed hepatocytes in vitro, and to analyze whether F. hepatica antigens (FhAg) trigger the release of ovine NETs under hypoxic conditions as well as the roles of matrix metalloproteinase-9 (MMP-9) and CD11b in this cellular process in vitro. Here, isolated ovine PMNs were co-cultured with FhAg under hypoxia (5% O2) and NETs were visualized via immunofluorescence analyses, confirming their classical characteristics. The quantification of NETs in response to FhAg in hypoxic conditions significantly enhanced the formation of anchored and cell-free NETs (p < 0.01), and NADPH oxidase (NOX) inhibitor diphenylene iodonium (DPI) significantly reduced their production (p < 0.05). Furthermore, the cytotoxic effect of NETs on hepatic cells was determined by using a live/dead-staining with Sytox Orange, thereby demonstrating that FhAg-induced NETs are cytotoxic for hepatic cells (p = 0.001). We additionally analyzed PMN supernatants to determine the enzymatic activity of MMP-9, observing that FhAg exposure enhances MMP-9 release in ovine PMNs (p < 0.05) but not in bovine PMNs. Interestingly, by using flow cytometric analysis, we determined that the exposure of PMNs to FhAg does not increase the CD11b surface expression of ovine PMNs. This could be an effect of the activation of other surface receptors or transcription factors involved in F. hepatica-induced NETosis. Consequently, we hypothesize that F. hepatica-induced NETs play a role in the pathogenesis of fasciolosis, contributing to liver tissue damage if released in an uncontrolled manner. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the potential role of ferroptosis/hypoxia-related genes in cervical cancer to improve early management and treatment of cervical cancer. Methods: All data were downloaded from public databases. Ferroptosis/hypoxia-related genes associated with cervical cancer prognosis were selected to construct a risk score model. The relationship between risk score and clinical features, immune microenvironment and prognosis were analysed. Results: Risk score model was constructed based on eight signature genes. Drug prediction analysis showed that bevacizumab and cisplatin were related to vascular endothelial growth factor A. Risk score, as an independent prognostic factor of cervical cancer, had a good survival prediction effect. The two groups differed significantly in degree of immune cell infiltration, gene expression, tumour mutation burden and somatic variation. Conclusions: We developed a novel prognostic gene signature combining ferroptosis/hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer. PLAIN LANGUAGE SUMMARY: Ferroptosis, hypoxia and immune regulation play important roles in cervical cancer progression. In this study, we developed a novel prognostic signature combining ferroptosis and hypoxia-related genes, which provides new ideas for individual treatment of cervical cancer patients. The risk score established by ferroptosis and hypoxia-related gene as an independent prognostic factor of cervical cancer has a good survival prediction effect. High and low risk groups showed significant differences in TIME, prognosis, biological metabolic pathway and tumour mutation burden. In addition, we found drugs associated with signature genes. In short, this study has laid a theoretical foundation for exploring the related molecular mechanisms and prognosis of cervical cancer. It also contributes to the exploration of clinical management and treatment. [ABSTRACT FROM AUTHOR]

Background: Respiratory dysfunction is an important contributor to morbidity and mortality in advanced Parkinson's disease (PD), but it is unclear what parameters are sensitive to diagnose and monitor respiratory dysfunction across disease phases. Objectives: We aimed to characterize respiratory dysfunction in mild to moderate PD. Methods: In 20 individuals without cardiopulmonary comorbidity, pulmonary and inspiratory muscle function testing were performed ON‐medication. Subsequently, the acute ventilatory response to hypoxia (HVR) was assessed by gradually decreasing FIO2 from 0.209 (room air) to 0.127, which was compared to eight age‐ and sex‐matched healthy controls under arterial blood gas monitoring. Lastly, on different days, the same 20 individuals with PD underwent six blinded exposures to 45‐min normobaric hypoxia at FiO2 0.163 and 0.127 or placebo OFF‐medication to assess breathing responses. Results: At rest, individuals with greatest PD severity had a lower tidal volume (pairwise comparisons: 0.59 vs. 0.74, P = 0.038–0.050) and tended to have a higher breathing frequency (17.7 vs. 14.4, P = 0.076), despite normal pulmonary function. A 45‐min exposure to hypoxia induced a significantly lower acute HVR in individuals with PD compared to controls (−0.0489 vs. 0.133 L.min/%, P = 0.0038). Acute HVR was reduced regardless of disease severity. Subacute HVR in individuals with milder disease tended to be higher compared to those with more advanced disease (P = 0.079). Conclusions: Respiratory dysfunction is present in individuals with PD, including those with relatively mild disease severity, and is characterized by altered breathing patterns at rest, as well as a lower HVR, despite normal pulmonary and inspiratory muscle function testing. [ABSTRACT FROM AUTHOR]

Fish kills in Southeast Asia are frequently associated with harmful algal blooms (HABs) and cause significant ecological and economic impacts and can have negative effects on the sustainability of aquatic ecosystems and the fisheries they support. This paper serves as a review of fish-kill events with focus on those related to HABs within the region. It examines the causative algal species, known mechanisms of fish mortality, and socio-economic consequences in order to better understand and manage this threat to sustainable fisheries. Fish kills have been reported across multiple countries within Southeast Asia, with notable hotspots in the Philippines, Malaysia, Singapore, Indonesia, and Thailand. The common harmful microalgal species span a diverse group including dinoflagellates (Karenia spp., Karlodinium spp., Margalefidinium polykrikoides, Noctiluca scintillans), raphidophytes (Chattonella spp.), diatoms (Skeletonema spp. and Chaetoceros spp.), and cyanobacteria (Trichodesmium spp.). These microalgae lead to fish kills through mechanisms such as hypoxia, physical gill damage, and ichthyotoxin production. Freshwater fish kills linked to HABs have also been documented for the Philippines, but there is no or limited information for the region. Our review highlights the widespread and recurring nature of fish kills, their impact on fisheries and aquaculture, and challenges in managing and mitigating their effects. There are efforts at enhancing management and mitigation using clay and early warning systems. However, it is essential to further improve monitoring efforts, the development and deployment of early warning systems, and viable and holistic mitigation strategies to protect the region's aquatic resources and dependent communities, especially as aquaculture and coastal development are increasing concurrent with a changing climate that can exacerbate the risks of fish kills and HABs in Southeast Asia. [ABSTRACT FROM AUTHOR]

Manganese dioxide (MnO2) nanoparticles are increasingly recognized for their potential in biomedical applications, particularly in the realm of hypoxic cancer therapy, due to their unique physicochemical characteristics. This investigation introduces a novel, template‐free synthesis strategy. The reducing groups inherent in bovine serum albumin (BSA) facilitate a redox reaction with potassium permanganate (KMnO4), while the abundance of functional groups in BSA is instrumental in the formation of MnO2. The transmission electron microscopy (TEM) analysis has characterized the synthesized MnO2 nanoparticles, termed BM NPs, as spherical particles with a mean diameter of 210 nm and zeta potential of −40.1 mV measured by dynamic light scattering (DLS). The Fourier transform infrared (FT‐IR) spectrum of BM NPs exhibits the characteristic peak of MnO2 at 1113 cm−1 and 620 cm−1. Furthermore, the elemental composition of BM NPs has been ascertained through energy‐dispersive X‐ray (EDX) elemental mapping analysis. Though concentration of BM NPs up to 200 μg/mL, the survival rate of 4T1 cells remained approximately 75 %. Given that BM NPs at a concentration of 100 μg/mL significantly alleviate cellular hypoxia, the high oxygen‐generating capacity of these nanoparticles is proved, suggesting their suitability as a drug delivery system, especially in the context of hypoxic tumor microenvironments. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a highly malignant tumor, which is still a major global health problem. Chemotherapy and radiotherapy are regularly used in adjuvant therapy for pancreatic cancer but their therapeutic efficacy is limited. In the present study, nanoparticle（MSN-AuNPs） was used as a drug carrier loaded with tirapazamine(TPZ) and hyaluronic acid (HA) to synthesize a multifunctional nanoplatform HA@TPZ-MSN-AuNPs (HTMA) for hypoxia activation and radiotherapy sensitization, which can be combined with radiotherapy therapy and synergistically enhance the therapeutic effect in pancreatic cancer. The anti-tumor performance of the nano platform was verified by in vivo and in vitro experiments. First, the HA@TPZ-MSN-AuNPs (HTMA) was successfully synthesized. Drug release experiments showed that acidic environment and hyaluronidase promoted drug release in the nanoplatform. In vitro experiments, CCK-8, live-dead staining, clonal formation assay and flow cytometry confirmed the combined anti-tumor effect of hypoxia activation and radiotherapy sensitization with HTMA. In the drug uptake experiment, the nanoplatform showed the function of targeting and binding pancreatic cancer cells. In vivo, HTMA demonstrated good antitumor properties and good biocompatibility. The nanoplatform had a good targeting effect and synergistic anti-tumor effect. The combination of hypoxia activation and radiotherapy sensitization is a promising strategy for the treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: Carbonic anhydrase IX (CAIX) is a well‐established prognostic marker in breast cancer (BC). Nevertheless, this prognostic value is yet to be confirmed in BC subtypes. This study aims to investigate the prognostic effects of CAIX in oestrogen receptor (ER)‐negative (ER−) BCs and to establish pathways related to cytoplasmic CAIX expression in ER− and lymph node‐negative BCs. Methods: Immunohistochemistry was performed to identify the prognostic role of CAIX protein expression in ER− tissue microarrays (TMAs) (n = 191). CAIX‐positive samples (n = 37) were transcriptionally profiled by TempO‐Seq and analysed by STRING. Real‐time quantitative PCR (RT‐qPCR) analysis was used to validate differentially expressed genes. Results: Overexpression of cytoplasmic CAIX was an independent predictor of recurrence free survival, disease‐free survival and overall survival in ER− cohort. RNA transcriptomic analysis identified 10 significant genes in ER− cohort and 3 genes in the node‐negative group. The STRING database demonstrated a significant interaction between MUCL1 and GALNT6, which were linked with extracellular matrix organisation, degradation of the extracellular matrix and disease of glycosylation pathways. In the node‐negative group, SPNS2 is mainly involved in the sphingolipid de novo biosynthesis pathway. A significant correlation between cytoplasmic SphK1 and cytoplasmic hypoxia‐inducible factor‐1α was observed. Among the 10 genes, 7 genes (SERHL2, GALNT6, MUCL1, MMP7, PITX2, CEACAM6 and SPNS2) were selected, and their expression was quantitatively assessed by RT‐qPCR. The PCR data of these genes showed that SERHL2, GALNT6, MUCL1, PITX2, and SPNS2 mRNA levels were expressed in MDA‐MB‐231 BC cell lines at variable levels of hypoxic exposure. Conclusion: Cytoplasmic CAIX was independently associated with poor prognosis in ER− BC. Gene expression profiles shed light on the pathways and genes associated with hypoxia in ER− BC. In node‐negative patients, SPNS2 was of particular interest. [ABSTRACT FROM AUTHOR]

Even though N6-methyladenosine (m6A) RNA modifications are increasingly being implicated in human disease, their mechanisms are not fully understood in smokers with coronary artery disease (CAD). Thirty m6A-related regulators' expression (MRRE) in CAD individuals (smokers and non-smokers) were analyzed from GEO. Support Vector Machine, random forest, and nomogram models were constructed to assess its clinical value. Consensus clustering, principal component analysis, and ssGSEA were used to construct a full picture of m6A-related regulators in smokers with CAD. Oxygen-glucose deprivation (OGD) and qRT-PCR were used to validate hypoxia's effect on MRRE. A comparison between smokers with CAD and controls revealed lower expression levels of RBM15B, YTHDC2, and ZC3H13. Based on three key MRREs, all models showed good clinical value, and smokers with CAD were divided into two distinct molecular subgroups. The correlations were found between key MRRE and the degree of immune infiltration. Three key MRREs in HUVECs and FMC84 mouse cardiomyocytes were reduced in the OGD group. Through hypoxia, smoking might reduce the expression levels of RBM15B, YTHDC2, and ZC3H13 in smokers with CAD. Our findings provide an important theoretical basis for the treatment of smokers with CAD. [ABSTRACT FROM AUTHOR]

Copyright of Korean Journal of Anesthesiology is the property of Korean Society of Anesthesiologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The integrity of the colon and the development of colon cancer depend on the sphingolipid balance in colon epithelial cells. In this review, we summarize the current knowledge on how ceramides and their complex derivatives influence normal colon development and colon cancer development. Ceramides, glucosylceramides and sphingomyelin are essential membrane components and, due to their biophysical properties, can influence the activation of membrane proteins, affecting protein–protein interactions and downstream signalling pathways. Here, we review the cellular mechanisms known to be affected by ceramides and their effects on colon development. We also describe which ceramides are deregulated during colorectal carcinogenesis, the molecular mechanisms involved in ceramide deregulation and how this affects carcinogenesis. Finally, we review new methods that are now state of the art for studying lipid-protein interactions in the physiological environment. [ABSTRACT FROM AUTHOR]

Sulfide in sediment porewaters, is toxic to rooted macrophytes in both marine and freshwater environments. Current research on sulfide stress in seagrasses primarily focuses on morphological and physiological aspects, with little known about the molecular response and resistance mechanisms. This study first investigated the damage caused by sulfide to eelgrass (Zostera marina L.) using transcriptomic, metabolomic, and other physiological and biochemical indicators and explored the potential resistance of eelgrass at molecular level through laboratory simulated and in‐situ sulfide stress experiments. Comprehensive results showed that sulfide stress severely inhibited the growth, photosynthesis, and antioxidant enzyme activities of eelgrass. Importantly, transcriptome analysis revealed significant activation of pathways related to carbohydrate and sulfur metabolism. This activation served a dual purpose: providing an energy source for eelgrass stress response and achieving detoxification through accelerated sulfur metabolism—a potential resistance mechanism. The toxicity of sulfide increased with rising temperature as evidenced by a decrease in EC50. Results from recovery experiments indicated that when Fv/Fm reduced to about 0 under sulfide stress, the growth and photosynthesis of eelgrass recovered to normal level after timely removal of sulfide. However, prolonged exposure to sulfide resulted in failure to recover, leading ultimately to plant death. This study not only enhances our understanding of the molecular‐level impacts of sulfide on seagrasses but also provides guidance for the management and ecological restoration of seagrass meadows under sulfide stress. Summary statement: Little is known about the molecular response and resistance mechanisms of seagrass to sulfide stress. This study indicates that photosynthesis‐related pathways in eelgrass are significantly inhibited under sulfide stress, while carbohydrate and sulfur metabolism‐related pathways are markedly activated, which may represent potential resistance mechanisms. [ABSTRACT FROM AUTHOR]

Oxygen depletion in coastal waters is increasing globally due primarily to eutrophication and warming. Hypoxia responses to nutrient loading and climate change have been extensively studied in large systems like the Chesapeake Bay and the Baltic Sea, while fewer studies have investigated smaller, shallower hypoxic zones. Thus, an improved understanding of the interactions of eutrophication and warming on hypoxia expansion (or reduction) in the wide variety of different estuarine environments is needed. We examined interannual controls on oxygen depletion in the Patuxent River estuary, a eutrophic sub-estuary of Chesapeake Bay where seasonal hypoxia develops annually. We conducted a spatial and temporal analysis of dissolved oxygen (DO) trends, timing, and several metrics of depletion over a long-term record (1985–2021). We found an internally generated hypoxic zone that initiates in the middle estuary, spreading upstream and downstream as the summer progresses, and that hypoxic volume days (HVD) have been increasing (0.11 per year, p = 0.03) over the record despite reduced watershed nitrogen loads and stable phosphorus loads. River flow and temperature have been increasing and are major drivers of increased HVD, with river flow explaining 40% of the interannual variation in HVD (temperature has increased 0.03 and 0.06 °C per year in summer and fall, respectively). Apparent oxygen utilization (AOU) is increasing in bottom waters in the fall, consistent with increasing trends of both water temperature and stratification strength. HVD was negatively related (r2 = 0.34, slope = −0.59*HVD) to the biomass of benthic invertebrates in the middle region of the estuary, suggesting that benthic forage for higher trophic levels will be limited by sustained hypoxia. These results indicate that current and future climate variability plays an important role in regulating oxygen depletion in the Patuxent River estuary, which reinforces the need to factor climate change into strategies for the restoration and management of estuaries. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is a highly aggressive cancer with limited therapeutic options. Hypoxia is a common feature of the tumor microenvironment that reportedly promotes tumorigenesis. Long non-coding RNAs (lncRNAs) are a class of regulatory molecules with diverse functions in cancer biology. This study aimed to identify hypoxia-induced lncRNAs associated with HCC and evaluate their potential as prognostic and therapeutic biomarkers. Methods: We employed microarray and The Cancer Genome Atlas (TCGA) data to identify hypoxia-induced lncRNAs in HCC. Subsequently, we focused on CTD-2510F5.4, a candidate lncRNA, and predicted its functional roles in HCC using Gene Ontology (GO) and Guilt-by-Association (GBA) analyses. We validated its expression under hypoxia in Huh7 and HepG2 cells using RT-PCR. Functional assays, including CCK8, wound-healing, and transwell assays, were performed to assess the effects of CTD-2510F5.4 overexpression on HCC cell proliferation, invasion, and metastasis potential. Furthermore, we investigated the association between CTD-2510F5.4 expression and patient prognosis, tumor mutation signature, immune microenvironment characteristics, and therapeutic response to different treatment modalities. Results: Our data demonstrated a significant upregulation of CTD-2510F5.4 expression in response to hypoxia. Functional enrichment analyses revealed the involvement of CTD-2510F5.4 in cell cycle regulation, E2F targets, G2M checkpoint control, and MYC signaling pathways. Functionally, CTD-2510F5.4 overexpression promoted HCC cell proliferation, invasion, and metastasis. Patients with high CTD-2510F5.4 expression exhibited a worse prognosis, a higher prevalence of TP53 mutations, increased infiltration by immunosuppressive regulatory T cells, elevated expression of immune checkpoint molecules, and higher TIDE scores indicative of immune dysfunction and exclusion. Notably, patients with low CTD-2510F5.4 expression displayed greater sensitivity to immunotherapy and antiangiogenic therapy, while those with high expression responded better to chemotherapy. Conclusion: Our findings suggest that CTD-2510F5.4 plays a critical role in HCC progression and immune modulation. Its potential as a prognostic biomarker and a predictor of therapeutic response warrants further investigation for personalized treatment strategies in HCC patients. [ABSTRACT FROM AUTHOR]

Copyright of HNO is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Mouse models are crucial for understanding pulmonary hypertension (PH) mechanisms and developing therapies, but existing mouse models under hypoxia only exhibit mild PH. To address this, we established a double‐hit model combining unilateral pneumonectomy (LPx) or left pulmonary artery ligation (LPAL) with hypoxia exposure in C57BL/6 mice. Our detailed haemodynamic and histological evaluations post‐surgery demonstrated pronounced elevations in right ventricular systolic pressure (RVSP) (LPAL: 41.1 ± 4.63 mmHg, P = 0.005; LPx: 38.4 ± 2.95 mmHg, P = 0.002; Sham: 32.1 ± 2.21 mmHg) and pulmonary vascular wall thickness (LPAL: 56.9 ± 3.34%, P = 0.02; LPx: 54.3 ± 4.65%, P = 0.04; Sham: 44.8 ± 3.76%) compared to hypoxia‐exposed sham‐operated controls, reflecting a more severe PH phenotype. These novel models, which exhibit haemodynamic alterations akin to the established hypoxia with SU5416‐induced PH model as per published data, could offer a substantial contribution to future PH research and therapeutic development. What is the central question of this study?Existing mouse models of pulmonary hypertension (PH) under hypoxia exhibit only mild PH: can a mouse model of PH be established that exhibits a more severe PH phenotype?What is the main finding and its importance?Mouse models with more severe PH were successfully established through a combination treatment involving unilateral pneumonectomy or left pulmonary artery ligation followed by hypoxia exposure. This approach results in a more pronounced PH phenotype compared to traditional models that rely solely on hypoxia exposure. [ABSTRACT FROM AUTHOR]

Background: Peripherally measured oxygen saturation (SpO2) may often differ from arterial oxygen saturation (SaO2), measured by co‐oximetry, especially within the lower range of oxygen saturations. This can potentially impact clinical decisions and therapy in children with congenital heart disease, as critical hypoxemia might remain unnoticed. Aims: Our aim was to investigate the accuracy of two different pulse oximeters compared to SaO2 in infants with congenital heart diseases. Methods: Simultaneous recordings of SpO2, measured by two different pulse oximeters (Philips IntelliVue X3 Monitor and Nellcor™ OxiMax™), were compared to SaO2 obtained by arterial blood gas analysis. Results: A total of 153 measurements were performed in 44 infants with arterial oxygen saturation between 70 and 100%. We divided the measurements into 3 subgroups: group 1—SaO2 70.0%–85.0%, group 2—SaO2 85.1%–94.0%, group 3—SaO2 >94.1%. For Philipps, the median bias was 5.3 (IQR: 2.6–8.7) %, 2.3 (IQR: 0.9–6.0) % and 1.1 (IQR: −0.8–2.4) % in group 1, 2 and 3, respectively. For OxiMax™, the median bias was 2.7 (IQR: 0.5–5.1) %, 0.2 (IQR: −0.9–2.6) % and −0.5 (IQR: −1.3–0.6) % in group 1, 2 and 3, respectively. Regarding the accuracy of these oximeters, as evaluated with the Accuracy root mean squared index (Arms), it was 9.8 versus 4.5% in group 1, 4.5 versus 2.9% in group 2 and 2.4 versus 1.9% in group 3 for Philipps and OxiMax™, respectively. Conclusions: In lower range saturations between 70% and 85% the accuracy of both pulse oximeters exceeded the threshold of ≤3% recommended by the Food and Drug Administration (FDA). Therefore, peripheral pulse oximetry within the lower range of oxygen saturations should be interpreted with caution in infants with congenital heart diseases, taking into consideration its limitations. Direct co‐oximetry should be the preferred method to support clinical decisions in children with cyanotic congenital heart diseases. [ABSTRACT FROM AUTHOR]

Purpose: Obstructive Sleep Apnea (OSA) is the most common sleep-related disorder. Interoception is the collection of sensory and cognitive processes that involve receiving and interpreting physiological signals from internal body structures and conveying the perception of inner sensations. In this study, it was hypothesized that the impairment in cognitive functions associated with chronic hypoxemia and the insular effects due to OSA would negatively affect interoceptive functions. The aim of this study was to evaluate whether interoception in OSA changes consistent with the hypothesis. Methods: A total of 102 patients diagnosed with OSA were included in this study. All participants were divided into groups based on their T90 values: desaturated OSA (T90 ≥ 20%) and non-desaturated OSA (T90 < 20%). The Heartbeat Counting Task was used to assess interoceptive accuracy, while the Interoceptive Sense Questionnaire (ISQ) was employed to identify subjective challenges in evaluating interoception. Results: Interoceptive accuracy was lower in the desaturated OSA group than in the non-desaturated OSA group (Z = -2.463; p = 0.014). Interoceptive accuracy was negatively correlated with the body mass index (r = -0.228; p = 0.021), T90 (r = -0.269; p = 0.006), and positively correlated with the average SaO2 (r = 0.377; p < 0.001) and SaO2 nadir (r = 0.243; p = 0.014). Conclusion: This study examined interoceptive functions in patients with OSA. It was concluded that interoceptive accuracy is affected by the severity of hypoxia as hypothesized. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the impact of voluntary hypoventilation at low lung volumes (VHL) during upper body repeated sprints (RS) on performance, metabolic markers and muscle oxygenation in Brazilian Jiu-Jitsu (BJJ) athletes. Methods: Eighteen male well-trained athletes performed two randomized RS sessions, one with normal breathing (RSN) and another with VHL (RS-VHL), on an arm cycle ergometer, consisting of two sets of eight all-out 6-s sprints performed every 30 s. Peak (PPO), mean power output (MPO), and RS percentage decrement score were calculated. Arterial oxygen saturation (SpO2), heart rate (HR), gas exchange, and muscle oxygenation of the long head of the triceps brachii were continuously recorded. Blood lactate concentration ([La]) was measured at the end of each set. Bench press throw peak power (BPPP) was recorded before and after the RS protocol. Results: Although SpO2 was not different between conditions, PPO and MPO were significantly lower in RS-VHL. V ˙ E, HR, [La], and RER were lower in RS-VHL, and VO2 was higher in RS-VLH than in RSN. Muscle oxygenation was not different between conditions nor was its pattern of change across the RS protocol influenced by condition. [La] was lower in RS-VHL than in RSN after both sets. Conclusion: Performance was significantly lower in RS-VHL, even though SPO2 was not consistent with hypoxemia. However, the fatigue index was not significantly affected by VHL, nor was the neuromuscular upper body power after the RS-VHL protocol. Additionally, [La] was lower, and oxygen consumption was higher in RS-VHL, suggesting a higher aerobic contribution in this condition. [ABSTRACT FROM AUTHOR]

Background: Animal and human studies have shown that exposure to hypoxia can increase brain-derived neurotrophic factor (BDNF) protein transcription and reduce systematic inflammatory cytokine response. Therefore, the aim of this study was to investigate the acute and chronic effects of intermittent hypoxic-hyperoxic exposure (IHHE) prior to aerobic exercise on BDNF, interleukin-6 (IL-6), and C-reactive protein (CRP) blood levels in geriatric patients. Patients and Methods: Twenty-five geriatric patients (83.1 ± 5.0 yrs, 71.1 ± 10.0 kg, 1.8 ± 0.9 m) participated in a placebo-controlled, single-blinded trial and were randomly assigned to either an intervention (IG) or control group (CG) performing an aerobic cycling training (17 sessions, 20 min⋅session-1, 3 sessions⋅week-1). Prior to aerobic cycling exercise, the IG was additionally exposed to IHHE for 30 min, whereas the CG received continuous normoxic air. Blood samples were taken immediately before (pre-exercise) and 10 min (post-exercise) after the first session as well as 48 h (post-training) after the last session to determine serum (BDNFS) and plasma BDNF (BDNFP), IL-6, and CRP levels. Intervention effects were analyzed using a 2 x 2 analysis of covariance with repeated measures. Results were interpreted based on effect sizes with a medium effect considered as meaningful (ηp² ≥ 0.06, d ≥ 0.5). Results: CRP was moderately higher (d = 0.51) in the CG compared to the IG at baseline. IHHE had no acute effect on BDNFS (ηp² = 0.01), BDNFP (ηp² < 0.01), BDNF serum/plasma-ratio (ηp² < 0.01), IL-6 (ηp² < 0.01), or CRP (ηp² = 0.04). After the 6-week intervention, an interaction was found for BDNF serum/plasma-ratio (ηp² = 0.06) but not for BDNFS (ηp² = 0.04), BDNFP (ηp² < 0.01), IL-6 (ηp² < 0.01), or CRP (ηp² < 0.01). BDNF serum/plasma-ratio increased from pre-exercise to post-training (d = 0.67) in the CG compared to the IG (d = 0.51). A main effect of time was found for BDNFP (ηp² = 0.09) but not for BDNFS (ηp² = 0.02). Within-group post-hoc analyses revealed a training-related reduction in BDNFP in the IG and CG by 46.1% (d = 0.73) and 24.7% (d = 0.57), respectively. Conclusion: The addition of 30 min IHHE prior to 20 min aerobic cycling seems not to be effective to increase BDNFS and BDNFP or to reduce IL-6 and CRP levels in geriatric patients after a 6-week intervention. The study was retrospectively registered at drks.de (DRKS-ID: DRKS00025130). [ABSTRACT FROM AUTHOR]

To probe the mechanisms of gill remodeling in blunt snout bream under hypoxic conditions, we selected gill tissue for primary cell culture to establish and characterize the first blunt snout bream gill cell line, named MAG. The gill cells were efficiently passaged in M199 medium supplemented with 8% antibiotics and 15% fetal bovine serum at 28 °C, exhibiting primarily an epithelial-fibroblast mixed type. Additionally, the MAG cells (17th generation) were subjected to four experimental conditions—normoxia, hypoxia 12 h, hypoxia 24 h, and reoxygenation 24 h (R24h)—to evaluate the effects of hypoxia and reoxygenation on MAG cells during gill remodeling. We found that the MAG cell morphology underwent shrinkage and mitochondrial potential gradually lost, even leading to gradual apoptosis with increasing hypoxia duration and increased reactive oxygen species (ROS) activity. Upon reoxygenation, MAG cells gradually regain cellular homeostasis, accompanied by a decrease in ROS activity. Analysis of superoxide dismutase (SOD), glutathione (GSH), lactate dehydrogenase (LDH), catalase (CAT), anti-superoxide anion, and other enzyme activities revealed enhanced antioxidant enzyme activity in MAG cells during hypoxia, aiding in adapting to hypoxic stress and preserving cell morphology. After reoxygenation, the cells gradually returned to normoxic levels. Our findings underscore the MAG cells can be used to study hypoxic cell apoptosis during gill remodeling. Therefore, the MAG cell line will serve as a vital in vitro model for exploring gill remodeling in blunt snout bream under hypoxia. [ABSTRACT FROM AUTHOR]

Common tenrecs (Tenrec ecaudatus) are fossorial mammals that use burrows during both active and hibernating seasons in Madagascar and its neighboring islands. Prevailing thought was that tenrecs hibernate for 8–9 months individually, but 13 tenrecs were removed from the same sealed burrow 1 m deep from the surface. Such group hibernation in sealed burrows presumably creates a hypoxic and/or hypercapnic environment and suggests that this placental mammal may have an increased tolerance to hypoxia and hypercapnia. Higher tolerances to hypoxia and hypercapnia have been documented for other mammals capable of hibernation and to determine if this is the case for tenrecs, we exposed them to acute hypoxia (4 h of 16 or 7% O2), progressive hypoxia (2 h of 16, 10 and 4% O2), or progressive hypercapnia (2 h of 2, 5 and 10% CO2) at cold (16 °C) or warm (28 °C) ambient temperatures (Ta). Oxygen equilibrium curves were also constructed on the whole blood of tenrecs at 10, 25, and 37 °C to determine if hemoglobin (Hb)-O2 affinity contributes to hypoxia tolerance. In animals held at 16 °C, normoxic and normocapnic levels of oxygen consumption rate ( V ˙ O 2 ), body temperature (Tb), and heart rate (HR) were highly variable between individuals. This inter-individual variation was greatly reduced in animals held at 28 °C for oxygen consumption rate and body temperature. Both hypoxia (acute and progressive) and progressive hypercapnia led to decreases in V ˙ O 2 as well as the variation in V ˙ O 2 between animals held at 16 °C. The fall in oxygen consumption rate in 7% O2 independent of changes in body temperature in tenrecs held at 16 °C is unique and not consistent with the typical hypoxic metabolic response seen in other hibernating species that depends on concomitant falls in Tb. In animals held at 28 °C, exposure to O2 levels as low as 4% and CO2 levels as high as 10% had no significant effect on V ˙ O 2 , HR, or Tb, indicative of high tolerance to both hypoxia and hypercapnia. High variation in heart rate remained between individuals in all gas compositions and at all temperatures. Tenrec Hb–O2 affinity was similar to other homeothermic placental mammals and likely does not contribute to the increased hypoxia tolerance. Ultimately, our results suggest changes in Ta dictate physiological responses to hypoxia or hypercapnia in tenrecs, responses more characteristic of reptiles than of most placental mammals. Given that numerous anatomical and physiological characteristics of tenrecs suggest that they may be representative of an ancestral placental mammal, our findings suggest the typical hypoxic metabolic response evolved later in mammalian evolution. [ABSTRACT FROM AUTHOR]

The Pallas' spadefoot Pelobates vespertinus is a frog species native to eastern Europe and west Siberia. This species resists harsh winter conditions by moving up to 2 m underground. This amphibian is the first species known to withstand extreme air hypoxia. In this study, we investigated the metabolome of liver, heart, and brain of the Pallas' spadefoot after a month-long exposure of hypoxia, with oxygen levels reduced to approximately one-tenth of the air normal content. Surprisingly, our findings revealed a limited impact of hypoxia on the metabolomic profiles. Concentrations of glycolysis end products (lactate and alanine) increased only slightly compared to other amphibians under hypoxia, and no accumulation of succinate was observed. Furthermore, there were no notable changes in the content of adenosine phosphates. These results are consistent with a previous study, which indicated that the Pallas' spadefoot possesses relatively small glycogen and fat reserves before the winter compared to other frogs. It appears that this species conserves energy during winter by minimizing its metabolic activity. These findings corroborated the hypothesis that the survival of P. vespertinus under hypoxic conditions primarily relies on metabolic suppression rather than substantial energy reserves. [ABSTRACT FROM AUTHOR]

Group‐living in animals comes with a number of benefits associated with predator avoidance, foraging, and reproduction. A large proportion of fish species display grouping behaviour. Fish may also be particularly vulnerable to climate‐related stressors including thermal variation, hypoxia, and acidification. As climate‐related stressors are expected to increase in magnitude and frequency, any effects on fish behaviour may be increased and affect the ability of fish species to cope with changing conditions. Here we conduct a systematic review of the effects of temperature, hypoxia, and acidification on individual sociability and group cohesion in shoaling and schooling fishes. Searches of the published and grey literature were carried out, and studies were included or excluded based on selection criteria. Data from studies were then included in a meta‐analysis to examine broad patterns of effects of climate‐related stressors in the literature. Evidence was found for a reduction in group cohesion at low oxygen levels, which was stronger in smaller groups. While several studies reported effects of temperature and acidification, there was no consistent effect of either stressor on sociability or cohesion. There was some evidence that marine fishes are more strongly negatively affected by acidification compared with freshwater species, but results are similarly inconsistent and more studies are required. Additional studies of two or more stressors in combination are also needed, although one study found reduced sociability following exposure to acidification and high temperatures. Overall, there is some evidence that hypoxia, and potentially other climate‐related environmental changes, impact sociability and group cohesion in fishes. This may reduce survival and adaptability in shoaling and schooling species and have further ecological implications for aquatic systems. However, this synthesis mainly highlights the need for more empirical studies examining the effects of climate‐related factors on social behaviour in fishes. [ABSTRACT FROM AUTHOR]

Hypoxia plays an important role in the metastasis of hepatocellular carcinoma (HCC). Exosomes have been widely studied as mediators of communication between tumours and immune cells. However, the specific mechanism by which hypoxic HCC cell‐derived exosomes suppress antitumor immunity is unclear. Hypoxia scores were determined for The Cancer Genome‐Liver Hepatocellular Carcinoma (TCGA‐LIHC) dataset patients, and HCC patients in the hyperhypoxic group had a higher degree of M2 macrophage infiltration. Patients in the M2 high‐invasion group had a lower probability of survival than those in the low‐invasion group. In vivo and in vitro experiments demonstrated that exosomes secreted by hypoxic HCC cells promote M2 macrophage polarization. This polarization induces apoptosis in CD8+ T cells. Additionally, it encourages epithelial–mesenchymal transition (EMT), which increases HCC migration. Exosomal miRNA sequencing revealed that miR‐1290 was highly expressed in exosomes secreted by hypoxic HCC cells. Mechanistically, miR‐1290 in macrophages inhibited Akt2 while upregulating PD‐L1 to promote M2 polarization, induce apoptosis in CD8+ T cells, and enhance EMT in HCC. Animal studies found that the miR‐1290 antagomir in combination with the immune checkpoint inhibitor produced better antitumor effects than the monotherapies. In conclusion, the secretion of exosome‐derived miR‐1290 from HCC cells in a hypoxic environment supported immune escape by HCC cells by promoting M2 macrophage polarization to induce apoptosis in CD8+ T cells and enhance EMT that promoted HCC metastasis. Therefore, miR‐1290 is an important molecule in antitumor immunity in HCC, and inhibition of miR‐1290 could provide a novel immunotherapeutic approach for HCC treatment. [ABSTRACT FROM AUTHOR]

Hypoxia‐induced heterogeneity in colorectal cancer (CRC) significantly impacts patient survival by promoting chemoresistance. These conditions alter the regulation of miRNAs, key regulators of crucial processes like proliferation, apoptosis, and invasion, leading to tumor progression. Despite their promising potential as diagnostic and therapeutic targets, the underlying mechanisms by which miRNAs influence hypoxia‐mediated tumorigenesis remain largely unexplored. This study aims to elucidate the action of miRNAs in HCT‐116 colorectal cancer stem cells (CSCs) under hypoxia, providing valuable insights into their role in tumor adaptation and progression. MiRNA expression was determined using Nanostring nCounter, and bioinformatic analysis was performed to explain the molecular pathway. A total of 50 miRNAs were obtained with an average count of ≥ 20 reads for comparative expression analysis. The results showed that hypoxia‐affected 36 oncomiRs were increased in HCT‐116, and 14 suppressor‐miRs were increased in MSCs. The increase in miRNA expression occurred consistently from normoxia to hypoxia and significantly differed between mesenchymal stem cells (MSCs) and HCT‐116. Furthermore, miR‐16‐5p and miR‐29a‐3p were dominant in regulating the p53 signaling pathway, which is thought to be related to the escape mechanism against hypoxia and maintaining cell proliferation. More research with a genome‐transcriptome axis approach is needed to fully understand miRNAs' role in adapting CRC cells and MSCs to hypoxia. Further research could focus on developing specific biomarkers for diagnosis. In addition, anti‐miR can be developed as a therapy to prevent cancer proliferation or inhibit the adaptation of cancer cells to hypoxia. [ABSTRACT FROM AUTHOR]

Under the influence of hypoxia in plants, the transcription of genes responsible for adaptation to stress caused by low oxygen levels changes. Changes in metabolic pathways under stress conditions may be regulated by microRNAs. It was found that the content of microRNA775A increases in corn leaves under the influence of hypoxia. The use of the fluorescent probe miR775A-ROX made it possible to establish an increase in the number of RNA-inducing silencing complexes (RISC), formed on the basis of microRNA775A, in maize leaves during the development of hypoxic stress. The results we obtained indicate that microRNA775A is involved in the processes of adaptation of the body to hypoxic conditions by regulating the expression of target genes at the post-transcriptional level using the RNA interference mechanism. [ABSTRACT FROM AUTHOR]

The contribution of excitatory amino acids (AA) to ischemic brain injury has been widely described. In addition, we reported that a mixture of non-excitatory AA at plasmatic concentrations turns irreversible the depression of synaptic transmission caused by hypoxia. Here, we describe that the presence of seven non-excitatory AA (L-alanine, L-glutamine, glycine, L-histidine, L-serine, taurine, and L-threonine) during hypoxia provokes an irreversible neuronal membrane depolarization, after an initial phase of hyperpolarization. The collapse of the membrane potential correlates with a great increase in fiber volley amplitude. Nevertheless, we show that the presence of all seven AA is not necessary to cause the irreversible loss of fEPSP after hypoxia and that the minimal combination of AA able to provoke a solid, replicable effect is the mixture of L-alanine, glycine, L-glutamine, and L-serine. Additionally, L-glutamine seems necessary but insufficient to induce these harmful effects. We also prove that the deleterious effects of the AA mixtures on field potentials during hypoxia depend on both the identity and concentration of the individual AA in the mixture. Furthermore, we find that the accumulation of AA in the whole slice does not determine the outcome caused by the AA mixtures on the synaptic transmission during hypoxia. Finally, results obtained using pharmacological inhibitors and specific substrates of AA transporters suggest that system N and the alanine-serine-cysteine transporter 2 (ASCT2) participate in the non-excitatory AA-mediated deleterious effects during hypoxia. Thus, these AA transporters might represent therapeutical targets for the treatment of brain ischemia. [ABSTRACT FROM AUTHOR]