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Hypobaric hypoxia-induced brain injury (HHBI) is a progressive neurodegenerative disease that has still not been effectively treated. There are several different mechanisms involved in HHBI. Among them, oxidative stress and inflammation response predominate. 6-hydroxygenistein (4',5,6,7-tetrahydroxyisoflavone, 6-OHG) is a hydroxylated derivative of genistein with excellent antioxidant activity, however, the protective effects and underlying mechanisms against HHBI have not been clarified. In the present study, we aimed to explore the mechanisms of action of 6-OHG on HHBI using network pharmacology and experimental validation. Network pharmacology analysis revealed 186 candidate targets through the intersection of the targets of 6-OHG and related genes in HHBI, which were mainly enriched in oxidative stress and inflammation response. Moreover, key targets of 6-OHG against HHBI, namely Nrf2 and NF-κB, were screened and found to be closely related to oxidative stress and inflammation response. Subsequent in vivo experiments revealed that 6-OHG treatment attenuated oxidative stress and inflammation response, prevented energy disorder and apoptosis as well as maintained the BBB integrity in HHBI mice. In addition, 6-OHG administration up-regulated the expressions of Nrf2 and HO-1 and down-regulated the expressions of NF-κB and NLRP3, thereby inhibiting oxidative stress and inflammation response. Hence, the present study demonstrates that 6-OHG protects against HHBI by stimulating the Nrf2/HO-1 signaling pathway and suppressing the NF-κB/NLRP3 signaling pathway.

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Air travel is widely regarded as the safest mode of transportation, with the United States leading in airline passengers. However, travelers with pre-existing heart conditions face acute cardiovascular risks. Flight pilots and cabin crew are particularly vulnerable to air travel's physiological changes, which can significantly impair their health and performance. Cabin pressure differences and reduced oxygen levels at cruising altitudes of 5000-8000 feet make air travel challenging for individuals with underlying cardiac and pulmonary problems. This, along with dry air, sleep deprivation, missed medication and prolonged sitting, can lead to physiological changes. In-flight and pre-flight stressors contribute to increased health issues, and studies show a rise in medical emergencies during flights. Prolonged exposure to the airplane environment can lead to various health issues for pilots and cabin crew. These changes include impaired judgment, cognitive function and discomfort in the sinuses and ears due to pressure differentials. Therefore, thorough medical screening, skilled instrument use and compliance with safety measures are essential to mitigate these risks. This article reviews the cardiac implications of air travel, discussing the underlying pathophysiology, associated risks and preventive measures to ensure safer flights for individuals with cardiovascular diseases.

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This review examines the health risks of air travel for individuals with heart and lung conditions. Changes in cabin pressure and oxygen levels can lower blood oxygen, causing discomfort and health issues. Dry air, sleep problems and prolonged sitting also affect those with existing conditions. Pilots and flight attendants are especially vulnerable due to their continuous exposure.The authors reviewed how air travel impacts heart and lung health and found that in-flight medical emergencies are rising, affecting passengers and flight staff. Common issues include impaired cognitive function and discomfort from pressure changes. The article emphasizes the importance of pre-flight medical check-ups, carrying medical documents and having travel insurance. It also calls for thorough medical screening and skilled instrument use to ensure safety.Results show that current air travel conditions pose significant health risks for those with cardiovascular diseases. The study advocates for improvements in in-flight medical technology, cabin environments and personalized healthcare solutions to enhance safety. These findings suggest that future air travel should focus on reducing cardiovascular complications through advancements in medical support and cabin design.The study provides valuable insights into the physiological effects of flying and recommends measures to make air travel safer for people with heart and lung conditions. It highlights the need for ongoing research and collaboration among healthcare professionals, researchers and aviation authorities to address these health risks effectively.

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Introduction: Special Operations Forces (SOF) often conduct operations in physiologically stressful environments such as severe heat, cold, or hypoxia, which can induce decreases in a variety of cognitive abilities. Given the promising empirical demonstration of the efficacy of exogenous ketone monoester (KME) supplementation in attenuating cognitive performance decrease during hypoxia at rest in a laboratory setting, we conducted a real-world, field experiment examining KME's efficacy during high-altitude mountaineering, an austere environment in which US SOF have conducted increasing numbers of operations over the past two decades. Methods: Specifically, 34 students and cadre at the US Army 10th Special Forces Group Special Operations Advanced Mountaineering School (SOAMS) participated in a randomized, double-blind, placebo (PLA)-controlled crossover trial (KME vs. PLA) over 2 days of tactical mountain operations training. The participants ascended from 7,500 ft in altitude (basecamp) to 12,460 ft on 1 day and 13,627 ft the other day (in randomized order), while performing various training activities inducing high physical and cognitive loads over 8-12 h, and consumed six doses of KME or PLA 2-3 h apart throughout each training day. Results and Discussion: While KME increased blood ketone levels and decreased glucose levels, there were no clear indications that the elevated ketone level enhanced physical or cognitive performance. KME also produced a greater incidence of heartburn, nausea, and vomiting. In these elite operators, high-altitude mountaineering had a limited impact on cognitive performance, and KME supplementation did not demonstrate any benefit.

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At altitude, factors such as decreased barometric pressure, low temperatures, and acclimatization might affect lung function. The effects of exposure and acclimatization to high-altitude on lung function were assessed in 39 subjects by repetitive spirometry up to 6022 m during a high-altitude expedition. Subjects were classified depending on the occurrence of acute mountain sickness (AMS) and summit success to evaluate whether lung function relates to successful climb and risk of developing AMS. Peak expiratory flow (PEF), forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) increased with progressive altitude (max. +20.2 %pred, +9.3 %pred, and +6.7 %pred, all p<0.05). Only PEF improved with acclimatization (BC1 vs. BC2, +7.2 %pred, p=0.044). At altitude FEV1 (p=0.008) and PEF (p<0.001) were lower in the AMS group. The risk of developing AMS was associated with lower baseline PEF (p<0.001) and longitudinal changes in PEF (p=0.008) and FEV1 (p<0.001). Lung function was not related to summit success (7126 m). Improvement in PEF after acclimatization might indicate respiratory muscle adaptation.

Asunto(s)

Aclimatación , Mal de Altura , Altitud , Pruebas de Función Respiratoria , Humanos , Mal de Altura/fisiopatología , Masculino , Adulto , Aclimatación/fisiología , Femenino , Espirometría , Persona de Mediana Edad , Pulmón/fisiopatología , Capacidad Vital/fisiología , Volumen Espiratorio Forzado/fisiología , Ápice del Flujo Espiratorio/fisiología , Enfermedad Aguda

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Even while accelerated cardiomyocyte apoptosis is one of the primary causes of cardiac damage, the underlying mechanism is still mostly unknown. In addition to examining potential protective effects of bisoprolol and diosmin against CoCl2-induced cardiac injury, the goal of this study was to identify potential mechanisms regulating the hypoxic cardiac damage caused by cobalt chloride (CoCl2). For a period of 21 days except Cocl2 14 days from the first day of the experiment, rats were split into the following groups: Normal control group, rats received vehicle only (2 ml/kg/day, p.o.), (Cocl2, 150 mg/kg/day, p.o.), bisoprolol (25 mg/kg/day, p.o.); diosmin (100 mg/kg/day, p.o.) and bisoprolol + diosmin + Cocl2 groups. At the end of the experimental period, serum was taken for estimation of cardiac function, lipid profile, and pro/anti-inflammatory cytokines. Moreover, tissue samples were collected for evaluation of oxidative stress, endothelial dysfunction, α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Diosmin and bisoprolol, either alone or in combination, enhance heart function by reducing abnormalities in the electrocardiogram and the hypotension brought on by CoCl2. Additionally, they significantly ameliorate endothelial dysfunction by downregulating the cardiac expressions of α-SMA, PKC-α, MiR-143-3P, MAPK, ERK5, MCP-1, CXCR4, Orai-1, and STIM-1. Bisoprolol and diosmin produced modulatory activity against inflammatory state, redox balance, and atherogenic index concurrently. Together, diosmin and bisoprolol, either alone or in combination, significantly reduced all the cardiac alterations brought on by CoCl2. The capacity to obstruct hypoxia-induced α-SMA, PKC-α, MiR-143-3P/MAPK/MCP-1, MiR-143-3P/ERK5/CXCR4, Orai-1/STIM-1 signaling activation, as well as their anti-inflammatory, antioxidant, and anti-apoptotic properties, may be responsible for these cardio-protective results.

Asunto(s)

Bisoprolol , Cardiotoxicidad , Cobalto , Diosmina , MicroARNs , Proteína ORAI1 , Receptores CXCR4 , Transducción de Señal , Animales , Cobalto/toxicidad , Masculino , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Cardiotoxicidad/tratamiento farmacológico , Ratas , Bisoprolol/farmacología , Bisoprolol/uso terapéutico , Transducción de Señal/efectos de los fármacos , MicroARNs/metabolismo , MicroARNs/genética , Diosmina/farmacología , Diosmina/uso terapéutico , Proteína ORAI1/metabolismo , Proteína ORAI1/genética , Ratas Wistar , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Quimiocina CCL2

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Background: The reduced level of physical activity in individuals with chronic obstructive pulmonary disease (COPD) is associated with disease severity; however, mild COPD may or may not decrease individuals' physical fitness. Currently, it is unknown whether high-altitude hypoxia is a modifying factor of physical activity levels in COPD compared to healthy subjects. Objective: To compare physical activity levels in individuals with COPD versus healthy subjects residing in high-altitude environments. Methods: Individuals with COPD GOLD 1(A, B) and control subjects residing at high altitudes (>2500m) were studied. Physical activity level was measured for seven days using triaxial accelerometry. Measurement variables included METs/hour, energy expenditure in kcal/hour, total daily energy expenditure, and number of steps per day. Results: Daily caloric expenditure associated with physical activity showed only a slight decrease (3.1%) in COPD patients compared to the control group; there was a significant 61.32% lower hourly calorie consumption rate in the COPD group. Additionally, COPD patients exhibited lower MET/hour (9.64% difference) and a substantial difference in the number of steps per day, with 139.41% fewer steps compared to the control group. Conclusion: COPD patients in hypobaric hypoxia environments exhibit significantly lower levels of physical activity compared to healthy individuals. Altitude hypoxia contributes to low levels of physical activity in both COPD patients and healthy subjects.

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Hypobaric hypoxia is the main cause of high-altitude retinopathy (HAR). Retinal oedema is the key pathological change in HAR. However, its pathological mechanism is not clear. In this study, a 5000-m hypobaric hypoxic environment was simulated. Haematoxylin and eosin (H&E) staining and electrophysiological (ERG) detection were used to observe the morphological and functional changes in the retina of mice under hypobaric hypoxia for 2-72 h. Toluidine blue staining and transmission electron microscopy were used to observe the morphology of Müller cells in the hypobaric hypoxia groups. The functional changes and oedema mechanism of Müller cells were detected by immunofluorescence and western blotting. The expression levels of glutamine synthetase (GS), glial fibrillary acidic protein (GFAP), aquaporin 4 (AQP4), and inwardly rectifying potassium channel subtype 4.1 (Kir4.1) in Müller cells were quantitatively analysed. This study revealed that retinal oedema gradually increased with prolonged exposure to a 5000-m hypobaric hypoxic environment. In addition, the ERG showed that the time delay and amplitude of the a-wave and b-wave decreased. The expression of GS decreased, and the expression of GFAP increased in Müller cells after exposure to hypobaric hypoxia for 4 h. At the same time, retinal AQP4 expression increased, and Kir4.1 expression decreased. The oedema and functional changes in Müller cells are consistent with the time point of retinal oedema. In conclusion, Müller cell oedema is involved in retinal oedema induced by hypobaric hypoxia. An increase in AQP4 and a decrease in Kir4.1 are the main causes of Müller cell oedema caused by hypobaric hypoxia.

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Over 80 Mio people worldwide live >2500 m, including at least as many patients with pulmonary vascular disease (PVD), defined as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), as elsewhere (estimated 0.1‰). Whether PVD patients living at high altitude have altered disease characteristics due to hypobaric hypoxia is unknown. In a cross-sectional study conducted at the Hospital Carlos Andrade Marin in Quito, Ecuador, located at 2840 m, we included 36 outpatients with PAH or CTEPH visiting the clinic from January 2022 to July 2023. We collected data on diagnostic right heart catheterization, treatment, and risk factors, including NYHA functional class (FC), 6-min walk distance (6MWD), and NT-brain natriuretic peptide (BNP) at baseline and at last follow-up. Thirty-six PVD patients (83% women, 32 PAH, 4 CTEPH, mean ± SD age 44 ± 13 years, living altitude 2831 ± 58 m) were included and had the following baseline values: PaO2 8.2 ± 1.6 kPa, PaCO2 3.9 ± 0.5 kPa, SaO2 91 ± 3%, mean pulmonary artery pressure 53 ± 16 mmHg, pulmonary vascular resistance 16 ± 4 WU, 50% FC II, 50% FC III, 6MWD 472 ± 118 m, BNP 490 ± 823 ng/L. Patients were treated for 1628 ± 1186 days with sildenafil (100%), bosentan (33%), calcium channel blockers (33%), diuretics (69%), and oxygen (nocturnal 53%, daytime 11%). Values at last visit were: FC (II 75%, III 25%), 6MWD of 496 ± 108 m, BNP of 576 ± 5774 ng/L. Compared to European PVD registries, ambulatory PVD patients living >2500 m revealed similar blood gases and relatively low and stable risk factor profiles despite severe hemodynamic compromise, suggesting that favorable outcomes are achievable for altitude residents with PVD. Future studies should focus on long-term outcomes in PVD patients dwelling >2500 m.

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We aim to provide reference values for military aircrews participating in hypoxia awareness training (HAT). We describe several parameters with potential biomedical interest based on selected segments and slopes of the changes in oxygen saturation (SatO2) during a standard HAT. A retrospective analysis of 2298 records of the SatO2 curve was performed, including 1526 military men aged 30.48 ± 6.47 years during HAT in a hypobaric chamber. HAT consisted of pre-oxygenation at 100% and an ascent to 7620 m, followed by O2 disconnection starting the phase of descent of SatO2 until reaching the time of useful consciousness (TUC), and finally reconnection to 100% O2 in the recovery phase. Using an ad hoc computational procedure, the time taken to reach several defined critical values was computed. These key parameters were the time until desaturation of 97% and 90% (hypoxia) after oxygen mask disconnection (D97/D90) and reconnection (R97/R90) phases, the time of desaturation (TUC-D97) and hypoxia (TUC-D90) during disconnection, the total time in desaturation (L97) or hypoxia (L90), and the slopes of SatO2 drop (SDSAT97 and SDSAT90) and recovery (SRSAT97). The mean of the quartiles according to TUC were compared by ANOVA. The correlations between the different parameters were studied using Pearson's test and the effect size was estimated with ω2. Potentially useful parameters for the HAT study were those with statistical significance (p < 0.05) and a large effect size. D97, D90, R97, and R90 showed significant differences with small effect sizes, while TUC-D97, TUC-D90, L97, L90, and SDSAT97 showed significant differences and large effect sizes. SDSAT97 correlated with TUC (R = 0.79), TUC-D97 (R = 0.81), and TUC-D90 (R = 0.81). In conclusion, several parameters of the SatO2 curve are useful for the study and monitoring of HAT. The SDSAT97 measured during the test can estimate the TUC and thus contribute to taking measures to characterize and protect the aircrew members.

Asunto(s)

Hipoxia , Personal Militar , Saturación de Oxígeno , Humanos , Masculino , Adulto , Hipoxia/fisiopatología , Saturación de Oxígeno/fisiología , Estudios Retrospectivos , Oxígeno/metabolismo , Altitud

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BACKGROUND: Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury. METHODS: We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression. RESULTS: The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones. CONCLUSION: These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes.

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Lesiones Encefálicas , Fosfoglicerato Quinasa , Animales , Fosfoglicerato Quinasa/metabolismo , Fosfoglicerato Quinasa/genética , Ratones , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Lesiones Encefálicas/patología , Masculino , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/metabolismo , Hipoxia/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo

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IMPORTANCE: Emergency medical services (EMS) providers transiently ascend to high altitude for primary missions and secondary transports in mountainous areas in helicopters that are unpressurised and do not have facilities for oxygen supplementation. The decrease in cerebral oxygen saturation can lead to impairment in attention and reaction time as well as in quality of care during acute exposure to altitude. OBJECTIVE: The primary aim of the current study was to investigate the effect of oxygen supplementation on cognitive performance in Helicopter EMS (HEMS) providers during acute exposure to altitude. DESIGN, SETTING, AND PARTICIPANTS: This interventional, randomized, controlled, double-blind, cross-over clinical trial was conducted in October 2021. Each trial used a simulated altitude scenario equivalent to 4000 m, in which volunteers were exposed to hypobaric hypoxia with a constant rate of ascent of 4 m/s in an environmental chamber under controlled, replicable, and safe conditions. Trials could be voluntarily terminated at any time. Inclusion criteria were being members of emergency medical services and search and rescue services with an age between 18 and 60 years and an American Society of Anesthesiologists physical status class I. EXPOSURES: Each participant conducted 2 trials, one in which they were exposed to altitude with oxygen supplementation (intervention trial) and the other in which they were exposed to altitude with ambient air supplementation (control trial). MAIN OUTCOMES AND MEASURES: Measurements included peripheral oxygen saturation (SpO2), cerebral oxygenation (ScO2), breathing and heart rates, Psychomotor Vigilance Test (PVT), Digit-Symbol Substitution Test (DSST), n-Back test (2-BACK), the Grooved Pegboard test, and questionnaires on subjective performance, stress, workload, and positive and negative affect. Paired t-tests were used to compare conditions (intervention vs. control). Data were further analyzed using generalized estimating equations (GEE). RESULTS: A total of 36 volunteers (30 men; mean [SD] age, 36 [9] years; mean [SD] education, 17 [4] years) were exposed to the intervention and control trials. The intervention trials, compared with the control trials, had higher values of SpO2 (mean [SD], 97.9 [1.6] % vs. 86 [2.3] %, t-test, p = 0.004) and ScO2 (mean [SD], 69.9 [5.8] % vs. 62.1 [5.2] %, paired t-test, p = 0.004). The intervention trials compared with the control trials had a shorter reaction time (RT) on the PVT after 5 min (mean [SD], 277.8 [16.7] ms vs. 282.5 [15.3] ms, paired t-test, p = 0.006) and after 30 min (mean [SD], 276.9 [17.7] ms vs. 280.7 [15.0] ms, paired t-test, p = 0.054) at altitude. While controlling for other variables, there was a RT increase of 0.37 ms for each % of SpO2 decrease. The intervention trials showed significantly higher values for DSST number of correct responses (with a difference of mean [SD], 1.2 [3.2], paired t-test, p = 0.035). Variables in the intervention trials were otherwise similar to those in the control trials for DSST number of incorrect responses, 2-BACK, and the Grooved Pegboard test. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that oxygen supplementation improves cognitive performance among HEMS providers during acute exposure to 4000 m altitude. The use of oxygen supplementation may allow to maintain attention and timely reaction in HEMS providers. The impact of repeated altitude ascents on the same day, sleep-deprivation, and additional stressors should be investigated. Trial registration NCT05073406, ClinicalTrials.gov trial registration.

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Altitud , Estudios Cruzados , Humanos , Masculino , Adulto , Método Doble Ciego , Femenino , Terapia por Inhalación de Oxígeno/métodos , Cognición/fisiología , Oxígeno/sangre , Persona de Mediana Edad , Ambulancias Aéreas , Mal de Altura/terapia , Servicios Médicos de Urgencia

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease. AIM OF THE STUDY: To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS. MATERIALS AND METHODS: This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia. RESULTS: PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe2+ efflux and regulating mitochondrial Fe2+ transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer). CONCLUSIONS: This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS.

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Cistanche , Ferroptosis , Glicósidos , Fármacos Neuroprotectores , Animales , Ferroptosis/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/aislamiento & purificación , Cistanche/química , Ratones , Glicósidos/farmacología , Glicósidos/aislamiento & purificación , Masculino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Hipoxia/tratamiento farmacológico , Hipoxia/metabolismo , Trastornos de la Memoria/tratamiento farmacológico

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Background and objectives: Acute mountain sickness (AMS) is a pathology with different symptoms in which the organism is not adapted to the environment that occurs under the special environment of high altitude. Its main mechanism is the organism's tissue damage caused by acute hypobaric hypoxia. Traditional Chinese medicine (TCM) theory focuses on the holistic concept. TCM has made remarkable achievements in the treatment of many mountain sicknesses. This review outlines the pathogenesis of AMS in modern and traditional medicine, the progress of animal models of AMS, and summarizes the therapeutic effects of TCM on AMS. Methods: Using the keywords "traditional Chinese medicine," "herbal medicine," "acute mountain sickness," "high-altitude pulmonary edema," "high-altitude cerebral edema," "acute hypobaric hypoxia," and "high-altitude," all relevant TCM literature published up to November 2023 were collected from Scopus, Web of Science, PubMed, and China National Knowledge Infrastructure databases, and the key information was analyzed. Results: We systematically summarised the effects of acute hypobaric hypoxia on the tissues of the organism, the study of the methodology for the establishment of an animal model of AMS, and retrieved 18 proprietary Chinese medicines for the clinical treatment of AMS. The therapeutic principle of medicines is mainly invigorating qi, activating blood and removing stasis. The components of botanical drugs mainly include salidroside, ginsenoside Rg1, and tetrahydrocurcumin. The mechanism of action of TCM in the treatment of AMS is mainly through the regulation of HIF-1α/NF-κB signaling pathway, inhibition of inflammatory response and oxidative stress, and enhancement of energy metabolism. Conclusion: The main pathogenesis of AMS is unclear. Still, TCM formulas and components have been used to treat AMS through multifaceted interventions, such as compound danshen drip pills, Huangqi Baihe granules, salidroside, and ginsenoside Rg1. These components generally exert anti-AMS pharmacological effects by inhibiting the expression of VEGF, concentration of MDA and pro-inflammatory factors, down-regulating NF-κB/NLRP3 pathway, and promoting SOD and Na + -K + -ATPase activities, which attenuates acute hypobaric hypoxia-induced tissue injury. This review comprehensively analyses the application of TCM in AMS and makes suggestions for more in-depth studies in the future, aiming to provide some ideas and insights for subsequent studies.

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About 140 million people worldwide live at an altitude above 2500 m. Studies have showed an increase of the incidence of hyperuricemia among plateau populations, but little is known about the possible mechanisms. This study aims to assess the effects of high altitude on hyperuricemia and explore the corresponding mechanisms at the histological, inflammatory and molecular levels. This study finds that intermittent hypobaric hypoxia (IHH) exposure results in an increase of serum uric acid level and a decrease of uric acid clearance rate. Compared with the control group, the IHH group shows significant increases in hemoglobin concentration (HGB) and red blood cell counts (RBC), indicating that high altitude hyperuricemia is associated with polycythemia. This study also shows that IHH exposure induces oxidative stress, which causes the injury of liver and renal structures and functions. Additionally, altered expressions of organic anion transporter 1 (OAT1) and organic cation transporter 1 (OCT1) of kidney have been detected in the IHH exposed rats. The adenosine deaminase (ADA) expression levels and the xanthione oxidase (XOD) and ADA activity of liver of the IHH exposure group have significantly increased compared with those of the control group. Furthermore, the spleen coefficients, IL-2, IL-1ß and IL-8, have seen significant increases among the IHH exposure group. TLR/MyD88/NF-κB pathway is activated in the process of IHH induced inflammatory response in joints. Importantly, these results jointly show that IHH exposure causes hyperuricemia. IHH induced oxidative stress along with liver and kidney injury, unusual expression of the uric acid synthesis/excretion regulator and inflammatory response, thus suggesting a potential mechanism underlying IHH-induced hyperuricemia.

Asunto(s)

Hiperuricemia , Hipoxia , Riñón , Hígado , Estrés Oxidativo , Hiperuricemia/metabolismo , Animales , Masculino , Ratas , Hígado/metabolismo , Hígado/patología , Hipoxia/metabolismo , Hipoxia/complicaciones , Riñón/metabolismo , Riñón/patología , Altitud , Ácido Úrico/sangre , Ácido Úrico/metabolismo , Ratas Sprague-Dawley , Xantina Oxidasa/metabolismo , Mal de Altura/metabolismo , Mal de Altura/complicaciones , Mal de Altura/fisiopatología

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Lipids are components of cytomembranes that are involved in various biochemical processes. High-altitude hypoxic environments not only affect the body's energy metabolism, but these environments can also cause abnormal lipid metabolism involved in the hypoxia-induced cognitive impairment. Thus, comprehensive lipidomic profiling of the brain tissue is an essential step toward understanding the mechanism of cognitive impairment induced by hypoxic exposure. In the present study, mice showed reduced new-object recognition and spatial memory when exposed to hypobaric hypoxia for 1 day. Histomorphological staining revealed significant morphological and structural damage to the hippocampal tissue, along with prolonged exposure to hypobaric hypoxia. Dynamic lipidomics of the mouse hippocampus showed a significant shift in both the type and distribution of phospholipids, as verified by spatial lipid mapping. Collectively, a diverse and dynamic lipid composition in mice hippocampus was uncovered, which deepens our understanding of biochemical changes during sustained hypoxic exposure and could provide new insights into the cognitive decline induced by high-altitude hypoxia exposure.

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Hipocampo , Hipoxia , Lipidómica , Animales , Hipocampo/metabolismo , Hipocampo/patología , Ratones , Lipidómica/métodos , Hipoxia/metabolismo , Masculino , Espectrometría de Masas , Lípidos/análisis , Ratones Endogámicos C57BL , Metabolismo de los Lípidos

RESUMEN

This study investigated the effect of a resistance training (RT) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength development with respect to the same training in normoxia (N). Thirty-three strength-trained males were assigned to N (FiO2 = 20.9%), HH (2,320 m asl) or NH (FiO2 = 15.9%). The participants completed an 8-week RT program (3 sessions/week) of a full body routine. Muscle thickness of the lower limb and 1RM in back squat were assessed before and after the training program. Blood markers of stress, inflammation (IL-6) and muscle growth (% active mTOR, myostatin and miRNA-206) were measured before and after the first and last session of the program. Findings revealed all groups improved 1RM, though this was most enhanced by RT in NH (p = 0.026). According to the moderate to large excess of the exercise-induced stress response (lactate and Ca2+) in HH and N, results only displayed increases in muscle thickness in these two conditions over NH (ES > 1.22). Compared with the rest of the environmental conditions, small to large increments in % active mTOR were only found in HH, and IL-6, myostatin and miR-206 in NH throughout the training period. In conclusion, the results do not support the expected additional benefit of RT under hypoxia compared to N on muscle growth, although it seems to favour gains in strength. The greater muscle growth achieved in HH over NH confirms the impact of the type of hypoxia on the outcomes.

Asunto(s)

Hipoxia , Fuerza Muscular , Músculo Esquelético , Miostatina , Entrenamiento de Fuerza , Masculino , Humanos , Entrenamiento de Fuerza/métodos , Hipoxia/metabolismo , Hipoxia/fisiopatología , Músculo Esquelético/metabolismo , Músculo Esquelético/crecimiento & desarrollo , Miostatina/metabolismo , Adulto , Fuerza Muscular/fisiología , MicroARNs/metabolismo , MicroARNs/genética , Serina-Treonina Quinasas TOR/metabolismo , Interleucina-6/metabolismo , Interleucina-6/sangre , Adulto Joven , Desarrollo de Músculos

RESUMEN

Hypobaric Hypoxia (HH) negatively affects the cardiovascular and respiratory systems as well as gonadal development and the therefore next generation. This study investigated the effects of HH on zebrafish and SD rats, by exposing them to a low-pressure environment at 6000 m elevation for 30 days to simulate high-altitude conditions. It was indicated that parental zebrafish reared amh under HH had increased embryo mortality, reduced hatchability, and abnormal cartilage development in the offspring. Furthermore, the HH-exposed SD rats had fewer reproductive cells and smaller litters. Moreover, the transcriptome analysis revealed the down-regulation of steroid hormone biosynthesis pathways. The expression of the gonad-associated genes (amh, pde8a, man2a2 and lhcgr), as well as the gonad and cartilage-related gene bmpr1a, were also down-regulated. In addition, Western blot analysis validated reduced bmpr1a protein expression in the ovaries of HH-treated rats. In summary, these data indicate the negative impact of HH on reproductive organs and offspring development, emphasizing the need for further research and precautions to protect future generations' health.

Asunto(s)

Fertilidad , Hipoxia , Ratas Sprague-Dawley , Pez Cebra , Animales , Femenino , Masculino , Desarrollo Óseo , Embrión no Mamífero , Ratas

RESUMEN

A high prevalence of osteoarthritis (OA) has been observed among individuals living at high altitudes, and hypobaric hypoxia (HH) can cause bone mass and strength deterioration. However, the effect of HH on OA remains unclear. In this study, we aimed to explore the impact of HH on OA and its potential mechanisms. A rat knee OA model was established by surgery, and the rats were bred in an HH chamber simulating a high-altitude environment. Micro-computed tomography (Micro-CT), histological analysis, and RNA sequencing were performed to evaluate the effects of HH on OA in vivo. A hypoxic co-culture model of osteoclasts and osteoblasts was also established to determine their effects on chondrogenesis in vitro. Cartilage degeneration significantly worsened in the HH-OA group compared to that in the normoxia-OA (N-OA) group, 4 weeks after surgery. Micro-CT analysis revealed more deteriorated bone mass in the HH-OA group than in the N-OA group. Decreased hypoxia levels in the cartilage and enhanced hypoxia levels in the subchondral bone were observed in the HH-OA group. Furthermore, chondrocytes cultured in a conditioned medium from the hypoxic co-culture model showed decreased anabolism and extracellular matrix compared to those in the normoxic model. RNA sequencing analysis of the subchondral bone indicated that the glycolytic signaling pathway was highly activated in the HH-OA group. HH-related OA progression was associated with alterations in the oxygen environment and bone remodeling in the subchondral zone, which provided new insights into the pathogenesis of OA.

Asunto(s)

Osteoartritis , Oxígeno , Animales , Ratas , Microtomografía por Rayos X , Hipoxia , Osteoartritis/etiología , Remodelación Ósea