Effect of nitrate supplementation on oxygen saturation levels for acute mountain sickness prevention: A systematic review and meta-analysis.

PURPOSE: This study aimed to systematically review the effect of nitrate supplementation on blood oxygen saturation. METHODS: We searched PubMed, Scopus, and Cochrane Library databases from their inception up to October 2022. Two reviewers independently conducted two stages of the screening process to include a randomized controlled trial with nitrate supplementation versus placebo intervention assessing oxygen saturation among lowlanders going to either real or simulated high altitude environments. We used the Cochrane Risk of Bias 2.0 tool to assess the risk of bias in the included studies. Fixed-effect model meta-analyses were conducted for laboratory-based studies. Random-effect meta-analyses were conducted for real-world studies. RESULTS: We found 7 trials that met the eligibility criteria. A meta-analysis of studies with some bias concerns showed an increase of 1.26 % in the SpO2 with 44 % I2 during submaximal exercise at simulated high altitudes (GRADE: low). On the contrary, a meta-analysis of studies without heterogeneity showed that nitrate supplementation aggravated oxygen saturation decline (-2.64 %, p = 0.03, GRADE: high) during rest in real high-altitude environments. A meta-analysis also showed that nitrate supplementation did not affect Acute Mountain Sickness (AMS) symptoms (GRADE: high). CONCLUSION: Our results suggest that nitrate supplementation did not provide benefits for AMS prevention during rest at high altitudes. The low-quality evidence showing small beneficial effects of nitrate supplementation during exercise calls for further studies.

Loss of the adhesion G-protein coupled receptor ADGRF5 in mice induces airway inflammation and the expression of CCL2 in lung endothelial cells.

BACKGROUND: Adhesion G-protein coupled receptor F5 (ADGRF5) was recently identified as an essential regulator of pulmonary surfactant homeostasis in alveolar type II cells. We previously showed that in addition to abnormal surfactant accumulation, Adgrf5-deficient (Adgrf5-/-) mice exhibit emphysema-like signs, suggesting a possible role for ADGRF5 in immune regulation. Here, we extended the phenotypic analysis of Adgrf5-/- mice to help understand its biological role in the lung, and especially in immune regulation. METHODS: Histological features of lungs were evaluated by Alcian blue and Masson's trichrome staining. Quantitative real-time PCR (qPCR) and western blot analyses were performed to analyze the differential expression of genes/proteins related to airway inflammation in lungs between wildtype and Adgrf5-/- mice. Acid-base status was assessed by performing blood gas tests and urine pH measurements. Inflammatory cell counting was performed using Giemsa-stained bronchoalveolar lavage cells. Serum IgE concentrations were determined by enzyme-linked immunosorbent assay. The expression of Ccl2, S100a8, S100a9, and Saa3 in primary lung endothelial cells (ECs) was determined by qPCR and/or western blotting. Finally, the effect of administrating RS504393 to 2-week-old Adgrf5-/- mice on gene expression in the lungs was analyzed by qPCR. RESULTS: Adgrf5-/- mice exhibited several features of chronic airway inflammation (mucous cell metaplasia, mucus hyperproduction, subepithelial fibrosis, respiratory acidosis, high serum IgE, mast cell accumulation, and neutrophilia) in parallel with elevated expression of genes involved in mucous cell metaplasia (Muc5ac, Muc5b, Slc26a4, and Clca1), fibrosis (Tgfb1, Col1a1, Fn1, and Tnc), and type 2 immune response (Il4, Il5, Il13, IL-25, and IL-33) at 12 and/or 30 weeks of age. In contrast, mRNA expression of Ccl2, S100a8, and S100a9 was upregulated in embryonic or neonatal Adgrf5-/- lungs as well as in lung ECs of Adgrf5-/- mice at 1 week of age. RS504393 treatment suppressed the upregulation of S100a8, S100a9, Slc26a4, and Il5 in Adgrf5-/- lungs. CONCLUSIONS: Targeted disruption of ADGRF5 results in the development of airway inflammation, which is likely mediated by the type 2 immune response and possibly CCL2-mediated inflammation. ADGRF5 also has a potential role in the regulation of genes encoding CCL2 in lung ECs, thereby maintaining immune homeostasis.

The mediation role of physical fitness in association between muscle-strengthening physical activities and its component with blood pressure among young adults: considering gender and abnormal blood pressure as moderators, moderate-vigorous physical activity, sleep behavior, sedentary behavior, mental wellbeing and BMI as covariates.

Background: Global burden of hypertension among young people continues to increase. There have been many studies examining the effect of aerobic and muscle-strengthening physical activity on blood pressure, many of them didn't consider interdependence between them. Conflicting results of health-related fitness, particularly handgrip strength, as intermediate outcomes of muscle-strengthening physical activity on blood pressure also emerged. This research will carry out a mediation-moderation analysis to find out the relationship between muscle strengthening physical activity and blood pressure among young adults by considering health-related fitness and 24-hour movement behavior. Methods: A cross-sectional study among 221 Indonesian young adults attending a physical activity intervention collected participant's muscle-strengthening physical activity, and 24 h movement behavior, including aerobic physical activity, sedentary and sleep behavior, and mental well-being using validated questionnaires. Mediation and moderation analyses were conducted using Process Macro model 10 on SPSS 25 to investigate the association of muscle-strengthening physical activity on blood pressure, with gender and blood pressure as moderator, mediators consist of handgrip strength, muscle mass percentage and cardiorespiratory fitness. A subgroup analysis was conducted based on participant's cardiorespiratory fitness level. Results: Volume of muscle-strengthening physical activities in a week have a direct association with systolic blood pressure among prehypertensive male with an effect of 0,00989359 (95% CI 0,0046488 to 0,00336478). Considering its volume as mediator, the frequency of muscle-strengthening physical activity contributed to a significant direct effect on diastolic blood pressure in both genders, but the duration of MSPA has a significant direct effect on systolic blood pressure in male subjects. There is no component of physical fitness that provides a significant mediating effect. After a subgroup analysis, the relationship between MSPA Volume and blood pressure is not significant for individuals with a high level of cardiorespiratory fitness. Conclusions: This study shows that increased participation in muscle strengthening physical activity, especially in subject with low cardiorespiratory fitness, could increase blood pressure in prehypertensive young adult male population without mediation by physical fitness. Further research is needed to investigate other mechanisms that influence this relationship.