Int J Med Sci
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Receptor-interacting protein 3 (Ripk3) plays a crucial part in acute lung injury (ALI) by regulating inflammation-induced endothelial damage in the lung tissue. The precise mechanisms through which Ripk3 contributes to the endothelial injury in ALI still remain uncertain. In the current research, we employed Ripk3-deficient (Ripk3-/-) mice to examine the role of Ripk3 in ALI progression, focusing on its effects on endothelial cells (ECs), mitochondrial damage and necroptosis. ⋯ Ripk3 upregulation suppressed the AMP-activated protein kinase (AMPK) pathway and activated Drp1-mediated mitochondrial fission, increasing mitochondrial permeability transition pore (mPTP) opening and PMVEC necroptosis. Conversely, Ripk3 deletion activated the AMPK/Drp1-mitochondrial fission pathway, preventing mPTP opening and PMVEC necroptosis in ALI. These findings demonstrated that Ripk3 promotes necroptosis through the AMPK/Drp1/mPTP opening pathway, identifying a potential therapeutic target for ALI treatment.
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Excessive exercise can lead to fatigue, consequently affect exercise performance, and further have an adverse impact to human health. The synergistic effects of ginsenosides, salidroside, and syringin on improving exercise performance remain unknown. Hence, the effects of Chinese herb powder (CHP) which consisted of bioactive compounds such as ginsenosides (Rg1, Re, and Rb1), salidroside, and syringin on exercise performance, energy metabolism, tissue damage, antioxidant activity, and inflammatory cytokine were investigated in exhaustive exercise rats. ⋯ Abdominal arterial blood, liver, and gastrocnemius muscles were collected 4 hours after exhaustive exercise for further analysis. The high-dose CHP group increased the time to exhaustion, decreased serum lactate level, increased serum superoxide dismutase activity, and decreased liver interleukin-6 concentration. Therefore, CHP exhibits an anti-fatigue effect for prolonging the time to exhaustion through improving lactate clearance, and to a lesser extent, enhancing the capacity of antioxidation and anti-inflammation.
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Effective therapies for cognitive impairments induced by brain irradiation are currently lacking. This study investigated the therapeutic potential of hyperbaric oxygen therapy (HBOT) for radiation-induced brain injury in a randomized controlled experimental model using adult male Wistar rats. Adult male Wistar rats were divided into four experimental groups: 0 Gy whole brain radiotherapy (WBRT) with normal baric air (NBA) treatment, 0 Gy WBRT with HBOT, 10 Gy WBRT with NBA, and 10 Gy WBRT with HBOT. ⋯ In addition, HBOT prevented and reversed the increased apoptosis among newborn neural stem cells and neuroblasts caused by 10 Gy WBRT on 7 days. The findings suggest that WBRT disrupts neurogenesis and enhance microgliosis, apoptosis of neuronal progenitors, and lipid peroxidation in the dentate gyrus, potentially leading to cognitive deficits and neuronal death. HBOT may offer a protective effect against these cognitive impairments and their underlying mechanisms in adult male rats following WBRT.
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This study investigates the role of Fundc1 in cardiac protection under high-altitude hypoxic conditions and elucidates its underlying molecular mechanisms. Using cardiomyocyte-specific Fundc1 knockout (Fundc1CKO ) mice, we demonstrated that Fundc1 deficiency exacerbates cardiac dysfunction under simulated high-altitude hypoxia, manifesting as impaired systolic and diastolic function. Mechanistically, we identified that Fundc1 regulates cardiac function through the mitochondrial unfolded protein response (mito-UPR) pathway. ⋯ We identified ATF5 as a key downstream effector of Fundc1, as ATF5 overexpression effectively reversed cardiac dysfunction and restored mito-UPR-related gene expression in Fundc1-deficient hearts. Additionally, we discovered that Fundc1-mediated cardioprotection involves regulation of mitophagy, where its activation improved cardiac function and mitochondrial homeostasis in Fundc1-deficient mice. Our findings reveal a novel Fundc1-ATF5-mito-UPR axis in cardioprotection against high-altitude hypoxia and highlight the crucial role of mitophagy in this protective mechanism, providing new insights into potential therapeutic strategies for high-altitude heart disease.