Exercise training has been reported to alleviate cardiac fibrosis and ameliorate heart dysfunction after myocardial infarction (MI), but the molecular mechanism is still not fully clarified. Fibroblast growth factor 21 (FGF21) exerts a protective effect on the infarcted heart. This study investigates whether exercise training could increase FGF21 protein expression and regulate the transforming growth factor-β1 (TGF-β1)-Smad2/3-MMP2/9 signaling pathway to alleviate cardiac fibrosis following MI. Male wild type (WT) C57BL/6J mice and Fgf21 knockout (Fgf21 KO) mice were used to establish the MI model and subjected to five weeks of different types of exercise training. Both aerobic exercise training (AET) and resistance exercise training (RET) significantly alleviated cardiac dysfunction and fibrosis, up-regulated FGF21 protein expression, inhibited the activation of TGF-β1-Smad2/3-MMP2/9 signaling pathway and collagen production, and meanwhile, enhanced antioxidant capacity and reduced cell apoptosis in the infarcted heart. In contrast, knockout of Fgf21 weakened the cardioprotective effects of AET after MI. In vitro, cardiac fibroblasts (CFs) were isolated from neonatal mice hearts and treated with H₂O₂ (100 μM, 6 h). Recombinant human FGF21 (rhFGF21, 100 ng/mL, 15 h) and/or 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR, 1 mM, 15 h) inhibited H₂O₂-induced activation of the TGF-β1-Smad2/3-MMP2/9 signaling pathway, promoted CFs apoptosis and reduced collagen production. In conclusion, exercise training increases FGF21 protein expression, inactivates the TGF-β1-Smad2/3-MMP2/9 signaling pathway, alleviates cardiac fibrosis, oxidative stress, and cell apoptosis, and finally improves cardiac function in mice with MI. FGF21 plays an important role in the anti-fibrosis effect of exercise training.

Aerobic exercise mitigates oxidative stress and apoptosis caused by myocardial infarction (MI) even though the precise mechanisms remain completely elusive. In this study, we investigated the potential mechanisms of aerobic exercise in ameliorating the cardiac function of mice with MI. In vivo, MI was induced by left anterior descending (LAD) coronary artery ligation in wild‐type mice, alcat1 knockout, and fgf21 knockout mice. The mice were exercised under a moderate‐intensity protocol for 6 weeks at one week later post‐MI. In vitro, H9C2 cells were treated with lentiviral vector carrying alcat1 gene, recombinant human FGF21 (rhFGF21), PI3K inhibitor, and H₂O₂ to explore the potential mechanisms. Our results showed that aerobic exercise significantly increased the FGF21 expression and decreased the ALCAT1 expression in the hearts of mice with MI. fgf21 knockout weakened the inhibitory effects of aerobic exercise on oxidative stress, endoplasmic reticulum (ER) stress, and apoptosis in mice with MI. Both/either alcat1 knockout and/or aerobic exercise improved cardiac function by inhibiting oxidative stress and apoptosis in the MI heart. rhFGF21 inhibited both H₂O₂ and overexpression of ALCAT1‐induced oxidative stress and apoptosis by activating the PI3K/AKT pathway in H9C2 cells. In conclusion, our results showed that aerobic exercise alleviated oxidative stress and apoptosis by activating the FGF21/FGFR1/PI3K/AKT pathway or inhibiting the hyperexpression of ALCAT1, which ultimately improved the cardiac function in MI mice.

Myocardial infarction (MI) causes peripheral organ injury, in addition to cardiac dysfunction, including in the liver, which is known as cardiac hepatopathy. Aerobic exercise (AE) can effectively improve liver injury, although the mechanism and targets are currently not well established. Irisin, mainly produced by cleavage of the fibronectin type III domain-containing protein 5 (FNDC5), is a responsible for the beneficial effects of exercise training. In this study, we detected the effect of AE on MI-induced liver injury and explored the role of irisin alongside the benefits of AE. Wildtype and Fndc5 knockout mice were used to establish an MI model and subjected to AE intervention. Primary mouse hepatocytes were treated with lipopolysaccharide (LPS), rhirisin, and a phosphoinositide 3-kinase (PI3K) inhibitor. The results showed that AE significantly promoted M2 polarization of macrophages and improved MI-induced inflammation, upregulated endogenous irisin protein expression and activated the PI3K/ protein kinase B (Akt) signaling pathway in the liver of MI mice, while knockout of Fndc5 attenuated the beneficial effects of AE. Exogenous rhirisin significantly inhibited the LPS-induced inflammatory response, which was attenuated by the PI3K inhibitor. These results suggest that AE could effectively activate the FNDC5/irisin-PI3K/Akt signaling pathway, promote the polarization of M2 macrophages, and inhibit the inflammatory response of the liver after MI.

FGF21 activated FGFR1/PI3K/AKT/VEGF signaling pathway mediated angiogenesis in MI mice. FGF21 deficiency attenuated aerobic exercise-induced cardiac angiogenesis in MI mice. FGF21/FGFR1/PI3K/AKT/VEGF signal played an important role in aerobic exercise to promote myocardial angiogenesis and improved cardiac function.

Background: Cohen syndrome (OMIM No. # 216550) is a rare autosomal recessive disorder caused by homozygous mutation in the vacuolar protein sorting 13 homolog B (VPS13B) gene on chromosome 8q22.2. Clinical manifestations include hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, and neutropenia. To date, more than 200 mutations of VPS13B have been reported in over 1,000 Cohen syndrome patients. This article reviews the clinical data of two cases of Cohen syndrome diagnosed by whole exome sequencing. Results: Both children visited for psychomotor retardation. Gene detection showed a mutation in 8q22.2, NM_017890.4 Intron38 c.6940+1G > T and heterozygotic deletion of exon 3-19 of the VPS13B gene (Case 1), and a mutation in 8q22.2, NM_017890.4 Intron38 c.6940+1G > T and 8q22, NM_017890.4 Exon56 c10334_10335del in the VPS13B gene (Case 2). The variation was predicted to be pathogenic by related software, and they have not been reported. Conclusion: Cohen syndrome should be considered in the differential diagnosis of any child with developmental retardation and neutropenia. The present study increases the mutation spectrum of the VPS13B gene and could be helpful in genetic diagnosis and genetic counseling in Cohen syndrome patients.

Regular exercise and physical activity are beneficial in reducing the risk and progression of ischemic stroke. However, the underlying physiological mechanisms by which exercise confers these protective effects remain incompletely understood. Disruption of mitochondrial homeostasis is key contributors to the pathophysiology of ischemic stroke. Exercise training effectively attenuates the onset and progression of ischemic stroke by significantly maintaining mitochondrial homeostasis, including improving mitochondrial biogenesis, balancing mitochondrial dynamics, maintaining mitochondrial redox, promoting mitophagy and mitochondrial transport. This review systematically summarizes the beneficial effects of exercise in the context of ischemic stroke and highlights the critical link between mitochondrial homeostasis disruption and stroke pathology. By providing a detailed analysis of the underlying molecular mechanisms, this study offers novel insights into exercise-based therapeutic strategies for ischemic stroke.