APPL1 ameliorates myocardial ischemia-reperfusion injury by regulating the AMPK signaling pathway.

Myocardial ischemia-reperfusion injury results in elevated reactive oxygen species (ROS) production and causes oxidative stress damage. Therefore, the current study aimed to investigate whether adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) could induce the expression of antioxidant enzymes through AMP-activated protein kinase (AMPK) signaling in order to alleviate the injury caused by ischemia/hypoxia-reperfusion. Following induction of hypoxia-reoxygenation (H/R) injury in H9c2 cells, the liver kinase B1 (LKB1)/AMPK/acetyl-CoA carboxylase α (ACC) signaling pathway was investigated using western blot analysis, along with the detection of superoxide dismutase (SOD)2 and SOD3 expression. Additionally, cell viability was detected using a Cell Counting Kit-8 assay and ROS production was analyzed using ROS staining, whereas the expression levels of inflammatory mediators (TNF-α, monocyte chemoattractant protein 1 and IL-1ß), apoptosis mediators [cleaved caspase-3, cleaved poly (ADP-ribose) polymerase and Bcl-2] and nuclear factor erythroid 2-related factor 2 signaling pathway-related proteins were detected via western blot analysis following overexpression of APPL1 alone or in combination with compound C treatment (an AMPK inhibitor). The results indicated that H/R induction upregulated the phosphorylation levels of LKB1, AMPK and ACC, and decreased the expression levels of APPL1 and SOD enzyme activities. APPL1 overexpression increased the phosphorylation levels of LKB1, AMPK and ACC, SOD enzyme activity and cell viability whereas the expression levels of proinflammatory mediators and proapoptotic mediators, and the levels of ROS production were markedly decreased when compared with H/R group with empty plasmid transfection. APPL overexpression-mediated effects were significantly abrogated by compound C. Taken together, the data indicated that APPL1 inhibited ROS production and H/R-induced myocardial injury via the AMPK signaling pathway. Therefore, APPL1 may serve as a potential therapeutic target for myocardial H/R injury.

Alterations in intestinal microbiota diversity, composition, and function in patients with sarcopenia.

16S rRNA sequencing of human fecal samples has been tremendously successful in identifying microbiome changes associated with both aging and disease. A number of studies have described microbial alterations corresponding to physical frailty and nursing home residence among aging individuals. A gut-muscle axis through which the microbiome influences skeletal muscle growth/function has been hypothesized. However, the microbiome has yet to be examined in sarcopenia. Here, we collected fecal samples of 60 healthy controls (CON) and 27 sarcopenic (Case)/possibly sarcopenic (preCase) individuals and analyzed the intestinal microbiota using 16S rRNA sequencing. We observed an overall reduction in microbial diversity in Case and preCase samples. The genera Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, and Lachnoclostridium-known butyrate producers-were significantly less abundant in Case and preCase subjects while Lactobacillus was more abundant. Functional pathways underrepresented in Case subjects included numerous transporters and phenylalanine, tyrosine, and tryptophan biosynthesis suggesting that protein processing and nutrient transport may be impaired. In contrast, lipopolysaccharide biosynthesis was overrepresented in Case and PreCase subjects suggesting that sarcopenia is associated with a pro-inflammatory metagenome. These analyses demonstrate structural and functional alterations in the intestinal microbiota that may contribute to loss of skeletal muscle mass and function in sarcopenia.

Comparison of cardiac rehabilitation (exercise + education), exercise only, and usual care for patients with coronary artery disease: A non-randomized retrospective analysis.

Cardiac rehabilitation program is well-established but the Rehabilitation After Myocardial Infarction Trial (RAMIT) is reported that it does not affect mortality and morbidity of patients after myocardial infarction during follow-up period. The objectives of the study were to compare functional walking capacity, risk factor control, and morbidities in follow-up for cardiac rehabilitation (exercise + education), exercise only, and usual care among patients with coronary artery disease. A total of 492 male and female patients (age range: 45-73 years) with coronary artery disease after myocardial infarction or underwent percutaneous coronary intervention or coronary artery bypass grafting surgeries referred to cardiac rehabilitation were included in the study. Patients were participating in a cardiac rehabilitation program (exercise + education, CRP cohort, n = 125), exercise only (USC cohort, n = 182), or usual care (NCR cohort, n = 185). Data regarding incremental shuttle walk test, lipid profile, the Patient Health Questionnaire 9, and morbidities in follow-up of patients were retrospectively collected and analyzed. After completion of 1 year, cardiac rehabilitation program (p < 0.0001, q = 20.939) and exercise (p < 0.0001, q = 6.059) were successfully increased incremental shuttle walk test. After completion of 1 year, cardiac rehabilitation program reduced low-density lipoprotein (p = 0.007, q = 3.349) and depressive symptoms (p < 0.0001, q = 5.649). Morbidities were reported fewer in the patients of CRP cohort than those of USC (p = 0.003, q = 3.427) and NCR (p = 0.003, q = 4.822) cohorts after completion of 1 year of program. Cardiac rehabilitation program (exercise +education) improved functional walking capacity, controlled risk factors, and reduced morbidities of patients with coronary artery disease than exercise only and usual care (Level of evidence: III).