Cannabinoids improve mitochondrial function in skeletal muscle of exhaustive exercise training rats by inhibiting mitophagy through the PINK1/PARKIN and BNIP3 pathways.

Cannabidiol (CBD) is a pure natural phytocannabinoid derived from cannabis that has anti-inflammatory, antiapoptotic and antioxidative stress abilities. In recent years, an increasing number of studies have reported the regulatory effect of CBD on skeletal muscle injury induced by exercise, but its mechanism is still unclear. Mitochondria are the main organelles responsible for the energy supply within eukaryotic cells, and their function has been closely linked to cellular health. Moderate exercise improves mitochondrial function, but the excessive exercise has a negative impact on mitochondria. Therefore, we speculate that CBD may promote exercise induced skeletal muscle cell damage by improving mitochondrial function. In this study, by establishing an animal model of exhaustive exercise training in rats, the protective effect of CBD on skeletal muscle mitochondrial structure and function was elaborated, and the possible molecular mechanism was discussed based on transcriptomics. Our results indicate that skeletal muscle mitochondrial structure and function were improved after CBD intervention. GO and KEGG pathway enrichment analysis showed that exhaustive exercise training induced mitochondrial dysfunction in skeletal muscle is associated with excessive autophagy/mitophagy, the signaling pathways involved in FOXO3 and GABARAPL1 may play important roles. After CBD intervention, the protein expression of PINK1, PARKIN and BNIP3 was down-regulated, indicating that CBD may improve the mitochondrial function by inhibiting mitophagy through the PINK1/PARKIN and BNIP3 pathway.

A link between mitochondrial damage and the immune microenvironment of delayed onset muscle soreness.

BACKGROUND: Delayed onset muscle soreness (DOMS) is a self-healing muscle pain disorder. Inflammatory pain is the main feature of DOMS. More and more researchers have realized that changes in mitochondrial morphology are related to pain. However, the role of mitochondria in the pathogenesis of DOMS and the abnormal immune microenvironment is still unknown. METHODS: Mitochondria-related genes and gene expression data were obtained from MitoCarta3.0 and NCBI GEO databases. The network of mitochondrial function and the immune microenvironment of DOMS was constructed by computer algorithm. Subsequently, the skeletal muscle of DOMS rats was subjected to qPCR to verify the bioinformatics results. DOMS and non-DOMS histological samples were further studied by staining and transmission electron microscopy. RESULTS: Bioinformatics results showed that expression of mitochondria-related genes was changed in DOMS. The results of qPCR showed that four hub genes (AMPK, PGC1-α, SLC25A25, and ARMCX1) were differentially expressed in DOMS. These hub genes are related to the degree of skeletal muscle immune cell infiltration, mitochondrial respiratory chain complex, DAMPs, the TCA cycle, and mitochondrial metabolism. Bayesian network inference showed that IL-6 and PGC1-α may be the main regulatory genes of mitochondrial damage in DOMS. Transmission electron microscopy revealed swelling of skeletal muscle mitochondria and disorganization of myofilaments. CONCLUSIONS: Our study found that skeletal muscle mitochondrial damage is one of the causes of inflammatory factor accumulation in DOMS. According to the screened-out hub genes, this study provides a reference for follow-up clinical application.

Effectiveness of home-based exercise interventions on pain, physical function and quality of life in individuals with knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to evaluate the effectiveness of home-based exercise interventions on pain, physical function and quality of life in individuals with knee osteoarthritis (KOA). METHODS: Five databases (PubMed, Embase, Cochrane Library, CINAHL, Web of Science Core Collection) were searched for relevant randomized controlled trials (RCTs) published from database inception to 2 August 2022. The Cochrane Collaboration's standards were followed for study selection, eligibility criteria, data extraction and statistics, using the Cochrane Collaboration Risk of Bias Tool and PEDro for quality assessment. A meta-analysis and subgroup analyses, stratified by control condition and intervention duration, were conducted using RevMan 5.4. The study was reported in compliance with the PRISMA statement. RESULTS: A total of 12 independent RCTs with 1442 participants were included. The meta-analysis showed that the home-based exercise interventions significantly reduced pain in individuals with KOA (SMD = - 0.32, 95% CI [- 0.41, - 0.22], p < .01) and improved physical function (SMD = - 0.25, 95% CI [- 0.47, - 0.02], p = .03) and quality of life (SMD = 0.63, 95% CI [0.41, 0.85], p < .001). Subgroup analysis revealed that home-based exercise interventions were superior to health education and no treatment, in terms of pain and physical function, and similar to clinic-based exercise and pharmacologic treatment. CONCLUSIONS: The effect of home-based exercise intervention is significantly better than health education and no treatment for reducing knee pain and improving physical function, and was able to achieve the effects of clinic-based exercise treatment and pharmacologic treatment. With regard to quality of life, the unsupervised home strength exercise intervention showed a significant effect compared with the health education control and combined with cognitive behavioural therapies may produce better results. Although home-based intervention provides effective treatment options for individuals with clinical treatment limitations, individual disease complications and the dosimetry of exercise need to be considered in practice. Furthermore, growing evidence supports the effectiveness of Tai Chi in the rehabilitation of KOA.