Mitochondrial mechanisms in the pathogenesis of chronic inflammatory musculoskeletal disorders.

Chronic inflammatory musculoskeletal disorders characterized by prolonged muscle inflammation, resulting in enduring pain and diminished functionality, pose significant challenges for the patients. Emerging scientific evidence points to mitochondrial malfunction as a pivotal factor contributing to these ailments. Mitochondria play a critical role in powering skeletal muscle activity, but in the context of persistent inflammation, disruptions in their quantity, configuration, and performance have been well-documented. Various disturbances, encompassing alterations in mitochondrial dynamics (such as fission and fusion), calcium regulation, oxidative stress, biogenesis, and the process of mitophagy, are believed to play a central role in the progression of these disorders. Additionally, unfolded protein responses and the accumulation of fatty acids within muscle cells may adversely affect the internal milieu, impairing the equilibrium of mitochondrial functioning. The structural discrepancies between different mitochondrial subsets namely, intramyofibrillar and subsarcolemmal mitochondria likely impact their metabolic capabilities and susceptibility to inflammatory influences. The release of signals from damaged mitochondria is known to incite inflammatory responses. Intriguingly, migrasomes and extracellular vesicles serve as vehicles for intercellular transfer of mitochondria, aiding in the removal of impaired mitochondria and regulation of inflammation. Viral infections have been implicated in inducing stress on mitochondria. Prolonged dysfunction of these vital organelles sustains oxidative harm, metabolic irregularities, and heightened cytokine release, impeding the body's ability to repair tissues. This review provides a comprehensive analysis of advancements in understanding changes in the intracellular environment, mitochondrial architecture and distribution, biogenesis, dynamics, autophagy, oxidative stress, cytokines associated with mitochondria, vesicular structures, and associated membranes in the context of chronic inflammatory musculoskeletal disorders. Strategies targeting key elements regulating mitochondrial quality exhibit promise in the restoration of mitochondrial function, alleviation of inflammation, and enhancement of overall outcomes.

Recent advances of exosomes in soft tissue injuries in sports medicine: A critical review on biological and biomaterial applications.

Sports medicine is generally associated with soft tissue injuries including muscle injuries, meniscus and ligament injuries, tendon ruptures, tendinopathy, rotator cuff tears, and tendon-bone healing during injuries. Tendon and ligament injuries are the most common sport injuries accounting for 30-40% of all injuries. Therapies for tendon injuries can be divided into surgical and non-surgical methods. Surgical methods mainly depend on the operative procedures, the surgeons and postoperative interventions. In non-surgical methods, cell therapy with stem cells and cell-free therapy with secretome of stem cell origin are current directions. Exosomes are the main paracrine factors of mesenchymal stem cells (MSCs) containing biological components such as proteins, nucleic acids and lipids. Compared with MSCs, MSC-exosomes (MSC-exos) possess the capacity to escape phagocytosis and achieve long-term circulation. In addition, the functions of exosomes from various cell sources in soft tissue injuries in sports medicine have been gradually revealed in recent years. Along with the biological and biomaterial advances in exosomes, exosomes can be designed as drug carriers with biomaterials and exosome research is providing promising contributions in cell biology. Exosomes with biomaterial have the potential of becoming one of the novel therapeutic modalities in regenerative researches. This review summarizes the derives of exosomes in soft tissue regeneration and focuses on the biological and biomaterial mechanism and advances in exosomal therapy in soft tissue injuries.

Bio-Pulsed Stimulation Effectively Improves the Production of Avian Mesenchymal Stem Cell-Derived Extracellular Vesicles That Enhance the Bioactivity of Skin Fibroblasts and Hair Follicle Cells.

Mesenchymal stem cell (MSC)-derived extracellular vesicles (exosomes) possess regeneration, cell proliferation, wound healing, and anti-senescence capabilities. The functions of exosomes can be modified by preconditioning MSCs through treatment with bio-pulsed reagents (Polygonum multiflorum Thunb extract). However, the beneficial effects of bio-pulsed small extracellular vesicles (sEVs) on the skin or hair remain unknown. This study investigated the in vitro mechanistic basis through which bio-pulsed sEVs enhance the bioactivity of the skin fibroblasts and hair follicle cells. Avian-derived MSCs (AMSCs) were isolated, characterized, and bio-pulsed to produce AMSC-sEVs, which were isolated, lyophilized, characterized, and analyzed. The effects of bio-pulsed AMSC-sEVs on cell proliferation, wound healing, and gene expression associated with skin and hair bioactivity were examined using human skin fibroblasts (HSFs) and follicle dermal papilla cells (HFDPCs). Bio-pulsed treatment significantly enhanced sEVs production by possibly upregulating RAB27A expression in AMSCs. Bio-pulsed AMSC-sEVs contained more exosomal proteins and RNAs than the control. Bio-pulsed AMSC-sEVs significantly augmented cell proliferation, wound healing, and gene expression in HSFs and HFDPCs. The present study investigated the role of bio-pulsed AMSC-sEVs in the bioactivity of the skin fibroblasts and hair follicle cells as mediators to offer potential health benefits for skin and hair.

Simultaneous or Staged Bilateral Arthroscopic Rotator Cuff Repair: An Observational Study of Intraoperative and Postoperative Outcomes.

BACKGROUND: Bilateral arthroscopic rotator cuff repair (ARCR) is frequently performed in patients with symptomatic bilateral rotator cuff tears. PURPOSE: To compare patient-reported outcomes and mobility between simultaneous and staged bilateral ARCR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Included were 51 patients who underwent simultaneous (anesthetized once) and 42 patients who underwent staged (anesthetized twice) bilateral ARCR between January 2014 and January 2018; for the staged group, the interval between procedures was at least 12 months. All operations were performed by the same surgeon, and all patients had minimum 24-month follow up in both shoulders. Patient-reported outcomes and range of motion (ROM) were assessed preoperatively and postoperatively and compared between groups. Outcome measures included the Constant-Murley score (CMS) and American Shoulder and Elbow Surgeons (ASES) score as well as measures of psychological status, health-related quality of life, activities of daily living (ADL), and patient satisfaction with the state of one's shoulders. RESULTS: The mean follow-up times for the staged and simultaneous ARCR groups were 44.1 months (range, 36-60 months) and 37.5 months (range, 25-59 months), respectively. There were no significant differences in age, tear size, or fatty degeneration of rotator cuff muscles between the groups. The cumulative length of hospital stay in the staged group was significantly longer than in the simultaneous group (P < .001). At the final follow-up, both groups showed significant improvement in ROM, CMS, and ASES scores (P < .05). No significant differences between the groups were observed in terms of ROM, CMS, and ASES scores postoperatively. At 24 months postoperatively, psychological status and health-related quality of life in both groups improved significantly (P < .05), and there were no significant between-group differences. Patients were able to perform most essential ADL. Both groups had high patient satisfaction, but patient satisfaction for the second shoulder of the staged group was lower than that of the simultaneous group (P = .039). CONCLUSION: Simultaneous bilateral ARCR was shown to be effective, resulting in similar improvements in clinical outcomes to staged bilateral ARCR at 2-year follow-up. In addition to higher patient satisfaction, simultaneous bilateral ARCR also had a shorter treatment cycle.

Income related inequality and influencing factors: a study for the incidence of catastrophic health expenditure in rural China.

BACKGROUND: Catastrophic health expenditure (CHE) puts a heavy disease burden on patients' families, aggravating income-related inequality. In an attempt to reduce the financial risks of rural families incurring CHE, China began the New Rural Cooperative Medical System (NCMS) on a trial basis in 2003 and has raised the reimbursement rates continuously since then. Based on statistical data about rural families in sample area of Jiangsu province, this study measures the incidence of CHE, analyzes socioeconomic inequality related to CHE, and explores the influences of the NCMS on the incidence of CHE. METHODS: Statistical data were acquired from two surveys about rural health care, one conducted in 2009 and one conducted in 2010. In 2009, 1424 rural families were analyzed; in 2010, 1796 rural families were analyzed. An index of CHE is created to enable the evaluation of the associated financial risks. The concentration index and concentration curve are used to measure the income-related inequality involved in CHE. Multiple logistic regression is utilized to explore the factors that influence the incidence of CHE. RESULTS: The incidence of CHE decreased from 13.62% in 2009 to 7.74% in 2010. The concentration index of CHE was changed from -0.298 (2009) to -0.323 (2010). Compared with rural families in which all members were covered by the NCMS, rural families in which some members were not covered by the NCMS had a lower incidence of CHE: The odds ratio is 0.65 with a 95% confidence interval of 0.43 to 1.00. For rural families in which all members were covered by the NCMS, the increase in reimbursement rates is correlated to the decline in the incidence of CHE if other influencing factors were controlled: The odds ratio is 0.48 with a 95% confidence interval of 0.36 to 0.64. CONCLUSIONS: Between 2009 and 2010, the incidence rate of CHE in the sampled area decreased sharply, CHE was more concentrated among least wealthy and inequality increased during study period. As of 2010, the poorest rural families still had high risk of experiencing CHE. For rural families in which all members are covered by the NCMS, the rise in reimbursement rates reduces the probability of experiencing CHE.