Profound skeletal muscle loss can lead to severe disability and cosmetic deformities. Mesenchymal stem cell (MSC)-derived exosomes have shown potential as an effective therapeutic tool for tissue regeneration. This study aimed to determine the regenerative capacity of MSC-derived exosomes for skeletal muscle regeneration. Exosomes were isolated from human adipose tissue-derived MSCs (AD-MSCs). The effects of MSC-derived exosomes on satellite cells were investigated using cell viability, relevant genes, and protein analyses. Moreover, NOD-SCID mice were used and randomly assigned to the healthy control (n = 4), muscle defect (n = 6), and muscle defect + exosome (n = 6) groups. Muscle defects were created using a biopsy punch on the quadriceps of the hind limb. Four weeks after the surgery, the quadriceps muscles were harvested, weighed, and histologically analyzed. MSC-derived exosome treatment increased the proliferation and expression of myocyte-related genes, and immunofluorescence analysis for myogenin revealed a similar trend. Histologically, MSC-derived exosome-treated mice showed relatively preserved shapes and sizes of the muscle bundles. Immunohistochemical staining revealed greater expression of myogenin and myoblast determination protein 1 in the MSC-derived exosome-treated group. These results indicate that exosomes extracted from AD-MSCs have the therapeutic potential for skeletal muscle regeneration.

A large number of studies have focused on the role of substance P (SP) and the neurokinin-1 receptor (NK1R) in the pathogenesis of a variety of medical conditions. This review provides an overview of the role of the SP-NK1R pathway in the pathogenesis of musculoskeletal disorders and the evidence for its role as a therapeutic target for these disorders, which are major public health problems in most countries. To summarize, the brief involvement of SP may affect tendon healing in an acute injury setting. SP combined with an adequate conjugate can be a regenerative therapeutic option in osteoarthritis. The NK1R antagonist is a promising agent for tendinopathy, rheumatoid arthritis, and osteoarthritis. Research on the SP-NK1R pathway will be helpful for developing novel drugs for osteoporosis.

Only a few studies are available on the effect of the dosing interval of bisphosphonate on drug compliance. We analyzed the data of patients who were newly prescribed bisphosphonate using a national insurance claims database. Drug compliance was assessed by calculating medication possession ratio (MPR) over a minimum of a 1-year follow-up. This analysis included 281,996 new bisphosphonate users with a mean age of 68.9 years (92% women). The patients were divided into daily, weekly, monthly, 3-monthly, and switch groups (who changed the drug to other dosing intervals). The average MPR was the highest in the switch group (66%), and the longer the dosing interval, the higher the compliance (3-monthly, 56% vs. daily, 37%). “Non-compliant” was defined as an MPR under 80%. Various factors which were possibly associated with “non-compliant” MPR were investigated using multiple regression analysis. Multivariate analysis showed that male patients were more likely to be non-compliant with pharmacotherapy than female patients, with as odds ratio of 1.389. Younger patients had a significantly lower likelihood of being non-compliant than older patients for age 60–69 vs. age 80+. Long dosing intervals were recommended to improve compliance and special attention was given to older and male patients.

Inadequate vessel maintenance or growth causes ischemia in diseases such as myocardial infarction, stroke, and neurodegenerative disorders. Therefore, developing an effective strategy to salvage ischemic tissues using a novel compound is urgent. Drug repurposing has become a widely used method that can make drug discovery more efficient and less expensive. Additionally, computational virtual screening tools make drug discovery faster and more accurate. This study found a novel drug candidate for pro-angiogenesis by in silico virtual screening. Using Gene Expression Omnibus (GEO) microarray datasets related to angiogenesis studies, differentially expressed genes were identified and characteristic direction signatures extracted from GEO2EnrichR were used as input data on L1000CDS² to screen pro-angiogenic molecules. After a thorough review of the candidates, a list of compounds structurally similar to TWS-119 was generated using ChemMine Tools and its clustering toolbox. ChemMine Tools and ChemminR structural similarity search tools for small-molecule analysis and clustering were used for second screening. A molecular docking simulation was conducted using AutoDock v.4 to evaluate the physicochemical effect of secondary-screened chemicals. A cell viability or toxicity test was performed to determine the proper dose of the final candidate, ellipticine. As a result, we found ellipticine, which has pro-angiogenic effects, using virtual computational methods. The noncytotoxic concentration of ellipticine was 156.25 nM. The phosphorylation of glycogen synthase kinase-3β was decreased, whereas the β-catenin expression was increased in human endothelial cells treated with ellipticine. We concluded that ellipticine at sublethal dosage could be successfully repositioned as a pro-angiogenic substance by in silico virtual screening.

Objectives: This study aimed to investigate the relationship between the sarcopenia index (SI), which is derived from serum creatinine and cystatin C levels, and osteoporosis in chronic kidney disease (CKD). Methods: This study initially included patients who underwent dual-energy X-ray absorptiometry (DXA) and serum creatinine and cystatin C testing between 2005 and 2022. Subsequently, patients diagnosed with CKD were selected for the final analysis, totaling 102 patients. Both traditional and new SI were calculated, with each participant categorized into one of two groups (non-osteoporosis and osteoporosis) according to bone mineral density. To enhance statistical validity, the patients were further divided into low- and high-index groups based on the median value of both indices for comparative analysis. The association between SI and the risk of osteoporosis was estimated using multivariable logistic regression analysis. Results: Participants with lower SI values had lower bone mineral density and a higher diabetes mellitus prevalence. The non-osteoporotic group exhibited significantly higher mean values for both traditional and new SI. Multivariable logistic regression analysis identified three statistically significant variables: both indices, sex, and diabetes mellitus. Both traditional and new SI yielded individual odds ratios of 0.906 with estimated areas under the curve of 0.847 for traditional SI and 0.833 for new SI. Conclusions: This study confirmed that both traditional and new SI are associated with osteoporosis in patients with CKD. Therefore, clinicians can raise the suspicion of osteoporosis based on traditional and new SI in patients with CKD, even when DXA results are unavailable.