Background: Aging leads to sarcopenia, which is characterized by reduced muscle mass and strength. Many factors, including altered muscle protein turnover, diminished neuromuscular function, hormonal changes, systemic inflammation, and the structure and composition of muscle fibers, play a crucial role in age-related muscle decline. This study explored differences in muscle fiber types contributing to overall muscle function decline in aging, focusing on individuals with hip fractures from falls. Methods: A pilot study at Chungnam National University Hospital collected muscle biopsies from hip fracture patients aged 20 to 80 undergoing surgical treatment. Muscle biopsies from the vastus lateralis and gluteus maximus were obtained during hip arthroplasty or internal fixation. Handgrip strength, calf and thigh circumference, and bone mineral density were evaluated in individuals with hip fractures from falls. We analyzed the relationships between each clinical characteristic and muscle fiber type. Results: In total, 26 participants (mean age 67.9 years, 69.2% male) were included in this study. The prevalence of sarcopenia was 53.8%, and that of femoral and lumbar osteoporosis was 19.2% and 11.5%, respectively. Vastus lateralis analysis revealed an age-related decrease in type IIx fibers, a higher proportion of type IIa fibers in women, and an association between handgrip strength and type IIx fibers in men. The gluteus maximus showed no significant correlations with clinical parameters. Conclusion This study identified complex associations between age, sex, handgrip strength, and muscle fiber composition in hip fracture patients, offering insights crucial for targeted interventions combating age-related muscle decline and improving musculoskeletal health.

Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2∼4 and 2∼3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.

Background: The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. Methods: The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patientoriented composite outcome (POCO) at 2 years. Results: Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group.Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel.Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487–3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663–3.012,P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. Conclusion With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES.

Purpose: Healthy aging is an important concern in an aging society. Although the causal relationship between hypogonadism and erectile dysfunction in elderly men remains unclear, many physicians have achieved positive results after implementing exogenous testosterone supplementation therapy in patients with normal or slightly low blood testosterone. The purpose of this study was to conduct a systematic review and meta-analysis on whether testosterone replacement therapy (TRT) could improve sexual function in the elderly, as reported recently. Materials and Methods: As a comprehensive literature search was performed to find articles published in PubMed, Embase, and Cochrane databases by January 2022. The search used keywords of ‘aged’, ‘male’, ‘sexual behavior’, and ‘testosterone’. Randomized controlled trials (RCTs) were finally selected. As the main effect variable, results of a questionnaire on sexual function were analyzed and the effects of TRT were compared to those of placebo control. Results: Five RCT studies were included in this meta-analysis. The overall improvement by mean difference of sexual function for testosterone supplementation was 0.082 (95% CI: -0.049 to 0.213). In subgroup analysis, only intramuscular injection of 1,000 mg testosterone significantly improved sexual function of the elderly (0.229, 95% CI: 0.112 to 0.347). There was no significant difference in sexual function according to testosterone dose in meta-ANOVA (p=0.957). The difference was not statistically significant either in the meta-regression test (p=0.310). Egger’s regression coefficient test did not indicate a publication bias (p=0.132). Conclusions Although our overall effect size (that is, sexual function effect of TRT) did not show a significant improvement, the direction of improvement in erection and motivation was clearly shown. The injection formulation resulted in a significant sexual function improvement. Since only a few RCTs were included in the analysis, more well-designed prospective studies are needed to have a definite conclusion.

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways.Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC BMP2 ) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC BMP2 were associated with migration and growth. MSC BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC BMP2 . MSC BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3 + CD25 + Treg of CD4 + cells were further increased in ALI mice treated with MSC BMP2 . In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC BMP2 . Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

Background: Little is known about the adverse events (AEs) associated with coronavirus disease 2019 (COVID-19) vaccination in patients with type 2 diabetes mellitus (T2DM). Methods: This study used vaccine AE reporting system data to investigate severe AEs among vaccinated patients with T2DM. A natural language processing algorithm was applied to identify people with and without diabetes. After 1:3 matching, we collected data for 6,829 patients with T2DM and 20,487 healthy controls. Multiple logistic regression analysis was used to calculate the odds ratio for severe AEs. Results: After COVID-19 vaccination, patients with T2DM were more likely to experience eight severe AEs than controls: cerebral venous sinus thrombosis, encephalitis myelitis encephalomyelitis, Bell’s palsy, lymphadenopathy, ischemic stroke, deep vein thrombosis (DVT), thrombocytopenia (TP), and pulmonary embolism (PE). Moreover, patients with T2DM vaccinated with BNT162b2 and mRNA-1273 were more vulnerable to DVT and TP than those vaccinated with JNJ-78436735. Among patients with T2DM administered mRNA vaccines, mRNA-1273 was safer than BNT162b2 in terms of the risk of DVT and PE. Conclusion Careful monitoring of severe AEs in patients with T2DM may be necessary, especially for those related to thrombotic events and neurological dysfunctions after COVID-19 vaccination.

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung.Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods: and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSCcP1P ), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSCcP1P reduce inflammatory response in LPS exposed mice. hdMSCcP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSCcP1P treated mice. Conclusions Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSCcP1P provide a therapeutic potential for ALI/ARDS treatment.