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Exosomes Secreted During Myogenic Differentiation of Human Fetal Cartilage-Derived Progenitor Cells Promote Skeletal Muscle Regeneration through miR-145-5p
No full textBackground: Currently, there is no apparent treatment for sarcopenia, which is characterized by diminished myoblast function. We aimed to manufacture exosomes that retain the myogenic differentiation capacity of human fetal cartilage-derived progenitor cells (hFCPCs) and investigate their muscle regenerative efficacy in myoblasts and a sarcopenia rat model. Methods: The muscle regeneration potential of exosomes (F-Exo) secreted during myogenic differentiation of hFCPCs was compared to human bone marrow mesenchymal stem cells-derived (hBMSCs) exosomes (B-Exo) in myoblasts and sarcopenia rat model. The effect of F-Exo was analyzed through known microRNAs (miRNAs) analysis. The mechanism of action of F-Exo was confirmed by measuring the expression of proteins involved in the Wnt signaling pathway. Results: F-Exo and B-Exo showed similar exosome characteristics. However, F-Exo induced the expression of muscle markers (MyoD, MyoG, and MyHC) and myotube formation in myoblasts more effectively than B-Exo. Moreover, F-Exo induced greater increases in muscle fiber cross-sectional area and muscle mass compared to B-Exo in a sarcopenia rat. The miR-145-5p, relevant to muscle regeneration, was found in high concentrations in the F-Exo, and RNase pretreatment reduced the efficacy of exosomes. The effects of F-Exo on the expression of myogenic markers in myoblasts were paralleled by the miR-145-5p mimics, while the inhibitor partially negated this effect. F-Exo was involved in the Wnt signaling pathway by enhancing the expression of Wnt5a and β-catenin. Conclusion: F-Exo improved muscle regeneration by activating the Wnt signaling pathway via abundant miR-145-5p, mimicking the remarkable myogenic differentiation potential of hFCPCs
Exploring the prognostic value of ultra-low-pass whole-genome sequencing of circulating tumor DNA in hepatocellular carcinoma
Get PDFLarge-scale cross-ancestry genome-wide meta-analysis of serum urate
No full textHyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control
Patient preference, efficacy, and compliance with zoledronic acid for glucocorticoid-induced osteoporosis in patients with autoimmune diseases
No full textPurpose: We evaluated the preference, patient satisfaction, and efficacy of zoledronic acid compared with oral bisphosphonates (BPs) for glucocorticoid-induced osteoporosis (GIOP) in patients with autoimmune diseases. Methods: We enrolled 50 patients with new fractures or osteoporosis detected on follow-up bone densitometry after at least 1 year of oral BP use among patients diagnosed with GIOP during treatment for autoimmune diseases. After 1 year of zoledronic acid treatment, patients completed a survey for preference and satisfaction assessment. Treatment efficacy was analysed by comparing bone mineral density changes and fractures with those in a control group of patients who continued oral BP use. Results: Age, sex, treatment duration, and medication history did not differ significantly between the two groups. Among the participants, 86.7% preferred and were more satisfied with intravenous zoledronic acid than with oral BPs, primarily because of the convenience of its administration interval. Only two patients (4%) reported infusion-related adverse events with zoledronic acid. Furthermore, no significant differences were observed in the annualized percentage change in the bone mineral density of the lumbar spine, femur neck, and hip between patients receiving zoledronic acid and those receiving oral BPs. The occurrence of new fractures was consistent across both groups, with two cases in each, showing no significant differences. Conclusion: Patients showed a preference for and greater satisfaction with zoledronic acid, and its efficacy in treating osteoporosis was comparable to that of oral BPs. Therefore, zoledronic acid is a suitable treatment option for GIOP in patients with autoimmune diseases
Sarcopenia with decreased total psoas muscle area in children with high-risk neuroblastoma
Get PDFBackground: We calculated psoas muscle area (PMA) z-scores in high-risk neuroblastoma patients undergoing treatment to examine the clinical significance of sarcopenia in this cohort. Methods: We analyzed retrospective data from patients aged 0–18 who were diagnosed with abdominal neuroblastoma between 2005 and 2019 at Samsung Medical Center. Patients categorized as high-risk undergone induction chemotherapy, neuroblastoma excision, and tandem high-dose chemotherapy with autologous stem cell transplantation (HDCT/auto-SCT) were selected. L3-4 lumbar levels on axial CT images were identified and we measured the areas of the left and right psoas muscles to determine tPMA. Total PMA z-scores were calculated using an open online tool. Results: There were 45 boys and 25 girls with a mean age of 3.86 years. CT images taken at initial diagnosis and after tandem HDCT/auto-SCT were selected to calculate tPMA z-scores. Mean elapsed time between the two measurements was 12.91 ± 1.73 months. Mean tPMA z-score significantly decreased from −0.21 ± 1.29 to −0.66 ± 0.97 (p = 0.022). Length of hospital stay was significantly longer in the group of patients whose tPMA z-scores decreased by more than .45 (177.62 ± 28.82 days vs. 165.75 ± 21.34 days, p = 0.049). Presence of sarcopenia at initial diagnosis was a significant risk factor for bacterial infection during neuroblastoma treatment. Conclusion: tPMA z-scores in high-risk neuroblastoma patients decreased significantly following a treatment regimen that included induction chemotherapy, tumor resection surgery, and HDCT/auto-SCT. A greater decrease in tPMA z-score was associated with longer hospital stay during treatment
SGLT2i impact on HCC incidence in patients with fatty liver disease and diabetes: a nation-wide cohort study in South Korea
Get PDFThis study evaluated the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cancer development, particularly in hepatocellular carcinoma (HCC), in individuals with concomitant fatty liver disease (FLD) and type 2 diabetes mellitus (T2DM). Using data from Korea's Health Insurance Review and Assessment Service, we performed Kaplan-Meier and Cox regression analyses in patients with non-alcoholic fatty liver disease (NAFLD) and T2DM (NAFLD-T2DM cohort) and those with chronic viral hepatitis (CVH) alongside FLD and T2DM (FLD-T2DM-CVH cohort). In the propensity score (PS) matched NAFLD-T2DM cohort (N = 107,972), SGLT2i use was not associated with the occurrence of overall cancer, including HCC. However, old age, male sex, liver cirrhosis, and hypothyroidism were identified as independent risk factors for HCC occurrence, whereas statin and fibrate usage were associated with reduced HCC risk in this cohort in multivariate Cox analysis. In the PS-matched FLD-T2DM-CVH cohort (N = 2798), a significant decrease in HCC occurrence was observed among SGLT2i users (P = 0.03). This finding remained consistent in the multivariate Cox regression analysis (Hazard ratio = 2.21, 95% confidence interval = 1.01-4.85, P = 0.048). In conclusion, SGLT2i may be a beneficial option for diabetes management in patients with concomitant T2DM, FLD, and CVH while affirming the overall safety of SGLT2i in other types of cancer
소아청소년 대사증후군
Get PDFBackground: Metabolic syndrome is a serious condition associated with multiple diseases. The prevalence of metabolic syndrome is increasing caused by an increase in obesity rates among children and adolescents. Current Concepts: Owing to the various definitions used, there is lack of consensus regarding the diagnostic criteria for metabolic syndrome in children and adolescents. Although the exact pathogenesis remains unclear, insulin resistance and subsequent inflammation are key mechanistic contributors. Metabolic syndrome is characterized by overweight and obesity accompanied by abnormalities in glucose metabolism, dyslipidemia, and hypertension and is associated with other conditions such as fatty liver, polycystic ovary syndrome, and a pro-inflammatory state. Prevention and management of metabolic syndrome can be achieved through lifestyle modifications, behavioral interventions, pharmacotherapy, and surgical interventions. Discussion and Conclusion: Childhood and adolescent obesity serves as a risk factor for metabolic syndrome during later life. Early identification and intervention are important to prevent the progression of metabolic syndrome. Clinicians must identify at-risk children and adolescents and provide guidance for the prevention and management of metabolic syndrome
Comparison between Proton Pump Inhibitor and H2 Receptor Antagonist in Relieving Cyclosporine-Associated Adverse Gastrointestinal Events: A Single Center, Randomized Controlled Trial
No full textBackground: Cyclosporine (CS) has been effectively used in various skin diseases, but gastrointestinal (GI) adverse events are so common. However, there is no standardized treatment for managing CS-induced GI adverse events. Objective: To analyze the effectiveness of two empirical GI medications, an H2 receptor antagonist (H2RA) and proton pump inhibitor (PPI), in relieving CS-induced GI adverse events. Methods: This is a prospective, randomized clinical trial conducted at Ajou University Hospital. The patients completed a gastrointestinal symptom rating scale (GSRS) questionnaire to assess GI symptoms before and after taking the drugs. Results: A total of 60 patients, divided into a PPI group (n=30) and an H2RA group (n=30), were analyzed. The onset of GI events occurred in 6.04 days on average. GSRS scores improved significantly in both groups (p < 0.01). While abdominal pain, reflux syndrome, and indigestion syndrome consistently improved, changes in diarrhea syndrome and constipation syndrome were not statistically significant. The overall change in GSRS scores was higher in the PPI group, but the difference was not significant (p=0.76). Conclusion: Both PPI and H2RA significantly improved CS-induced GI side effects, with PPI showing a slight advantage over H2RA, but the cost of PPIs should be considered when deciding on first-line therapy. GI side effects typically appeared within 6.04 days of starting CS therapy, highlighting the importance of close monitoring and personalized intervention for improving patient compliance
A collagen biostimulator improves photoaging pigmentation
No full textPhotoaging pigmentation conditions such as senile lentigo and melasma show epidermal melanogenic activity and dermal abnormalities, including collagen degradation. A dermal rejuvenation strategy with skin-lightening therapy directly acting on melanocytes is suggested for photoaging pigmentation. This study investigates whether collagen biostimulation can result in skin lightening of photoaging skin. A split-face clinical trial was conducted, involving 40 subjects with facial melasma and senile lentigo. Subjects received a poly-DL-lactic acid (PDLLA) treatment on one side of their face, whereas the contralateral side received a treatment of normal saline as a control. Assessments were scheduled every month after completing treatments for up to 3 months. Pigmentation was evaluated using the L* value as measured with a chromameter and by investigator global assessment scores (IGA). Subjects reported different outcomes in terms of overall skin quality, including pigmentation, wrinkles and elasticity. Skin biopsies were obtained before the treatment and 4 weeks after completing the treatment. Fontana-Masson, Masson-Trichrome and Verhoeff-van Gieson staining, and fibroblast-specific protein 1 (FSP1) immunostaining were conducted. The PDLLA treatment demonstrated significant improvements in the L* values and IGA scores from 8 weeks after the subject completed their treatments. These improvements were sustained over a 12-week assessment period. The subjects reported substantial reductions in both pigmentation and wrinkle severity and elasticity throughout the assessment period. Fontana-Masson staining showed a marked decrease in pigmentation upon a PDLLA injection compared to the baseline values. Increased immunogenicity of FSP1 and increases in collagen and elastic fibre staining were observed. This study demonstrated remarkable improvements in photoaging pigmentation along with collagen production with a collagen biostimulator. Thus, collagen biostimulators represent a promising therapeutic approach for addressing photoaging signs associated with melasma and senile lentigo. (ClinicalTrials.gov Identifier: NCT05913102)
Uniform Synthesis of Bilayer Hydrogen Substituted Graphdiyne for Flexible Piezoresistive Applications
No full textGraphdiyne (GDY) has garnered significant attention as a cutting-edge 2D material owing to its distinctive electronic, optoelectronic, and mechanical properties, including high mobility, direct bandgap, and remarkable flexibility. One of the key challenges hindering the implementation of this material in flexible applications is its large area and uniform synthesis. The facile growth of centimeter-scale bilayer hydrogen substituted graphdiyne (Bi-HsGDY) on germanium (Ge) substrate is achieved using a low-temperature chemical vapor deposition (CVD) method. This material's field effect transistors (FET) showcase a high carrier mobility of 52.6 cm2 V−1 s−1 and an exceptionally low contact resistance of 10 Ω µm. By transferring the as-grown Bi-HsGDY onto a flexible substrate, a long-distance piezoresistive strain sensor is demonstrated, which exhibits a remarkable gauge factor of 43.34 with a fast response time of ≈275 ms. As a proof of concept, communication by means of Morse code is implemented using a Bi-HsGDY strain sensor. It is believed that these results are anticipated to open new horizons in realizing Bi-HsGDY for innovative flexible device applications