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Emerging evidence indicates that estrogen receptor (ER) α is an important modulator of bone homeostasis, which occurs partly by promoting osteoclast apoptosis. Sirtuin 6 (Sirt6) is an anti-aging molecule, and its deficiency in mice results in skeletal malformations associated with progeroid features. However, the effects of Sirt6 on ERα function in osteoclasts, and thus on aging- or estrogen deficiency-induced bone loss, have not been studied. Here, we show that myeloid-specific deletion of Sirt6 led to decreased ERα protein level and apoptotic cell death in preosteoclasts. Consequently, myeloid Sirt6 KO mice showed aggravated cancellous bone loss both with aging and following an ovariectomy compared to wild-type littermates. In contrast, Sirt6 transgenic mice were protected from ovariectomy-induced bone loss. Mechanistically, Sirt6 deacetylated ERα protein to prevent its proteasomal degradation, in which lysine 171 and lysine 299 were critical residues. Sirt6-mediated ERα stabilization promoted transcription of Fas ligand in preosteoclasts, resulting in apoptosis of osteoclasts. Finally, the level of Sirt6 in human preosteoclasts was correlated positively with bone density and ERα but negatively with age. In conclusion, our results suggest that deacetylation and upregulation of ERα by Sirt6 in preosteoclasts prevent bone loss by inhibiting osteoclast-mediated bone resorption. Activation of Sirt6 in preosteoclasts may provide a new therapeutic approach to attenuate osteoporosis in older or postmenopausal patients.

This study aimed to estimate the burden of cancer in Koreans attributable to smoking and alcohol consumption using disability-adjusted life years and population attributable fractions. We estimated the burden of 12 cancers due to simultaneous and independent smoking and alcohol exposure in Koreans aged ≥40 years. In men, the cancer burden attributable to the combined risk factors, smoking alone, and alcohol consumption alone were 9.5, 14.8, and 6.1%, respectively; the corresponding values for women were 1.1, 2.5, and 2.7%, respectively. In men, tracheal, bronchial, and lung cancers were the most common cancer types. The disease burden may have been reduced by 16.8, 32.3, and 4.1% in the absence of the combined risk factors, smoking alone, and alcohol consumption alone, respectively. Our findings suggest that risk factor-based intervention may have the greatest preventative effect for lung cancer among all cancers in men. Our real-world data methodology could provide further evidence-based methods to explore and facilitate effective health promotion interventions for specific target groups and may lay the foundation for the establishment of healthcare services according to population subgroups or regional characteristics.

Scarless wound healing is ideal for patients suffering from soft tissue defects. In this study, we prepared a novel wet dressing (β-CD-ic-CUR/GC) based on the visible light-cured glycol chitosan (GC) hydrogel and inclusion complex between beta-cyclodextrin (β-CD) and curcumin (CUR). We also evaluated its efficacy in the acceleration of wound healing as compared to that of CUR-loaded GC (CUR/GC). The conjugation of glycidyl methacrylate (GM) to GC for photo-curing was confirmed by 1H-NMR measurement, and the photo-cured GC hydrogel was characterized by the analyses of rheology, swelling ratio, SEM and degradation rate. After visible light irradiation, the surface/cross-sectional morphologies and storage (G′)/loss (G′′) moduli revealed the formation of hydrogel with interconnected porosity. The dressing β-CD-ic-CUR/GC exhibited a controlled release of 90% CUR in a sustained manner for 30 days. On the other hand, CUR/GC showed CUR release of 16%. β-CD acted as an excipient in improving the water-solubility of CUR and affected the release behavior of CUR. The in vivo animal tests including measurement of the remaining unhealed wound area and histological analyses showed that β-CD-ic-CUR/GC may have potential as a wet dressing agent to enhance soft tissue recovery in open fractures.

Diagnosing the current health status and disease burden in a population is crucial for public health interventions. The ability to compare the burden of different diseases through a single measure, such as disability-adjusted life years has become feasible and continues to be produced and updated through the Global Burden of Diseases (GBD) study. However, the disease burden values of the GBD study do not accurately reflect the unique situation in a specific country with various circumstances. In response, the Korean National Burden of Disease (KNBD) study was conducted to estimate the disease burden in Koreans by considering Korea’s cultural context and utilizing the available data sources at the national level. Both studies identified non-communicable diseases, such as diabetes mellitus (DM), as the primary cause of disease burden among Koreans. However, the extent of public health interventions currently being conducted by the central and local governments does not align with the severity of the disease burden. This review suggests that despite the high burden of DM in South Korea, the current policies may not fully address its impact, underscoring the need for expanded chronic disease management programs and a shift towards prevention-focused healthcare paradigms.

This study estimated the prevalence and incidence rate of schizophrenia, schizotypal, and delusional disorders (SSDD) in Korea from 2008 to 2017 and analyzed the hospital admission rate, re-admission rate, and hospitalization period. It used the Korean nationwide National Health Insurance Service claims database. SSDD patients who had at least one visit to Korea’s primary, secondary, or tertiary referral hospitals with a diagnosis of SSDD, according to the International Classification of Diseases, 10th Revision (ICD-10), were identified as SSDD cases if coded as F20-F29. Data were analyzed using frequency statistics. Results showed that the 12-month prevalence rate of SSDD increased steadily from 0.40% in 2008 to 0.45% in 2017. Analysis of the three-year cumulative prevalence rate of SSDD showed an increase from 0.51% in 2011 to 0.54% in 2017. In 2017, the five-year cumulative prevalence rate was 0.61%, and the 10-year cumulative prevalence rate was 0.75%. The hospital admission rate among SSDD patients decreased from 2008 (30.04%) to 2017 (28.53%). The incidence of SSDD was 0.05% and no yearly change was observed. The proportion of SSDD inpatients whose first hospital visit resulted in immediate hospitalization was 22.4% in 2017. Epidemiological indicators such as prevalence, incidence, and hospitalization rate play an important role in planning social and financial resource allocation. Therefore, efforts to produce more accurate epidemiological indicators are very important and this study’s findings could have a significant social impact.

Our recent studies have identified p21-activated kinase 4 (PAK4) as a key regulator of lipid catabolism in the liver and adipose tissue, but its role in glucose homeostasis in skeletal muscle remains to be explored. In this study, we find that PAK4 levels are highly upregulated in the skeletal muscles of diabetic humans and mice. Skeletal muscle-specific Pak4 ablation or administering the PAK4 inhibitor in diet-induced obese mice retains insulin sensitivity, accompanied by AMPK activation and GLUT4 upregulation. We demonstrate that PAK4 promotes insulin resistance by phosphorylating AMPKα2 at Ser491, thereby inhibiting AMPK activity. We additionally show that skeletal muscle-specific expression of a phospho-mimetic mutant AMPKα2 S491D impairs glucose tolerance, while the phospho-inactive mutant AMPKα2 S491A improves it. In summary, our findings suggest that targeting skeletal muscle PAK4 may offer a therapeutic avenue for type 2 diabetes. While AMPKα is known for its role in regulating GLUT4 trafficking and subsequent glucose uptake into cells, its upstream regulators are not well understood. The authors provide evidence that PAK4 acts as an inhibitory kinase for AMPKα, thus impairing glucose uptake in skeletal muscle.

Background Osteosarcopenia, characterised by concurrent bone loss and muscle atrophy, presents a significant challenge in aging populations, particularly in postmenopausal women. The current therapeutic options potentially treat bone and muscle loss independently, highlighting the importance of an integrated approach. This study aimed to investigate the effects of branched‐chain amino acid (BCAA) supplementation on muscle and bone health using ovariectomised (OVX) mice, a model for postmenopausal osteoporosis and sarcopenia. Methods Female C57BL/6 mice were divided into sham‐operated and OVX groups, with OVX mice further subdivided to receive 0.25 mg/kg (Low) or 1 mg/kg (High) of BCAA supplementation for 16 weeks. Muscle mass, function and mitochondrial health were assessed alongside bone mineral density (BMD), bone turnover markers and histological evaluations. Additionally, the study explored mechanistic insights into sclerostin modulation and its influence on Wnt signalling through plasma and tissue analyses. Results The hind limb fat mass was increased in the OVX group but reduced with BCAA supplementation, while hindlimb lean mass (p < 0.01) and total lean mass (p < 0.001) were significantly higher in the OVX + High‐BCAA group compared with the OVX group. Gastrocnemius muscle weight was lower in the OVX group but improved (p < 0.05) with both Low‐ and High‐BCAA supplementation. BCAA preserved bone microarchitecture by improving cortical thickness (p < 0.01) and modulating bone turnover markers, including osteocalcin (p < 0.01) levels. Plasma sclerostin levels were regulated, suggesting a role in bone remodelling. In muscle, BCAA enhanced hypertrophy by upregulating MHC expression (p < 0.05) and downregulating atrophy markers such as Atrogin‐1 (Low‐BCAA, p < 0.001; High BCAA, p < 0.001) and MuRF‐1 (Low‐BCAA, p < 0.01; High BCAA, p < 0.001). Additionally, BCAA mitigated the cytotoxic effects of H2O2 in osteocytic MLO‐Y4 cells, reducing sclerostin levels (p < 0.05) and improving cellular viability (p < 0.05). In C2C12 cells, BCAA reversed sclerostin‐induced muscle atrophy (p < 0.01), increasing MHC expression (p < 0.01) and myotube diameter (p < 0.01) while reducing Atrogin‐1 (p < 0.01) and MuRF‐1 (p < 0.001) expression. Conclusions BCAA supplementation alleviates muscle atrophy and partially preserves bone microarchitecture in OVX mice. Importantly, our data highlight bone‐derived sclerostin as a molecular link that transmits bone signals to muscle; BCAA mitigates osteosarcopenia by modulating this bone‐to‐muscle endocrine axis via Wnt signalling. Although improvements in bone structure were modest, the findings position BCAAs as a promising adjunct therapy targeting the integrated bone–muscle unit.

Background/Objectives: Sarcopenia, a condition marked by muscle wasting due to aging or inactivity, severely affects older populations. We previously showed that pasteurized Akkermansia muciniphila HB05 (HB05P), sourced from the breast milk of healthy Korean women, could mitigate muscle wasting in a dexamethasone-induced rat model. Here, we explored whether the oral administration of HB05P can enhance muscle strength and functionality in elderly individuals. Our objective was to determine if HB05P supplementation could benefit muscle performance in aging adults. Methods: We conducted a 12-week, double-blind, placebo-controlled clinical trial involving 100 individuals aged 60 and above, randomly assigned to receive either HB05P (1.0 × 1010 cells/day) or a placebo. Results: The HB05P group showed significant improvements in peak torque and peak torque per body weight of the left leg extensor muscles compared to the placebo group (p = 0.0103 and p = 0.0052). Furthermore, HB05P notably elevated follistatin levels, which counteract myostatin, relative to the placebo group (p = 0.0063). No notable safety concerns arose between the groups. Conclusions: HB05P is a promising postbiotic derived from Akkermansia muciniphila that may enhance muscle strength and be used as a safe postbiotic ingredient of Akkermansia muciniphila to improve muscle health.

Bone tissue engineering scaffolds offer the merits of minimal invasion as well as localized and controlled biomolecule release to targeted sites. In this study, we prepared injectable hydrogel systems based on visible light-cured glycol chitosan (GC) hydrogels containing bone morphogenetic protein-2 (BMP-2) and/or transforming growth factor-beta1 (TGF-β1) as scaffolds for bone formation in vitro and in vivo. The hydrogels were characterized by storage modulus, scanning electron microscopy (SEM) and swelling ratio analyses. The developed hydrogel systems showed controlled releases of growth factors in a sustained manner for 30 days. In vitro and in vivo studies revealed that growth factor-loaded GC hydrogels have no cytotoxicity against MC3T3-E1 osteoblast cell line, improved mRNA expressions of alkaline phosphatase (ALP), type I collagen (COL 1) and osteocalcin (OCN), and increased bone volume (BV) and bone mineral density (BMD) in tibia defect sites. Moreover, GC hydrogel containing BMP-2 (10 ng) and TGF-β1 (10 ng) (GC/BMP-2/TGF-β1-10 ng) showed greater bone formation abilities than that containing BMP-2 (5 ng) and TGF-β1 (5 ng) (GC/BMP-2/TGF-β1-5 ng) in vitro and in vivo. Consequently, the injectable GC/BMP-2/TGF-β1-10 ng hydrogel may have clinical potential for dental or orthopedic applications.

Wound recovery close to the function of the native skin is the goal of wound healing. In this study, we prepared foam dressings (FDs; 2-GHC-FD-1–9, 5-GHC-FD-1–9, and 10-GHC-FD-1–9) composed of various concentrations of gelatin, hyaluronic acid, and carboxymethyl chitosan, which are chemically interconnected through amide bond formation, for evaluating wound healing. Tensile and cell proliferation tests showed that 2-GHC-FD-1–9 are suitable for wound dressing. For further evaluation, three types of FDs, 2-GHC-FD-1, 2-GHC-FD-4, and 2-GHC-FD-8 were chosen. The results of animal intradermal reactivity, water vapor transmission rate, and absorption rate of the three FDs indicated that 2-GHC-FD-8 is the most appropriate scaffold for wound healing. For wound healing acceleration, various concentrations of fibroblast growth factor-7 (FGF-7) was soaked in 2-GHC-FD-8 (2-GHC-FD-8/F1-6) and evaluated by using scanning electron microscopy, cell proliferation, release behavior, and in vivo animal tests. The FDs showed interconnected porous structures, increased cell proliferation until 8.0 × 10−11 M, controlled release with initial burst within 1 h, and sustained release for 48 h. The results of the animal test showed an appropriate concentration of FGF-7 for wound healing. In addition, 2-GHC-FD-8 is a suitable scaffold for wound healing. Therefore, we suggest that 2-GHC-FD-8/F3 is a useful wound dressing for accelerating wound healing.