Ultraviolet (UV) exposure triggers skin aging primarily by disrupting skin barrier function, resulting in dry skin and wrinkle formation. Oyster hydrolysate (OH), as a functional food, has been reported for anti-cancer, anti-oxidant and anti-apoptotic effects. This study investigated the underlying mechanism of OH effect on UVB-induced skin aging in SKH1 hairless mice. Mice were exposed to UVB three times per week while they were fed with a normal diet or diet containing OH for 10 weeks. Additionally, a randomized, double-blind, and placebo-controlled clinical trial was performed to investigate the OH effect on human skin moisturizing to evaluate its efficacy and safety. UVB exposure increased parameters of skin aging; dehydration, transepidermal water loss, and macroscopic dorsal skin lesions. OH significantly reduced these features of skin aging. Histological analysis demonstrated that OH decreased skin epidermal and dermal thickness and collagen degradation induced by UVB. OH significantly reduced ROS production, suppressed macrophage activation and neutrophil infiltration, and downregulated pro-inflammatory cytokine production. OH improved skin barrier function by increasing the expression of filaggrin, aquaporin-3, and hyaluronic acid synthesis enzymes and promoting recovery from skin damage. Importantly, the results from a human clinical trial demonstrated that OH improved skin moisturization and integrity with no side effects. Taken together, OH supplementation ameliorates skin damage via anti-oxidant and anti-inflammatory properties and enhances skin hydration and barrier function. OH has a therapeutic potential for skin photoaging.

Extracellular ATP plays an important role in renal physiology as well as the pathogenesis of acute kidney injury induced by renal ischemia and reperfusion (IR). Expression of the purinergic P2Y2 receptor has been shown on inflammatory and structural cells of the kidney, and P2Y2R is preferably activated by ATP (or UTP). Here, we investigated the molecular mechanism of P2Y2R during IR injury by using P2Y2R knockout (KO) mice and a selective P2Y2R agonist, MRS2768. After renal IR, P2Y2R KO mice showed greater increases in plasma creatinine, tubular damage and neutrophil infiltration, and significant induction of proinflammatory cytokines and apoptotic markers than wild-type (WT) mice. In contrast, treatment with MRS2768 reduced plasma creatinine levels, tubular damage and inflammation, and renal apoptosis in mice subjected to renal IR. In cultured human proximal tubular HK-2 cells, MRS2768 upregulated P2Y2R mRNA levels and decreased TNF-α/cycloheximide-induced apoptosis and inflammation. Importantly, P2Y2R activation by MRS2768 increased the phosphorylation of protein kinase C (PKC), Src, and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, the inhibition of PI3K/Akt abolished the protective effects of MRS2768 against TNF-α/cycloheximide-induced apoptosis and inflammation in HK-2 cells. In conclusion, activation of P2Y2R protects against tubular apoptosis and inflammation during renal IR via the PKC/Src/Akt pathway, suggesting P2Y2R is a promising therapeutic target for acute kidney injury.

Chronic kidney disease is defined as a progressive loss of kidney function associated with impaired recovery after acute kidney injury. Renal ischemia-reperfusion (IR) induces oxidative stress and inflammatory responses leading to severe tissue damage, where incomplete or maladaptive repair accelerates renal fibrosis and aging. To investigate the role of the purinergic P2Y2 receptor (P2Y2R) in these processes, we used P2Y2R knockout (KO) mice subjected to IR. KO mice showed severe kidney dysfunction and structural damage compared to WT mice. KO mice showed higher senescence-associated β-galactosidase expression and shorter telomere length than WT mice. Consistently, interstitial collagen accumulation and fibrogenic mediators were significantly upregulated in KO mice. Renal apoptosis and inflammation were highly elevated in KO mice. Interestingly, cell proliferation as shown by Ki-67 and PCNA expression, was increased for 3 days after IR in WT mice, whereas it maintained increased for 14 days in KO mice. Cell cycle inhibitors, p16 and p21, and regulators JunB and cyclin E were significantly increased after IR in KO mice, suggesting that cell cycle progression was impaired during recovery after IR. Proximal tubular cells treated with JunB siRNA showed a reduced expression of fibrogenic mediators and proinflammatory cytokines, consistent with the mice treated with MRS2768, a P2Y2 agonist that downregulated JunB levels. In conclusion, P2Y2R reduces kidney tissue damage after IR and repairs the tissue properly by regulating JunB-mediated signaling during the recovery process.

Background/Objectives: Aging and metabolic disorders are associated with a decline in muscle function, referred to as age-related sarcopenia. The underlying mechanisms of sarcopenia include cellular senescence, imbalanced protein homeostasis, accumulation of oxidative and inflammatory stressors, and mitochondrial dysfunction. Probiotic supplementation improves the gut microbiome and enhances muscle function via the gut–muscle axis. However, details of molecular mechanisms and the development of an appropriate treatment are under active investigation. Methods: We have examined the effects of Lactiplantibacillus plantarum LM1001, a probiotic that reportedly improves the digestibility of branched-chain amino acids in myocyte cultures, but exactly how it contributes to muscle structure and function remains unclear. Results: We show that aged mice (male C57BL6/J) fed a high-fat diet (HFD) exhibit weak muscle strength, as reflected by a reduction in grip strength. LM1001 supplementation increases muscle strength and restores myofibril size, which has been altered by HFD in aged mice. Expression of myogenic proteins is increased, while protein markers for muscle atrophy are downregulated by LM1001 treatment via the IGF-1/Akt/FoxO3a pathway. LM1001 improves gut microbiota that are altered in aged HFD-fed mice, by increasing their abundance in beneficial bacteria, and efficiently maintains the epithelial lining integrity of the large intestine. Conclusions: We conclude that LM1001 supplementation serves a beneficial role in patients suffering from sarcopenia and metabolic disorders, improving their muscle function, gut microbiota, and intestinal integrity.

Diabetic nephropathy (DN) is a serious complication in diabetic patients, leading to kidney dysfunction and ultimately end-stage renal disease. Although several pharmacological agents have been developed, treating DN remains challenging due to its complex and multifaceted pathogenesis. Endoplasmic reticulum (ER) stress plays a crucial role in DN pathology; however, the molecular mechanisms underlying reduced ER stress remain poorly understood. This study investigated the protective effects of 4-phenylbutyrate (4-PBA), an ER stress inhibitor, on DN and the related regulatory molecules through gene expression network analysis. A C57BL/6 mouse model of DN was used in combination with a high-fat diet and streptozotocin after unilateral nephrectomy and treated with 4-PBA by intraperitoneal injection for 6 weeks. The 4-PBA treatment effectively improves DN-induced renal structural and functional abnormalities by reducing albuminuria, podocyte loss, glomerular and tubular injury, and renal inflammation and cell death. These changes induced by 4-PBA were associated with decreased expression of ER stress markers and increased autophagy activities in diabetic kidneys. Importantly, 4-PBA reduced components of the complement C1q pathway, the NADPH oxidase complex, and chemokines, thereby attenuating chronic renal dysfunction. Conclusively, inhibition of ER stress is a promising pharmacological target for treating patients with DN.

Geohelminthiasisremain a major public health problem, in tropical and sub-tropical regions. Though infections are prevalent among all age groups, the World Health Organization recommended strategies to control those infectionsandnow pre-school aged children are involved. This study aimed at determining the prevalence of Geohelminthsand associated risk factors among pre-school aged children attending Kabutare District hospital. A cross-sectional study was conducted at Kabutare district hospital. The pre-school aged children were selected by convenience sampling method and invited to participate in the study. Formal-ether concentration technique was employed for parasitological analysis of stool samples and structured questionnaire survey was used to gather the information related to the factors. Total of 308 pre-school aged children were recruited. The study showed that 24.4% of children were infected with one or more species of Geohelminths. A. lumbricoideswas the most prevalent soil-transmitted helminth (12.0%), followed by T. trichiura(6.5%), hookworm (2.6%) and co-infection of A. lumbricoidesand Hookworm (3.2).Geohelminthswere a public health problem among pre-school aged children in the study area necessitating deworming and developing measures to control morbidities associated with STH. Besides, the existing health education program should also be strengthened to preventre-infection in the pre-school aged children.