Diabetes-induced muscle wasting: molecular mechanisms and promising therapeutic targets.

Diabetes has become a serious public health crisis, presenting significant challenges to individuals worldwide. As the largest organ in the human body, skeletal muscle is a significant target of this chronic disease, yet muscle wasting as a complication of diabetes is still not fully understood and effective treatment methods have yet to be developed. Here, we discuss the targets involved in inducing muscle wasting under diabetic conditions, both validated targets and emerging targets. Diabetes-induced skeletal muscle wasting is known to involve changes in various signaling molecules and pathways, such as protein degradation pathways, protein synthesis pathways, mitochondrial function, and oxidative stress inflammation. Recent studies have shown that some of these present potential as promising therapeutic targets, including the neuregulin 1/epidermal growth factor receptor family, advanced glycation end-products, irisin, ferroptosis, growth differentiation factor 15 and more. This study's investigation and discussion of such pathways and their potential applications provides a theoretical basis for the development of clinical treatments for diabetes-induced muscle wasting and a foundation for continued focus on this disease.

Dietary Isoeugenol Supplementation Attenuates Chronic UVB-Induced Skin Photoaging and Modulates Gut Microbiota in Mice.

Photoaging, the primary cause of skin aging damage, results from chronic ultraviolet (UV) exposure, leading to dryness and wrinkle formation. Nutritional intervention has emerged as a practical approach for preventing and addressing the effect of skin photoaging. The primary aromatic compound isolated from clove oil, isoeugenol (IE), has antibacterial, anti-inflammatory, and antioxidant qualities that work to effectively restrict skin cancer cell proliferation. This investigation delved into the advantages of IE in alleviating skin photoaging using UVB-irradiated skin fibroblasts and female SKH-1 hairless mouse models. IE alleviated UVB-induced photodamage in Hs68 dermal fibroblasts by inhibiting matrix metalloproteinase secretion and promoting extracellular matrix synthesis. In photoaged mice, dietary IE reduced wrinkles, relieved skin dryness, inhibited epidermal thickening, and prevented collagen loss. Additionally, the intestinal dysbiosis caused by prolonged UVB exposure was reduced with an IE intervention. The results of Spearman's analysis showed a strong correlation between skin photoaging and gut microbiota. Given the almost unavoidable UVB exposure in contemporary living, this research demonstrated the efficacy of dietary IE in reversing skin photoaging, presenting a promising approach to tackle concerns related to extrinsic skin aging.

Dietary supplementation with α-ionone alleviates chronic UVB exposure-induced skin photoaging in mice.

Photoaging is widely regarded as the most significant contributor to skin aging damage. It is triggered by prolonged exposure to ultraviolet (UV) light and typically manifests as dryness and the formation of wrinkles. Nutritional intervention is a viable strategy for preventing and treating skin photoaging. In previous studies, we demonstrated that α-ionone had ameliorating effects on photoaging in both epidermal keratinocytes and dermal fibroblasts. Here, we investigated the potential anti-photoaging effects of dietary α-ionone using a UVB-irradiated male C57BL/6N mouse model. Our findings provided compelling evidence that dietary α-ionone alleviates wrinkle formation, skin dryness, and epidermal thickening in chronic UVB-exposed mice. α-Ionone accumulated in mouse skin after 14 weeks of dietary intake of α-ionone. α-Ionone increased collagen density and boosted the expression of collagen genes, while attenuating the UVB-induced increase of matrix metalloproteinase genes in the skin tissues. Furthermore, α-ionone suppressed the expression of senescence-associated secretory phenotypes and reduced the expression of the senescence marker p21 and DNA damage marker p53 in the skin of UVB-irradiated mice. Transcriptome sequencing results showed that α-ionone modifies gene expression profiles of skin. Multiple pathway enrichment analyses on both the differential genes and the entire genes revealed that α-ionone significantly affects multiple physiological processes and signaling pathways associated with skin health and diseases, of which the p53 signaling pathway may be the key signaling pathway. Taken together, our findings reveal that dietary α-ionone intervention holds promise in reducing the risks of skin photoaging, offering a potential strategy to address skin aging concerns.

Revitalizing Photoaging Skin through Eugenol in UVB-Exposed Hairless Mice: Mechanistic Insights from Integrated Multi-Omics.

Chronic ultraviolet (UV) exposure causes photoaging, which is primarily responsible for skin damage. Nutritional intervention is a viable strategy for preventing and treating skin photoaging. Eugenol (EU) presents anti-inflammatory and antioxidant properties, promotes wound healing, and provides contact dermatitis relief. This study explored the ability of EU to mitigate skin photoaging caused by UVB exposure in vitro and in vivo. EU alleviated UVB-induced skin photodamage in skin cells, including oxidative stress damage and extracellular matrix (ECM) decline. Dietary EU alleviated skin photoaging by promoting skin barrier repair, facilitating skin tissue regeneration, and modulating the skin microenvironment in photoaged mice. The transcriptome sequencing results revealed that EU changed the skin gene expression profiles. Subsequent pathway enrichment analyses indicated that EU might reverse the pivotal ECM-receptor interaction and cytokine-cytokine receptor interaction signaling pathways. Furthermore, EU alleviated the intestinal dysbiosis induced by chronic UVB exposure. Spearman analysis results further revealed the close connection between gut microbiota and skin photoaging. Considering the near-inevitable UVB exposure in modern living, the findings showed that the EU effectively reverted skin photoaging, offering a potential strategy for addressing extrinsic skin aging.

Oleuropein Supplementation Ameliorates Long-Course Diabetic Nephropathy and Diabetic Cardiomyopathy Induced by Advanced Stage of Type 2 Diabetes in db/db Mice.

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of diabetic nephropathy and diabetic cardiomyopathy. However, the efficacy of OP on the long-course of these diabetes complications has not been investigated. Therefore, in this study, to investigate the relieving effects of OP intake on these diseases, and to explore the underlying mechanisms, db/db mice (17-week-old) were orally administrated with OP (200 mg/kg bodyweight) for 15 weeks. We found that OP reduced expansion of the glomerular mesangial matrix, renal inflammation, renal fibrosis, and renal apoptosis. Meanwhile, OP treatment exerted cardiac anti-fibrotic, anti-inflammatory, and anti-apoptosis effects. Notably, transcriptomic and bioinformatic analyses indicated 290 and 267 differentially expressed genes in the kidney and heart replying to OP treatment, respectively. For long-course diabetic nephropathy, OP supplementation significantly upregulated the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. For long-course diabetic cardiomyopathy, p53 and cellular senescence signaling pathways were significantly downregulated in response to OP supplementation. Furthermore, OP treatment could significantly upregulate the transcriptional expression of the ATPase Na+/K+ transporting subunit alpha 3, which was enriched in the cGMP-PKG signaling pathway. In contrast, OP treatment could significantly downregulate the transcriptional expressions of cyclin-dependent kinase 1, G two S phase expressed protein 1, and cyclin B2, which were enriched in p53 and cellular senescence signal pathways; these genes were confirmed by qPCR validation. Overall, our findings demonstrate that OP ameliorated long-course diabetic nephropathy and cardiomyopathy in db/db mice and highlight the potential benefits of OP as a functional dietary supplement in diabetes complications treatment.

Enhanced Survival with Lymphadenectomy in Early-Stage Metachronous Second Primary Lung Cancer: A Retrospective Analysis.

INTRODUCTION: Lymphadenectomy is a cornerstone in the surgical management of resectable primary lung cancer. However, its prognostic significance in early-stage metachronous second primary lung cancer (MSPLC) remains poorly understood. This retrospective study aimed to evaluate the prognostic impact of lymphadenectomy in these patients using data from the Surveillance, Epidemiology, and End Results (SEER) Database. METHODS: A retrospective cohort study was conducted using data from the SEER Database for patients surgically treated for stage I MSPLC between 2004 and 2015. Propensity score-matching was employed to create comparable cohorts, and the Cox proportional hazards model was utilized to estimate the hazard ratio (HR) for overall survival after lymphadenectomy compared to non-lymphadenectomy. Survival analysis was performed using Kaplan-Meier curves and the log-rank test. RESULTS: Among 920 identified patients with MSPLC, 574 (62.4%) underwent lymphadenectomy. Propensity score-matching yielded 255 patients in both the lymphadenectomy and non-lymphadenectomy groups. Over a median follow-up of 38 months, the 5-year overall survival probability after a diagnosis of MSPLC was 58.7% in the lymphadenectomy group and 43.9% in the non-lymphadenectomy group (HR: 0.76; 95% confidence interval 0.64-0.90; p = 0.002). CONCLUSION: In this population-based study, lymphadenectomy is associated with prolonged overall survival in patients with stage I MSPLC. These findings suggest the potential benefit of incorporating lymphadenectomy into the surgical management of MSPLC, providing valuable guidance for thoracic surgeons in clinical decision-making.