Cognitive frailty, characterized by the coexistence of physical frailty and cognitive impairment, has emerged as a major challenge in aging populations and is closely linked to sarcopenia, neurodegeneration, and chronic inflammation. Increasing evidence suggests that the gut microbiota acts as a central regulator of neuromuscular and neurocognitive aging through the integrated gut–brain–muscle axis. This review highlights how microbial dysbiosis, reduced short-chain fatty acid (SCFA) production, systemic endotoxemia, and altered microbial metabolites contribute to mitochondrial dysfunction, neuroinflammation, anabolic resistance, and impaired neuroplasticity. Key signaling mediators, including SCFAs, bile acids, tryptophan-derived metabolites, cytokines, and myokines such as irisin, brain-derived neurotrophic factor (BDNF), and cathepsin B, orchestrate bidirectional communication among the gut, skeletal muscle, and brain. We further discuss the role of exercise-induced microbiota remodeling and muscle endocrine signaling in promoting mitochondrial biogenesis and cognitive resilience. In addition, emerging translational strategies including probiotics, prebiotics, postbiotics, polyphenol-rich functional foods, marine bioactives, and precision nutrition are explored as potential interventions targeting this axis. Collectively, the gut–brain–muscle axis provides a novel systems biology framework for understanding cognitive frailty and developing integrated therapeutic strategies for healthy longevity.

Prediabetes is increasingly recognized as a risk factor for sarcopenia, driven by chronic low-grade inflammation, insulin resistance, and impaired anabolic signaling. Nutritional interventions containing whey protein, hydroxymethylbutyrate (HMB), glucosamine, and micronutrients may offer a multi-target strategy to counteract muscle deterioration. This study aimed to evaluate the efficacy of HiLo Platinum™ supplementation in attenuating muscle strength decline in a prediabetic rat model, with integrated analysis of metabolic biomarkers and gut microbiome profiles. A randomized preclinical trial was conducted using male Sprague Dawley rats assigned to four groups: normal diet (ND), prediabetic control induced by cholesterol- and fat-enriched diet with fructose (CFEDF), and two treatment groups receiving low-dose (0.63 g/kg BW) or high-dose (1.26 g/kg BW) HiLo Platinum™. The intervention lasted six weeks. Muscle strength was assessed via a four-limb grip strength test (reverse hang time and holding impulse). Biomarkers related to inflammation, mitochondrial function, and anabolic signaling (TNF-α, IL-10, PGC-1α, IGF-1, SIRT-1, AMPK, mTOR, and myostatin), lipid profile, and blood glucose were analyzed. Gut microbiome composition and diversity were evaluated using taxonomic profiling and multivariate analyses. HiLo Platinum™ supplementation significantly improved muscle strength, evidenced by increased reverse hang time and holding impulse (p < 0.001). Both doses reduced blood glucose and improved lipid profiles, including increased HDL and decreased LDL, triglycerides, and total cholesterol. Anti-inflammatory effects were observed with reduced TNF-α and elevated IL-10 levels. Mitochondrial and metabolic regulators (PGC-1α, SIRT-1, AMPK) and anabolic mediators (IGF-1) were significantly upregulated, while mTOR levels decreased. Gut microbiome analysis revealed increased genus richness (Chao1 index) and distinct microbial shifts associated with improved metabolic and inflammatory markers. HiLo Platinum™ effectively mitigates prediabetes-induced muscle strength decline through integrated modulation of inflammatory pathways, mitochondrial function, metabolic homeostasis, and gut microbiome composition. These findings support its potential as a nutritional therapeutic strategy for preventing sarcopenia in prediabetic conditions, although further studies are needed to evaluate long-term effects and implications on muscle hypertrophy.

Osteosarcoma remains the most common primary malignant bone tumor in adolescents and is characterized by aggressive metastasis, resistance to therapy, and extensive bone microenvironment remodeling. Therefore, the identification of novel multi-target therapeutic agents capable of simultaneously inducing ferroptosis and disrupting tumor-supportive signaling is urgently needed. This study employed a multi-omics-guided approach to investigate the anti-osteosarcoma potential of metabolites derived from the sea cucumber Holothuria scabra. LC–MS/MS profiling identified major bioactive constituents, including holothurins, scabrasides, fucosterol, desmosterol, and 24-methylenecholesterol. Integrated transcriptomic analysis of the GSE42352 dataset revealed key ferroptosis- and bone microenvironment-associated targets, including CXCR4, CTSK, RUNX2, VEGFA, and TFRC. In silico pharmacological prediction and molecular docking demonstrated favorable anticancer properties and strong binding affinities of several metabolites toward these targets, with fucosterol and holothurin A exhibiting the most promising interactions. Functional validation in MG-63 osteosarcoma cells showed concentration-dependent reductions in cell viability and migration following H. scabra treatment. Furthermore, treatment decreased GPX4, NRF2, and GSH levels while increasing TFRC and MDA, indicating activation of ferroptotic cell death. In a MG-63/RAW264.7 co-culture model, H. scabra suppressed RANKL, VEGFA, MMP9, and TRAP-positive osteoclast formation, suggesting inhibition of osteoclastogenesis, angiogenesis, and metastatic potential. Collectively, these findings identify H. scabra as a promising marine source of multi-target compounds for osteosarcoma management through coordinated induction of ferroptosis and remodeling of the bone tumor microenvironment.

Introduction: Cleft lip with or without cleft palate requires timely surgical management to optimize feeding, speech development, and facial growth. In archipelagic regions, geographic isolation and limited healthcare infrastructure may delay access to specialized cleft care. Hospital ship–based outreach programs have emerged as an alternative strategy to deliver surgical services to underserved island communities. This report presents a descriptive case series of cleft lip repairs performed during a hospital ship mission in remote islands of South Sulawesi, Indonesia. Case Presentation: Two patients with untreated cleft lip deformities were identified during surgical screening conducted as part of a hospital ship outreach mission. Both presented in adolescence or adulthood after prolonged delays in accessing definitive treatment. Cleft lip repair using a modified Millard rotation–advancement technique was performed under general anesthesia. Early postoperative outcomes were assessed based on surgical complications and scar evaluation. Postoperative follow-up was limited to 7 days. Conclusion: Hospital ship–based cleft lip repair may represent a feasible approach to delivering surgical care in remote island settings. However, evidence remains limited to early postoperative outcomes, and further studies with larger cohorts and standardized long-term follow-up are needed to evaluate functional and aesthetic results.