Precision nutrition has emerged as a promising strategy for the prevention of type 2 diabetes mellitus (T2DM) by targeting molecular pathways underlying insulin resistance and impaired glucose metabolism. Accumulating evidence indicates that dietary patterns, caloric intake, and specific nutrients can modulate gene expression and epigenetic mechanisms involved in insulin signaling, inflammation, and energy homeostasis. This narrative review synthesizes recent human and experimental studies (2025–2026) examining how dietary components influence transcriptional and epigenetic regulation of insulin signaling and glucose metabolism in the context of T2DM prevention. A total of 29 peer-reviewed studies were included, encompassing dietary patterns, macronutrient manipulation, micronutrient and bioactive supplementation, and gene–diet interactions. Very-low-calorie diets consistently induced coordinated modulation of key metabolic genes, including downregulation of glucose transporter type 4 (GLUT4) and upregulation of PDK4, CPT1, and AMPK, reflecting a metabolic shift toward enhanced fatty acid oxidation and improved insulin sensitivity. In contrast, high-fat and fructose-rich diets promoted proinflammatory gene expression and immune activation, contributing to insulin resistance. Plant-based and vegan dietary patterns were associated with reduced epigenetic aging and improved insulin sensitivity through DNA methylation changes. Targeted interventions, including vitamin D combined with probiotics, dietary fiber, nucleotides, and trace elements such as copper, further demonstrated favorable transcriptional and epigenetic effects linked to improved glycemic control. Collectively, these findings highlight diet-driven modulation of insulin signaling and glucose metabolism at the molecular level and support nutrigenomics-guided precision nutrition as a viable preventive approach for T2DM. Integrating genetic and epigenetic insights into dietary strategies may enable more personalized and effective interventions to curb the growing global burden of type 2 diabetes.

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine–metabolic disorder characterized by interconnected dysregulation of steroidogenesis and insulin signaling. Multi-target therapeutic strategies are increasingly needed to address its heterogeneous pathophysiology. Methods: An integrative approach combining transcriptomic analysis of GSE137684, including stratification of normoandrogenic and hyperandrogenic PCOS subtypes to capture androgen-related heterogeneity, network pharmacology, molecular docking, and in vitro validation was employed. Principal component analysis (PCA), differential expression analysis, and enrichment analyses were used to identify candidate genes and pathways. Molecular docking evaluated interactions between phytochemicals from Cinnamomum burmannii and Myristica fragrans and key PCOS targets. Functional validation was performed in insulin-resistant 3T3-L1 adipocytes and DHEA-induced KGN cells, assessing cell viability, lipid accumulation, glucose uptake, gene expression, and hormone levels. Results: PCA revealed partial separation between PCOS and the control samples, with PC1 and PC2 explaining 44.8% and 12.5% of variance, respectively. No genes remained significant after multiple testing correction; however, nominally significant candidates (p < 0.01) highlighted pathways related to steroidogenesis and metabolic regulation. Network analysis identified key hub genes including CYP17A1, CYP19A1, AKT1, ESR1, and MAPK1. Molecular docking demonstrated strong binding affinities, with top compounds showing binding energies up to −11.4 kcal/mol (CYP17A1) and −10.9 kcal/mol (AKT1). In vitro, cell viability remained above 80% across all tested concentrations, indicating low cytotoxicity. Treatment significantly reduced lipid accumulation and enhanced glucose uptake in insulin-resistant 3T3-L1 cells (p < 0.05). Additionally, expression of AKT1 and MAPK1 was significantly restored (p < 0.05). In KGN cells, testosterone levels were significantly decreased while the estradiol levels increased (p < 0.05), accompanied by the downregulation of CYP17A1 and upregulation of CYP19A1 (p < 0.05). The combination treatment exhibited more consistent effects across metabolic and hormonal endpoints. Conclusions:Cinnamomum burmannii and Myristica fragrans exert multi-target effects on metabolic and steroidogenic pathways relevant to PCOS. This integrative study demonstrates that transcriptomics-guided network pharmacology combined with experimental validation can identify synergistic phytotherapeutic strategies for complex endocrine disorders.

This review aims to comprehensively examine spent coffee grounds (SCGs) as a sustainable source of antioxidant and immunomodulatory bioactives, with a specific focus on their capacity to modulate membrane-level signaling through ion channels and G-protein-coupled receptors (GPCRs) in the context of lifestyle-related chronic diseases. SCGs, the major solid by-product of coffee brewing, represent an underutilized yet highly abundant source of bioactive compounds, including chlorogenic acids, phenolic acids, melanoidins, diterpenes, and residual alkaloids. Lifestyle-related chronic diseases, including type 2 diabetes, obesity, cardiovascular disease, and chronic inflammatory disorders, are increasingly recognized as immunometabolic conditions driven by persistent low-grade inflammation, redox imbalance, and dysregulated membrane signaling. This review synthesizes current evidence demonstrating that bioactives contained in SCG extracts exert antioxidant and immunomodulatory effects that extend beyond radical scavenging. Crucially, these compounds also act as modulators of membrane-level signaling, representing a mechanistic perspective that has not been previously integrated for SCGs in the context of chronic disease. The different extraction methodologies and the obtained results are evaluated with the aim to identify the most effective experimental approach and extraction conditions. The paper also discusses how SCG compounds regulate redox-sensitive ion channels (including calcium channels, TRP channels, and potassium channels), and key GPCR pathways (such as GPR120, GPR43, and adenosine receptors), thereby influencing immune cell activation, cytokine production, insulin signaling, and metabolic inflammation. Particular attention is given to the role of microbial fermentation and enzymatic processing in enhancing SCG bioavailability, generating postbiotic metabolites that further engage GPCR–ion channel crosstalk. By integrating extraction approaches, antioxidant chemistry, immunology, membrane signaling, and nutritional metabolism, this review positions SCG as a sustainable functional ingredient capable of restoring immune tolerance and metabolic homeostasis. These insights support the valorization of SCGs within the circular economy framework and highlight their potential application in next-generation immunonutrition strategies for chronic disease prevention and management.

Tauopathies, including Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal lobar degeneration with tau pathology, are unified by pathogenic tau misfolding, post-translational modification, aggregation, and network-level spread. Yet decades of drug development that predominantly pursued single nodes (e.g., one kinase, one aggregation inhibitor, one monoclonal antibody epitope) have repeatedly delivered late-stage disappointments, underscoring a central lesson: tauopathy behaves less like a linear pathway and more like a coupled system of proteostasis failure, neuroinflammation, synaptic-mitochondrial stress, and metabolic dysregulation. This review examines rhizomes (notably Zingiberaceae genera such as Curcuma, Zingiber, Alpinia, Kaempferia, and Boesenbergia) as chemically diverse “multi-target platforms” whose bioactives can engage several tau-relevant nodes simultaneously. We synthesise evidence across tau phosphorylation (GSK-3β/CDK5 and upstream stress signalling), tau aggregation and seeding, autophagy-lysosome and proteasome pathways, redox-mitochondrial resilience, neuroinflammatory circuits (NF-κB/NLRP3), and neuro-metabolic signalling (insulin-PI3K-AKT, AMPK-mTOR). A translational lens is applied throughout, focusing on drug-likeness and CNS multiparameter optimisation; BBB permeability and efflux; metabolism and bioavailability constraints; and formulation strategies (nanoparticles, phytosomes, engineered exosomes) that may render rhizome-derived scaffolds more clinically plausible. We conclude that rhizomes offer credible mechanistic hypotheses for tau modulation, but progress depends on rigorous standardisation, realistic exposure matching, biomarker-driven study design, and a shift from “single-compound optimism” to network pharmacology with translational discipline.

Polysaccharide-based bioactive materials have emerged as versatile and biocompatible platforms at the intersection of pharmacy, biomedicine, and engineering, offering innovative solutions for complex diseases such as diabetes. In this comprehensive review, we discuss the translational design of polysaccharide-based biomaterials (spanning smart drug delivery systems, 3D scaffolds, and injectable hydrogels), elucidate their mechanistic insights in therapeutic contexts, and evaluate their clinical prospects, with a particular focus on diabetes management. Evidence from recent studies indicates that polysaccharide carriers can enable controlled and stimulus-responsive delivery of anti-diabetic agents (e.g. insulin, GLP-1 analogs), enhance tissue engineering approaches for diabetic wound healing and pancreatic islet transplantation, and even exert direct anti-hyperglycemic effects by modulating biological pathways. Mechanistically, these polymers can mimic extracellular matrix functions, promote cell adhesion and angiogenesis, modulate immune responses, and respond to physiological triggers (such as glucose or pH) to release therapeutics on-demand. Clinically, polysaccharide-based hydrogels (e.g. alginate and hyaluronic acid dressings) are already in use or trials for chronic wounds, and encapsulated-cell therapies are being explored to improve glycemic control without immunosuppression. Ongoing interdisciplinary research and numerous clinical studies underscore the translational potential of these bioactive materials in improving outcomes for diabetes and related complications. The future outlook is optimistic, as polysaccharide biomaterials continue to advance toward smarter, more personalized medicine, bridging the gap from bench to bedside. Graphical abstract The alternative text for this image may have been generated using AI.

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex, multi-system disorder involving interactions among metabolic dysfunction, chronic low-grade inflammation, and neuroendocrine dysregulation, rather than a condition confined to the ovary. While current management strategies primarily target symptomatic manifestations, such as menstrual irregularity, hyperandrogenism, and insulin resistance, they do not directly address the underlying integrative pathways linking the gut microbiome, cellular energy sensing, and hypothalamic reproductive control. This review proposes a mechanistic framework in which algae-derived bioactives modulate a gut–SIRT1–kisspeptin axis, thereby offering a systems-level perspective on PCOS pathophysiology and intervention. Gut dysbiosis in PCOS contributes to altered bile acid signaling, disrupted microbial metabolite profiles, and increased inflammatory tone, all of which may impair both metabolic and reproductive functions. Concurrently, reduced activity of the NAD⁺-dependent deacetylase SIRT1 has been documented across ovarian, endometrial, and metabolic tissues, linking energy imbalance to oxidative stress, inflammation, and impaired steroidogenesis. At the neuroendocrine level, dysregulated kisspeptin signaling contributes to abnormal gonadotropin-releasing hormone pulsatility and luteinizing hormone hypersecretion, key features of PCOS. Algae-derived compounds, including polysaccharides, phlorotannins, fucoidan, fucoxanthin, and microalgae bioactives, exhibit prebiotic, anti-inflammatory, and metabolic regulatory properties that intersect with these pathways, particularly through modulation of gut microbiota and activation of AMPK/SIRT1 signaling. The central proposition of this review is that algae-derived bioactives may act across interconnected biological layers: reshaping gut microbial ecology, restoring SIRT1-mediated metabolic balance, and retuning kisspeptin-driven neuroendocrine activity. While individual components of this axis are supported by substantial evidence, direct experimental validation of the complete pathway remains limited. Therefore, this framework is positioned as a translationally grounded but hypothesis-driven model that integrates currently fragmented findings into a coherent and testable paradigm. Future research should prioritize multi-level experimental and clinical studies that simultaneously assess microbiota composition, metabolic signaling, and reproductive neuroendocrine outcomes to establish the therapeutic potential of algae-based interventions in PCOS.