Search Results (178)

Sustained abiotic stress severely impairs fruit crop growth and development. As plants’ primary environmental sensing organ, fruit tree roots experience disrupted morphogenesis and physiological functions, reducing yield, lowering fruit quality, and threatening orchard ecosystem stability. Abiotic stress is diverse: water deficit from drought, extreme temperature fluctuations, and salinization-induced ion imbalance, heavy metal accumulation, or nutrient disorders. Its complexity requires synergistic and crosstalk regulation of multiple root-specific signaling modules and pathways in root stress perception and transduction. When responding to stress, roots activate hormone, reactive oxygen species (ROS), and calcium ion (Ca²⁺) signaling. These pathways mediate early stress recognition and regulate downstream gene expression and physiological metabolic reprogramming via transcription factors (TFs) and other regulators, determining stress tolerance and adaptability. Using typical abiotic stresses as models, this review outlines the composition, activation mechanisms, specificity, and synergistic effects of root-specific signaling modules/pathways, along with modern biotechnologies for decoding these modules and current research limitations, aiming to reveal the root signal network’s integration mode. Full article

Berberine (BBR), a protoberberine alkaloid with a long history of medicinal use, has consistently demonstrated benefits in glucose–lipid metabolism and inflammatory balance across both preclinical and human studies. These diverse effects are not mediated by a single molecular target but by BBR’s capacity to restore network coordination among metabolic, immune, and microbial systems. At the core of this regulation is an AMP-activated Protein Kinase (AMPK)-centered mechanistic hub, integrating signals from insulin and nutrient sensing, Sirtuin 1/3 (SIRT1/3)-mediated mitochondrial adaptation, and inflammatory pathways such as nuclear Factor Kappa-light-chain-enhancer of Activated B cells (NF-κB) and NOD-, LRR- and Pyrin Domain-containing Protein 3 (NLRP3). This hub is dynamically regulated by system-level inputs from the gut, mitochondria, and epigenome, which in turn strengthen intestinal barrier function, reshape microbial and bile-acid metabolites, improve redox balance, and potentially reverse the epigenetic imprint of metabolic stress. These interactions propagate through multi-organ axes, linking the gut, liver, adipose, and vascular systems, thus aligning local metabolic adjustments with systemic homeostasis. Within this framework, BBR functions as a negentropic modulator, reducing metabolic entropy by fostering a coordinated balance among these interconnected systems, thereby restoring physiological order. Combination strategies, such as pairing BBR with metformin, Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors, and agents targeting the microbiome or inflammation, have shown enhanced efficacy and substantial translational potential. Berberine ursodeoxycholate (HTD1801), an ionic-salt derivative of BBR currently in Phase III trials and directly compared with dapagliflozin, exemplifies the therapeutic promise of such approaches. Within the hub–axis paradigm, BBR emerges as a systems-level modulator that recouples energy, immune, and microbial circuits to drive multi-organ remodeling. Full article

Cystinosis is a rare lysosomal storage disorder characterized by defective cystine transport and progressive multi-organ damage, with the kidney being the primary site of pathology. In addition to the traditional perspective on lysosomal dysfunction, recent studies have demonstrated that cystinosis exerts a substantial impact on cellular energy metabolism, with a particular emphasis on oxidative pathways. Mitochondria, the central hub of ATP production, exhibit structural abnormalities, impaired oxidative phosphorylation, and increased reactive oxygen species. These factors contribute to proximal tubular cell failure and systemic complications. This review highlights the critical role of energy metabolism in cystinosis and supports the emerging idea of organelle communication. A mounting body of evidence points to a robust functional and physical association between lysosomes and mitochondria, facilitated by membrane contact sites, vesicular trafficking, and signaling networks that modulate nutrient sensing, autophagy, and redox balance. Disruption of these interactions in cystinosis leads to defective mitophagy, accumulation of damaged mitochondria, and exacerbation of oxidative stress, creating a vicious cycle of energy failure and cellular injury. A comprehensive understanding of these mechanisms has the potential to reveal novel therapeutic avenues that extend beyond the scope of cysteamine, encompassing strategies that target mitochondrial health, enhance autophagy, and restore lysosome–mitochondria communication. Full article

This study prepared oregano essential oil-loaded liposomes (OEO-Lip) and systematically evaluated their physicochemical properties, stability, and antioxidant/antibacterial activities, along with the underlying mechanisms. Characterization revealed OEO-Lip exhibited a unilamellar vesicle structure with a particle size of approximately 190 nm, uniform dispersion (PDI = 0.183), a high zeta potential (−39.8 mV), and an encapsulation efficiency of 77.52%. Analyses by FT-IR, XRD, and DSC confirmed the successful encapsulation of OEO within the liposomes. Hydrogen bonding interactions with phospholipid components promoted the formation of a more ordered crystalline structure, thereby enhancing thermal stability. Storage stability tests demonstrated that OEO-Lip stored at 4 °C for 30 days exhibited significantly superior physicochemical properties compared to samples stored at 25 °C. Furthermore, liposomal encapsulation effectively preserved the antioxidant activity of OEO. Antimicrobial studies revealed that OEO-Lip exerted stronger and more sustained inhibitory effects against Escherichia coli and Staphylococcus aureus than free OEO, primarily by disrupting bacterial membrane integrity and inducing the leakage of ions and intracellular contents. Transcriptomic analysis further indicated that OEO-Lip exerts synergistic antibacterial effects by downregulating genes associated with phospholipid synthesis and nutrient transport while concurrently interfering with multiple pathways, including quorum sensing and energy metabolism. Release experiments indicated that OEO-Lip displays both burst and sustained release characteristics. In summary, OEO-Lip serves as an efficient delivery system that significantly enhances the stability and antibacterial efficacy of OEO, demonstrating considerable potential for application in food preservation. Full article

Type 2 diabetes mellitus (T2D) affects hundreds of millions worldwide, with recent estimates indicating approximately 589 million adults living with diabetes, most with type 2 disease. Beyond classical insulin signaling pathways, increasing evidence implicates altered protein glycosylation in metabolic dysfunction. The solute carrier 35 (SLC35) family of nucleotide sugar transporters mediates the import of activated sugars into the endoplasmic reticulum and Golgi lumen, thereby influencing global glycosylation patterns. Dysregulation of these transporters can perturb glucose homeostasis, insulin responsiveness, and nutrient-sensing pathways through changes in glycosylation flux. In this review, we dissect the molecular mechanisms by which these transporters modulate glucose homeostasis, insulin signaling pathways, protein O-GlcN acylation, and broader glycosylation processes. We integrate findings from human genetic studies, rodent models, and in vitro functional analyses to characterize how altered SLC35 activity is associated with T2D and metabolic syndrome. Four members demonstrate particularly compelling evidence: SLC35B4 modulates hepatic glucose metabolism, SLC35D3 mutations impair dopaminergic signaling and energy balance, and SLC35F3 variants interact with high-carbohydrate intake to increase metabolic-syndrome risk. SLC35A3, though less studied, may influence glycosylation-dependent insulin signaling through its role in N-glycan biosynthesis. Beyond these characterized transporters, this review identifies potential metabolic roles for understudied family members, suggesting broader implications across the entire SLC35 family. We also discuss how such alterations can lead to disrupted hexosamine flux, impaired glycoprotein processing, aberrant cellular signaling, and micronutrient imbalances. Finally, we evaluate the therapeutic potential of targeting SLC35 transporters, outlining both opportunities and challenges in translating these insights into novel T2D treatments. Full article

Background: Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and are strongly influenced by dietary habits. Beyond caloric intake, nutrients act as molecular signals that regulate cardiac metabolism, mitochondrial function, inflammation, and epigenetic remodeling. Objectives: This review aims to synthesize current evidence on how dietary patterns and specific nutritional interventions regulate cardiac metabolism and function through interconnected molecular and epigenetic mechanisms, highlighting their relevance for cardiovascular disease prevention. Methods: A narrative review of the literature was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2006 and 2025. Experimental, translational, and clinical studies addressing diet-induced modulation of cardiac metabolic pathways, oxidative and inflammatory signaling, epigenetic regulation, and gut microbiota-derived metabolites were included. Results: The analyzed literature consistently shows that unbalanced diets rich in saturated fats and refined carbohydrates impair cardiac metabolic flexibility by disrupting key nutrient-sensing pathways, including AMP-activated protein kinase (AMPK), proliferator-activated receptor alpha (PPARα), mammalian target of rapamycin (mTOR), and sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (SIRT1/PGC-1α), leading to mitochondrial dysfunction, oxidative stress, chronic inflammation, and maladaptive remodeling. In contrast, cardioprotective dietary patterns, such as caloric restriction (CR), intermittent fasting (IF), and Mediterranean and plant-based diets, enhance mitochondrial efficiency, redox balance, and metabolic adaptability. These effects are mediated by coordinated activation of AMPK-SIRT1 signaling, suppression of mTOR over-activation, modulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways, and favorable epigenetic remodeling involving DNA methylation, histone modifications, and non-coding RNAs. Emerging evidence also highlights the central role of gut microbiota-derived metabolites, particularly short-chain fatty acids, in linking diet to epigenetic and metabolic regulation of cardiac function. Conclusions: Diet quality emerges as a key determinant of cardiac metabolic health, acting through integrated molecular, epigenetic, and microbiota-mediated mechanisms. Targeted nutritional strategies can induce long-lasting cardioprotective metabolic and epigenetic adaptations, supporting the concept of diet as a modifiable molecular intervention. These findings provide a mechanistic rationale for integrating personalized nutrition into cardiovascular prevention and precision cardiology, complementing standard pharmacological therapies. Full article

Lake eutrophication exhibits pronounced spatial heterogeneity at the watershed scale, yet a systematic and quantitative understanding of how landscape characteristics drive these variations remains limited. In this study, a long-term and internally consistent trophic state dataset for the Liangzi Lake Basin was constructed by integrating Landsat imagery from 1990 to 2022 with a semi-analytical water color inversion method. A multi-scale landscape feature system incorporating both land use composition and landscape pattern metrics was developed at the sub-basin level to elucidate the mechanisms by which landscape characteristics influence eutrophication dynamics. The XGBoost model was employed to characterize the nonlinear relationships between landscape attributes and trophic conditions, while the SHAP interpretability approach was applied to quantify the relative contribution of individual landscape components and their interaction pathways. The analytical framework demonstrates that landscape pattern attributes—such as fragmentation, diversity, and connectivity—play essential roles in shaping the spatial variability of eutrophication by modulating hydrological processes, nutrient transport, and ecological buffering capacity. By integrating remote sensing observations with interpretable machine learning, the study reveals the complexity and scale dependence of landscape–water interactions, providing a methodological foundation for advancing the understanding of eutrophication drivers. The findings offer theoretical guidance and practical references for optimizing watershed landscape planning, controlling non-point source pollution, and supporting ecological restoration efforts in lake basins. Full article

Pancreatic β-cells are metabolically active endocrine cells with a high oxygen demand to sustain glucose-stimulated insulin secretion (GSIS). Hypoxia, arising from vascular disruption, islet isolation, or pathological states such as type 2 diabetes (T2D) and obstructive sleep apnoea (OSA), is a potent metabolic stressor that impairs β-cell function, survival, and differentiation. At the molecular level, hypoxia-inducible factors (HIF-1α and HIF-2α) orchestrate transcriptional programs that shift β-cell metabolism from oxidative phosphorylation to glycolysis, modulate mitochondrial function, and regulate survival pathways such as autophagy and mitophagy. Crosstalk with nutrient-sensing mechanisms, redox regulation, growth factor signaling, and protein synthesis control further shapes adaptive or maladaptive outcomes. Hypoxia alters glucose, lipid, and amino acid metabolism, while mitochondrial dysfunction, oxidative stress, and inflammatory signaling contribute to progressive β-cell failure. Therapeutic strategies including incretin hormones, GABAergic signaling, erythropoietin, ChREBP inhibition, and activation of calcineurin–NFAT or oxygen-binding globins—offer potential to preserve β-cell viability under hypoxia. In islet transplantation, oxygen delivery technologies, ischemic preconditioning, mesenchymal stem cell–derived exosomes, and encapsulation systems show promise in mitigating hypoxic injury and improving graft survival. This review synthesizes current knowledge on β-cell responses to hypoxic stress, with emphasis on metabolic reprogramming, molecular signaling, and translational interventions, underscoring that targeted modulation of β-cell metabolism and oxygen handling can enhance resilience to hypoxia and improve outcomes in diabetes therapy and islet transplantation. Full article

Insulin resistance, dyslipidemia, hypertension, and visceral adiposity are the leading causes of the growing worldwide health burden associated with metabolic syndrome, obesity, and cardiovascular diseases (CVDs). Despite the “obesity paradox,” which emphasizes the varied cardiovascular outcomes among obese people, obesity is now acknowledged as an active contributor to cardiometabolic dysfunction through endocrine, inflammatory, and metabolic pathways. Growing evidence indicates that nutrition is a key determinant of cardiometabolic risk, highlighting the need to understand diet-mediated mechanisms linking adipose tissue to cardiac function. Adipokines, including adiponectin, leptin, TNF-α, and resistin, which regulate systemic inflammation, metabolic homeostasis, and myocardial physiology, are secreted by adipose tissue, which is no longer thought of as passive energy storage. Its heterogeneous phenotypes, white, brown, and beige adipose tissue, exhibit distinct metabolic profiles that influence cardiac energetics and inflammatory status. Nutrient-driven transitions between these phenotypes further underscore the intricate interplay between diet, adipose biology, and cardiac metabolism. Central nutrient-sensing pathways, including mTOR, AMPK, SIRT1, PPAR-γ, and LKB1, integrate macronutrient and micronutrient signals to regulate adipose tissue remodeling and systemic metabolic flexibility. These pathways interact with hormonal mediators such as insulin, leptin, and adiponectin, forming a complex regulatory network that shapes the adipose-cardiac axis. This review synthesises current knowledge on how nutrient inputs modulate adipose tissue phenotypes and signaling pathways to influence cardiac function. By elucidating these mechanisms, we highlight emerging opportunities for precision nutrition and targeted therapeutics to restore metabolic balance, strengthen cardiac resilience, and reduce the burden of cardiometabolic disease. Full article

Obesity remains a major global health challenge, with glucagon-like peptide-1 receptor agonists (GLP-1RAs) providing substantial yet sensitive benefits in weight reduction, glycemic control, and cardiovascular protection. Despite robust trial data, real-world persistence is limited by cost, tolerability, and hedonic adaptation. Intermittent fasting and time-restricted eating offer physiologically complementary, low-cost strategies that enhance fat oxidation, insulin sensitivity, and metabolic flexibility while engaging behavioral mechanisms of self-control and dietary regularity. This narrative review synthesizes current evidence and proposes a pragmatic, phased framework integrating GLP-1RA therapy with structured intermittent fasting and protein-optimized nutrition. The model emphasizes sequential initiation, transition, and maintenance phases designed to align pharmacologic appetite suppression with lifestyle-driven metabolic remodeling. Mechanistically, GLP-1RAs target vascular and neuroendocrine pathways, whereas fasting activates nutrient-sensing networks (AMPK, mTOR, sirtuins) associated with autophagy and longevity. Combined application may preserve lean mass, improve psychological autonomy, and reduce healthcare costs. Future research should validate this hybrid strategy in randomized trials assessing long-term weight durability, functional outcomes, and cost-effectiveness. By uniting pharmacologic potency with behavioral sustainability, phased GLP-1–fasting integration may represent an effective, affordable, and longevity-oriented paradigm for metabolic health. Full article

The pursuit of youth and longevity has accompanied human societies for millennia, evolving from mythological and esoteric traditions toward a scientific understanding of aging. Early concepts such as Greek ambrosia, Taoist elixirs, and medieval “aqua vitae” reflected symbolic or spiritual interpretations. A major conceptual transition occurred between the late nineteenth and early twentieth centuries, when aging began to be framed as a biological process. Pioneering ideas by Metchnikoff, together with early and sometimes controversial attempts such as Voronoff’s grafting experiments, marked the first efforts to rationalize aging scientifically. In the mid-twentieth century, discoveries including the Hayflick limit, telomere biology, oxidative stress, and mitochondrial dysfunction established gerontology as an experimental discipline. Contemporary geroscience integrates these insights into a coherent framework linking cellular pathways to chronic disease risk. Central roles are played by nutrient-sensing networks such as mTOR, AMPK, and sirtuins, together with mitochondrial regulation, proteostasis, and cellular senescence. Interventions, including caloric restriction, fasting-mimicking diets, rapalogues, sirtuin activators, metformin, NAD⁺ boosters, senolytics, and antioxidant combinations such as GlyNAC, show consistent benefits across multiple model organisms, with early human trials reporting improvements in immune function, mitochondrial activity, and biomarkers of aging. Recent advances extend to epigenetic clocks, multi-omic profiling, gender-specific responses, and emerging regenerative and gene-based approaches. Overall, the evolution from historical elixirs to molecular geroscience highlights a shift toward targeting aging itself as a modifiable biological process and outlines a growing translational landscape aimed at extending healthspan and reducing age-related morbidity. Full article

This article aims to point out new perspectives opened by genomics and epigenomics in skin rejuvenation strategies which target the main hallmarks of the ageing. In this respect, this article presents a concise overview on: the clinical relevance of the most important clocks and biomarkers used in skin anti-ageing strategy evaluation, the fundamentals, the main illustrating examples preclinically and clinically tested, the critical insights on knowledge gaps and future research perspectives concerning the most relevant skin anti-ageing and rejuvenation strategies based on novel epigenomic and genomic acquisitions. Thus the review dedicates distinct sections to: senolytics and senomorphics targeting senescent skin cells and their senescent-associated phenotype; strategies targeting genomic instability and telomere attrition by stimulation of the deoxyribonucleic acid (DNA) repair enzymes and proteins essential for telomeres’ recovery and stability; regenerative medicine based on mesenchymal stem cells or cell-free products in order to restore skin-resided stem cells; genetically and chemically induced skin epigenetic partial reprogramming by using transcription factors or epigenetic small molecule agents, respectively; small molecule modulators of DNA methylases, histone deacetylases, telomerases, DNA repair enzymes or of sirtuins; modulators of micro ribonucleic acid (miRNA) and long-non-coding ribonucleic acid (HOTAIR’s modulators) assisted or not by CRISPR-gene editing technology (CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats); modulators of the most relevant altered nutrient-sensing pathways in skin ageing; as well as antioxidants and nanozymes to address mitochondrial dysfunctions and oxidative stress. In addition, some approaches targeting skin inflammageing, altered skin proteostasis, (macro)autophagy and intercellular connections, or skin microbiome, are very briefly discussed. The review also offers a comparative analysis among the newer genomic/epigenomic-based skin anti-ageing strategies vs. classical skin rejuvenation treatments from various perspectives: efficacy, safety, mechanism of action, evidence level in preclinical and clinical data and regulatory status, price range, current limitations. In these regards, a concise overview on senolytic/senomorphic agents, topical nutrigenomic pathways’ modulators and DNA repair enzymes, epigenetic small molecules agents, microRNAs and HOTAIRS’s modulators, is illustrated in comparison to classical approaches such as tretinoin and peptide-based cosmeceuticals, topical serum with growth factors, intense pulsed light, laser and microneedling combinations, chemical peels, botulinum toxin injections, dermal fillers. Finally, the review emphasizes the future research directions in order to accelerate the clinical translation of the (epi)genomic-advanced knowledge towards personalization of the skin anti-ageing strategies by integration of individual genomic and epigenomic profiles to customize/tailor skin rejuvenation therapies. Full article

Boron (B) remains one of the least understood trace elements in human nutrition. Traditionally regarded as non-essential, its biological role has been reevaluated in light of emerging microbiome research. We provide a narrative synthesis of mechanistic, preclinical, and clinical studies to assess whether the colonic actions of B meet accepted criteria for nutritional essentiality. This review revisits B bioavailability through a dual-pathway framework distinguishing plasma-accessible boron (PAB)—small, fully absorbable species with transient systemic effects—from microbiota-accessible boron complexes (MABCs)—indigestible conjugates that reach the colon intact. Evidence indicates that PAB exerts short-term metabolic modulation, whereas MABCs act as prebiotic cofactors that stabilize microbial quorum sensing (autoinducer-2–borate; AI-2B), reinforce the colonic mucus barrier through borate–diol crosslinking, and support host–microbiota symbiosis. Deficiency or low intake of MABCs leads to dysbiosis, barrier fragility, and low-grade inflammation along gut–organ axes—effects reversible by MABC-rich diets. Analytical and clinical tools are proposed to discriminate between PAB and MABC pathways, including fecal B/speciation, AI-2B assays, and mucus-penetration markers. Recognizing B’s essentiality as a microbiota-dependent nutrient reframes its nutritional assessment, guiding future dietary guidelines and prebiotic design toward the microbiome–mucus interface. Full article

Post-translational modifications (PTMs) provide an integrated regulatory layer that couples nutrient and hormonal signals to whole-body energy homeostasis across metabolic organs. PTMs modulate protein activity, localization, stability, and metabolic networks in a tissue- and state-specific manner. Through network remodeling, PTMs integrate receptor signaling with chromatin and organelle function and align transcriptional control with mitochondrial function, proteostasis, and membrane trafficking. PTM crosstalk connects kinase cascades, nutrient-sensing pathways, and ubiquitin-family modifiers to orchestrate gluconeogenesis, lipolysis, glucose uptake, thermogenesis, and insulin secretion in response to nutrient cues. The metabolic state regulates PTM enzymes through changes in cofactors, redox tone, and compartmentalization, and PTM-dependent changes in transcription and signaling feedback to metabolic tone. In obesity and diabetes, dysregulated post translational modification networks disrupt insulin receptor signaling, disturb organelle quality control, and impair beta cell function, which promotes insulin resistance and beta cell failure. Consequently, PTMs organize metabolic information flow and modulate tissue responses to overnutrition and metabolic stress. A systems-level understanding of PTMs clarifies mechanisms of whole-body energy homeostasis and supports the discovery of new therapeutic targets in metabolic disease. Full article

While free amino acids (FAAs) are often regarded as simple building blocks for proteins, various studies show they have more complex roles in the body. This review expands on the FAA’s functions, emphasizing their influence on diverse biological processes. It covers their significance in metabolism, energy production, and the synthesis of neurotransmitters, hormones, and antioxidants. FAAs also serve as signaling molecules that regulate critical pathways related to cell growth, autophagy, and metabolic control. The review highlights their impact on the immune system and their essential roles in gut health, nutrient sensing, and metabolic communication. Drawing on recent findings, we emphasize the importance of measuring FAA levels in biological samples and suggest that their supplementation could be beneficial in clinical nutrition, treating metabolic or immune disorders, and preventing sarcopenia. Overall, FAAs are presented as key signaling agents and biomarkers, with potential for targeting their levels to improve health and treat diseases. Full article