Search Results (3,167)

Chronic diabetic wound remain difficult to heal because persistent inflammation, oxidative stress, and impaired regeneration delay repair, while effective noninvasive options are limited. In this study, graphene-based far-infrared radiation (FIR) therapy was evaluated in a streptozotocin (STZ)-induced diabetic rat full-thickness wound model, and mechanisms were examined in vivo and in vitro. Wound closure was quantified by serial imaging, whereas tissue remodeling and angiogenesis were assessed by H&E and Masson’s trichrome staining and CD34-based analyses. Transcriptomic responses were profiled by RNA sequencing with qRT-PCR validation, immune phenotypes were characterized by immunofluorescence, and high-glucose cell assays were performed. Re-epithelialization, collagen deposition, and neovascularization were quantified histologically. These datasets enabled integrated evaluation of inflammation, oxidative stress, and repair programs over time. Graphene FIR accelerated closure, reaching 83.9% healing by day 14 vs. 66.8% in untreated controls. Treatment was associated with downregulation of Cxcl2/Cxcl3, suppression of M1 polarization with enhanced M2 polarization, and reduced ROS accumulation. Consistently, NF-κB signaling was inhibited, supporting restoration of a pro-regenerative microenvironment. Collectively, graphene FIR represents a promising noninvasive strategy for diabetic wound repair via coordinated immunomodulatory and antioxidant actions. Full article

Radiation-associated soft tissue fibrosis represents a progressive structural remodeling process characterized by extracellular matrix accumulation, septal thickening, and reduced tissue compliance, which complicates reconstructive interventions. Reliable longitudinal experimental frameworks capable of non-invasive structural monitoring remain limited. This study aimed to develop and implement a standardized ultrasonographic protocol for the evaluation of bleomycin-induced subcutaneous fibrosis and to assess remodeling dynamics following autologous fat grafting in a rat model. Twenty-two adult female Wistar rats were included. Subcutaneous fibrosis was induced using submaximal bleomycin administration (1 mg/kg/day for three consecutive days). High-frequency ultrasonography (12 MHz) was performed at baseline (Day 0), post-bleomycin (Day 17), and post-lipofilling (Day 31). A predefined semi-quantitative 0–3 scoring system was applied to characterize global echogenicity, septal thickening, and architectural organization. At Day 17, all animals demonstrated structural alteration with a mean score of 2.15 ± 0.58. At Day 31, the mean score decreased to 1.50 ± 0.50, with complete disappearance of high-grade architectural disorganization (score 3). Focal hypoechoic areas consistent with graft integration were observed in 88.9% of animals without ultrasonographic signs of necrosis or fluid collection. This standardized imaging-based framework enables reproducible longitudinal monitoring of early-stage subcutaneous fibrotic remodeling and provides a non-invasive tool for evaluating regenerative interventions in translational soft tissue engineering research. Full article

Heart failure (HF) is the leading cause of morbidity and mortality worldwide, while myocardial fibrosis acts as a pivotal hallmark, which exacerbates ventricular dysfunction and remodeling in HF. In this study, we found FGF23, a critical endocrine regulator, which regulates phosphate and vitamin D metabolism, was significantly upregulated in fibrotic mouse hearts after transverse aortic constriction (TAC). By using the FGF23 monoclonal antibody, we found that inhibition of FGF23 alleviated TAC-induced cardiac fibrosis, while injection of recombinant FGF23 (rFGF23) protein exacerbated tissue fibrosis in mouse hearts after TAC. RNA sequencing indicated that FGF23 may promote cardiac fibroblast proliferation and activation in stressed mouse hearts. In human primary cardiac fibroblasts, rFGF23 treatment further upregulated the expression of Ki67, Cyclin D1, Cyclin E1, PCNA, α-SMA, and collagen 1A1 after TGF-β stimulation. Further results indicated that FGF23 promoted cardiac fibroblast proliferation and activation through FGFR4 and activated the downstream MAPK/ERK signaling. This study suggests a role of FGF23 in the regulation of myocardial fibrosis, which shows the potential of targeting FGF23 in the treatment of HF and cardiac fibrosis. Full article

Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular aging, yet their impact on myocardial deformation in pediatric patients remains incompletely characterized. Objectives: To evaluate subclinical myocardial dysfunction and arterial stiffness in children with β-TM and to investigate hemolysis-related changes in asymmetric dimethylarginine (ADMA) and L-arginine as biomarkers of endothelial dysfunction in relation to cardiovascular involvement. Methods: Twenty-four children with β-TM and 20 age-matched healthy controls were included. Cardiac structure and myocardial deformation were assessed by conventional echocardiography, tissue Doppler imaging, and speckle-tracking strain analysis. Arterial stiffness was evaluated using oscillometric pulse wave analysis and bilateral carotid intima–media thickness (CIMT). Serum ADMA and L-arginine levels were measured, and hemoglobin, reticulocyte count, and ferritin levels were recorded. Results: Children with β-thalassemia major demonstrated significantly increased arterial stiffness compared with controls, including higher PWV (4.61 ± 0.37 vs. 4.38 ± 0.31), AIx@75 (augmentation index at 75 bpm) (28.5 ± 8.34 vs. 22.8 ± 6.51), left CIMT [0.45 (0.39–0.51) vs. 0.41 (0.38–0.46)], and right CIMT [0.43 (0.39–0.54) vs. 0.40 (0.34–0.46)]. In addition, patients exhibited reduced global longitudinal strain (−19.3 ± 2.91 vs. −21.84 ± 1.91), prolonged isovolumetric relaxation time [53 (37–71) vs. 45 (37–55)], and elevated E/Em (8.44 ± 2.19 vs. 6.92 ± 1.10). ADMA levels were significantly higher in patients (0.54 ± 0.19 vs. 0.39 ± 0.22) and were positively associated with reticulocyte counts and inversely correlated with hemoglobin levels. In addition, both ADMA and ferritin levels were positively correlated with arterial stiffness indices and left ventricular filling pressures. Conclusions: Children with β-thalassemia major exhibit features suggestive of early cardiovascular aging, including impaired myocardial deformation, diastolic involvement, and increased arterial stiffness. The observed association between ADMA levels and markers of hemolysis, vascular stiffness, and myocardial deformation highlights the potential involvement of endothelial dysfunction in premature myocardial–vascular remodeling. These findings suggest that ADMA may serve as a promising biomarker for early cardiovascular risk in pediatric β-thalassemia major; however, further longitudinal and multi-center studies are needed to confirm its clinical utility for risk stratification. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) constitute the most common underlying cause of chronic kidney disease in pediatric populations. Maternal hypovitaminosis D links to mesoderm-related birth defects, leading to our hypothesis that maternal vitamin D deficiency (VDD) impairs renal development (a mesoderm-derived process) and induces offspring CAKUT. To investigate whether a low-vitamin D level can cause CAKUT, we used vitamin D-free diets to induce a maternal vitamin D deficiency mice model. The maternal vitamin D deficiency (VDD) mice models and normal vitamin D status (CON) were successfully established by administering a vitamin D-free or vitamin D-sufficient diet for 4 weeks prior to pregnancy. The overall incidence of CAKUT was significantly increased in VDD neonatal mice (19.4% vs. 2.44%; p = 0.0006), with a higher incidence of early duplicated budding in E11.5. E11.5 ureteric bud tissue revealed significantly increased activity of Gdnf-Ret-p-Erk1/2 signaling in the VDD group. In vivo intervention with the p-Erk1/2 antagonist U0126 in the pregnant VDD mice model at E10.5 improved CAKUT occurrence in offspring with p-Erk1/2 expression decreasing toward normal levels. Early metanephric ureteric bud H3K4me3 CUT&TAG analysis at E12.5 revealed chromatin activation patterns, which revealed that the downregulation of Hnf1β promoter region peaks was accompanied by reduced Hnf1β expression, and Robo2 promoter region peak was upregulated with increased Robo2 expression in the VDD group. Maternal vitamin D deficiency in mice significantly increased offspring CAKUT incidence. This phenotype was mediated by enhanced Gdnf-Ret-p-Erk1/2 signaling and reversed by p-Erk1/2 inhibition, with VDD inducing epigenetic remodeling of Hnf1β and Robo2 promoters. Full article

The 2025 approval of the selective NaV1.8 blocker suzetrigine for acute pain marked a pivotal advance in analgesic drug development. Yet the subsequent failure of Vertex’s next-generation NaV1.8 inhibitor VX993 to demonstrate clinical analgesia underscores enduring challenges in translating mechanistic promise into patient benefit. This review examines why promising targets and compounds, spanning NaV and TRP channels, often falter and outlines a path toward more reliable target selection and validation. I first summarize the pain pathway, from nociceptor transduction through spinal processing to cortical perception, emphasizing how inflammation and peripheral sensitization reshape excitability. Historically serendipitous, pain drug discovery now prioritizes molecular precision. Most approved chronic pain therapies act in the CNS and are limited by modest efficacy and adverse effects. Nociceptor-enriched targets (NaV1.7/1.8/1.9; TRP channels) remain attractive, yet redundancy among NaV subtypes and the necessity of blocking targets at the correct anatomical sites complicate translation. Human genetics and multi-omics provide a powerful, unbiased engine for target discovery. Rare high-impact variants offer strong causal hypotheses, while common polygenic contributions illuminate broader susceptibility. Large biobanks increasingly reveal a mismatch between legacy pain targets and genetically supported candidates across neuronal and non-neuronal cells. Human DRG transcriptomics highlight NaV channel redundancy. Human in vitro electrophysiology and PK/PD analyses show suzetrigine achieves ~90–95% NaV1.8 engagement, yet neurons can still fire unless additional channels are blocked. Species differences and drug distribution (including BBB/PNS penetration and P-gp efflux) critically influence efficacy; centrally accessible blockade (e.g., for NaV1.7 or TRPA1) may be necessary to achieve robust analgesia, challenging peripherally restricted strategies. Osteoarthritis illustrates how obesity-driven metabolic inflammation, synovial immune activation, subchondral bone remodeling, and specific nociceptor subtypes converge to drive mechanical pain. Multi-omic integration across diseased human tissues can pinpoint causal processes and cell types, enabling more selective and safer target choices. I propose a practical framework for target validation that integrates: (i) rigorous human genetic support; (ii) cell-type and site-of-action mapping; (iii) human-relevant electrophysiology and PK/PD with verified target engagement; (iv) species-appropriate models; (v) consideration of modality (small molecule, biologic, RNA, targeted protein degradation). Advancing genetically and anatomically aligned targets, tested at the right sites and exposures, offers the best path to genuinely effective, better-tolerated pain therapeutics. Full article

Objectives: Downregulation of the endogenous gasotransmitter hydrogen sulfide (H₂S) contributes to the pathogenesis of pulmonary arterial hypertension (PAH). While prophylactic H₂S supplementation prevents PAH initiation in different rat models, its ability to reverse fully established PAH and pulmonary vascular structural remodeling is unknown. In this study, we aimed to test whether H₂S donor therapy can reverse the existing PAH in a chronic-hypoxia rat model. Methods: After 3 weeks of hypoxia exposure, rats with established hypoxia-induced pulmonary hypertension (HPH) were randomized to receive either continued hypoxia alone or hypoxia plus the H₂S donor NaHS (56 μmol/kg·d, ip) for an additional 6 weeks. Pulmonary artery pressure, pulmonary artery muscularization, and right ventricular hypertrophy were assessed. Furthermore, the cell proliferation (Ki-67 and PCNA), ERK1/2 phosphorylation, and persulfidation of the endothelin type A receptor (ETAR) were examined and detected in rat lung tissues and pulmonary artery smooth muscle cells (PASMCs). Results: H₂S therapy effectively reversed established HPH and pulmonary artery structural remodeling, reducing RVSP, mPAP, and the proportion of fully muscularized small pulmonary arteries by 13.8%, 12.0%, and 62.7%, respectively. Moreover, the PAT/PET ratio was normalized to normoxic levels. The right ventricular hypertrophy index decreased by 29.2%. Mechanistically, H₂S therapy suppressed PASMC proliferation, reduced ERK1/2 phosphorylation, and enhanced ETAR persulfidation. Furthermore, dithiothreitol-mediated reduction of ETAR persulfidation abrogated these antiproliferative effects of H₂S therapy, establishing persulfidation as an obligatory mechanism. Conclusions: H₂S donor therapy effectively reverses established HPH and pulmonary vascular structural remodeling by inhibiting PASMC proliferation, which is linked to enhanced ETAR persulfidation. These data provide preclinical proof-of-concept for H₂S-based interventions in patients with manifest PAH. Full article

At the dawn of the 20th century, seminal studies revealed that muscle fibers produce less heat and generate greater force during elongation than during shortening actions, laying the foundation for contemporary research on eccentric exercise. Today, eccentric exercise is widely used by athletes to enhance strength and by older adults to maintain functional capacity, yet it may cause muscle damage, particularly in unaccustomed muscles. Despite more than a century of investigation, the precise mechanisms of eccentric exercise-induced muscle damage remain incompletely resolved. Nevertheless, eccentric exercise serves as a valuable model for studying muscle injury and repair and adaptation. This review organizes current evidence into nine key themes: (1) eccentric exercise-induced muscle damage and flawed biomarkers, (2) satellite cell-mediated and alternative repair pathways, (3) high-force, low-cost contractions and metabolic impact, (4) repeated bout effect and protective adaptations, (5) architectural remodeling of fascicles, sarcomeres and tendon, (6) distinct neural control, proprioception, and cross-education adaptations, (7) mitochondrial, sarcoplasmic reticulum, and cytoskeletal stress remodeling, (8) connective tissue perturbation, remodeling, and joint stability, and (9) targeted, cautious use of antioxidant supplementation. Rather than offering a comprehensive overview, this review highlights pivotal experiments, concepts, and controversies within these themes to guide readers to the most impactful discoveries in eccentric exercise and muscle damage. Full article

Background: Post-episiotomy wound healing remains largely managed through supportive care, despite growing evidence that local biochemical conditions critically influence tissue regeneration. Lactic acid is of particular interest in this context because it is both an endogenous metabolic intermediate and a physiologic component of the vaginal microenvironment, where it contributes to acidic pH maintenance, microbial homeostasis, and mucosal protection. Beyond these local effects, lactate has emerged as a signaling metabolite involved in angiogenesis, immune regulation, and extracellular matrix remodeling, making it a relevant candidate for regenerative wound care. Methods: This narrative translational review integrates evidence from molecular biology, biomaterials science, and clinical obstetrics to examine the therapeutic potential of lactic acid-loaded hydrogels for post-episiotomy tissue repair. Literature from PubMed, Scopus, and Web of Science was analyzed to evaluate physicochemical design parameters, lactate-mediated signaling pathways, and available clinical outcomes. Results: Lactic acid may function both as a microenvironmental regulator and as a metabolic signal capable of stabilizing hypoxia-inducible factor-1α signaling, enhancing vascular endothelial growth factor expression, modulating macrophage polarization, and influencing fibroblast-mediated extracellular matrix synthesis. Hydrogel matrices provide tunable platforms for controlled lactate release, pH buffering, and mucosal compatibility. Clinical studies suggest improved epithelialization, reduced infection risk, and lower pain scores following topical lactic acid formulations in episiotomy repair. In parallel, platelet-rich plasma provides autologous growth factor enrichment that may complement regenerative signaling pathways. Conclusions: Integrating microenvironment stabilization through lactic acid-based hydrogels with biologically active regenerative strategies represents a promising direction for post-episiotomy wound healing. Further controlled trials and standardized biomaterial characterization are required to define optimal therapeutic protocols and confirm long-term clinical benefit. Full article

Aquaporins (AQPs) are transmembrane channel proteins that transport water and small solutes. Their dysregulation in cancer reveals functions beyond maintaining osmotic balance. This review summarizes that AQPs drive tumor progression through three core mechanisms: metabolic reprogramming, enhanced motility, and remodeling of the immune microenvironment. Specifically, AQP3, AQP7, and AQP9 serve as metabolic hubs for glycerol, while AQP3 and AQP8 help maintain redox homeostasis. AQP1 and AQP4 facilitate cell migration via hydrodynamic mechanisms, and AQP5 promotes invasion through signaling pathways such as Ras/NF-κB. In immune regulation, AQP9 and AQP3 modulate immune cell function by transporting metabolites, and AQP1 influences angiogenesis. Other isoforms, including AQP0, AQP2, AQP6, AQP10, and AQP11, also play roles in malignancy. Collectively, AQPs form a multifunctional network linking tumor metabolism, physical properties, and immunity, offering insights for novel diagnostic and therapeutic strategies. However, tissue-specific functions, complex regulatory mechanisms, and challenges in developing targeted therapies remain significant hurdles in translational medicine. Full article

Background: Wild jujube (Ziziphus jujuba var. spinosa) exhibits remarkable tolerance to saline-alkali stress, yet its molecular mechanisms remain poorly understood. 3-ketoacyl-CoA synthase (KCS) is a key enzyme involved in the biosynthesis of very-long-chain fatty acids (VLCFAs), which constitute pivotal precursors for membrane lipids involved in stress adaptation. Methods: Through genome-wide analysis and molecular biology techniques, 20 ZjKCS genes were identified. Results: The ZjKCS genes were grouped into nine subfamilies, exhibiting highly conserved gene structures, motifs, and functional domains within each subfamily. Two pairs of collinear gene pairs were identified, with the ZjKCS12-ZjKCS18 pair retaining core conserved functions despite intense purifying selection. ZjKCS genes are rich in cis-acting elements associated with light transduction, phytohormone responses, and abiotic stress adaptation. Tissue-specific expression patterns of ZjKCS under light, ABA (abscisic acid), and MeJA (methyl jasmonate) treatments were analyzed by quantitative real-time PCR (qRT-PCR). Under saline-alkali stress, ZjKCS genes were significantly upregulated, with most showing strong sustained induction during later treatment stages. Conclusions: These findings indicate that the ZjKCS family participates in saline-alkali stress and abiotic stress adaptation, potentially by enhancing VLCFA synthesis to reinforce and remodel membrane lipid structure. This study provides a foundation for elucidating lipid-mediated stress resistance mechanisms in stress-tolerant fruit trees. Full article

Background/Objectives: Wound healing is a complex biological process involving coordinated interactions among inflammatory cells, growth factors, extracellular matrix components, and resident tissue cells. Despite significant advances in experimental research, translation of these findings into clinical practice remains limited, partly due to the lack of reproducible and ethically accessible human wound models. Pilonidal disease, a chronic inflammatory condition of the sacrococcygeal region, is frequently treated by surgical excision with healing by secondary intention. The resulting open wound provides a unique opportunity to study the natural progression of human tissue repair. Methods: This narrative review examines current knowledge on wound-healing physiology, commonly used experimental wound models, and clinical studies related to pilonidal disease. Evidence from experimental, translational, and clinical literature was evaluated to explore the potential of open pilonidal excision wounds as a standardized human model for wound-healing research. Results: Following open excision, healing typically occurs within 4–10 weeks through the classical phases of inflammation, proliferation, and tissue remodeling. During this period, the wound remains externally accessible, allowing repeated clinical observation and serial collection of tissue samples, wound fluid, and exudate. This accessibility facilitates investigation of key biological processes, including angiogenesis, fibroblast proliferation, epithelial migration, cytokine signaling, and extracellular matrix remodeling. Compared with in vitro systems and animal models, the open pilonidal wound offers direct insight into human wound biology under clinically relevant conditions. Conclusions: Open pilonidal excision wounds constitute a reproducible and ethically feasible in vivo human model for translational wound-healing research. This model may support biomarker discovery and contribute to the development of new therapeutic strategies for impaired healing and chronic wounds. Full article

Osteocalcin (OCN) is increasingly recognized as a multifunctional hormone whose actions extend far beyond its traditional role as a marker of bone turnover. This review provides an integrated examination of the molecular, endocrine, and translational dimensions of osteocalcin biology, with emphasis on its bioactive undercarboxylated form (ucOCN), which links skeletal remodeling to systemic physiological processes. The structural determinants, biosynthetic pathways, and vitamin K-dependent carboxylation mechanisms underlying OCN isoform diversity are summarized, together with analytical limitations arising from assay variability and differences between N-MID and ucOCN-specific measurements. Mechanistic evidence demonstrates that ucOCN signals through GPRC6A and GPR158 to modulate insulin secretion, muscle glucose uptake, adipokine production, testosterone synthesis, neurocognitive function, hepatic lipid metabolism, and acute stress response. These receptor-level pathways position osteocalcin as a central regulator at the intersection of bone metabolism and whole-body homeostasis. The review synthesizes data across major clinical contexts, including metabolic syndrome, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease–mineral and bone disorder (CKD-MBD), cardiovascular dysfunction, and neurodegeneration, highlighting the modifying influence of vitamin K status, circadian rhythms, renal clearance, and local tissue microenvironments. The need for biomarker standardization, methodological harmonization, and receptor-targeted translational strategies is emphasized, alongside emerging therapeutic concepts involving vitamin K supplementation and exercise-induced activation of OCN. Collectively, the evidence reframes osteocalcin as a versatile endocrine mediator at the interface of bone physiology, systemic metabolic regulation, and disease mechanisms. Full article

Background: Gene expression and cellular identity are regulated by epigenetics that occurs through chromatin modifications, RNA changes, chromatin accessibility, and three-dimensional genome organization. Although DNA methylation has been the focus of most epigenetics studies in the past, other non-methyl epigenetic processes, including histone post-translational modifications (PTMs), epitranscriptomic marks, and chromatin remodeling, are dynamic, reversible, and context-dependent, and thus are difficult to accurately interrogate using endpoint sequencing-based assays, especially in heterogeneous tissues, developing systems, and therapeutic response environments. Scope and Approach: The present review discusses epigenetic modifications other than DNA methylation regarding sensor-based technologies that can measure live, dynamic, and spatially resolved measurements. Epigenetic sensors include any genetically encoded sensors (GECs) based on resonance energy transfer, CRISPR/dCas-derived sensors, or aptamer-based sensors, and hybrid biochemical/imaging sensors that can be used in live or semi-live settings. It lays emphasis on the technologies, which have been developed recently, that allow real-time kinetic measurements, working in three-dimensional and organoid models, and being applied to disease-relevant perturbations. On these platforms, performance properties such as specificity, sensitivity, spatial and temporal resolution, ability to perform dynamic versus locus-specific interrogation, and perturbed endogenous chromatin states are compared. Key Conclusions and Outlook: Together, these sensing strategies are complementary to the traditional methods of measuring epigenomics in that they show epigenetic dynamics unobservable with static measurements. We list the important technical issues, including specificity, quantitation, multiplexing, and chromatin perturbation, and report the barriers and solutions in development and design. Lastly, we provide a conceptual map of how live epigenetic sensing and multi-omics and translational models can be integrated, and how the two methodologies can be used to develop functional epigenetics and guide disease modeling and drug development. Full article

Ginkgetin (GK) is a naturally occurring biflavonoid predominantly isolated from Ginkgo biloba and has attracted increasing attention because of its broad pharmacological activities. Structurally, GK belongs to the 3′-8″-linked biflavone subclass, which distinguishes it from other biflavonoids like amentoflavone (the parent compound of this subclass) and its monomeric counterparts such as apigenin. This unique C-C linked dimeric architecture confers distinct molecular planarity and lipophilicity, contributing to its enhanced membrane permeability and multitarget engagement capabilities. GK has been shown to exert pleiotropic biological effects in preclinical studies, including anti-inflammatory, antioxidant, antifibrotic, anticancer, neuroprotective, cardioprotective, metabolic regulatory and antibacterial activities. Mechanistically, preclinical evidence indicates that GK functions as a multitarget modulator of key signaling pathways involved in oxidative stress, inflammation, cell death and tissue remodeling, such as nuclear factor erythroid 2–related factor 2/heme oxygenase-1 (Nrf2/HO-1), nuclear factor kappa-B(NF-κB), Janus kinase/signal transducer and activator of transcription(JAK/STAT), mitogen-activated protein kinases(MAPKs), AMP-activated protein kinase/mechanistic target of rapamycin(AMPK/mTOR), phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) and cyclic GMP-AMP synthase–stimulator of interferon genes(cGAS–STING). Notably, GK has been observed to display context-dependent regulation of cell fate decisions, including apoptosis, autophagy and ferroptosis, thereby enabling the selective elimination of pathological cells while preserving normal tissue function. Preclinical studies further demonstrate that GK exhibits therapeutic potential across diverse disease systems, including cancer, metabolic disorders, cardiovascular diseases, neurological disorders and musculoskeletal diseases. In addition, emerging evidence highlights its antibacterial and antivirulence properties through the inhibition of biofilm formation and quorum sensing. It is crucial to note, however, that this promising profile is predominantly derived from preclinical studies, and clinical evidence in humans remains to be established. Despite these promising findings, the clinical translation of GK remains limited by challenges related to pharmacokinetics, bioavailability and druggability. This review systematically summarizes the chemical characteristics, pharmacological activities and molecular mechanisms of GK, with an emphasis on its multitarget actions and therapeutic potential across disease systems, and discusses current limitations and future perspectives to facilitate the rational development of GK-based interventions. Full article