Search Results (545)

Background: Papillary thyroid carcinoma (PTC) is the most common malignant tumor of the thyroid gland. Although most patients have favorable outcomes, a subset of patients develop aggressive disease characterized by lymph node metastasis and recurrence. Increasing evidence indicates that inflammatory factors participate in tumor progression. However, the expression pattern and functional role of interleukin-1 beta (IL1β) in PTC remain unclear. This study aimed to investigate the expression, biological function, and underlying molecular mechanisms of IL1β in PTC progression. Methods: IL1β expression and its clinical relevance were evaluated using public databases, 152 paired PTC and adjacent non-cancerous tissue samples, and PTC cell lines. Functional assays, including cell proliferation, colony formation, wound-healing, transwell invasion, and flow cytometry assays, were performed to investigate the effects of IL1β on malignant phenotypes. RNA sequencing, proteomic analysis, co-immunoprecipitation assays, rescue experiments, and a xenograft mouse model were conducted to identify and validate the downstream molecular mechanisms of IL1β. Results: IL1β expression was significantly reduced in PTC tissues and cell lines and was negatively associated with lymph node metastasis. Overexpression or recombinant protein treatment of IL1β inhibited PTC cell proliferation, migration, invasion, epithelial–mesenchymal transition, and tumor growth, while promoting apoptosis. Mechanistically, IL1β increased the expression of SMDT1 gene and suppressed MAPK signaling activity by reducing MEK/ERK phosphorylation. Knockdown of SMDT1 gene partially reversed the inhibitory effects of IL1β on PTC cell progression and MAPK pathway activation. Conclusions: This study demonstrates that IL1β functions as a tumor suppressor in PTC through regulation of the SMDT1-MAPK signaling axis. These findings provide new insights into the role of inflammatory regulation in thyroid cancer (THCA) progression and suggest that IL1β-related molecular pathways may represent potential biomarkers or therapeutic targets for aggressive PTC. Full article

Resveratrol (RSV) is a naturally occurring polyphenol with well-documented antioxidant, anti-inflammatory, antimicrobial, photoprotective, wound-healing, depigmenting, and anticancer properties, making it an attractive candidate for dermocosmetic and dermatological applications. However, its clinical translation into effective topical products remains limited by poor aqueous solubility, chemical instability, photoisomerization, rapid cutaneous metabolism, and restricted skin penetration, all of which compromise local bioavailability and therapeutic efficacy. This narrative review critically examines the molecular mechanisms underlying the cutaneous effects of RSV and discusses how its physicochemical and pharmacokinetic characteristics influence topical performance. Particular emphasis is placed on advanced delivery strategies developed to overcome these limitations, including lipid-based nanocarriers, polymeric nanoparticles (NPs), nanofibers, inorganic nanocarriers, microneedles, hydrogels, and other emerging delivery platforms. The mechanisms by which these systems improve RSV solubility, stability, controlled release, skin retention, and dermal penetration are critically evaluated together with their reported therapeutic outcomes. Although advanced delivery systems have consistently improved the topical performance of RSV in preclinical studies, clinical evidence remains limited. To date, only one published placebo-controlled clinical trial has specifically evaluated topical RSV as the active ingredient, and none of the advanced RSV-nanocarrier platforms discussed in this review has undergone clinical evaluation. Bridging this substantial translational gap will require not only further optimization of formulation design but also scalable manufacturing, rigorous clinical validation, and regulatory pathways capable of supporting the development of safe, effective and evidence-based next-generation dermocosmetic and dermatological products. Full article

Bioactive polysaccharides (e.g., fucoidan, β-glucans, and medicinal plant polysaccharides) contain functional groups that interact with drug molecules, and some also retain their own biological activities. Through reversible noncovalent interactions, they can associate with small-molecule drugs and form supramolecular nanocomplexes, defined here as nanoscale assemblies in which the polysaccharide is a main structural component and its association with the drug contributes to assembly or drug retention. Multicomponent composites and bulk local matrices are discussed separately as related or extended systems. The review covers hydrogen bonding, hydrophobic association, electrostatic complexation, π–π stacking, and the cooperation among these interactions, together with the effects of pH, ionic strength, concentration, and solvent composition. Nanoprecipitation/solvent exchange, polyelectrolyte complexation, direct aqueous self-assembly, and microfluidic-assisted assembly are compared with respect to nanostructure formation, process control, and reproducibility. Molecular, colloidal, solid-state, and computational evidence is examined together when interpreting structure–assembly–performance relationships. Reported advantages include improved drug dispersibility, colloidal stability, release control, bioavailability, cellular uptake, biodistribution, and safety. In some systems, the polysaccharide itself may also contribute to therapeutic effects in tumors, inflammatory diseases, and wound healing. Related local-matrix systems are considered separately. Further development of these nanocomplexes will require better quantitative analysis of assembly mechanisms, more consistent polysaccharide characterization, careful biocompatibility assessment, scalable preparation, and longer-term safety evaluation. Full article

Cutaneous wound healing is governed by dynamically interacting mechanical, redox, and bioelectrical signals that regulate cell migration, inflammation, angiogenesis, extracellular-matrix remodeling, and tissue regeneration. Hydrogels are increasingly engineered to modulate these cues; however, most systems are still described through independently measured properties such as stiffness, antioxidant activity, and conductivity, without demonstrating functional coupling among them. This review examines regenerative hydrogels from a cross-domain perspective, integrating the biological basis of mechanotransduction, redox signaling, endogenous bioelectricity, and their molecular convergence with the network-level mechanisms that control hydrogel behavior. Particular emphasis is placed on dynamic crosslinking, viscoelastic relaxation, hydration, redox-active chemistry, ionic and electronic transport, conductive and piezoelectric phases, and degradation-dependent evolution of material function. A conceptual hierarchy is proposed to distinguish property coexistence, structural integration, directional transduction, and adaptive feedback, together with experimental criteria and quantitative approaches for evaluating coupling. Current evidence indicates that mechanoelectrical coupling is the most mature, whereas mechanoredox and redox–electrical interactions remain less systematically quantified. Moving beyond descriptive multifunctionality toward controllable cross-domain transduction may enable hydrogels to function as adaptive soft interfaces capable of responding to the evolving physicochemical conditions of cutaneous regeneration. Full article

Gelatin hydrogels combine biological origin, biodegradability, abundant chemical functionality, and broad processability, but their native thermoreversible physical networks generally lack the stability required for sustained operation. Crosslinking overcomes this limitation while regulating hydration, mechanics, transport, degradation, and responsiveness. This review examines gelatin hydrogel crosslinking from a structure–property–function perspective, connecting molecular design with physicochemical characterization and functional performance. Temperature-induced gelation and ion-mediated physical interactions are compared with small-molecule- and coupling-agent-mediated, enzyme-catalyzed, and photoinduced covalent crosslinking strategies, highlighting their different balances among reversibility, stability, processability, and biocompatibility. Particular attention is given to the characterization methods required to relate junction chemistry and network organization to swelling, thermal behavior, mechanical response, degradation, and molecular or ionic transport. These relationships are evaluated across drug delivery and controlled release, tissue engineering and wound healing, food packaging, preservation and delivery, water remediation and environmental management, wearable sensing and bioelectronics, and energy storage. Across these fields, the central challenge is not to maximize crosslinking, but to balance network stability with the molecular mobility required for function. By integrating complementary crosslinking mechanisms with multiscale characterization, gelatin can be engineered as a programmable platform for advanced soft materials. Full article

Background/Objectives: Ovarian cancer is one of the most lethal gynecological malignancies worldwide, largely due to late diagnosis and rapid disease progression. Increasing evidence suggests that dysregulation of calcium-binding proteins and microRNA-mediated regulatory networks contributes to ovarian cancer progression. However, the role of S100A6 and its upstream regulatory mechanisms in ovarian cancer remain poorly understood. Methods: S100A6 expression in ovarian cancer cell lines and tissues was assessed by transcriptome sequencing, qPCR, and immunohistochemistry. Functional assays (CCK-8, EdU, Transwell, wound-healing, flow cytometry) and a xenograft model were used to evaluate S100A6 effects. Bioinformatic analysis, dual-luciferase reporter assays, and rescue experiments identified upstream miRNAs. JAK-STAT involvement was examined by Western blot. Survival analysis was performed using Kaplan–Meier Plotter. Results: S100A6 expression was significantly upregulated in ovarian cancer cells and tumor tissues compared with normal controls. Silencing S100A6 inhibited cell proliferation, migration, and invasion while promoting apoptosis in vitro and suppressed tumor growth in vivo. Mechanistically, S100A6 activated the JAK–STAT pathway, and pharmacological inhibition of STAT3 with Stattic reversed S100A6-promoted migration. Further analyses identified Let-7c-3p as a direct upstream regulator of S100A6. Let-7c-3p bound to the 3′-UTR of S100A6 and suppressed its expression, thereby reversing S100A6-mediated oncogenic phenotypes and inhibiting JAK-STAT signaling. Survival analysis revealed that elevated S100A6 expression was associated with shorter progression-free survival in ovarian cancer patients. Conclusions: Our findings identify a novel Let-7c-3p/S100A6/JAK-STAT regulatory axis that promotes ovarian cancer progression. This study provides new insights into the molecular mechanisms underlying ovarian cancer development and suggests that targeting this regulatory network may represent a potential therapeutic strategy. Full article

Efficient cutaneous wound healing relies on the phenotypic transition of macrophages toward an anti-inflammatory, pro-reparative M2-like state. Non-healing chronic wounds are pathologically characterized by the breakdown of this polarization balance. In this review, we synthesize recent research on biomaterials fabricated from naturally occurring polysaccharides with intrinsic immunomodulatory activity, mainly represented by hydrogels that modulate macrophage phenotypic transitions. We first dissect the immune microenvironment of wound healing and elaborate on the core regulatory networks governing M1/M2 polarization, with a particular focus on signaling pathways and metabolic reprogramming. On this basis, we classify pro-M2 natural polysaccharides into mannose-containing and mannose-free categories according to their core structural motifs that mediate immunomodulatory activity, and detail their molecular mechanisms, including pattern recognition receptor engagement (MR, Dectin-1, CD44, etc.) and downstream signaling cascades (STAT6, PI3K/Akt, NF-κB, etc.). Representative polysaccharides such as konjac glucomannan (KGM), Ganoderma lucidum polysaccharide (GLP), chitosan (CS) and hyaluronic acid (HA) are discussed with a clarified structure–activity relationship (SAR). Finally, we highlight emerging design strategies for multi-functional immunomodulatory hydrogels, including mechano-biochemical coupling platforms and spatiotemporally controlled delivery systems, and analyze ongoing controversies and translational bottlenecks in this field. The relationship between material structure and function enables the rational design of purpose-built polysaccharide dressings that regulate immunity. This review highlights these materials as promising preclinical platforms for chronic wound management, although their clinical translation requires further validation. Full article

Background/Objectives: Excessive inflammation is a critical contributor to impaired oral mucosal wound healing, yet effective therapeutic strategies are still lacking. Although dehydrocorydaline (DHC) has been reported to exhibit anti-inflammatory and analgesic properties, its role in wound healing and the underlying mechanisms have not been fully elucidated. This study aimed to investigate whether DHC accelerates palatal wound healing and to elucidate the role of the p38 mitogen-activated protein kinase (MAPK)/CCL2 signaling axis in DHC-mediated regulation of macrophage chemotaxis. Methods:In vitro, macrophages were stimulated with 1 μg/mL lipopolysaccharide (LPS) and treated with DHC at 0.1, 1, and 10 μM. The chemotactic response and inflammatory function of macrophages were assessed using real-time PCR, ELISA, Western blotting, and Transwell assays. Molecular docking simulations and Western blotting analyses were performed to examine the regulatory effect of DHC on MAPK signaling pathway. In vivo, a full-thickness palatal mucoperiosteal wound extending from the left maxillary first to third molars was established in mice by scalpel scraping. The effects of topical 10 μM DHC gel on wound healing were evaluated using stereomicroscopy, histological staining, and real-time PCR at 0, 3, and 5 days post-modeling. Results:In vitro, DHC effectively downregulated the expression of chemokines, including C-C motif chemokine ligand 2 (Ccl2), Ccl5, Ccl22, C-X-C motif chemokine ligand 10 (Cxcl10), and Ccl24, with the most significant inhibitory effect on Ccl2 (70.8% inhibition). In Transwell assays, DHC reduced macrophage migration by 68.2%. Mechanistically, DHC prominently inhibited the activation of the MAPK signaling pathway. In vivo, DHC treatment accelerated wound healing and markedly reduced macrophage infiltration in mouse palatal wound tissues. Conclusions: These findings demonstrated that DHC accelerated palatal wound healing 1.6-fold in mice. DHC suppressed macrophage chemotaxis by 68.2% through modulation of the MAPK signaling pathway. Full article

Wound healing is a dynamic and highly coordinated process that involves inflammation, cell proliferation, angiogenesis, re-epithelialization, extracellular matrix remodeling, and tissue maturation. The altered expression of important signaling pathways, such as transforming growth factor-β (TGF-β)/Smad, nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), and Wnt/β-catenin, may be responsible for slower wound healing, chronic inflammation, excessive fibrosis, and impaired tissue regeneration. Multifunctional nanomaterials are a promising strategy for tuning these highly coordinated processes due to their tunable physicochemical properties, high surface area, and the ability to deliver cargo, as well as the integration of antimicrobial, antioxidant, anti-inflammatory, and pro-angiogenic properties. The aim of current review is to summarize the potential of multifunctional nanomaterials to promote wound healing, with a focus on mechanisms of action and modulation of key cellular signaling pathways. A systematic review of the literature was conducted using PubMed, Scopus, Web of Science, and Google Scholar, searching for publications from 1996 to June 2026, and representative experimental, mechanistic, preclinical, and translational studies were critically evaluated. In this review, the authors discuss the role of nanomaterial properties, therapeutic payload, molecular targets, modulation of cellular signaling pathways, and regenerative effects. These platforms have been shown in in vitro and animal studies to influence inflammatory signaling, oxidative stress, angiogenesis, collagen remodeling, re-epithelialization, cellular proliferation, and migration. However, the modulation of these pathways are dose-responsive, time-dependent, and cell- and wound-stage-specific. Despite the promising therapeutic potential of nanomaterial-based wound care strategies, the available evidence remains predominantly preclinical, with relatively limited clinical data supporting their use in humans. Concerns regarding long-term toxicity, biodistribution, batch-to-batch reproducibility, sterilization, scalable manufacturing, regulatory approval, and commercial feasibility further challenge translation into clinical practice. Multifunctional nanomaterials may offer a promising approach for pathway-specific and multimodal wound management; however, comprehensive mechanistic studies, long-term safety and biodistribution assessments, and well-designed clinically relevant investigations are required to establish their efficacy, safety, and true translational potential. Full article

Background: As a member of the T-box transcription factor family, TBX18 was found to be involved in ESCC progression, while its role in regulating radiotherapy resistance in ESCC remains unclear. This study was designed to investigate the molecular mechanisms underlying the regulation of radioresistance in ESCC by TBX18. Methods: Sphere formation assay, Transwell invasion assay, and wound healing assay were conducted to show the influence of TBX18 on tumor stemness and epithelial–mesenchymal transition (EMT). Western blot, immunofluorescence, chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase reporter assay were preformed to identify regulatory networks. A nude mouse xenograft tumor model was established to assess the regulatory effect of TBX18 and SIX1 on radioresistance of ESCC in vivo. Results: TBX18 expression was positively associated with stemness markers, including CD44, CD271, and SOX2. TBX18 promoted stemness-associated phenotypes, EMT, migration, invasion, and radioresistance in ESCC cells. Mechanistically, TBX18 directly bound to the SIX1 promoter and transcriptionally activated SIX1 expression. In turn, SIX1 enhanced TBX18 protein stability by suppressing ubiquitin–proteasome-mediated degradation, thereby forming a positive feedback loop. Functional rescue experiments demonstrated that the TBX18/SIX1 axis coordinately maintained stemness and EMT phenotypes and attenuated radiotherapy-induced apoptosis. In vivo studies further confirmed that TBX18 knockdown enhanced radiosensitivity, whereas SIX1 overexpression partially reversed this effect. In addition, immunohistochemical analysis revealed that TBX18 and SIX1 were significantly upregulated in ESCC tissues and positively correlated with each other. Full article

Localized therapeutic delivery has gained increasing attention as an effective strategy in enhancing treatment efficacy while at the same time minimizing systemic side effects. However, conventional hydrogel-based therapeutic delivery systems often suffer from poor tissue retention and insufficient control over delivery. This drawback is highly pronounced in wet and dynamic biological environments. So, catechol-based adhesive hydrogels have emerged as promising biomaterials for localized therapeutic applications and are inspired by the remarkable wet-adhesion capability of marine mussels. As a highlight, catechol chemistry enables robust tissue adhesion through multiple intermolecular interactions, including hydrogen bonding, metal coordination, and covalent coupling. At the same time, it contributes to hydrogel cohesion and structural stability. Recent advances in hydrogel engineering have expanded the functionality of these systems through integration of injectable formulations, self-healing networks, nanocomposite reinforcement, and stimuli-responsive biointerfaces. These developments have transformed adhesive hydrogels from tissue sealants into multifunctional therapeutic platforms capable of enhancing tissue retention, regulating therapeutic release, and dynamically interacting with biological microenvironments. Here, we review molecular mechanisms underlying catechol-mediated adhesion and discuss recent progress in advanced adhesive hydrogel systems. We further highlight their therapeutic applications in wound healing, musculoskeletal regeneration, exosome and gene delivery, immunomodulatory therapies, and localized cancer therapy. Finally, current translational challenges and future opportunities in developing next-generation smart biointerfaces for precision regenerative medicine are discussed. Full article

Melatonin, a methoxyindole synthesized by the pineal gland, is secreted in response to photoperiodic cues relayed from the retina through an endogenous circadian oscillator within the suprachiasmatic nucleus. Consequently, melatonin secretion regulates the circadian rhythm. Melatonin has been reported to have antioxidant, photoprotective, anti-inflammatory, anticancer, and wound-healing properties. It has also been reported to promote hair growth, although the underlying mechanisms remain unclear. In this study, we explored the potential molecular mechanisms of melatonin-induced hair growth by using an in vivo C57BL/6 mouse model. We observed morphological changes in the dorsal area and changes in the hair cycle and anagen induction were observed through hematoxylin–eosin staining. The molecular mechanisms were explored using Western blotting and immunofluorescence assay. Our findings indicate that topical melatonin promotes anagen entry and hair regrowth in C57BL/6 mice, accompanied by the modulation of Wnt/β-catenin-related signaling proteins. The decrease in grayscale value, increase in hair length and skin thickness and histological change in hair follicles in the melatonin-treated group indicated hair regrowth in the dorsal skin of mice. Moreover, the expression of the Wnt/β-catenin pathway was remarkably regulated. These findings further our understanding of the molecular mechanisms underlying topical melatonin-induced hair growth. Full article

Background: Lower limb exoprostheses often lead to stump dermatological pathologies. The mechanisms by which mechanical microtraumas progress to non-healing ulcerative defects due to dysbiosis remain poorly understood. The objective of this study was to analyze mechanical, inflammatory, and infectious stump skin complications and justify the role of bacterial and mycological dysbiosis in blocking tissue regeneration. Methods: A critical narrative review guided by SANRA principles was conducted (PubMed/Scopus, 1980–2026). Data were extracted with a structured query focusing on amputation stumps, prosthetic interfaces, and skin/microbiological complications (dysbiosis, biofilms, and inflammatory markers). Evidence was graded using predefined clinical matrices and integrated through structured evidence collations to synthesize stump–prosthesis pathogenesis. The PRISMA method was not applied due to study heterogeneity. Results: Skin damage dynamics were categorized into three stages: adaptation (up to 12 months), chronic reactive changes (12–24 months), and late proliferative-infectious destruction (>24 months). The sealed liner space creates 100% humidity and alkalization (pH > 6.5). This causes a mycological shift, where resident Malassezia spp. lose dominance to invasive Candida albicans and non-dermatophyte molds (Aspergillus spp., Fusarium spp.). These pathogens form polymicrobial biofilms with Staphylococcus aureus. At the molecular level, delayed regeneration is driven by “frustrated phagocytosis”: macrophages, unable to engulf large fungal hyphae, continuously release reactive oxygen species and enzymes, trapping the wound in the inflammatory phase. Excessive matrix degradation and suppressed angiogenic factors further block epithelialization. Conclusions: The skin under a prosthesis socket forms a unique pathological biotope. Successful regeneration requires preventive mycobiota correction and targeted management of biophysical parameters (pH, humidity) within the “skin–liner” interface. Full article

Konjac glucomannan (KGM) is a plant-derived polysaccharide with a long history of food use and a rapidly expanding portfolio of biomedical applications. Yet despite decades of research, translation of KGM-based materials from laboratory proof-of-concept to clinical and commercial products remains slow, hampered by unresolved structural controversies, batch-to-batch variability, and a lack of quantitative design rules. This review provides a critical, mechanism-focused analysis of KGM across its molecular architecture, extraction and modification, and translational applications, moving beyond cataloguing uses to evaluate conflicting findings in the literature. We examine how hierarchical structural features—molecular weight, acetylation pattern, and chain topology—govern solution behavior, gelation, and biological performance, and compare KGM with competing biopolymers to define its unique advantages and inherent limitations. Current progress in colon-targeted delivery, wound healing, microbiome modulation, and metabolic health is synthesized, and persistent barriers to translation are evaluated, including the absence of quantitative structure–activity models, limited human pharmacokinetic data, and incomplete toxicological characterization of modified derivatives. We also address longstanding debates over branching frequency, acetylation distribution, and dose–response relationships that have generated inconsistent results across studies. Finally, we outline a research agenda integrating computational polymer design, multi-omics mechanistic studies, and precision nutrition to support development of next-generation KGM biomaterials. Full article

The corneal epithelium serves as the outermost transparent barrier of the eye and depends on rapid and coordinated cellular responses for wound repair. Although negative pressure (NP) has been shown to accelerate wound healing in other tissues, its cellular and molecular effects on corneal epithelium remain undefined. This study investigates how NP regulates corneal epithelial cell physiology and identifies the molecular mechanisms underlying NP-induced migration. Human corneal epithelial cells were exposed to normal or NP conditions, and cell motility was quantified using scratch-wound and transwell migration assays. Nuclear and cytoplasmic fractions were isolated for proteomic profiling to identify NP-responsive proteins. G3BP1 was selected as a candidate regulator and subsequently examined using molecular, biochemical, and functional assays to determine its role in NP-mediated signaling. Proteomic analysis revealed a significant NP-induced upregulation of G3BP1. Mechanistically, G3BP1 suppressed epithelial junctional proteins, including E-cadherin, p120-catenin, and ZO-1, while activating key pro-migratory signaling pathways involving AKT, ERK1/2, FAK, and Paxillin. These coordinated changes enhanced cytoskeletal dynamics and promoted corneal epithelial cell migration under NP stimulation. G3BP1 functions as a critical mechanotransduction mediator of NP, orchestrating adhesion remodeling and activating pro-migratory signaling cascades to facilitate corneal epithelial cell motility. These findings reveal a previously unrecognized cellular mechanism through which NP promotes epithelial repair and highlight G3BP1 as a potential therapeutic target for persistent corneal epithelial defects. Full article