Search Results (3,652)

Per- and polyfluoroalkyl substances (PFAS) have been associated with thyroid dysfunction, but their relationship with papillary thyroid carcinoma (PTC) and relevant molecular processes remains unclear. We integrated bioinformatics analyses, a hospital-based case–control study, and in vitro experiments to investigate associations between PFAS exposure and PTC and to explore potentially relevant post-transcriptional RNA regulatory processes. Transcriptomic data, PFAS-associated genes, and m⁷G-associated genes were integrated to identify candidate genes. Among 24 overlapping candidates, 21 remained differentially expressed between PTC and normal thyroid tissues after false discovery rate correction, and EIF4E, NCBP1, and AGO2 were identified as candidate hub genes. The case–control study included 60 patients with newly diagnosed PTC and 60 controls. Serum concentrations of 17 PFAS were measured, and individual and mixture associations with PTC status were evaluated using logistic regression, weighted quantile sum regression, quantile g-computation, and Bayesian kernel machine regression. Higher concentrations of several PFAS were associated with lower odds of PTC, although the findings were not fully consistent across analytical models. In vitro, high concentrations of PFOA and PFOS reduced relative thyroid-cell viability, whereas wound-healing responses were variable and did not show a consistent enhancement. PFOA and PFOS exposure was also accompanied by altered EIF4E and NCBP1 mRNA expression, respectively. Overall, these findings support an association between PFAS exposure and PTC and identify m⁷G-associated post-transcriptional regulatory candidates, particularly EIF4E and NCBP1, that may contribute to PFAS-related thyroid cellular responses and warrant further mechanistic investigation. Full article

This study evaluated Leptospermum scoparium, (manuka) essential oil (LSEO, for its antibacterial activity, cyto/genotoxicity, antioxidant potential, and its effects on wound closure, reflecting the growing interest in natural compounds with antimicrobial and potential wound-related cellular effects. Analyses were performed on the human keratinocyte cell line HaCaT. The genotoxic effect and the scratch assay of LSEO on human keratinocytes are described for the first time. The results revealed that LSEO did not induce significant DNA damage in vitro after 24 h of treatment. Moreover, treating HaCaT cells with LSEO increased the total antioxidant status level and enhanced wound closure at a concentration of 0.008 µg/mL. Additionally, the inhibitory effect of LSEO against several multidrug-resistant bacterial strains, including Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli, Enterobacter cloacae, and Staphylococcus aureus, was investigated. LSEO exhibited strong antibacterial activity, with inhibition zones ranging from 25 to 44 mm. The minimal inhibitory concentration and minimal bactericidal concentration of LSEO ranged from 0.10 to 0.5 μg/mL and from 0.25 to 0.75 μg/mL, respectively. The findings indicate that LSEO exhibits antibacterial activity against the tested multidrug-resistant bacterial isolates and may warrant further investigation as a potential antimicrobial agent. Full article

Background: Hypoalbuminemia is a common complication after burn injury, exacerbated by surgical debridement, and contributes to edema, delayed healing, infection, and mortality. NovoSorb^® biodegradable temporizing matrix (BTM) is a dermal substitute that may reduce protein loss from open wounds. Objective: To evaluate the effect of BTM on serum albumin levels compared with conventional split-thickness skin grafting. Method: This retrospective review included burn patients (TBSA ≥ 10%, length of stay > 30 days) admitted between 2020 and 2025 who underwent debridement followed by BTM or skin grafting. Serial albumin levels were analyzed as weekly means. Result: Baseline characteristics were comparable between BTM (n = 14) and non-BTM (n = 16) groups. Albumin decreased in both groups at week 1. From week 3 onward, albumin levels rose only in the BTM group, with significant intergroup differences at weeks 5–7 (p < 0.05 to p < 0.01), but not at week 8. Conclusions: In this observational, exploratory, and hypothesis-generating study, BTM application was associated with faster albumin recovery compared with conventional methods. This is the first study to suggest that a dermal substitute may positively influence systemic albumin dynamics in burn patients, highlighting its potential role in reducing protein loss and supporting metabolic recovery. However, given the preliminary nature of these findings, it requires confirmation in larger, prospective, randomized controlled trials. Full article

Curcuma longa L. (turmeric) is an economically and medicinally important species widely utilized as a spice, traditional medicine, and source of bioactive compounds. Although research and commercial exploitation have predominantly focused on the rhizome and its major curcuminoids, evidence increasingly shows that other plant parts also contain chemically diverse and biologically active constituents. This review integrates current knowledge of the botany, traditional uses, phytochemistry, pharmacological activities, industrial applications, and sustainable utilization of C. longa, with particular emphasis on whole plant utilization. Unlike previous reviews that have largely focused on the rhizome and curcuminoids, this review synthesizes evidence across underutilized plant organs and links their tissue-specific phytochemistry with biological activities, industrial applications, and circular-bioeconomy potential. Rhizomes are rich in curcuminoids and turmerone-dominated essential oils, whereas leaf, flower, root, and root tuber contain diverse phenolics, flavonoids, terpenoids, and other specialized metabolites. However, these non-rhizome tissues remain substantially less studied, and their distinct phytochemical and functional value has not yet been systematically established. Preclinical studies have linked these constituents to antioxidant, anti-inflammatory, antimicrobial, antiviral, anticancer, antidiabetic, hepatoprotective, and wound-healing effects. However, clinical evidence remains variable across these activities. Beyond therapeutic applications, underutilized aerial parts and processing residues may serve as source of essential oils, natural preservatives, fibers, biodegradable materials, fermentation products, and bioenergy. Cascading biorefinery approaches that integrate tissue-specific phytochemistry may broaden turmeric utilization beyond the rhizome, reduce agricultural waste, and contribute to circular-bioeconomy development. Further research should prioritize underexplored plant organs, standardized phytochemical characterization, safety assessment, well-designed clinical studies, and techno-economic and life-cycle assessments. Full article

Background: Persistent inflammation and excessive neutrophil extracellular trap (NET) formation hinder the healing of bacteria-infected diabetic wounds. The Salvia miltiorrhiza–Astragalus membranaceus herb pair possesses anti-inflammatory activity, but its poor solubility, rapid metabolic clearance, and unclear material basis limit direct wound application. Extracellular vesicles (DH-EVs) isolated from this herb pair may improve local delivery and stability. Therefore, this work constructs a DH-EV-incorporated hydrogel dressing aimed at inhibiting NET formation and facilitating diabetic wound healing. Methods: DH-EVs were isolated from the Salvia miltiorrhiza–Astragalus membranaceus pair, characterized by lipidomics and small-RNA sequencing, and incorporated into a hydrogel. The dressing was evaluated for physicochemical properties, mechanical performance, biocompatibility, NET inhibition, anti-inflammatory activity, and therapeutic efficacy in vitro and in bacteria-infected diabetic wounds. Results: DH-EVs were isolated, and sequencing identified miRNAs potentially regulating inflammation- and NET-related pathways. Incorporation into hydrogel did not significantly alter mechanical integrity or biocompatibility. In vitro and in vivo, the DH-EV-loaded hydrogel suppressed excessive NET formation, reduced local inflammation, and improved wound closure and tissue regeneration in bacteria-infected diabetic wounds. Conclusions: The DH-EV-loaded hydrogel promotes bacteria-infected diabetic wound repair by suppressing excessive NET formation and inflammation, providing a promising strategy for localized wound treatment. Full article

Chronic wounds are characterized by prolonged inflammation, excess oxidative stress, unregulated angiogenesis, and faulty tissue regeneration that are associated with slow wound healing and poor clinical outcomes. Reactive oxygen species (ROS) signaling deregulation is involved in the pathway of chronic wound pathophysiology, altering redox balance, augmenting the inflammatory response, and inhibiting the cellular response. In this review, a structured literature search and evidence-screening process was used to synthesize evidence on probiotics, EVs, and engineered EVs derived from probiotics in the context of wound healing. Studies suggest that EVs from probiotics may impact redox-sensitive processes of wound healing, including changes associated with Nrf2/HO-1, NF-κB signaling, modulation of mitochondrial ROS, macrophage polarization, and repair of the epithelial barrier. Many of these mechanistic links are derived from pathway-based markers or indirect experiments, however, and will need further mechanistic validation. Probiotic-EVs may offer potential advantages over traditional antioxidant delivery and mammalian-EV systems, including being cell-free, compatible with the microbiome, and easy to engineer. Recent progress in synthetic biology, cargo loading, biomaterial-assisted delivery systems, and ROS-responsive platforms may enable engineered probiotic-EVs to serve as programmable redox nanotherapies. However, major issues regarding EV standardization, biosafety, biodistribution, pharmacokinetics, and clinical validation remain unresolved. Importantly, the evidence for the application of probiotic-derived EVs to wound healing is predominantly preclinical, and there is a lack of direct clinical evidence to date. Collectively, EVs secreted from probiotics might hold potential for chronic wound care and redox-oriented regenerative medicine as a therapeutic platform. Full article

Background: Cold atmospheric plasma (CAP) has emerged as a promising experimental anticancer strategy, yet its influence on oral squamous cell carcinoma (OSCC) migration and viability remains moderately understood. The aim of this workpaper was to examine how CAP exposure influences wound closure, WST-1 metabolic signal, and key proteins involved in epithelial adhesion and cell-cycle regulation in OSCC models. Methods: HSC-3 and CAL27 head and neck squamous cell carcinoma (HNSCC) cells were exposed to CAP generated via Piezoelectric Direct Discharge (PDD) technology for 20 s under standardized conditions. Wound closure was assessed by wound-healing assay under proliferation-restricted conditions (50 μM Ara-C), while relative cellular metabolic activity was measured using WST-1. E-cadherin, N-cadherin, and Cyclin A were evaluated by Western blot. Publicly available baseline transcriptomic data were additionally analyzed to characterize migration- and cytoskeleton-related expression patterns in the two HNSCC models. These transcriptomic data were independent of CAP treatment. Results: A 20 s CAP exposure significantly delayed wound closure in both HNSCC cell lines under proliferation-restricted conditions and reduced the WST-1 signal. Cyclin A levels also decreased, supporting an effect on cell growth and cell-cycle regulation, although the available data do not establish cell-cycle arrest. E-cadherin increased after CAP treatment, whereas N-cadherin remained low without a statistically significant change. Baseline transcriptomic mapping further showed differences between HSC-3 and CAL27 in genes related to actin-cytoskeleton organization, focal adhesion, and migration. These data were used to contextualize the experimental phenotype and were not interpreted as CAP-induced transcriptional changes. Conclusions: In these in vitro OSCC models, CAP exposure was associated with slower wound closure, lower WST-1 signal, increased E-cadherin, and reduced Cyclin A expression. These findings suggest further investigation of CAP as a potential modulator of OSCC cellular metabolic activity, adhesion-related markers, and cell-cycle-associated proteins. Full article

The high cost of conventional carbon sources has limited the widespread application of bacterial cellulose (BC). In this study, tobacco stem waste extract (TWE) was evaluated as an alternative substrate for BC production via fermentation with Gluconacetobacter xylinus, and a silver-loaded composite (BC-Ag) was further developed for potential wound dressing applications. Medium optimization with the addition of citric acid and (NH₄)₂SO₄ effectively alleviated salt stress and acid inhibition inherent to TWE, achieving a BC yield of 2.40 ± 0.12 g/L while preserving a native cellulose I crystalline structure and three-dimensional nanofibrous network. The resulting TWE-BC exhibited enhanced mechanical properties (ultimate tensile strength: 0.67 MPa; Young’s modulus: 1.56 MPa) and improved thermal stability (glass transition temperature: 58.5 °C). The BC-Ag composite, fabricated via in situ chemical reduction, contained 8.84 wt% silver and demonstrated potent antibacterial activity against Staphylococcus aureus and Escherichia coli, along with favorable sustained-release behavior. Cytotoxicity assays confirmed good biocompatibility, with cell viability exceeding 70% at extract concentrations of 12.5–50%. In a rat infected-wound model, the BC-Ag dressing effectively eradicated local infection and significantly accelerated wound healing compared to commercial medical gauze, pure BC, and silver-loaded gauze controls. Collectively, this work presents a sustainable and potentially cost-effective strategy for valorizing tobacco waste into a high-value BC-based wound dressing material. Full article

Background: The incidence of diabetes-related chronic wounds has been increasing annually, characterized by delayed wound healing due to persistent inflammatory responses. To alleviate patient suffering, there is an urgent need to discover novel wound-healing agents that reduce local inflammatory reactions. Animal peptides emerge as promising candidates due to their low molecular weight, low toxicity, low resistance potential, high sensitivity, potent activity, and ease of transmembrane absorption. However, the precise mechanism by which animal peptides accelerate skin wound healing remains unclear. Method: Scorpion peptides were extracted using ultrafiltration, followed by de novo analysis after library searching with Peaks 8 software and combined LC-MS/MS detection to identify peptide components in scorpions. A full-thickness skin defect model in diabetic mice was established to evaluate the wound-healing promotion capacity of scorpion peptides. In vitro experiments were conducted using mouse monocyte–macrophage leukemia cells (RAW264.7 cells). Enzyme-linked immunosorbent assay (ELISA) evaluated inflammatory cytokine expression, flow cytometry analyzed macrophage phenotypes, Western blotting (WB) measured P-P65 and P65 protein levels, immunofluorescence to observe P-P65 nuclear translocation, molecular docking and molecular dynamics simulations, and the Cellular Thermal Shift Assay (CETSA) to evaluate the binding capacity of scorpion peptides to target proteins, and the TUNEL assay to detect apoptosis, among other methods, to investigate the mechanisms by which scorpion peptides promote wound healing. Result: This study successfully identified 2331 peptides from a scorpion peptide extract. In a full-thickness skin defect model in diabetic mice, treatment with scorpion peptides significantly promoted wound healing and induced M2 polarization of macrophages at the wound site. Further in vitro mechanism studies were conducted using a RAW264.7 cell inflammation model established by combining lipopolysaccharide (LPS) with high glucose. The results showed that scorpion peptide reduced the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), increased the anti-inflammatory cytokine interleukin-10 (IL-10), downregulate the P-P65/P65 protein expression ratio, and reduce the number of TUNEL-positive apoptotic cells, suggesting that the NF-κB pathway may be involved in mediating its anti-inflammatory and anti-apoptotic effects. To further identify the target, molecular docking and molecular dynamics simulations showed that the active peptide segments PPPPPP and GPPPPP adopt stable binding conformations with the P65 protein; CETSA further validated that they enhance the thermal stability of the P-P65 protein. Through repeated validation using active peptide fragments, ELISA, flow cytometry, Western blot, and immunofluorescence assays consistently confirmed that scorpion peptide, PPPPPPP, and GPPPPP not only inhibit P65 phosphorylation but also inhibit the nuclear translocation of P-P65, and exhibit anti-inflammatory, macrophage M2 polarization-promoting, and anti-apoptotic effects. Conclusions: Scorpion peptides and their active peptide fragments block the activation of the NF-κB pathway by interfering with P65 phosphorylation and nuclear translocation, effectively inducing M2 polarization of macrophages, reducing inflammation and apoptosis, and ultimately promoting the healing of diabetic wounds. Full article

Cutaneous wound healing is a complex biological process that remains challenging, particularly in chronic wounds requiring effective and safe therapeutic strategies. Copaifera species are rich sources of bioactive terpenoids with recognized pharmacological properties and increasing potential for dermocosmetic applications. This systematic review aimed to critically evaluate the phytochemical composition and wound-healing activities of Copaifera-derived products. The review followed the PRISMA 2020 guidelines and searched MEDLINE/PubMed, SciELO, PEDro, and Scopus. Studies published between 2015 and 2025 were screened, and 20 studies met the eligibility criteria for qualitative synthesis. The available evidence demonstrated that Copaifera-derived products, particularly oleoresins, exhibit anti-inflammatory, antioxidant, antimicrobial, antinociceptive, and regenerative activities that promote wound contraction, re-epithelialization, collagen deposition, and extracellular matrix remodeling. β-Caryophyllene was the most frequently identified phytochemical, followed by β-bisabolene, α-humulene, α-bergamotene, copalic acid, and kaurenoic acid. Recent investigations also indicated the incorporation of Copaifera bioactive compounds into biomaterials and nanotechnology-based delivery systems to increase topical therapeutic performance. Despite these promising findings, the current evidence remains predominantly preclinical and is limited by methodological heterogeneity and the scarcity of clinical trials. Overall, Copaifera represents a promising natural source for developing innovative wound-healing therapies and dermocosmetic formulations. Full article

Advanced wound dressings should actively promote tissue repair while preventing microbial infection and excessive inflammation. In this study, multifunctional electrospun nanofibers composed of poly(vinyl alcohol)/chitosan/gelatin were developed by incorporating green-synthesized mesoporous silica nanoparticles (MSNs), Acacia gum, and Hypericum perforatum extract (HPE). Biological activity and safety were evaluated using disk-diffusion antimicrobial testing, MTT cell viability assays, nitric oxide measurement in LPS-stimulated RAW 264.7 macrophages, an L929 fibroblast scratch assay, and Ames and comet assays. The optimized nanofibers exhibited a uniform morphology with an average fiber diameter of approximately 400 nm and high encapsulation efficiencies (86–96%). MSN incorporation significantly prolonged hypericin release, producing a biphasic release profile with approximately 1.4-fold slower release than nanofibers without MSNs, while increasing Young’s modulus from 2.1 to 2.5 MPa. The hybrid nanofibers demonstrated broad-spectrum antimicrobial activity against Gram-positive bacteria, Gram-negative bacteria, and Candida albicans, achieving approximately 70% of the efficacy of standard antimicrobial agents. In lipopolysaccharide-stimulated RAW 264.7 macrophages, the optimized formulation reduced nitric oxide production by approximately 51%, comparable to indomethacin and L-NAME. Although fibroblast migration was not significantly enhanced, the nanofibers exhibited acceptable cytocompatibility and showed no mutagenic or genotoxic effects in Ames and comet assays. These findings demonstrate that green-synthesized MSN-enhanced herbal nanofibers represent a safe and promising platform for sustained drug delivery and advanced wound-healing applications. Full article

This work evaluates agarose (AG)- and chitosan (CS)-based hydrogels incorporating a dexamethasone–cyclodextrin complex (Dex) as potential bioink candidates for wound healing applications. For this purpose, biopolymer hydrogels were formulated and tested to determine their structure, morphology, and rheological behavior under different strain, frequency, and temperature conditions, as well as their swelling behavior, surface functionality, protein adhesion capability, and antibacterial activity. Scanning electron microscopy revealed an interconnected membrane-like porous structure in the agarose/chitosan (BAC) hydrogels, which also showed a fibril-like microstructure when Dex was added. X-ray diffraction showed that these structures had a semicrystalline nature, with a main broad peak from approximately 15 to 20°. Rheological tests confirmed the viscoelastic behavior of the developed hydrogels. Chitosan incorporation reduced the rigidity of the formulations, whereas dexamethasone did not significantly affect the viscoelastic response of the BAC hydrogel. Additionally, the temperature sweep showed that Dex did not substantially alter the viscoelastic response of the BAC hydrogel while reducing mass loss after immersion in phosphate-buffered saline and not significantly affecting the swelling behavior. Further, Coomassie blue staining tests demonstrated favorable protein interaction with the BAC-based hydrogels, indicating that Dex incorporation did not compromise their adsorption capacity. Regarding their antibacterial activity, the hydrogels showed no major effects on Escherichia coli and Staphylococcus aureus in disk diffusion tests. However, liquid diffusion tests showed almost no bacterial growth for hydrogels incorporating CS. Thus, the present results demonstrate the potential of the BAC hydrogel system for biomedical and cosmetic applications. Full article

Excessive reactive oxygen species (ROS) and bacterial infection were the important obstacles to impaired wound healing. Herein, by the use of innate bioactivities of natural polysaccharides and flavonoid glycosides, a multifunctional hydrogel was engineered through the Schiff base reaction between oxidized fucoidan (oFu) and lysine-modified chitosan (CS-Ly) for wound dressing. Rutin and silver nanoparticle (AgNP)-modified polydopamine (PDA) nanoparticles were incorporated into the hydrogel matrix, thereby exhibiting favorable ROS scavenging ability and adhesive property. Moreover, the hydrogel demonstrated strong antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with antibacterial rates of 81.8% and 78.2%, respectively. Moreover, the dynamic crosslinking endowed the hydrogel with adjustable degradation behavior and self-healing ability. When cocultured with NIH-3T3 cells, the hydrogel exhibited good biocompatibility. Based on the above results, these multifunctional hydrogels with excellent performance have great appealing potential in clinical materials for wound healing. Full article

Background/Objectives: Rubus crataegifolius Bunge (Rosaceae, RC), a wild raspberry native to East Asia, has been investigated for the biological properties of its leaves and roots, while the dermatological potential of its fruit remains largely unexplored. This research evaluated the dermatological effects of RC fruit extracts, focusing on their potential for skin regeneration and anti-aging applications. Methods: RC fruit extracts were prepared by ultrasound-assisted extraction (UAE) and maceration extraction (ME) with distilled water or 70% ethanol as solvents. Phytochemical profiling was performed by liquid chromatography–electrospray ionization–time-of-flight mass spectrometry (LC-ESI-TOF-MS). Dermatological activities were evaluated using fibroblast and keratinocyte proliferation, collagen synthesis, wound healing, and gene expression assays. Safety was assessed by cytotoxicity and inflammation assays. Skin hydration was evaluated in a human application test. Results: Various phytochemicals, including flavonoids, phenolic acids, organic acids, and terpenoids, were putatively annotated by LC-ESI-TOF-MS in the RC fruit extracts. Ethanol extracts exhibited higher flavonoid content and antioxidant activity; however, dermatological activities were not correlated with antioxidant activity. UAE-derived extracts enhanced fibroblast proliferation. All extracts promoted collagen synthesis, with ME-EtOH showing the highest increase. In wound-healing assays, ME-DW extracts promoted fibroblast wound closure, while UAE-DW enhanced keratinocyte migration. In keratinocytes, UAE-DW specifically upregulated HAS1 and HAS2 mRNA expression. Clinically, UAE-DW extract produced a significant increase in skin hydration and moisture distribution in healthy volunteers. Conclusions: RC fruit extracts exhibit biological activities, including enhanced fibroblast proliferation, collagen synthesis, wound healing, and skin hydration. Full article

Traditionally, chronic wounds including diabetic foot ulcers (DFUs), pressure ulcers (PUs), venous leg ulcers (VLUs), arterial ulcers, inflammatory and autoimmune-associated ulcers, infected chronic wounds, and non-healing post-surgical wounds are treated as localized diseases of skin and soft tissue damage. However, these lesions are increasingly acknowledged as chronic inflammatory states with consequences extending beyond the wound bed and often arising in the setting of systemic dysfunction. Across wound types, shared features include persistent inflammation, oxidative stress, endothelial dysfunction, immune imbalance, protease dysregulation, infection or biofilm burden, metabolic disturbance, and impaired regenerative signaling. These abnormalities may promote systemic cytokine release, vascular dysfunction, neurohumoral activation, oxidative injury, and maladaptive remodeling. Cardiac dysfunction is already known to impair wound healing. In contrast, whether chronic non-healing wounds are associated with or may contribute to cardiac damage resulting in heart failure remains insufficiently defined. Emerging epidemiologic and mechanistic evidence suggests that chronic non-healing wounds may amplify cardiovascular stress, particularly in vulnerable patients with diabetes, obesity, frailty, kidney disease, or pre-existing vascular disease. This narrative review explores the conceptual hypothesis that chronic non-healing wounds may contribute to systemic cardiovascular stress and cardiac dysfunction. It integrates clinical and mechanistic opportunities, outlines potential pathways, including extracellular vesicle (EV) signaling, and highlights key knowledge gaps and therapeutic implications in the wound–heart axis. Full article