Search Results (8,946)

Background/Objectives: Cannabinoid receptor type 2 (CB₂) agonists have attracted attention because of their potential effects on tumor-related cellular processes in different cancer models. In the present study, we investigated the effects of the selective CB₂ agonist JWH-133 on prostate cancer cell lines (LNCaP, DU-145, and PC3). Methods: Cell viability was evaluated using the MTT assay, while colony-forming capacity and migration-related responses were assessed by colony formation and wound-healing assays, respectively. In addition, the expression levels of selected cell-cycle- and apoptosis-related genes were analyzed by quantitative real-time PCR. Results: JWH-133 reduced cell viability in a time- and concentration-dependent manner, although the magnitude of this effect differed among prostate cancer cell lines. The compound also reduced colony formation in PC3 and LNCaP cells and decreased wound closure in PC3 cells under the experimental conditions used. Furthermore, JWH-133 altered the expression of several cell-cycle- and apoptosis-related genes in DU-145 and PC3 cells. Conclusions: Overall, these findings suggest that JWH-133 modulates multiple cellular responses in prostate cancer cells in a cell-line-dependent manner. However, additional mechanistic studies are required to clarify the molecular pathways underlying these effects. Full article

Background and Objectives: The effects of nicotine on wound healing and flap survival remain controversial. While smoking is associated with increased flap complications, emerging evidence suggests that nicotine may exert dose- and duration-dependent effects. This study aimed to investigate how short-term, low-dose nicotine affects flap survival and to evaluate its potential role in oxidative stress and ferroptosis. Materials and Methods: Twelve adult male BALB/c mice were randomly assigned to either a control group or a nicotine-treated group, with six mice in each group. Nicotine, at a dose of 2 mg/kg, was given subcutaneously for fourteen days before flap surgery. This treatment continued for seven days after the surgery. A dorsal random-pattern skin flap model was established in all animals. The flap necrosis area was assessed on postoperative day 7 using planimetric analysis. Serum and tissue glutathione peroxidase 4 (GPX4) levels and serum malondialdehyde (MDA) levels were measured. Histopathological evaluation included epithelialization, microvascular density, neovascularization, fibroblast density, and inflammatory cell infiltration. Results: Nicotine treatment significantly reduced flap necrosis compared with the control group. Histopathological analysis demonstrated significantly increased epithelialization and microvascular density in the nicotine-treated group, whereas no significant differences were observed in neovascularization, fibroblast density, or inflammatory cell infiltration. Biochemical analyses revealed no significant differences in serum or tissue GPX4 levels or serum MDA levels between the groups. Conclusions: Short-term nicotine administration enhanced flap survival, correlating with increased epithelialization and microvascular density, while not significantly affecting markers of oxidative stress or ferroptosis. These results imply that the positive impact of nicotine on flap viability might be largely attributable to vascular processes rather than pathways involving oxidative stress. Full article

Background: Thyroid carcinoma (THCA), especially papillary thyroid carcinoma (PTC), remains clinically challenging because recurrence and metastasis occur in a subset of patients. SMDT1 is an essential regulator of the mitochondrial calcium uniporter complex that may influence tumor progression, but its role in thyroid carcinoma is unclear. This study investigated the expression, clinical significance, and biological functions of SMDT1 in thyroid carcinoma. Methods: Public databases were used to analyze SMDT1 expression, diagnostic value, prognostic relevance, co-expression networks, functional enrichment, protein interactions, and immune infiltration. SMDT1 expression was validated in 50 paired PTC and adjacent non-tumorous tissues. In vitro SMDT1 overexpression was performed in PTC cell lines, followed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting (WB), CCK-8, colony formation, wound healing, and transwell assays. Results:SMDT1 was significantly downregulated in thyroid carcinoma tissues, PTC tissues, and PTC cell lines. Low SMDT1 expression was associated with lymph node metastasis and shorter disease-free survival. Functional analyses linked SMDT1 with mitochondrial calcium transport, oxidative phosphorylation, apoptosis, cellular senescence, and immune infiltration, including CD8⁺ T cells and activated NK cells. SMDT1 overexpression significantly suppressed PTC cell proliferation, colony formation, migration, and invasion. Conclusions:SMDT1 may function as a tumor suppressor in thyroid carcinoma and has potential diagnostic and prognostic value. Its effects may involve mitochondrial calcium homeostasis, metabolic regulation, and immune microenvironment remodeling. Full article

Plant-derived extracellular vesicles (PDEVs), also referred to as plant exosomes or exosome-like nanovesicles, have emerged as promising natural bioactive nanoparticles for cosmetic and regenerative applications. Owing to their biocompatibility, intrinsic bioactive cargo, and ability to interact with mammalian cells, PDEVs are increasingly investigated as agents for skin rejuvenation, wound healing, photoprotection, pigmentation control, and skin barrier enhancement. However, the available evidence remains fragmented across different plant sources and experimental models. This review aimed to summarize and critically evaluate the current evidence regarding the cosmetic and regenerative properties of PDEVs. Experimental studies investigating the effects of PDEVs on skin cells, reconstructed skin models, animals, or human subjects were systematically identified and analyzed. The available evidence consistently demonstrated that PDEVs promote skin regeneration and tissue repair. The most frequently reported effects included enhanced keratinocyte and fibroblast proliferation and migration, accelerated wound closure, increased collagen synthesis, reduced oxidative stress, activation of antioxidant defense pathways, and suppression of inflammatory responses. Additional studies reported improvements in skin barrier function, hydration, photoprotection, pigmentation control, and cellular senescence. Collectively, the available studies demonstrate consistent regenerative, antioxidant, anti-inflammatory, and skin-protective effects of PDEVs. Overall, PDEVs represent multifunctional bioactive nanomaterials with substantial potential for cosmetic applications. While clinical translation remains limited by regulatory and standardization challenges, cosmetic use appears to offer a more immediate route toward commercialization. Further standardization, mechanistic studies, and clinical investigations are required to support the broader implementation of PDEV-based technologies. Full article

Extracellular vesicles have emerged as promising cell-free therapeutic agents for wound healing due to their remarkable ability to modulate inflammatory responses, promote angiogenesis, and enhance tissue regeneration. These biological nanocarriers deliver bioactive cargo, including regulatory miRNAs, proteins, and lipids, to recipient cells, thereby modulating key signaling pathways governing tissue repair. However, the clinical translation of extracellular vesicle (EV)-based therapies is substantially limited by challenges in delivery efficiency. Local drug delivery systems (LDDSs) offer several key advantages, including reduced clearance by the reticuloendothelial system, enhanced biodistribution to wound sites, prolonged local residence time, and precise spatial targeting of therapeutic effects. This review systematically summarizes recent advances in EV-based therapies for wound repair, with a particular focus on in situ forming and implantable LDDSs, such as stimuli-responsive hydrogels. We comprehensively discuss the molecular and cellular mechanisms through which EVs facilitate healing across all phases of wound repair. Furthermore, we critically evaluate the evolution of these delivery platforms, transitioning from conventional passive-release systems to advanced stimuli-responsive hydrogels and microneedle systems, assessing their design rationale and integration with EV biology. We also address key translational challenges and opportunities: scalable manufacturing, standardized quality control, and regulatory pathways, offering a forward-looking view on clinical implementation of EV-LDDS hybrids in precision regenerative therapy. Full article

Objective: The usefulness of available wound debridement strategies, including endogenous autolysis and enzymatic, larval, and surgical approaches, is often limited by poor wound bed biology, availability, and invasiveness. Although copper oxide-containing dressings (CODs) have demonstrated broad wound-healing activity in basic science and clinical studies, their potential to modulate debridement has not been specifically characterized. Methods: We conducted a retrospective analysis of five severe clinical cases (six limbs) characterized with extensive necrosis, impaired perfusion, and frequently compromised systemic conditions. Sequential clinical imaging and detailed follow-up were used to assess wound bed dynamics. All cases demonstrated a period of clinical stagnation prior to COD initiation under standard wound care, ranging from 1–4 weeks in the acute cases to approximately 8 years in the chronic venous ulcer, allowing within-case temporal comparison of wound behavior before and after COD introduction, during which no other major changes in local wound management were made. Observations were interpreted in the context of relevant published basic science. Results: In five of the six limbs, major amputation or revision to a higher level had been indicated prior to COD initiation. In all cases, application of COD was associated with rapid and extensive clearance of devitalized tissue, with major wound-bed changes observed within 2–6 weeks, consistent with activation of endogenous autolytic mechanisms. Relevant published literature identifies copper-dependent pathways (CDPs), including the MMP–TIMP axis, inflammatory signaling via NF-κB, and macrophage polarization, that may provide a biologically plausible explanation for these clinical observations. Analysis of serial photographs demonstrated concurrent emergence of granulation tissue and vascularization, supporting synergism among angiogenesis, granulation tissue formation, and debridement, all induced by COD. Conclusions: The observations support the hypothesis that copper ions and CODs may amplify autolytic tissue clearance through CDPs, with concurrent synergistic interaction between angiogenesis and debridement. Full article

Sequestration is the most common complication following equine cheek tooth extraction, occurring predominantly in the mandible of younger horses. Extraction-related trauma to the peridental region may impair healing. Despite its clinical relevance, detailed knowledge of peridental anatomy remains limited. This study investigated age-related differences in the peridental region of maxillary and mandibular equine cheek teeth 07 to 09. The peridental region of 24 cheek teeth rows from six cadaver heads was sectioned horizontally at approximately 10 mm intervals. Sections were photographed and the proportion of adjacent structures (compact bone, spongy bone, maxillary sinus, nasal cavity) was quantified within a 1 mm zone of the peridental gap. Horses were assigned to three age groups. Maxillary teeth were surrounded by approximately 50% compact bone, while mandibular teeth showed a higher proportion of compact bone occlusally (60.3%) that decreased apically (to 23.7%). The proportion of compact bone generally increased with age. This descriptive anatomical study provides a novel anatomical characterization of the equine peridental region. The higher proportion of compact bone in the mandible suggests reduced bleeding into the empty alveolus. This could impair wound healing and reduce resorption capacity for bone fragments. This may explain the increased risk of sequestration. Full article

Background: Disruption of the corneal epithelial (CE) cell layer is a pathological feature of several ocular disorders including the potentially severe condition, neurotrophic keratitis (NK). The drug, Oxervate™, whose active principle is recombinant human nerve growth factor (NGF), has been shown to promote healing of the corneal epithelial layer in NK. This effect could result from NGF stimulating the repair and regeneration of corneal nerves so that they provide better trophic support for CE healing and general health. Another mechanism of NGF in promoting CE layer healing may be through direct stimulation of the division and migration of CE cells. Fetal bovine serum (FBS) has also been found to promote CE layer healing in experimental studies. Like Oxervate™, FBS contains NGF, but it also contains several other bioactive components including other growth factors. The present study compares the effects of FBS to those of NGF to examine whether the combination of bioactive components in FBS might be more effective than NGF alone in producing corneal wound healing. Methods: CE cells of the HCE-S line were grown in 96-well plates fitted with a silicon plug that occluded a 1 mm circular area in the center of each well. When the cells reached confluence, the plugs were removed, resulting in the cell layers each containing a similar central defect. Different amounts of NGF, FBS, and a combination of the two were then added to each well. The effect of these treatments on the amount of closure of the defect after 24 h was measured and compared. Results: NGF increased the amount of closure of the defect after 24 h. At a concentration of 250 nM, NGF produced a significant, 25 ± 9% increase in closure. No further increase in effect was seen when the NGF concentration was increased to 500 nM. FBS also produced an increase in the closure. At an FBS concentration of 10%, this increase was 118 ± 27%, which was significantly greater than the percentage increase produced by NGF. The addition of both 250 nM NGF and 10% FBS together produced no greater amount of closure than that produced by FBS alone. Conclusions: These findings are consistent with earlier data suggesting that NGF can promote corneal healing through a direct effect on CE cells. They also show that FBS is more effective than NGF alone in producing this effect. Since the therapeutic activity of NGF in NK may be partly mediated through a direct action on corneal epithelial cells, identifying the factors in FBS that promote corneal healing might lead to more effective treatments for NK. Full article

Neuroblastoma is an aggressive pediatric malignancy with limited therapeutic options for high-risk disease, underscoring the need for alternative treatment strategies. Drug repurposing offers a promising approach to accelerate the identification of effective anti-cancer agents. In this study, we investigated the anti-carcinogenic effects of hydroquinidine, a class IA antiarrhythmic ion channel blocker, and spiramide, a dopamine D₂/serotonin 5-HT₂ receptor antagonist and endoplasmic reticulum stress inducer, in SH-SY5Y human neuroblastoma cells. Cells were treated with increasing concentrations of each compound and evaluated using cell viability, colony formation, wound healing, proliferation, apoptosis, and quantitative gene expression assays. Both compounds induced a dose-dependent reduction in cell viability, with spiramide exhibiting greater potency than hydroquinidine. Functional assays revealed significant suppression of clonogenic survival, cell migration, and DNA synthesis, accompanied by increased oxidative stress and cell death. Molecular analyses demonstrated coordinated transcriptional regulation of apoptosis- and cell cycle-related genes, characterized by upregulation of BAX, CDKN1A, and CDKN1B, and downregulation of BCL-2 and CCND1. Notably, spiramide consistently produced stronger cytotoxic and wound-closure inhibitory effects, suggesting a greater contribution of oxidative stress- and apoptosis-associated pathways. Collectively, these findings indicate that hydroquinidine and spiramide disrupt neuroblastoma cell growth through complementary stress- and cell cycle-associated pathways and identify them as promising candidates for further preclinical evaluation. Full article

Selenium biofortification of edible sprouts is a promising strategy to enhance the cancer cell growth-inhibitory potential of plant-based foods. This study investigated the effects of selenium (Se)-enriched sunflower sprout extracts on human colorectal adenocarcinoma HT-29 cells in comparison with non-enriched sprouts. Cytotoxicity was evaluated by MTT assay, clonogenic survival by colony formation assay, wound closure by wound-healing assay, apoptosis- and cell cycle-related gene expression by qRT-PCR, and protein expression by Western blotting. Metabolite profiles were characterized using LC-MS/MS-based untargeted metabolomics. Se enrichment markedly enhanced cytotoxicity, reducing the IC₅₀ from 413.80 ± 6.00 (control) to 152.90 ± 6.00 µg/mL and increasing Emax from 59.29 ± 0.11% (control) to 75.70 ± 0.49%. The Se-enriched extract showed greater inhibition of colony formation (IC₅₀ 53.72 ± 1.12 µg/mL) and wound closure (IC₅₀ 76.07 ± 0.06 µg/mL). At the molecular level, Se-enriched sprouts upregulated Bax, caspase-3 and p21, downregulated Bcl-2, CDK4, NF-κB p65 and MMP-9, and increased Bax and p21 protein levels, linked with apoptosis-related signaling and cell cycle modulation. Metabolomics revealed significant increases in purine-related metabolites, lysophosphatidylcholine (LPC) 18:3, and choline, alongside decreases in several quinic acid derivatives and related phenolic metabolites. Se enrichment enhanced the in vitro antiproliferative activity of sunflower sprout extract in HT-29 cells and may modulate apoptosis- and cell cycle-related markers. These findings support further mechanistic and in vivo investigations of Se-enriched sunflower sprouts as a candidate functional food ingredient. Full article

Wound dressings play a crucial role in promoting tissue regeneration while protecting damaged tissue from microbial infections. The aim of this study is to produce antimicrobial PVA-chitosan membranes for wound dressing applications using Stevia rebaudiana Bertoni leaf extract (stevia) as a natural bioactive agent. Although widely recognized as a natural sweetener, stevia contains a high concentration of diterpene glycosides, particularly stevioside and rebaudioside A, together with phenolic compounds that contribute to its biological activities. Therefore, stevia was first evaluated against selected microorganisms and demonstrated effective antimicrobial activity. PVA-chitosan (P/Ch) membranes were prepared by solvent casting method by incorporating different amounts of stevia (P/Ch, P/Ch@20, P/Ch@40, and P/Ch@60). The antimicrobial activity of stevia was also successfully maintained in P/Ch membranes. Good antibacterial activity was observed against Bacillus subtilis and Escherichia coli, whereas the antifungal activity against Candida albicans was comparatively modest. Contact surface analysis showed complete bactericidal activity in Gram-negative and spore-forming bacteria. The cytocompatibility of the membranes was investigated by MTT assay. All formulations maintained a high cell viability (>80%) while the P/Ch@40 membrane increased the metabolic activity to above 100% at higher extract concentrations. In conclusion, stevia-incorporated membranes exhibited high antimicrobial activity, acceptable characteristic properties, and good cytocompatibility, suggesting that they are promising alternative biomaterials for tissue engineering applications. Full article

Diabetic wounds remain a major clinical challenge owing to persistent dysregulation of the wound microenvironment, which substantially limits the effectiveness of conventional therapies. In recent years, multifunctional hydrogels have emerged as promising platforms for diabetic wound management, attributed to their excellent biocompatibility, tunable physicochemical properties, and unique capacity to actively remodel pathological microenvironments through integrated therapeutic functions. This comprehensive narrative review provides an in-depth synthesis of the pathogenesis and current therapeutic strategies for diabetic wounds, with a particular focus on recent advances in multifunctional hydrogels, as well as their classification, design principles, mechanisms of action, and translational potential. Furthermore, emerging directions are discussed as promising approaches for next-generation therapies, including intelligent closed-loop systems, interdisciplinary technological convergence, and the integration of bioactive components derived from traditional Chinese medicine. Collectively, these advances are poised to facilitate the transition from passive wound coverage to active microenvironment remodeling, paving the way for precision and personalized diabetic wound care. Full article

Background/Objectives: A hydrogel with enhanced therapeutic properties was developed using chitosan, dextran sulfate, and Aloe vera-coated nanoparticles encapsulating eucalyptus extract. Methods: The physicochemical characteristics of the synthesized nanoparticles were evaluated using transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and antibacterial activity assays. The in vitro release profile of Eucalyptus staigeriana extract was assessed at physiological pH 7.4, and the in vivo wound healing performance was subsequently investigated in a rat model. Results: The results indicated that the nanocarrier system provided a controlled and sustained release of eucalyptus extract. Aloe vera-coated dextran sulfate/chitosan nanoparticles encapsulating E. staigeriana inhibited the growth of Staphylococcus aureus by 40%. Moreover, animals treated with Aloe vera @ DX/CS/EE nanoparticles exhibited markedly improved wound contraction, with mean reductions of 27.45%, 19.18%, 18.12%, and 7.03% compared with the control, DX/CS nanoparticles, Aloe vera @ DX/CS nanoparticles, and DX/CS/EE nanoparticles groups, respectively. Histological analysis further confirmed that treatment with Aloe vera @ DX/CS/EE nanoparticles led to superior tissue organization and accelerated dermal regeneration. Conclusions: Overall, the dextran sulfate/chitosan hydrogel coated with Aloe vera and loaded with eucalyptus extract demonstrates strong potential as an effective wound dressing material capable of enhancing healing outcomes. Full article

Background: Streptococcus mutans (S. mutans) plays a major role in dental biofilm-related infections and contributes to antimicrobial resistance. Therefore, the development of biocompatible nanomaterials with antibacterial, antibiofilm, and regenerative properties is important for dental applications. Methods: In this study, hyaluronic acid and clove extract were used as natural precursors to synthesize hyaluronic acid-clove carbon dots (HCCDs) through a hydrothermal method. The synthesized HCCDs were characterized by XRD, FTIR, TEM, SEM, SAED and EDAX analysis. The antibacterial and antibiofilm activities against S. mutans were tested. Cell viability tests, AO/PI staining, morphological observation and wound-healing assays were used to evaluate cytocompatibility in MG-63 cells. Results: A broad peak (23.449) observed from XRD coincided with an amorphous graphitic carbon structure. TEM images showed the presence of a spherical nanostructure with an average size of 4 ± 2 nm. The FTIR result verified the presence of hydroxyl, carbonyl and oxygen-containing functional groups on the HCCD surface. Their synthesized HCCDs exhibited noteworthy antibacterial and antibiofilm activity with an MIC of 62.5 µg/mL against the S. mutans. Low toxicity toward MG-63 cells was observed, with 86% cell viability at 200 µg/mL in the cytocompatibility study. Additional good cellular compatibility was confirmed using AO/PI staining and morphological analysis. Furthermore, normal cell migration was observed, as wound healing assays showed no significant difference in closure between the treated and control groups. Conclusion: HCCDs exhibited antibacterial, antibiofilm, biocompatible, and wound-healing properties, highlighting their potential for dental nanomedicine and the treatment of oral biofilm-associated infections. Full article

Background: Platelet concentrates are widely used in regenerative dentistry and maxillofacial surgery; however, the lack of protocol standardization and selection criteria results in contradictory clinical outcomes. This study aimed to perform a comparative analysis of the biological activity of various platelet concentrates obtained via different fractionation and activation procedures under uniform in vitro experimental conditions. Methods: Rat adipose-derived stem cells (ADSCs) and human EA.hy926 endothelial cells were used to evaluate four platelet concentrate types via tube formation, wound healing (scratch), and cell proliferation assays. Results: Platelet concentrates obtained by the single-centrifugation protocol (L-PRP-1) exhibited maximal retained platelet potential, corresponding to a peak 5-fold increase in cell migration. Chemical activation of plasma-based concentrates (L-PRP, P-PRP) with calcium/thrombin was critically required to trigger angiogenesis and accelerate endothelial chemotaxis. Conversely, plasma-free platelet concentrate (PFPC) exhibited a unique capacity for spontaneous activation and clot formation without exogenous inducers, triggering rapid angiogenesis and sustaining ADSC proliferation. Conclusions: Within the framework of our in vitro model, activated plasma-based forms are biologically justified for accelerated soft tissue healing and socket preservation, whereas the complete removal of plasma proteins suggests the potential utility of PFPC as a biomimetic matrix-carrier for maxillofacial tissue engineering. Full article