Search Results (2,836)

Objective: Visceral adipose tissue is a primary driver of insulin resistance and dysglycemia in type 2 diabetes (T2D), yet its clinical assessment remains challenging. This study aimed to validate neck circumference (NC) as a novel, practical anthropometric biomarker for estimating visceral fat area (VFA) and identifying metabolic risk in a T2D cohort, facilitating its integration into public health and primary care screening strategies. Methods: In a cross-sectional study of 1139 T2D patients, we collected data on NC, biochemical parameters (fasting plasma glucose, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and precisely measured VFA and subcutaneous fat area (SFA) via bioelectrical impedance analysis (Omron HDS-2000). We employed Pearson’s correlation and multivariate logistic regression to analyze the relationship between NC and metabolic indicators. Receiver operating characteristic (ROC) curve analysis was used to establish sex-specific NC cut-off values for predicting abnormal VFA. Results: The cohort comprised 687 (60.3%) males and 452 (39.7%) females. NC demonstrated strong positive correlations with VFA (p < 0.001), as did body mass index (BMI), waist–hip ratio (WHR), and SFA. In males, NC was further positively correlated with key metabolic biomarkers including fasting insulin, Insulin Resistance Index, triglycerides, and creatinine. ROC analysis identified NC > 39.5 cm for males and >35.5 cm for females as the optimal cut-off points for detecting abnormal visceral adiposity, highlighting its diagnostic utility. Conclusions: NC serves as a highly accessible and effective biomarker for visceral adiposity and associated metabolic dysfunction in patients with T2D. The established sex-specific cut-off values provide a simple, non-invasive tool for risk stratification in clinical and public health settings, enabling early intervention and improved management of metabolic disease. Full article

Background and Objectives: Glioblastoma (GBM) is the most aggressive primary tumor of the central nervous system, characterized by high invasiveness and poor prognosis. Inflammation in the tumor microenvironment, including the presence of immunosuppressive M2-macrophages (CD163+), plays a key role in disease progression. The aim of this study was to evaluate serum levels of interleukin-22 (IL-22) in Bulgarian patients with GBM and to analyze its diagnostic role, its relationship with systemic inflammatory markers (NLR), metabolic parameters, and the infiltration of CD163+ cells. Materials and Methods: The study included 41 newly diagnosed patients with GBM and 46 healthy controls. Serum IL-22 levels were measured by ELISA, and the density of CD163+ cells in the tumor tissue was analyzed immunohistochemically. Statistical analysis included Mann–Whitney test, ROC analysis, binary logistic regression, and Kaplan–Meier survival analysis. Results: GBM patients showed significantly higher levels of IL-22 compared to healthy controls (p = 0.001). ROC analysis demonstrated moderate diagnostic ability of IL-22 (AUC = 0.713), with high levels being a potential risk factor for the disease (OR= 2.51). A weak inverse correlation was found between IL-22 and neutrophil-to-lymphocyte ratio (NLR) (p = 0.048). Although IL-22 levels alone did not affect overall survival, patients with high levels of the cytokine and dense stromal infiltration of CD163+ macrophages tended to have shorter overall survival (p = 0.080). Conclusions: IL-22 is a potential diagnostic biomarker, probably reflecting the systemic inflammatory response in GBM. Its prognostic value might be contextually dependent on the tumor microenvironment, as high levels of IL-22 in combination with immunosuppressive macrophages may contribute to a more aggressive course of the disease. Full article

Background: Catheter ablation is a validated treatment for ventricular arrhythmias (VA), but conventional radiofrequency (RF) energy may cause collateral injury due to non-selective thermal damage. Pulsed Field Ablation (PFA), a non-thermal modality based on irreversible electroporation, offers myocardial tissue selectivity and enhanced safety. While PFA is widely adopted for atrial arrhythmias’ ablation, its application in the ventricles remains an evolving frontier. Methods: We report a single-center experience using the Centauri PFA system integrated with a focal, contact-force sensing irrigated catheter (Tacticath™ SE, Abbott Laboratories, St. Paul, MN, USA) in four consecutive patients with drug-refractory VA. Two patients presented with frequent premature ventricular complexes (PVC) arising from the right and left ventricular outflow tract, respectively, while two had ischemic cardiomyopathy with recurrent scar-related ventricular tachycardia (VT). All procedures were guided by high-density mapping using the EnSite X system (Abbott Laboratories, St. Paul, MN, USA). Procedural safety, acute efficacy, and early follow-up outcomes were assessed. Results: All ablations achieved acute procedural success without complications. In both PVC cases, PFA led to immediate and complete suppression of ectopy, with a ≥95% reduction in arrhythmic burden at 12- and 9-months follow-up, respectively. In the VT cases, the arrhythmogenic substrate was effectively modified, rendering the clinical VT non-inducible. ICD interrogation during a 9-month follow-up showed complete absence of recurrent sustained VT. No coronary spasm, atrioventricular block, pericardial effusion, or other adverse events occurred. Conclusions: In this initial experience, focal PFA using a contact-force sensing catheter appeared feasible and effective for both focal and scar-related VA. This system provides an intuitive workflow similar to RF ablation. While our data suggest a favourable safety profile, larger studies are required to definitively confirm safety margins near critical structures. Full article

Spinal cord injury (SCI) remains a major clinical challenge due to the limited regenerative capacity of the central nervous system (CNS). Effective scaffolds for repair must combine mechanical compatibility with host tissue, controlled degradation matching the time course of regeneration, and microarchitectural features that promote neuronal survival. Electrospun nanofibrous scaffolds mimic the structural and mechanical features of the extracellular matrix, providing critical cues for neuronal adhesion and glial modulation in neural regeneration. Here, we fabricated biodegradable poly(lactic acid)/poly(ε-caprolactone) (PLA/PCL) scaffolds using a dichloromethane/tetrahydrofuran (DCM/THF) solvent system to induce surface porosity via solvent-driven phase separation. The DCM/THF solvent system formulation produced nanofibers with porous surfaces and increased area for cell interaction. PLA/PCL scaffolds showed a Young’s modulus of ~26 MPa and sustained degradation, particularly under oxidative conditions simulating the post-injury microenvironment. In vitro, these scaffolds enhanced neuronal density up to fivefold and maintained ~80% viability over 10 days in primary neuron–glia cultures. Morphometric analysis revealed that DCM/THF-based scaffolds supported astrocytes with preserved process complexity and reduced circularity, indicative of a less reactive morphology. In contrast, scaffolds fabricated with 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) displayed reduced bioactivity and promoted morphological features associated with astrocyte reactivity, including cell rounding and process retraction. These findings demonstrate that solvent-driven control of scaffold microarchitecture is a powerful strategy to enhance neuronal integration and modulate glial morphology, positioning DCM/THF-processed PLA/PCL scaffolds as a promising platform for CNS tissue engineering. Full article

Flowering promoting factor 1 (FPF1) is a key regulator of plant flowering time. While the functions of the FPF family have been characterized in species such as Arabidopsis and rice, systematic studies on the tomato FPF family remain limited. In this study, we comprehensively analyzed the FPF family in tomato (Solanum lycopersicum L.), identifying five SlFPF members in the tomato genome. Phylogenetic analysis classified these genes into five distinct subgroups, and chromosome mapping revealed their distribution across three chromosomes, with the highest density on chromosome 1. Promoter analysis identified a range of putative cis-acting elements related to abiotic stress and hormonal responses. Differential expression analysis of various tissues showed that the five SlFPF genes exhibit varying expression levels, where SlFPF1 had a significantly higher expression compared to the others. Following treatments with abiotic stresses (NaCl, PEG, dark, and low light) and phytohormones (GA, MeJA, ABA, and SA), SlFPF1 expression is notably higher under GA treatment than under other conditions. Based on these findings, SlFPF1 and GA treatments were selected for further functional analysis. The results show that GA treatment significantly promotes multiple morphological traits, including root length, stem diameter, leaf area, plant height, dry weight, and fresh weight. However, silencing SlFPF1 expression led to a reduction in all these traits. Moreover, in SlFPF1-silenced plants, GA treatment failed to enhance root length, leaf area, fresh weight, and dry weight, indicating that GA-dependent growth promotion in tomato plants relies on SlFPF1. This study provides a theoretical foundation for understanding the SlFPF gene family and its role in plant growth and stress responses. Full article

Background: Age-related declines in respiratory muscle strength and ventilatory efficiency can impair functional capacity and metabolic health in older adults. Inspiratory muscle training (IMT) has been proposed as a practical intervention to counteract these changes, yet its systemic effects remain unclear. This study aimed to examine the effects of short-term IMT on functional capacity, diaphragm thickness, and liver tissue characteristics in healthy elderly men. Methods: Thirty community-dwelling men aged 60–80 years were randomly assigned to an IMT or control group. The IMT group performed four weeks of breathing exercises using a POWERbreathe^® device at 40% of maximal inspiratory pressure, with a weekly 10% increase in pressure. Pre- and post-intervention assessments included the six-minute walk test (6MWT), diaphragm thickness and liver density via computed tomography, and quality of life (QoL; SF-12). Results: Four weeks of inspiratory muscle training significantly improved diaphragm thickness (11.7%), fatty liver density (FLD) (+16.7%), and six-minute walk performance (+5.3%), with large time × group effects favoring the IMT group. While the physical quality of life showed modest, comparable improvements, mental health outcomes demonstrated a moderate, time-dependent improvement without a significant group-by-time interaction. Conclusions: Short-term IMT improved diaphragmatic function and functional capacity in older men and was associated with favorable changes in a liver-related biomarker; however, given that only a single liver-related metric was assessed, these findings should not be interpreted as evidence of overall improvements in liver health. Full article

Background/Objectives: Advanced glycation end products (AGEs) and carotenoids are systemic indicators of metabolic and oxidative status, yet their influence on ocular tissue biomechanics remains unclear. This study investigated the relationships between systemic AGEs and skin carotenoid levels, as well as corneal biomechanical properties in glaucoma patients. Methods: A retrospective observational analysis was performed on 676 patients (1278 eyes) who attended the glaucoma clinic at Shimane University Hospital between May 2019 and August 2024. Fingertip skin autofluorescence (sAF)-based AGE scores using AGE Sensor^® and skin carotenoid scores using the Veggie Meter^® were collected as part of systemic evaluation. Corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal compensated intraocular pressure (IOPcc) were measured using the ocular response analyzer (ORA). Associations between systemic variables, AGEs, carotenoids, and ORA parameters were analyzed using univariate tests, mixed-effects regression models, and quartile-based comparisons. Results: The mean AGEs and carotenoid scores were 0.42 ± 0.10 arbitrary units and 338.5 ± 130.8 optical density units, respectively. Via a univariate analysis, an inverse association was found between carotenoid level and CRF; however, via multivariate analyses, neither AGEs nor carotenoid levels were associated with IOPg, IOPcc, CH, or CRF in any analysis. In contrast, demographic parameters showed significant associations with ORA parameters. Via quartile-based comparisons, a significant inverse correlation was found between AGEs and carotenoids (p < 0.0001). Conclusions: In conclusion, sAF-measured AGEs and skin carotenoids showed no remarkable associations with corneal biomechanical properties. AGEs and carotenoids demonstrated an inverse relationship with each other, and each marker was associated with several demographic parameters. Full article

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and many patients cannot undergo curative surgery due to frailty. Multimodal prehabilitation: combining exercise, nutrition, and psychological support improves functional readiness, but its biological impact on the PDAC tumor microenvironment (TME) is unclear. In this exploratory pilot study, we profiled resected PDAC tissues from prehabilitation-treated patients and matched controls using NanoString GeoMx Digital Spatial Profiling across immune, tumor, and stromal compartments (n = 4). Transcriptomic signatures were analyzed via differential expression, pathway enrichment, and MCP-counter deconvolution; protein-level validation used multiplex immunofluorescence (n = 8). Ligand–receptor modeling assessed cell–cell communication, and prognostic relevance was evaluated in TCGA-PDAC (n = 178). Prehabilitation was associated with increased NK-cell cytotoxicity, interferon response, and chemokine recruitment, as well as higher neutrophil signatures (p < 0.01) and reduced fibroblast signatures (p < 0.05). Tumor regions showed lower MAPK and PI3K/AKT activity, while stroma exhibited decreased TGF-β and Wnt signaling. Immunofluorescence confirmed neutrophil infiltration and reduced fibroblast density. TCGA analysis linked neutrophil-high/fibroblast-low profiles to longer survival (1044.6 vs. 458.7 days, p = 0.0052). These findings suggest prehabilitation may promote a more immune-active, less fibrotic TME in PDAC, resembling transcriptional states associated with improved survival. Prospective studies integrating biological and clinical endpoints are warranted. Full article

Gibberellin (GA)-based seedless cultivation is widely used in the skin-edible interspecific table grape (Vitis labruscana × Vitis vinifera) ‘Shine Muscat’, yet when and how GA treatment reshapes fracture-type texture during berry development remains unclear. This study aimed to identify developmental stages and tissue/cell-wall features associated with GA-dependent differences in berry fracture behavior. We integrated intact-berry fracture testing at harvest (DAFB105), quantitative histology of pericarp/mesocarp tissues just before veraison (DAFB39) and at harvest, sequential cell-wall fractionation assays targeting pectin-rich (uronic acid) and hemicellulose/cellulose-related pools at cell division period, cell expansion period and harvest, and stage-resolved RNA-Seq across the same three developmental stages. GA-treated berries had a larger diameter and showed a higher fracture load and a lower fracture strain than non-treated berries at harvest, while toughness did not differ significantly. Histology revealed thicker pericarp tissues and lower mesocarp cell density in GA-treated berries, together with increased cell-size heterogeneity and enhanced radial cell expansion. Cell wall analyses showed stage-dependent decreases in uronic acid contents in water-, EDTA-, and Na₂CO₃-soluble fractions in GA-treated berries. Transcriptome profiling indicated GA-responsive expression of putative cell expansion/primary-wall remodeling genes, EXORDIUM and xyloglucan endotransglucosylase/hydrolases, at DAFB24 and suggested relatively enhanced ethylene-/senescence-associated transcriptional programs together with pectin-modifying related genes, Polygaracturonase/pectate lyase and pectin methylesterase, in non-treated mature berries. Collectively, GA treatment modifies mesocarp cellular architecture and pectin-centered wall status in a stage-dependent manner, providing a tissue- and cell wall–based framework for interpreting fracture-related texture differences under GA-based seedless cultivation in ‘Shine Muscat’. Full article

Objectives: Polycystic ovary syndrome (PCOS) is a heterogeneous disorder with diverse pathogenetic mechanisms and clinical manifestations. Phenotype D PCOS is characterized by oligomenorrhoea and polycystic ovaries without hyperandrogenism. Altered adipokine profiles may contribute to reproductive and metabolic disturbances. Chemerin is an adipokine involved in inflammatory and metabolic processes. It remains unclear whether altered chemerin levels in PCOS reflect metabolic dysfunction alone or are directly associated with hyperandrogenism. The aim of this study was to compare serum chemerin levels in women with normoandrogenic PCOS and a control group. Methods: This cross-sectional preliminary study included 49 women with phenotype D PCOS and 40 healthy, age- and body mass index (BMI)-matched controls. Anthropometric, biochemical, hormonal parameters, and serum chemerin concentrations were assessed. Results: Serum chemerin concentrations did not differ significantly between the groups. In the PCOS group, the 95% confidence interval ranged from 198.61 to 234.37, while in the controls, it ranged from 187.13 to 216.21. In women with PCOS, chemerin showed significant positive correlations with weight, BMI, waist and hip circumference, total adipose tissue, and both gynoid and android fat content. Positive correlations were also observed with highly sensitive C-reactive protein (hs-CRP), insulin, glucose, triglycerides, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and a negative correlation was found with high-density lipoprotein (HDL) cholesterol. Chemerin was weakly negatively correlated with sex hormone binding globulin (SHBG) and positively correlated with the free androgen index (FAI). In the control group, chemerin correlated positively with CRP, insulin, triglycerides, total and gynoid adipose tissue, and negatively correlated with HDL cholesterol and SHBG. Conclusions Although chemerin levels did not differ from controls, chemerin was associated with metabolic and inflammatory markers in both groups. These findings should be considered preliminary due to the limited sample size. Chemerin may reflect metabolic and inflammatory status rather than hyperandrogenism in normoandrogenic PCOS. Full article

This study aimed to evaluate the effects of an ethanolic extract from Punica granatum L. (EE-PG) on bovine ovarian tissue vitrification, focusing on follicular morphology, ultrastructure, stromal cell density, collagen distribution, redox status, and mRNA expression of antioxidant-related genes. Bovine ovarian cortex fragments were divided into a fresh control group for in vivo tissue evaluation or vitrified either with the base vitrification solution (αMEM) alone or supplemented with different concentrations of EE-PG (10, 50, and 100 µg/mL), and subsequently stored in liquid nitrogen for 5 days. After warming, fragments were allocated for morphological and oxidative stress analyses or incubated for 24 h to resumption of cellular metabolism. The concentrations of 10 and 100 µg/mL preserved follicular morphology immediately after warming, and were therefore selected for ultrastructural evaluation. Both concentrations mitigated vitrification-induced damage. Gene expression analysis showed decreased levels of catalase (cat), Glutathione Peroxidase 1 (gpx1), and Nuclear Factor Erythroid 2-Related Factor 2 (nrf2) compared with the fresh control, whereas Superoxide Dismutase (SOD) enzymatic activity increased after incubation with 10 µg/mL EE-PG compared with all experimental groups. Moreover, Malondialdehyde (MDA) levels in tissues treated with 10 or 100 µg/mL were comparable to fresh controls after incubation. Overall, EE-PG at 10 or 100 µg/mL in the vitrification solution supported the maintenance of tissue morphology, redox balance—despite the downregulation of essential antioxidant genes, which may be associated with a reduced demand for enzymatic antioxidant defense—and cellular metabolism, indicating potential for improving bovine ovarian tissue vitrification outcomes. Full article

Background: Irisin, a muscle-derived hormone, enhances the energy metabolism by activating the brown adipose tissue and acts as a bone-forming agent across the entire life span. No consistent clinical data in humans have been published so far to highlight if blood irisin as glucose/bone biomarker should be refined based on the vitamin D status (deficient or sufficient). Therefore, we aimed to objectively assess the level of irisin in female adults with abnormal and normal vitamin D status, as reflected by the level of 25-hydroxyvitamin (25OHD) in relationship with glucose and bone metabolic parameters. Methods: This pilot, prospective, exploratory study included eighty-nine menopausal women aged over 50. We excluded subjects with malignancies, bone and metabolic disorders, insulin treatment, and active endocrine disorders. Fasting profile included glycaemia, insulin, and glycated haemoglobin A1c (HbA1c). Then, 75 g oral glucose tolerance test (OGTT) included glycaemia and insulin assay after 60 and 120 min. Bone status involved bone turnover markers and central dual-energy X-ray absorptiometry providing bone mineral density (BMD) and trabecular bone score. Results: Eighty-nine subjects were included in the following two groups depending on 25OHD: vitamin D-deficient (VDD) group (N = 48; 25OHD < 30 ng/mL) and vitamin D-sufficient (VDS) group (N = 41; 25OHD ≥ 30 ng/mL). The two groups had similar age and menopausal period (62.29 ± 10.19 vs. 63.56 ± 8.16 years, respectively; 15.82 ± 9.55 vs. 16.11 ± 9.00 years, p > 0.5 for each). A statistically significant higher body mass index (BMI) was found in VDD vs. VDS group (32.25 ± 5.9 vs. 28.93 ± 4.97 kg/m², p = 0.006). Circulating irisin was similar between the groups as follows: median (IQR) of 91.85 (44.76–121.76) vs. 71.17 (38.76–97.43) ng/mL, p = 0.506. Fasting profile and OGTT assays showed no between-group difference. Median HOMA-IR in VDD group pointed out insulin resistance of 2.67 (1.31–3.29). Lowest mean/median T-scores at DXA for both groups were consistent with osteopenia category, but they were confirmed at different central sites as follows: femoral neck in both groups [VDD versus VDS group: −1.1 (−1.20–−0.90) vs. −1.1 (−1.49–−0.91), p = 0.526, respectively], only at lumbar spine for VDS group (T-score of −1.18 ± 1.13). The correlations between irisin and the mentioned parameters displayed a different profile when the analysis was performed in the groups with different 25OHD levels. In VDD group, irisin levels statistically significantly correlated with serum phosphorus (r = −0.32, p = 0.022), osteocalcin (r = −0.293, p = 0.038), P1NP (r = −0.297, p = 0.04), HbA1c (r = 0.342, p = 0.014), and BMI (r = 0.408, p = 0.003). Conclusions: This pilot study brings awareness in the analysis of irisin in relationship with glucose and bone-related biomarkers correlates, showing a distinct type of association depending on 25OHD level, which might represent an important crossroad in the multitude of irisin-activated signal transduction pathways. Full article

Background: Mechanical loading is a fundamental regulator of bone remodelling; however, the mechanotransduction mechanisms governing alveolar bone adaptation under tensile-dominant orthodontic loading remain insufficiently defined. In particular, the molecular pathways associated with tension-driven cortical modelling in the periodontal ligament (PDL)–bone complex have not been systematically interpreted in the context of advanced biomechanical simulations. Methods: A nonlinear finite element model of the alveolar bone–PDL–tooth complex was developed using patient-specific CBCT data. Three loading configurations were analysed: (i) conventional orthodontic loading, (ii) loading combined with corticotomy alone, and (iii) a translation-dominant configuration generated by the Bone Protection System (BPS). Pressure distribution, displacement vectors, and stress polarity within the PDL and cortical plate were quantified across different bone density conditions. The mechanical outputs were subsequently interpreted in relation to established mechanotransductive molecular pathways involved in osteogenesis and angiogenesis. Results: Conventional loading generated compression-dominant stress fields within the marginal PDL, frequently exceeding physiological thresholds and producing moment-driven root displacement. Corticotomy alone reduced local stiffness but did not substantially alter stress polarity. The BPS configuration redirected loads toward a tensile-favourable mechanical environment characterised by reduced peak compressive pressures and parallel (translation-dominant) displacement vectors. The predicted tensile stress distribution is compatible with activation profiles of key mechanosensitive pathways, including integrin–FAK signalling, Wnt/β-catenin–mediated osteogenic differentiation and HIF-1α/VEGF-driven angiogenic coupling, suggesting a microenvironment that may be more conducive to cortical apposition than to resorption. Conclusions: This study presents a computational–molecular framework linking finite element–derived tensile stress patterns with osteogenic and angiogenic signalling pathways relevant to alveolar bone remodelling. The findings suggestthat controlled redirection of orthodontic loading toward tensile domains may shift the mechanical environment of the PDL–bone complex toward conditions associated with osteogenic than resorptive responses providing a mechanistic basis for tension-induced cortical modelling. This mechanobiological paradigm advances the understanding of load-guided alveolar bone adaptation at both the tissue and molecular levels. Full article

Hair loss disorders, particularly androgenetic alopecia (AGA), are common conditions that carry significant psychosocial impact. Current standard therapies, including minoxidil, finasteride, and hair transplantation, primarily slow progression or re-distribute existing follicles and do not regenerate lost follicular structures. In recent years, regenerative medicine has been associated with a gradual shift toward approaches that aim to restore follicular function and architecture. Stem cell-derived conditioned media and exosomes have shown the ability to activate Wnt/β-catenin signaling, enhance angiogenesis, modulate inflammation, and promote dermal papilla cell survival, resulting in improved hair density and shaft thickness with favorable safety profiles. Autologous cell-based therapies, including adipose-derived stem cells and dermal sheath cup cells, have demonstrated the potential to rescue miniaturized follicles, although durability and standardization remain challenges. Adjunctive interventions such as microneedling and platelet-rich plasma (PRP) further augment follicular regeneration by inducing controlled micro-injury and releasing growth and neurotrophic factors. In parallel, machine learning-based diagnostic tools and deep hair phenotyping offer improved severity scoring, treatment monitoring, and personalized therapeutic planning, while robotic Follicular Unit Excision (FUE) platforms enhance surgical precision and graft preservation. Advances in tissue engineering and 3D follicle organoid culture suggest progress toward producing transplantable follicle units, though large-scale clinical translation is still in early development. Collectively, these emerging biological and technological strategies indicate movement beyond symptomatic management toward more targeted, multimodal approaches. Future progress will depend on standardized protocols, regulatory clarity, and long-term clinical trials to define which regenerative approaches can reliably achieve sustainable follicle renewal in routine cosmetic dermatology practice. Full article

Extracellular vesicle (EV)-based therapies have emerged as promising, cell-free approaches for dental tissue regeneration. This narrative review integrates mechanistic insights, therapeutic efficacy data, and safety and delivery considerations from in vitro and in vivo studies to elucidate the molecular mechanisms by which EVs, particularly those from dental pulp stem cells (DPSCs) and mesenchymal stem cells (MSCs), drive regenerative processes via key signalling axes (PI3K/Akt, MAPK, BMP/Smad, and Hedgehog). Preclinical studies demonstrate that unmodified and engineered EVs enhance odontogenic differentiation, angiogenesis, bone repair, and immunomodulation in models of pulp regeneration, alveolar bone defects, osteonecrosis, and periodontitis. Isolation and purification methodologies were also evaluated, comparing ultracentrifugation, size-exclusion chromatography, and density-cushion approaches, and discussing how protocol variations affect EV purity, dosing metrics, and functional reproducibility. Early-phase clinical evaluations report only low-grade transient adverse events, underscoring a generally favourable safety profile. Despite these encouraging results, significant challenges remain: heterogeneity in EV cargo composition, lack of standardised potency assays, and incomplete long-term safety data. The review highlights the urgent need for rigorous, harmonised regulatory frameworks and robust quality control measures to ensure that EV-based modalities can be translated into safe, effective, and reproducible therapies in regenerative dentistry. Full article