Search Results (9,422)

Background: Type 1 diabetes (T1D) is a complex autoimmune disease demonstrating substantial heterogeneity in age of onset, residual C-peptide levels, clinical outcomes, and therapeutic response. Although the autoimmune classification of T1D has traditionally relied on detection of autoantibodies indicating B-cell involvement, studies targeting total CD3⁺ T cells have underscored the importance of T-cell regulation. Th40 cells, a pathogenic subset of CD3⁺ T cells, first identified in NOD mice, become significantly increased during diabetogenesis. Human subjects with T1D exhibit variable but significantly elevated Th40 levels in peripheral blood. Methods: To target pathogenic effector Th40 cells, we developed OPT101, a 15-mer peptide, and found that it interacts with CD40 in association with an activated integrin, identifying a novel inflammatory receptor complex. We conducted a phase 1b, double-blind, first-in-human clinical trial to evaluate OPT101 and met the primary objectives of safety and tolerability. Results: OPT101 generated only Grade 1 and 2 adverse events. Across eight doses, administered over six weeks, no product-related immune suppression was observed. Secondary objectives included immunologic outcomes and potential efficacy. Subjects with higher Th40 levels had low or undetectable C-peptide, higher (>7.0%) HbA1c, and elevated inflammatory cytokines. Th40 levels were significantly higher in subjects diagnosed before age eighteen. OPT101 treatment significantly reduced Th40 percentages without cell ablation, increased Treg levels, and decreased inflammatory cytokines. Serum blood glucose levels and HbA1c were significantly reduced by visit 8 in treated subjects. In two subjects, 11 and 13 years post-diagnosis, with undetectable C-peptide at screening, C-peptide became detectable post-treatment. Conclusions: OPT101 proved safe and effective in human T1D subjects with only mild and a few moderate adverse events. In this short-term study, OPT101 improved beta cell functions thus warranting further exploration. Full article

Background: Sertraline, a selective serotonin reuptake inhibitor widely prescribed for depressive disorders, has been proposed to exert immunomodulatory effects through modulation of inflammatory pathways; however, clinical evidence regarding its effects on circulating cytokines remains inconsistent. This systematic review and meta-analysis evaluated the effects of sertraline on inflammatory cytokines in adults. Methods: Searches were conducted in LILACS, CINAHL, MEDLINE/PubMed, Cochrane Library, Scopus, and Web of Science to identify randomized single- or double-blind placebo-controlled trials assessing sertraline and inflammatory biomarkers. Ten studies met the eligibility criteria. Random-effects meta-analyses were performed for interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). Results: Sertraline did not significantly reduce circulating IL-6 (MD −1.06, 95% CI −2.32 to 0.19; I² = 86%; p = 0.10), IL-10 (MD < 0.01, 95% CI −0.23 to 0.23; I² = 72%; p = 0.98), or TNF-α levels (MD −0.84, 95% CI −4.04 to 2.37; I² = 72%; p = 0.61). Heterogeneity was substantial, all studies showed high overall risk of bias, and the certainty of evidence was very low for all outcomes. Conclusions: Current evidence does not support a significant or reliable anti-inflammatory effect of sertraline on circulating cytokines, and further well-designed trials using standardized inflammatory assessments are warranted. Full article

Background/Objectives: Mental and neurological disorders contribute substantially to the global burden of disease, affecting people of all ages and backgrounds. As their prevalence increases with age, their overall impact is expected to grow in the coming decades. Although psychological and pharmacological treatments are available, many patients fail to achieve satisfactory outcomes, underscoring the need for improved therapeutic strategies. Cannabis sativa L. has been used for medicinal purposes for centuries, and cannabidiol (CBD) has attracted increasing attention because of its broad therapeutic potential. Scientific studies indicate that CBD may be beneficial in several mental and neurological disorders. Methods: A comprehensive literature search was conducted to identify articles investigating the therapeutic potential of CBD and cannabis in selected disorders. Results: Evidence from preclinical and clinical studies, together with findings from the broader cannabis literature, indicates that CBD may offer therapeutic benefits in a range of conditions, including Alzheimer’s and Parkinson’s disease, anxiety disorders, and epilepsy. Emerging data also support its potential use as an adjunctive therapy for COVID-19. Current research has improved understanding of the neurobiological mechanisms underlying these disorders and the molecular pathways through which CBD may exert its effects. CBD has demonstrated good tolerability, with predominantly mild adverse effects and a favorable safety profile. Conclusions: Despite promising findings, many available studies are preclinical or involve small patient cohorts, and the mechanisms underlying the therapeutic effects of CBD remain incompletely understood. Further well-designed, randomized, controlled, multicenter trials are needed to establish the efficacy and safety of CBD and support its integration into clinical practice. Full article

Background/Objectives: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which gut–skin axis dysregulation is increasingly implicated. We conducted a prospective pilot study to describe the clinical evolution of pediatric AD following individualized, stool-guided microbiota-targeted therapy and to explore whether baseline dysbiosis markers predict outcomes beyond baseline disease severity. Methods: Twenty-one children with AD and laboratory-confirmed gut dysbiosis were enrolled consecutively at a tertiary pediatric center in Romania in a single-arm prospective pilot study. Gut microbiota was assessed using targeted culture-based stool analysis, generating a Flora Index and a binary High Putrefaction Flora classification. Individualized treatment consisted of strain-specific probiotics, prebiotics, and antifungals when indicated. Disease severity was assessed using the Patient-Oriented Eczema Measure (POEM) and Scoring Atopic Dermatitis (SCORAD) at baseline, 30 days, and 90 days. Longitudinal changes were evaluated using repeated-measures ANOVA and hierarchical regression models. Results: High Putrefaction Flora was present in 71.4% of participants. Mean POEM decreased from 14.67 ± 5.22 at baseline to 7.10 ± 3.82 at 90 days, while mean SCORAD decreased from 41.66 ± 15.28 to 17.93 ± 11.68 (both p < 0.001). Approximately 76% of participants achieved a ≥50% reduction in POEM, and 71% achieved a ≥50% reduction in SCORAD. Individualized microbiota-targeted therapy was associated with substantial improvements in both clinical and patient-reported disease severity over the 90-day follow-up. Although children with High Putrefaction Flora exhibited higher disease severity scores in unadjusted analyses, baseline disease severity was the only significant predictor of 90-day outcomes. The Flora Index provided no independent explanatory value. Conclusions: In this exploratory single-arm pilot study, individualized microbiota-targeted therapy was associated with substantial and clinically meaningful improvement in AD severity over 90 days. Dysbiosis markers were associated with disease burden but did not independently predict outcomes, suggesting that they may function primarily as indicators of baseline severity rather than prognostic biomarkers. Because of the uncontrolled study design, causal inferences regarding treatment effects cannot be made, and these findings should be considered hypothesis-generating. Adequately powered randomized controlled trials are required to determine the efficacy of individualized microbiota-targeted interventions in pediatric atopic dermatitis. Full article

Background and Objectives: Cardiovascular disease remains the leading cause of premature mortality worldwide. Subclinical glucose dysregulation, a contributor to accelerated vascular aging, is undetectable by conventional screening in apparently healthy individuals; even within the normal glycemic range, postprandial glucose excursions promote endothelial injury and inflammatory pathways independently of mean glucose levels. Hypothesis: Continuous glucose monitoring (CGM)-guided metabolic phenotyping, combined with personalized dietary optimization, structured fasting protocols, and selective longevity-oriented pharmacotherapy, constitutes a mechanistically coherent, hypothesis-generating preventive strategy that may attenuate cardiovascular risk and biological aging in apparently healthy non-diabetic adults, pending confirmation in prospective outcome trials. Materials and Methods: This narrative review synthesizes evidence from prospective cohort studies, randomized controlled trials, and mechanistic investigations connecting CGM-guided metabolic assessment with preventive cardiology and the emerging field of longevity medicine, focusing on glycemic variability biology, nutrient-sensing pathways, and the cardiovascular and longevity profiles of low-dose metformin and acarbose. Results: CGM-derived metrics capture inter-individual glycemic variability invisible to standard assessments and provide behavioral feedback for dietary personalization. Structured fasting and low-dose metformin converge on shared nutrient-sensing pathways implicated in both vascular aging and longevity, with CGM enabling objective confirmation of metabolic adaptation. Acarbose has shown cardiovascular and lifespan benefit signals in secondary trial analyses and preclinical longevity models, though these findings require replication and are not yet established in non-diabetic populations. Conclusions: We propose a four-phase research framework integrating CGM metabolic phenotyping, dietary optimization, fasting titration, and selective pharmacological augmentation for apparently healthy adults at cardiovascular risk. Prospective hard-endpoint trials are lacking, and this framework should be regarded as hypothesis-generating rather than an established clinical strategy, warranting rigorous outcome-based evaluation before clinical adoption. Full article

Background: Between 33% and 75% of women who experience intimate partner violence (IPV) sustain an IPV-related traumatic brain injury (TBI). Although IPV-related TBI is associated with adverse psychosocial outcomes, its impact on response to healthcare-based IPV interventions remains unclear. Methods: Using data from a randomized clinical trial within the Veterans Health Administration, we examined psychosocial outcomes among 60 woman veterans with past-year IPV experiences participating in two brief IPV interventions: Enhanced Care As Usual (ECAU) and Recovering from IPV through Strengths and Empowerment (RISE). Results: At pretreatment, 21 women (35%) reported a history of probable IPV-related TBI. Multilevel modeling revealed no significant main or interaction effects of TBI history for self-efficacy, empowerment, patient activation, depression, physical health symptoms, or resilience. However, there was a significant interaction of time and probable IPV-related TBI history for valued living, such that women with probable IPV-related TBI history demonstrated greater initial gains followed by slight posttreatment decline; F(2, 76.55) = 2.96, p = 0.049. There was also a significant interaction between probable IPV-related TBI history, treatment condition, and pretreatment anxiety symptoms for anxiety symptoms as an outcome, such that women with probable IPV-related TBI history in the RISE condition, who had more severe anxiety symptoms at pretreatment, reported higher anxiety symptoms on average across the study period than women without probable IPV-related TBI history in RISE; F(1, 48) = 5.04, p = 0.029. Furthermore, there was a significant interaction of probable IPV-related TBI history and pretreatment physical health symptoms for physical health symptoms as an outcome, such that women with probable IPV-related TBI histories maintained higher physical symptoms from pretreatment to the last follow-up assessment; F(1, 134) = 8.99, p = 0.004. Conclusions: No evidence of differential treatment response was detected for women with and without probable IPV-related TBI history. Findings related to valued living and anxiety suggest areas where additional support may improve implementation of brief healthcare-based IPV interventions. Full article

Background: Squamous cell carcinomas (SCCs) share squamous differentiation and may engage the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway, although their causes, biology, and treatment differ by anatomical site. We evaluated tumor response, short-term survival, and grade 3–4 adverse events after neoadjuvant immune-checkpoint blockade, with or without chemotherapy, followed by surgery. Methods: A comprehensive search of PubMed, Embase, the Cochrane Library, and clinical trial registries was conducted from inception to October 2024. Prospective and retrospective studies evaluating neoadjuvant immunotherapy, with or without chemotherapy, before surgery in patients with SCC were included. In mixed-histology studies, data were eligible only when SCC outcomes could be extracted separately. Pooled proportions and 95% confidence intervals (CIs) were estimated with random-effects models. Results: A total of 44 studies involving 2586 patients with six anatomical SCC groups were included. The pooled objective response rate (ORR) was 0.70 (95% CI, 0.59–0.80), clinical complete response (cCR) rate was 0.17 (95% CI, 0.10–0.28), and pathological complete response (pCR) rate was 0.30 (95% CI, 0.27–0.34). The pooled 1-year progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS) rates were 0.82 (95% CI, 0.79–0.86), 0.86 (95% CI, 0.75–0.92), and 0.92 (95% CI, 0.90–0.93), respectively. The pooled incidence of grade 3–4 adverse events was 0.18 (95% CI, 0.14–0.23). Because the PD-L1 subgroup contained only one study for most outcomes, checkpoint-target subgroup findings were considered exploratory. Conclusions: Existing predominantly single-arm evidence suggests antitumor activity of neoadjuvant immune-checkpoint blockade, with or without chemotherapy, in selected patients with resectable SCC. Because esophageal SCC accounted for most studies and clinical heterogeneity was substantial, these pooled proportions should not be interpreted as comparative effects or as evidence of uniform benefit across SCC sites. Full article

Cancer remains a leading global cause of morbidity and mortality, with oxidative stress playing a central role in its pathogenesis, progression, and response to therapy. Nutrition has emerged as a modifiable factor capable of influencing redox homeostasis, thereby contributing to both cancer prevention and therapeutic outcomes. This narrative review summarizes current evidence on dietary patterns, specific nutrients, and bioactive compounds that modulate oxidative stress and are associated with reduced cancer risk and improved response to treatment. A literature search was conducted using PubMed, Scopus, and Google Scholar, covering the period from 2002 to 2025 to capture contemporary dietary approaches and clinical evidence. Eligible studies addressed nutrient compounds, dietary strategies, obesity, gut microbiota, conventional cancer therapies, and clinical outcomes, with particular emphasis on mechanisms related to oxidative stress, inflammation, and immune modulation. Epidemiological evidence consistently supports the protective role of plant-based dietary patterns and reduced intake of red and processed meat, partly due to their antioxidant and anti-inflammatory properties. Nutrients such as dietary fiber, polyphenols, and omega-3 fatty acids are associated with decreased oxidative damage, improved immune responses, and enhanced therapeutic efficacy across multiple tumor types, including colorectal, breast, lung, and ovarian cancers, as well as glioblastoma. Emerging data also suggest that dietary interventions, including ketogenic diets and fasting, may influence tumor metabolism and redox balance, potentially increasing sensitivity to conventional therapies. The gut microbiota has been identified as a key mediator linking diet, oxidative stress, and cancer-related pathways. Although current evidence supports the role of nutritional strategies in targeting oxidative stress for cancer prevention and treatment, further large-scale randomized clinical trials are required to clarify their impact on survival and treatment efficacy. The integration of nutritional counseling into oncology practice represents a cost-effective, accessible, and patient-centered approach with the potential to modulate oxidative stress and improve clinical outcomes. Full article

Osteosarcopenia—defined as the coexistence of sarcopenia and osteoporosis—is increasingly recognized as a clinically important geriatric syndrome associated with falls, fractures, frailty, disability, and mortality. Beyond the simple coexistence of bone and muscle loss, emerging data suggest that osteosarcopenia may reflect systemic dysregulation of the bone–muscle–immune–metabolic network. In this narrative review, we synthesize evidence linking inflammaging, immune-cell polarization, mitochondrial dysfunction, nutrient metabolic dyshomeostasis, and gut-derived metabolites to the pathogenesis of osteosarcopenia. Multiple pathological processes—including chronic low-grade inflammation, Th17/Treg imbalance, macrophage polarization, oxidative stress, impaired mitophagy, insulin resistance, ectopic fat accumulation, and altered microbial metabolites—may converge to disrupt bone–muscle crosstalk. Notably, direct evidence from osteosarcopenic populations remains limited, and many mechanistic insights are extrapolated from osteoporosis, sarcopenia, and aging models. We further discuss current and emerging therapeutic strategies, including exercise, nutritional interventions, anti-osteoporotic agents, metabolic modulators, mitochondrial-targeted therapies, and gut-directed approaches. Longitudinal cohorts, multi-omics studies, and randomized controlled trials are urgently required to validate immunometabolic biomarkers and develop integrated interventions for osteosarcopenia. Full article

Background/Objectives: To evaluate the clinical and microbiological effects of adjunctive gaseous ozone therapy combined with full-mouth ultrasonic debridement and scaling and root planing (FMUD–SRP) in patients with generalized periodontitis. Materials and Methods: Thirty-nine patients with stage II–IV generalized periodontitis were enrolled in a randomized split-mouth clinical trial. Quadrants were assigned to receive FMUD–SRP alone or FMUD–SRP plus adjunctive gaseous ozone therapy. Ozone (2100 ppm, 80% oxygen) was applied subgingivally immediately after instrumentation during three treatment sessions. Clinical parameters were recorded at baseline, 45, and 90 days. Subgingival plaque samples were analyzed using qualitative polymerase chain reaction to detect six periodontal pathogens. Results: Both treatments resulted in significant clinical improvements over time (p < 0.05). At 90 days, ozone-treated sites showed greater probing pocket depth reduction (−1.6 ± 0.8 mm vs. −1.2 ± 0.8 mm; p = 0.02) and clinical attachment level gain (−1.1 ± 1.0 mm vs. −0.6 ± 1.0 mm; p = 0.03) compared with control sites. No significant intergroup differences were observed for bleeding on probing, plaque index, or gingival recession. A significantly greater reduction in the detection frequency of periodontal pathogens was observed in the ozone group, including complete suppression of Treponema denticola and marked reductions in other anaerobic species. Conclusions: Adjunctive gaseous ozone therapy enhances the clinical outcomes of non-surgical periodontal treatment and exerts a selective antimicrobial effect against anaerobic periodontal pathogens. Full article

Background: Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD), termed COPD-associated pulmonary hypertension (COPD-PH), and is associated with worse clinical outcomes. The efficacy and safety of pulmonary vasodilators in COPD-PH remain uncertain. Methods: We performed a systematic review and meta-analysis of randomized studies evaluating pulmonary vasodilators in adults with COPD-PH. Fifteen studies were identified, with 11 contributing to quantitative analyses. Outcomes included six-minute walk distance (6MWD), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), partial pressure of arterial oxygen (PaO₂), and systolic pulmonary arterial pressure (sPAP). Results: Pulmonary vasodilators significantly reduced mPAP (MD −3.88 mmHg, 95% CI −7.23 to −0.53) and PVR (SMD −0.90, 95% CI −1.70 to −0.10). However, no significant improvements were observed in 6MWD or PaO₂. An exploratory composite hemodynamic score supported an overall hemodynamic benefit. Subgroup analyses suggested a more favorable profile for nitric oxide donors, whereas endothelin receptor antagonists were associated with worsened oxygenation. Conclusions: Pulmonary vasodilators improve pulmonary hemodynamics in COPD-PH but do not consistently improve exercise capacity or oxygenation. Current evidence does not support routine use outside specialized centers or clinical trials, and treatment effects appear to vary by drug class. Full article

Background: The treatment paradigm for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) has undergone significant change with the advent of CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies and CD20 × CD3 bispecific antibodies (BsAbs). Although both approaches have shown high response rates in single-arm studies, the absence of prospective randomized head-to-head comparisons has resulted in true clinical equipoise. Methods: A narrative synthesis was conducted, incorporating pivotal and updated phase 2 and 3 trial data, real-world evidence, and published meta-analyses. Results: In the second-line setting, CAR-T therapy demonstrates superior event-free survival, progression-free survival, and overall survival compared to standard-of-care chemo-transplant regimens. In the third-line setting, a pooled meta-analysis indicates significantly higher complete response rates for CAR-T compared with BsAbs, as well as superior 12-month progression-free survival. BsAbs provide immediate availability, greater accessibility, more favorable neurotoxicity profiles, and are feasible for frail or elderly patients. Real-world data show that BsAb complete response rates are consistently lower than those observed in clinical trials, whereas CAR-T real-world effectiveness closely aligns with pivotal trial outcomes. Emerging phase 3 data on fixed-duration and monotherapy bispecific regimens suggest that a genuine, if less mature, curative fraction may also be achievable among BsAb-treated complete responders. Conclusions: CAR-T therapy remains the standard of care for fit, eligible patients with R/R LBCL in second- and third-line settings with curative intent, providing superior depth and durability of response and a growing potential for long-term cure. BsAbs constitute a critical therapeutic alternative for patients ineligible for CAR-T, those with rapidly progressive disease, frail or elderly individuals, and as bridging strategies. A patient-centered, scenario-specific clinical decision framework is recommended. Full article

Diabetic kidney disease (DKD) remains a major cause of advanced chronic kidney disease (CKD) and cardiovascular (CV) mortality, despite optimization of renin–angiotensin–aldosterone system (RAAS) blockade and the use of sodium–glucose cotransporter-2 inhibitors (SGLT2i). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cardiometabolic agents with significant efficacy on glycemic control, body weight, blood pressure (BP), lipid profile, and systemic inflammation. In experimental studies, GLP-1 RAs showed direct renal effects by modulating natriuresis, intrarenal hemodynamics, oxidative stress, endothelial dysfunction, and tubular apoptosis. Randomized clinical trials and real-life analyses have demonstrated reductions in albuminuria and slowing of glomerular filtration rate (GFR) decline. The first study with a primary renal endpoint for semaglutide confirms its nephroprotective potential. This narrative review synthesizes the renal mechanisms involved. The clinical evidence for GLP-1 RA in DKD positions this class alongside SGLT2i and non-steroidal mineralocorticoid receptor antagonists (ns-MRAs) for the management of patients with type 2 diabetes mellitus (T2D), CKD, and very high cardiorenal risk. Full article

Background/Objectives: Watercress (Nasturtium officinale R.Br.) is a glucosinolate-rich cruciferous vegetable with reported cardioprotective properties. However, previous human studies have relied on targeted clinical and biochemical biomarkers, limiting insight into its broader metabolic effects. This exploratory study investigated plasma metabolomic changes associated with watercress supplementation in adults with low-to-moderate cardiovascular risk using untargeted proton nuclear magnetic resonance (¹H-NMR) spectroscopy. Methods: In this randomized, single-blind, placebo-controlled pilot trial (Thai Clinical Trials Registry: TCTR20251119004), 26 participants aged 40–59 years received dried watercress capsules (8 g/day; approximately 195 mg glucosinolates/day) or placebo for 28 days. Fasting plasma samples collected at baseline and Day 28 underwent untargeted ¹H-NMR profiling. Partial least squares-discriminant analysis (PLS-DA) assessed group discrimination, while Kyoto Encyclopedia of Genes and Genomes (KEGG)-based pathway enrichment and topology analyses identified perturbed metabolic pathways. Results: A total of 209 plasma metabolites were identified. PLS-DA demonstrated modest discrimination between groups (Q² = 0.268), with 27 discriminant metabolites (variable importance in projection > 1.5) involving amino acid, nucleotide, carbohydrate, and gut microbial metabolism. Eighteen metabolic pathways were significantly perturbed, particularly galactose and fructose/mannose metabolism (p < 0.001), together with glycerolipid, purine, glycolysis/gluconeogenesis, and tryptophan metabolism. Watercress supplementation reduced metabolites associated with oxidative DNA damage, inflammatory kynurenine metabolism, and microbial co-metabolism, while increasing glycine and dimethylglycine and altered gut microbial activity. Conventional biomarkers showed a significant decrease in low-density lipoprotein cholesterol but no consistent effects on other lipids. Conclusions: Watercress supplementation was associated with coordinated metabolic alterations across multiple pathways, generating mechanistic hypotheses for its antioxidant and cardiometabolic effects. These findings are exploratory and warrant confirmation in larger, adequately powered clinical trials. Full article

Genitourinary syndrome of menopause (GSM) is a common hypoestrogenic condition marked by vulvovaginal atrophy and lower urinary tract symptoms that significantly impair quality of life in peri- and postmenopausal women. Although local estrogen therapy remains the standard of care, its use is constrained by contraindications, adherence challenges, and concerns regarding long-term safety, particularly in women with estrogen-sensitive conditions. As a result, interest has grown in regenerative, non-hormonal alternatives. Stem cell-based therapy, particularly using mesenchymal stem cells (MSCs), has emerged as a potential therapeutic strategy for restoring urogenital tissue structure and function. The current body of evidence largely consists of preclinical studies, small clinical case series, and investigations in related but distinct conditions, which provide potential mechanistic insights. Preclinical studies suggest that MSCs from adipose tissue, bone marrow, and umbilical cord promote vaginal epithelial regeneration through paracrine mechanisms, including angiogenesis, immunomodulation, extracellular matrix remodeling, and restoration of local estrogen signaling and vaginal microbiota. To date, current clinical studies have not provided direct evidence on the efficacy of characterized MSC-based therapies specifically in GSM populations. Early clinical evidence, primarily involving adipose-derived tissue products such as micro-fragmented adipose tissue, reports improvements in symptoms overlapping with GSM, including vaginal dryness, dyspareunia, urinary symptoms, and sexual function, with benefits lasting up to two to three years after a single treatment and no serious adverse events reported. However, available data are limited by small cohorts, the absence of randomized trials, and regulatory variability. This review summarizes current evidence and outlines key scientific, ethical, and regulatory challenges that must be addressed to guide future research and clarify the therapeutic potential of MSC-based approaches in GSM, ultimately enabling translation. Full article