Search Results (535)

Allergic asthma is associated with a reduction in the number of regulatory T cells (Tregs). Although interleukin-27 (IL-27) has been shown to modulate Tregs potentially through the Lymphocyte-activation gene 3 (Lag3) pathway, the underlying mechanism remains incompletely defined. Objective: This study sought to determine whether IL-27 ameliorates airway inflammation in asthma by modulating Tregs in a Lag3-dependent manner. Acute asthma was induced in wild-type (WT) and Lag3 knockout (Lag3^−/−) mice through sensitization and challenge with house dust mite (HDM). A treatment group received intranasal recombinant IL-27 prior to challenges. In WT mice, IL-27 administration significantly attenuated airway inflammation, goblet cell hyperplasia, and total cell counts in bronchoalveolar lavage fluid (BALF), along with reduced levels of Th2 cytokines (IL-4, IL-5). It also upregulated T-bet (Th1) mRNA expression, downregulated GATA-3 (Th2) and RORγt (Th17) levels, and increased the proportions of CD4⁺ Foxp3⁺ Tregs, CTLA4⁺ Tregs, and Lag3⁺ Tregs in lung tissue. Conversely, in Lag3^−/− mice, the protective effects of IL-27 were completely abrogated, with no observed increases in Treg populations or suppression of Th2/Th17 immune responses. The anti-asthmatic effect of exogenous IL-27 is associated with increased Treg frequency and upregulation of inhibitory markers, with Lag3 serving as a pivotal target on Tregs. Full article

Background: Bladder dysfunction is a complicated condition that substantially impairs quality of life for both men and women. Due to the adverse effects and limited efficacy of current therapies, new strategies must be rapidly developed. Female bladder dysfunction arises from multifaceted etiologies distinct from the predominantly male benign prostatic hyperplasia (BPH) that is the focus of existing drug development. In this study, we investigated the therapeutic potential of Quisqualis indica extract (QIE), a traditional medicinal herb that attenuates BPH-induced lower urinary symptoms (LUTS), to elucidate its underlying mechanisms in a female bladder dysfunction model. Methods and Results: A bladder dysfunction model was established by inducing partial bladder outlet obstruction (pBOO) in female Sprague Dawley rats, followed by the oral administration of QIE for 7 weeks. Voiding pattern analysis and cystometry were conducted to evaluate indicators such as voiding frequency, voiding volume, and intravesical pressure. Histological analysis of excised bladder tissue quantified smooth muscle hypertrophy and collagen deposition. Gene expression profiling of inflammatory cytokines and fibrosis-related markers within the bladder tissue was performed to assess tissue remodeling. Furthermore, pharmacological contraction studies examined the direct effects of QIE on detrusor muscle responsiveness to muscarinic and purinergic agonists. QIE administration significantly improved the elevated voiding pressure and abnormal inter-contraction intervals observed in the pBOO rats, restoring normal voiding patterns. Histological examination revealed a marked decrease in muscle hypertrophy and collagen deposition. Expression levels of pro-inflammatory cytokines (TNFα, IL-1β) and fibrosis-associated genes (TGF-β, α-SMA) were downregulated. Pharmacological contraction assays demonstrated that QIE attenuated the hypercontractile response of bladder smooth muscle to a muscarinic agonist, with concurrent reduced expression of muscarinic receptors (M₂, M₃) at the mRNA level. Conclusions:QIE ameliorates key aspects of bladder dysfunction, voiding abnormalities, inflammation, fibrosis, and hypercontractility by modulating muscarinic receptor signaling and fibrotic pathways. This study suggests that QIE warrants further investigation as a natural product-based therapeutic candidate for female bladder dysfunction. Full article

Corneal transparency depends on quiescence of stromal cells derived from neural crest cells and a well-controlled extracellular matrix. Disruption of this homeostasis causes fibrotic scarring, a leading cause of blindness. Transforming growth factor-β/Smad3 signaling drives corneal fibrogenesis, but the distinct roles of Smad2 versus Smad3 remain unclear. Smad2 ablation in neural crest cells using Wnt1-Cre mice triggers spontaneous severe corneal opacification along with massive stromal hypercellularity and fibrosis. The fibrotic phenotype occurs in the absence of injury, indicating that Smad2 is essential for balancing Smad3 activity in driving fibrotic signaling. Single-cell RNA sequencing and virtual knockout of Smad2 reveal prominent activation of Smad3-Yes-associated protein (YAP)/TEAD2-transcriptional program in Smad2-null corneas. Biochemical assays confirm that Smad2 loss results in increased Smad3 phosphorylation and formation of nuclear Smad3–YAP–TEAD2 complex. This trimeric complex induces the expression of collagen I, connective tissue growth factor, and cyclin D1. Importantly, pharmacologic inhibition of YAP/TEAD interaction with verteporfin blocks stromal hyperplasia and corneal fibrosis by suppressing the expression of fibrotic and cell cycle genes, which lead to restoration of corneal transparency in Smad2-neural crest-deficient mice. Our findings reveal a unique convergence of YAP/TEAD and TGF-β/Smad3 signaling that can be targeted with verteporfin to prevent corneal scarring and blindness. Full article

Background/Objectives: Contemporary minimally invasive surgical therapies (MISTs) for benign prostatic hyperplasia carry retreatment rates up to 32%, with holmium laser enucleation of the prostate (HoLEP) increasingly used as salvage therapy. Prior reviews focused on salvage HoLEP (sHoLEP) following transurethral resection; however, technical challenges specific to the post-MIST field remain uncharacterised. We aimed to characterise technical barriers during sHoLEP following contemporary MISTs, with secondary evaluation of efficacy, safety and feasibility. Methods: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines (PROSPERO: CRD420261321711), five databases were searched from inception to February 2026. Studies reporting sHoLEP outcomes in adults with prior MIST were included. Qualitative findings were synthesised thematically; quantitative outcomes reported by three or more studies underwent random-effects meta-analysis. Risk of bias was assessed using methodological index for non-randomized studies methodological index for non-randomized studies (MINORS) and certainty of evidence using grading of recommendations, assessment, development, and evaluation (GRADE). Results: Ten studies (354 sHoLEP, 3618 primary HoLEP (pHoLEP) patients) were included. Technical difficulty was MIST-type dependent: thermoablative procedures and prostatic artery embolisation preserved the enucleation plane, while prostatic urethral lift (PUL) introduced morcellation-specific challenges including blade jamming and staged procedures. Meta-analysis revealed no difference in operative time or tissue weight, but reduced enucleation efficiency (weighted mean difference; WMD −0.11 g/min, p = 0.027) and peak urinary flow improvement (WMD −3.0 mL/s, p < 0.001). Both findings were sensitive to analysis, losing significance on restriction to predominantly MIST cohorts, and the enucleation efficiency result additionally lost significance on removal of the most heavily weighted study (p = 0.94). Complication rates were equivalent (odds ratio (OR) 0.92, p = 0.787). Conclusions: sHoLEP is safe and efficacious following contemporary MIST. Surgeons should anticipate MIST-specific challenges, particularly morcellation difficulties after PUL requiring tailored instrumentation. Prospective MIST-specific studies are needed. Full article

Lipedema is a chronic adipose tissue disorder characterized by disproportionate and often painful enlargement of the extremities, occurring predominantly in women. Despite increasing clinical recognition, the underlying pathophysiology remains incompletely understood and is likely multifactorial. Existing evidence suggests contributions from vascular alterations, adipose tissue remodeling, inflammatory activation, hormonal influences, and lymphatic dysfunction. This review proposes a hypothesis-generating integrative framework in which lipedema may reflect a regenerative imbalance of subcutaneous adipose tissue. Within this model, genetically and hormonally modulated endothelial permeability could promote activation of perivascular adipose-derived stromal/stem-cell niches and stromal vascular fraction signaling pathways, thereby facilitating coupled angiogenesis and adipogenesis. Progressive adipocyte hyperplasia and hypertrophy may subsequently contribute to inflammatory remodeling, pain generation, and secondary impairment of dermal and subdermal lymphatic drainage. The proposed framework attempts to integrate clinical, histological, imaging, molecular, and endocrine observations into a biologically coherent conceptual model. At the same time, the review emphasizes the current limitations of the available evidence, the heterogeneity of lipedema phenotypes, and the ongoing controversies regarding disease progression, obesity overlap, and the relative role of lymphatic dysfunction. Finally, the potential mechanistic rationale of lymphatic-sparing liposuction is discussed in the context of tissue decompression, restoration of lymphatic transport, and interruption of persistent adipose remodeling. The model presented here should be interpreted as a hypothesis-generating conceptual scaffold requiring prospective validation. Importantly, the present framework should be interpreted as a biologically plausible and hypothesis-generating conceptual model rather than a definitive mechanistic doctrine. Several proposed interactions remain associative and require prospective biological validation. Full article

Background/Objectives: To compare the incidence of postoperative acute urinary retention (AUR) between traditional open laminectomy and percutaneous endoscopic lumbar surgery (PELS) using a large-scale real-world database, with specific stratification by urologic status, age, and sex. Methods: A retrospective, propensity score-matched analysis was conducted using the TriNetX Global Health Research Network (2015–2024). Adult patients undergoing PELS were compared to those undergoing open laminectomy. To rule out the confounding effect of routine intraoperative catheterization, the primary outcome was defined as de novo AUR occurring between 24 h and 3 months postoperatively. Subgroup analyses were performed for patients with benign prostatic hyperplasia (BPH), females, and age-stratified cohorts (<70 vs. ≥70 years). This study was approved by the Institutional Review Board (IRB/REC: CE25727C) and conducted under a waiver of informed consent. Results: In the matched cohorts of non-BPH males, females, and patients aged < 70 years, PELS was associated with a statistically significant reduction in AUR risk (Hazard Ratios: 0.445, 0.649, and 0.403, respectively) compared to open surgery. However, in males with BPH, the protective benefit of the endoscopic technique was attenuated and did not reach statistical significance (p = 0.0744), suggesting the study was underpowered for this subgroup or that baseline obstruction remains a dominant risk factor. Conclusions: Percutaneous endoscopic lumbar surgery was associated with a significantly lower risk of postoperative AUR compared to open laminectomy, particularly in patients without preexisting urologic obstruction. This benefit is likely attributable to minimized tissue trauma and the anti-inflammatory effects of continuous saline irrigation. However, in patients with BPH, baseline pathology outweighs surgical factors, necessitating medical prophylaxis regardless of the surgical approach. Full article

Background: Acrylamide (ACR), a toxic compound formed during high-temperature cooking of carbohydrate-rich foods, is known to induce multi-organ toxicity, including oxidative and inflammatory lung injury. N-Acetylcysteine (NAC), a precursor of glutathione (GSH), possesses potent antioxidant and anti-inflammatory properties that may counteract ACR-induced pulmonary damage. This study investigated the protective effects of NAC against ACR-mediated lung toxicity, with an emphasis on the GSK-3β/Nrf2/NF-κB signaling axis. Methods: Forty male Wistar rats were allocated into four groups: control, NAC (250 mg/kg/day), ACR (50 mg/kg/day), and NAC + ACR. After 11 days of treatment, lung tissues were examined histopathologically using H&E, PAS, and Masson’s trichrome stains. Oxidative stress biomarkers (MDA, SOD, GPx, CAT, GSH) were quantified biochemically. Immunohistochemistry and qRT PCR assessed expression of Nrf2, NF-κB, IL-1β, and Caspase 3, while ELISA measured TNF α, IL-6, Bax, Bcl 2, and GSK 3β. Results: ACR exposure resulted in severe lung injury characterized by alveolar wall edema, epithelial hyperplasia, leukocytic infiltration, goblet cell hyperplasia, and peribronchiolar collagen deposition. These pathological changes were accompanied by a marked increase in MDA, NF-κB, IL-1β, TNF α, IL-6, Bax, Caspase 3, and GSK 3β, together with significant reductions in antioxidant enzymes and Nrf2/HO 1/NQO1 expression. NAC co-administration significantly ameliorated ACR-induced lung damage, restoring normal histological architecture, reducing fibrosis, and normalizing goblet cell activity. NAC also reversed oxidative stress, enhanced Nrf2 and downstream antioxidant responses, suppressed NF-κB-mediated inflammation, and mitigated apoptosis. Notably, NAC downregulated ACR-induced GSK 3β activation, thereby contributing to balanced redox and inflammatory signaling. Conclusions: NAC confers significant protection against ACR-induced pulmonary toxicity through its antioxidant, anti-inflammatory, and anti-apoptotic activities. These effects are mediated, at least in part, by modulation of the GSK 3β/Nrf2/NF-κB pathway. NAC demonstrates promising therapeutic potential for preventing chemically induced lung injury. Full article

Cryptocaryon irritans, a ciliated protozoan parasite, is the causative agent of marine white spot disease and results in significant economic losses in mariculture. In this study, golden pompano (Trachinotus ovatus) were challenged with C. irritans at different infection doses (2000, 4000, and 8000 theronts per fish) for 48 h to evaluate histopathological, oxidative stress, immune, and intestinal microbiota responses. Histopathological analysis revealed pronounced tissue damage in the gills, skin, intestine, and liver, with severity positively correlated with infection intensity. Typical lesions included intestinal mucosal damage, hepatic vacuolation, gill epithelial hyperplasia, and skin epidermal thickening. Hepatic malondialdehyde (MDA) levels increased significantly with infection intensity, while superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) showed non-linear activation patterns. Catalase (CAT), alkaline phosphatase (AKP), and acid phosphatase (ACP) activities were consistently suppressed. Immune-related gene expression exhibited tissue-specific regulation, with myd88 downregulated in gills but upregulated in skin, while pro-inflammatory cytokines (il-1β and il-8) and il-10 were significantly elevated. Infection also altered intestinal microbiota composition, reducing beneficial bacteria (e.g., Photobacterium) and increasing opportunistic pathogens such as Vibrio. These findings provide insights into host–parasite–microbiota interactions in T. ovatus and improve our understanding of the physiological and immune responses of fish to C. irritans infection. Full article

Coronary artery bypass grafting (CABG) using the autologous saphenous vein (SV) remains widely performed for obstructive atherosclerosis; however, vein graft disease drives recurrent ischaemia through early thrombosis and progressive intimal hyperplasia, and accelerated atherosclerosis developing within the grafts. Extracellular vesicles (EVs) are membrane-bound particles that transfer proteins, lipids, and microRNAs between cells. They modulate endothelial dysfunction, vascular smooth muscle cell phenotypic switching, inflammation, and coagulation, which are core processes in vein graft remodelling. Arterialisation exposes the vein to abrupt rises in shear stress, cyclic stretch, and intraluminal pressure. These forces increase EV release and reshape EV cargo in experimental systems, suggesting a potential mechanism for amplifying early graft injury which warrants direct investigation in vein tissue. This review synthesises current evidence for cell-specific EV contributions from ECs, vascular smooth muscle cells, platelets, and macrophages, and appraises EV-associated microRNAs with biomarker potential relevant to graft failure pathways. We also review therapeutic strategies that may modulate EV signalling including antiplatelet therapy, statins, KCa3.1 inhibition, and pro-reparative mesenchymal stromal cell-derived EVs. No published clinical studies evaluate EV-based biomarkers specifically for saphenous vein graft patency, and none prospectively predict saphenous graft failure. CABG provides a well-defined time zero event that enables longitudinal sampling and risk stratification. Prospective studies linking EV phenotypes and miRNA signatures to imaging-defined graft outcomes are needed to support clinical translation. Full article

As survival rates among patients with gynaecological cancers continue to improve, fertility preservation has become an increasingly important aspect of comprehensive cancer care, particularly for younger women diagnosed during their reproductive years. The impact of treatment on fertility varies according to cancer type, stage, and modality, necessitating individualised preservation strategies. Fertility preservation is both feasible and safe in carefully selected patients with early-stage gynaecological cancers. Oocyte and embryo cryopreservation remain the most widely accepted techniques, particularly when time allows for ovarian stimulation. Fertility-sparing surgeries, such as radical trachelectomy and conservative management of early endometrial cancer, have shown promising oncological and reproductive outcomes. However, barriers including access, timing, and awareness continue to limit broader implementation. In modern society, fertility-preserving strategies should form an integral part of treatment planning for reproductive-aged women with gynaecological malignancies. Early referral to a fertility specialist, patient-centred counselling, and a coordinated multidisciplinary approach are essential to optimise both oncological and reproductive outcomes. Further research and education are required to refine guidelines and expand access to fertility-preserving care. This review presents the current fertility preservation options available to women with gynaecological cancers, including cervical, ovarian, and endometrial malignancies, and highlights the importance of early multidisciplinary intervention in delivering personalised care. Full article

Titanium dioxide nanoparticles (TiO₂ NPs), widely used as food additives, frequently coexist with high-fat diets (HD) in modern dietary patterns, yet their combined in vivo toxicity remains poorly understood. This study investigated the multi-organ effects of co-exposure to TiO₂ NPs or food-grade E171 and HD in male C57BL/6J mice. Mice were randomly assigned to six groups and fed regular or high-fat diets containing 1 wt% TiO₂ NPs or E171 for 13 weeks. Histopathology, serum biochemistry, organ coefficients, and open-field behavioral tests were used to assess tissue injury and functional alterations. Co-exposure to TiO₂ NPs and HD markedly exacerbated tissue damage across multiple organs. In the liver, more severe ballooning degeneration, necrosis, and inflammatory infiltration were observed, accompanied by altered liver enzymes and reduced organ coefficients. Intestinal injury was characterized by crypt distortion and increased inflammation, particularly in the HD + TiO₂ group. Testicular tissues showed disorganized seminiferous tubules, loss of spermatogenic cells, and interstitial hyperplasia. In the brain, hippocampal neurons exhibited pyknosis and disarray, with decreased brain coefficients and impaired exploratory behavior. E171 induced similar but milder effects. These findings indicate that HD enhances TiO₂ NPs induced multi-organ toxicity, highlighting the health risks of realistic co-exposure to dietary nanoparticles and high-fat foods. Full article

Aging is characterized by progressive degeneration of neuromuscular junctions (NMJs), which significantly contributes to muscle weakness and the development of sarcopenia. Photobiomodulation (PBM), a non-invasive therapeutic method based on the use of low-intensity light, has shown promising results in mitigating muscle degeneration in both experimental and clinical studies. The aim of this study was to evaluate the ultrastructural effects of photobiomodulation on neuromuscular junctions and skeletal muscle fibers in the m. vastus lateralis muscle of aged rats using light and transmission electron microscopy. Male Wistar rats (18 months old, body weight 650–800 g, n = 10) were subjected to photobiomodulation of the right m. vastus lateralis muscle (650 nm, 6 J/cm², four consecutive daily sessions of 3 min each). The contralateral left limb served as an untreated control. Muscle samples were analyzed by light and transmission electron microscopy. Histological examination revealed typical age-related changes in control muscles, including variability in muscle fiber diameter, centrally located nuclei, and an increased volume of connective tissue. Ultrastructural analysis confirmed signs of skeletal muscle aging, such as myofibril fragmentation, sarcomere disorganization, lipofuscin accumulation, and tubular aggregate formation. Morphometric analysis of neuromuscular junctions after photobiomodulation showed an increase in the number of active zones on the presynaptic membrane, elongation of the postsynaptic membrane, and a reduction in the width of the synaptic cleft. In addition, mitochondrial hyperplasia was observed in presynaptic terminals, while the total number of synaptic vesicles decreased. These findings indicate a compensatory reorganization of neuromuscular junctions and suggest that photobiomodulation can enhance their functional activity in aged skeletal muscle. Full article

Background: Unhealthy expansion of adipose tissue (AT) due to excessive dietary intake of omega-6 or overnutrition stimulates the overaccumulation of the extracellular matrix (ECM), resulting in AT metabolic dysregulation. Hypertrophic conditions, excessive adipose depots, and hypoxia stimulate the overproduction of collagenous and non-collagenous proteins, which pathophysiologically initiate the pro-fibrotic signaling pathway associated with fibrosis progression, resulting in atherosclerosis and cardiovascular diseases. Methods: We aimed to investigate adipocyte plasticity in response to a varying ratio of omega-3 (ω3) to omega-6 (ω6) supplementation during the chemically induced adipogenic differentiation of human mesenchymal stem cells. Additionally, changes in lipid accumulation, adipocyte hypertrophy and hyperplasia, active lipid metabolites, and inflammatory cytokine profiles were evaluated. Furthermore, conditioned media from adipocytes treated with different ω3/ω6 ratios were applied to platelets to assess inflammatory responses through prostaglandin and thromboxane measurements. Results: A 1:3 ratio of ω3/ω6 (20:60 µM) significantly reduced lipid accumulation, promoted brown-like adipocyte morphology, and decreased apoptosis and reactive oxygen species (ROS) generation, as confirmed via FACS analysis. Transcriptional control of adipose tissue expansion was confirmed by the downregulation of LIPIN1 and COL1A1 mRNA expression and p-prostaglandin12-R protein levels in a 1:3 ratio when compared with 1:1, 1:2, 1:4, or 2:6 ratios of ω3/ω6. Notably, a 1:3 ratio of fatty-acid-treated adipocyte-conditioned media-treated platelets significantly reduced platelet activation and aggregation, as evidenced by lower p-thromboxane A2 protein levels. Conclusions: Supplementation with a 1:3 (20:60 µM) ω3/ω6 ratio favored the development of lean adipocytes, evidenced by the decreased lipid storage achieved by mitochondrial thermogenesis, which attenuated minimal adipocyte expansion and metabolic inflammation. Full article

This study aims to evaluate the therapeutic efficacy of emodin (EMO) in rheumatoid arthritis (RA) and to verify whether its underlying mechanism involves the blockade of pathological angiogenesis via the inhibition of the nuclear factor-kappa B (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling axis. Bovine type II collagen-induced arthritis (CIA) mouse models and lipopolysaccharide (LPS)-stimulated EA.hy926 endothelial cells were utilized in this study. The effects of EMO on joint pathological alterations, the expression of NF-κB/HIF-1α/VEGF axis proteins, inflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β)), and angiogenic capacity were assessed using histopathological analysis, Western blotting, immunohistochemistry (IHC), immunofluorescence, and tube formation assays. Furthermore, small interfering RNA (siRNA) interference targeting key molecules was employed to validate the molecular mechanisms underlying the therapeutic effects of EMO. In the CIA model group, the ankle joints of mice exhibited pronounced inflammatory infiltration, synovial hyperplasia, and bone destruction. Compared with the model group, both the EMO and methotrexate (MTX) treatment groups demonstrated attenuated synovial hyperplasia and cartilage destruction, along with significantly downregulated expression levels of key NF-κB pathway proteins, HIF-1α, and VEGF in joint tissues (p < 0.001). In vitro experiments revealed that EMO treatment significantly reduced the LPS-induced secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) (p < 0.001), and decreased both the number and total length of tubular structures formed by endothelial cells compared to the control (p < 0.001). Notably, siRNA-mediated knockdown of p65 resulted in decreased intracellular protein levels of HIF-1α and VEGF, accompanied by a significant reduction in tube formation (p < 0.001). This study demonstrates that EMO alleviates pathological damage in RA by inhibiting the activation of the NF-κB signaling pathway, which subsequently downregulates pathological angiogenesis and inflammatory responses mediated by the HIF-1α/VEGF axis. These findings provide a robust experimental basis for the potential application of EMO as a therapeutic agent for RA. Full article

Background/Objectives: Finasteride and dutasteride are 5α-reductase inhibitors that block the conversion of testosterone to dihydrotestosterone, reducing androgenic stimulation of tissues such as the prostate and hair follicles. Used mainly for benign prostatic hyperplasia and androgenic alopecia, finasteride selectively inhibits type-2 5α-reductase isoenzyme, while dutasteride inhibits both type-1 and type-2. Although sexual adverse effects like erectile dysfunction are well-documented, emerging evidence suggests possible neuropsychiatric reactions—including depression, suicidal ideation, and cognitive decline—potentially linked to reduced neurosteroid synthesis, such as that of allopregnanolone. Causality cannot be inferred from spontaneous reporting data. This study aimed to assess pharmacovigilance signals for psychopathological disorders associated with finasteride and dutasteride in the FAERS database. Methods: Cleaned FAERS data referring to years up to 2025 after deduplication were analyzed, excluding non-serious cases and those without the drug as the sole suspect (MedDra 29.0). Reporting Odds Ratios (RORs) with 95% CIs were calculated to compare psychiatric reactions between finasteride and dutasteride. Python 3.11 was used to screen and summarize relevant cases, accounting for differences in total case numbers. Results: This pharmacovigilance study analyzed FAERS data to assess the neuropsychiatric and sexual adverse reactions associated with finasteride and dutasteride. Depression, anxiety, suicidality, and libido-related issues were reported more frequently for finasteride, especially in younger men using low-dose therapy for alopecia. Potential mechanisms include reduced neurosteroid synthesis, androgen/sex-hormone axis disruption, altered hippocampal neurogenesis, and dopaminergic changes. Conclusions: A baseline psychiatric assessment and the regular monitoring of mood, sexual function, and suicidal ideation are recommended. Limitations include under-reporting, reporting bias, and a lack of incidence data. The findings underscore the need for ongoing surveillance and controlled studies to clarify the clinical significance of these signals. Full article