Background Lower urinary tract symptoms (LUTS), highly prevalent among aging men, adversely affect the quality of life. Pharmacological management has evolved with multiple drug classes, but real-world prescribing patterns in India have not been adequately studied. Thus, we evaluated prescription trends among Indian urologists for the management of male LUTS, assessed symptom patterns, evaluated factors influencing choice of fixed-dose combination (FDC), with special focus on silodosin-mirabegron FDC, and identified adverse events (AEs) and adherence. Methods This cross-sectional, questionnaire-based survey was performed over three months (January 2, 2026, to April 5, 2026) and included 110 Indian urologists actively managing male patients with LUTS. A 27-item structured questionnaire captured demographic characteristics, clinical practice patterns, and prescribing preferences for LUTS pharmacotherapy, including monotherapies, combination therapies, and FDCs, along with AEs and adherence. Results Of 135 urologists invited, 110 (81.48%) completed the survey. LUTS mainly involved a combination of storage, voiding, and post-micturition symptoms (n = 59, 53.6%). As a class, α1-blockers were the most frequently prescribed monotherapy (n = 109, 99.1% frequent/very frequent use), with silodosin (n = 98, 89.1%) and tamsulosin (n = 84, 76.4%) being most preferred. Use of dutasteride (n = 108, 98.2%) exceeded finasteride (n = 13, 11.8%). In patients with benign prostatic hyperplasia (BPH) with overactive bladder, silodosin-mirabegron was the most favored FDC (n = 97, 88.2%). FDCs of α1-blockers with muscarinic receptor antagonists and β-3 adrenergic agonists were preferred due to their proven efficacies (n = 83, 75.5% and n = 87, 79.1%, respectively) and lower incidences of AEs (n = 69, 62.7% and n = 80, 72.7%). Common AEs included dry mouth (n = 73, 66.4%), anejaculation (n = 69, 62.7%), and headache (n = 67, 60.9%). Moderate adherence (25%-75%) was reported by 95 (86.4%) urologists. Conclusion Adherence to pharmacotherapy, as assessed by participating urologists, was moderate, with urologists preferring silodosin as first-line therapy and silodosin-mirabegron FDC for mixed LUTS.

Background and Objectives: The main neurodegenerative diseases (NDs)-Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS)-represent a growing global health burden with no available disease-modifying therapies. Curcumin, a polyphenol from Curcuma longa, is a promising candidate owing to its pleiotropic antioxidant, anti-inflammatory, and neuroprotective profile observed mainly in preclinical models, but the poor oral bioavailability (<1%) and negligible BBB penetration (<0.1%) have substantially limited curcumin's clinical translation. The objective of this work was to critically examine the therapeutic potential of curcumin in NDs, focusing on advanced drug delivery systems (DDSs) designed to overcome its pharmacokinetic barriers. Methods: This is a narrative, non-systematic review of PubMed/MEDLINE, Scopus, and Web of Science. The review is organized around five complementary thematic areas selected to span the full translational pipeline of curcumin in neurodegeneration, from mechanistic rationale to clinical applicability: (1) molecular mechanisms, addressing the pleiotropic activities that justify therapeutic interest; (2) pharmacokinetic barriers, the principal obstacle to clinical translation; (3) the evolution of drug delivery systems (DDSs), documenting the technological strategies developed to overcome these barriers; (4) disease-specific applications, evaluating the available evidence across the four main NDs; and (5) translational limitations, identifying the methodological and regulatory gaps that must be closed to enable clinical implementation. Results: Curcumin exhibits neuroprotective activity in preclinical models of the four NDs analysed, acting on six interconnected mechanisms and the gut-brain axis. Four generations of DDSs have been developed, from phytosomes and clinically used lipid dispersions (Meriva[®], BCM-95[®], Longvida[®], and Theracurmin[®]) to fourth-generation systems (biomimetic nanoparticles, MOFs, microneedles, 3D scaffolds, hydrogels, and carbon dots) that substantially increase the bioavailability in preclinical studies. Combination strategies, such as curcumin with resveratrol and dutasteride, show preliminary clinical signals in ALS. However, clinical translation remains limited: over 80% of positive animal findings have not been replicated in humans, formulation characterization is frequently incomplete, and most trials lack CNS-exposure biomarkers. Importantly, most of the reported bioavailability claims are based on total curcumin measurements (parent aglycone plus its inactive Phase II conjugates) rather than the active aglycone alone, a methodological limitation that should be considered when interpreting the magnitude of the bioavailability improvements reported for novel formulations. Conclusions: Curcumin exhibits pleiotropic neuroprotective activity in preclinical models of AD, PD, MS, and ALS, mediated by interconnected antioxidant, anti-inflammatory, anti-amyloidogenic, mitochondrial, and gut-brain axis mechanisms. However, its poor systemic bioavailability (<1%), minimal blood-brain barrier penetration, and extensive first-pass metabolism have limited clinical translation. Advanced drug delivery systems (including lipid-based carriers (liposomes, solid lipid nanoparticles, and nanostructured lipid carriers), polymeric nanoparticles (PLGA and chitosan), and bioinspired vesicles (exosomes)) are essential in order to overcome these barriers. Nevertheless, the formulation heterogeneity, limited long-term safety data, and reliance on preclinical models remain major obstacles; a definitive clinical translation will therefore require well-characterized formulations validated in phase II/III trials with cerebrospinal fluid exposure biomarkers, the pharmacokinetic monitoring of active aglycone (rather than total curcumin including inactive conjugates), and adaptive trial designs in neurological populations.

Background/Objectives: Colorectal cancer (CRC) remains a leading cause of cancer-associated mortality worldwide. The current therapeutic interventions are heavily constrained by the development of resistance and severe systemic toxicity. To address these challenges, this study integrated a multi-disciplinary framework involving high-throughput in silico screening followed by in vitro experimental validation to identify novel genetic targets of CRC and evaluate the efficacy of FDA-approved drugs. The primary objective was to identify safe and selective therapeutic agents capable of modulating their effect. Methods: The methodology employed a systematic screening of recent large-scale Genome-Wide Association Studies (GWASs) to pinpoint novel targets, followed by in silico pathogenicity prediction, homology modelling and high-throughput virtual screening of over 1615 FDA-approved drugs. The prioritized candidates were validated in vitro using MTT cytotoxicity assays and differential gene expression analysis across CRC cell lines (HCT116 and HT29) and a non-tumorigenic control, Human embryonic kidney cell line HEK293. Results: In silico analysis identified CLUH, CLSTN3 and SLC11A2 as novel potential targets. Based on in silico predicted deleterious mutations and subsequent molecular docking-based virtual screening, Telmisartan, Dutasteride and Venetoclax were prioritized. This prioritization was supported by their high binding affinity and dose-dependent cytotoxicity in MTT assays; thus, suggesting their repurposing potential for CRC treatment. Telmisartan exhibited a superior therapeutic profile not only in terms of the statistically significant cytotoxicity (p < 0.01), but also its selective effect on HCT116 and HT29 when compared to high safety profile in HEK293. This was further validated when Telmisartan selectively downregulated CLUH and SLC11A2 in CRC cell lines, HCT116 and HT29 while maintaining expression levels in the non-cancerous HEK293 cell line remained significantly unaffected. Furthermore, a 100 ns molecular dynamics simulation confirmed the stable binding conformation and structural reliability of the SLC11A2 (Trp179Ser)-Telmisartan complex. Conclucions: Our findings conclude that Telmisartan is a promising candidate for drug repurposing for CRC treatment and capable of modulating selected novel biomarkers CLUH and SLC11A2. However, further multi-omics-based confirmatory studies and pre-clinical validation studies are needed in the future to confirm the long-term efficacy of this repositioning strategy.

Hair follicle homeostasis is influenced by hormonal pathways, the scalp microenvironment, and environmental stressors such as pollution, UV radiation, and oxidative stress. Elissara[®], a polyphenol-enriched botanical ingredient, has shown benefits for scalp moisturization, barrier function, sebum regulation, and redness. Building on these scalp-level benefits, we investigated Elissara's effects on follicular signaling, survival-associated biomarkers, oxidative damage, and androgen-related pathways as potential contributors to follicular health, using in silico, in vitro, and ex vivo models. Molecular docking (AutoDock Vina) of the main Elissara bioactives (oleuropein, hydroxytyrosol, verbascoside, carnosic acid, carnosol, and quercetin) identified SRD5A2 as a favorable predicted target, with individual binding energies ranging from -8.70 to -9.73 kcal/mol, approaching finasteride/dutasteride reference values. As an exploratory approach, simultaneous multi-ligand docking showed favorable global docking outputs for several targets, indicating that multiple bioactives could be structurally accommodated within complementary regions of the binding site. In human follicle dermal papilla cells, Elissara significantly increased BrdU incorporation to 245.70% of control at 0.002% and reduced SRD5A2 protein levels by 18.48% at 0.006%. In human scalp explants, Elissara at 200 µg/mL increased β-catenin, Bcl-2, and collagen IV under basal conditions and counteracted acute PM2.5/UVA-induced alterations in β-catenin, Ki67-positive cells, Bcl-2, IGF-1, collagen IV, and protein carbonylation. Together, these findings support the potential of Elissara as a promising nutricosmetic ingredient for supporting follicular resilience through multiple follicle-relevant pathways. Clinical studies assessing hair growth outcomes are needed to determine whether these preclinical findings translate into measurable benefits.

This study aimed to construct a ready-to-use, spheronized drug particle-embedded iron(III)-reinforced carboxymethyl cellulose hydrogel (Fe[3+]-CMC HG) as a novel long-acting injectable (LAI) platform for hydrophobic drugs. Dutasteride (DTS), a lipophilic 5α-reductase inhibitor prescribed for benign prostatic hyperplasia, was selected as a model compound. Uniform spherical DTS particles (∼180 μm) were fabricated using a dual centrifugation technique, with excellent flowability. Low-molecular-weight CMC (90 kDa, 100 mg/mL) formed a mechanically reinforced HG with 0.1% (w/v) Fe[3][+] (designated 90K-0.1) through coordination with carboxyl and hydroxyl groups, yielding high viscoelasticity and restricted spreading. Prior to administration, the spherical drug particles were homogeneously incorporated into the CMC HG via hydrogen bonding through two-syringe mixing process, preserving their original particle size and crystallinity. In vivo studies in rats exhibited that intramuscular administration of 90K-0.1 provided a markedly prolonged pharmacokinetic profile over 56 days, comparable to that of native high-molecular-weight CMC HG (700 kDa, 20 mg/mL) and a poly(lactic-co-glycolic acid)-based in situ forming implant (ISFI). Furthermore, Fe[3][+]-CMC HG elicited substantially reduced local inflammation at the injection site compared with native CMC HG and ISFI. Collectively, these findings support Fe[3][+]-CMC HG as an effective and biocompatible LAI platform for hydrophobic drugs such as DTS.

Steroid 5α-reductases (5αRs) catalyze the irreversible, NADPH-dependent reduction of Δ[4]-3-ketosteroids. This process regulates major steroid signaling pathways, including neurosteroid biosynthesis, androgen activation, and glucocorticoid metabolism. By governing these processes, 5αRs influence GABAergic and dopaminergic neurotransmission, and behavioral responses to stress and reward. Although the two principal isoenzymes, 5αR1 and 5αR2, have overlapping functions, they are increasingly recognized as functionally distinct. 5αR1 supports constitutive neurosteroid synthesis in several brain regions. Conversely, 5αR2, long known for converting testosterone to dihydrotestosterone during male sexual differentiation, has emerged as the enzyme that mediates rapid allopregnanolone production in the prefrontal cortex of males during acute stress. These advances may provide a framework for understanding the complex neurobehavioral profile of 5αR inhibitors such as finasteride and dutasteride. These drugs have been associated with depression, anxiety, suicidality, sexual dysfunction, and, in some individuals, persistent sexual, somatic, and neuropsychiatric symptoms after discontinuation. At the same time, 5αR inhibition may have therapeutic value in conditions characterized by excessive or maladaptive neurosteroid signaling, including tic disorders, impulse-control disorders, and substance use disorders. In this comprehensive review, we synthesize pharmacological, genetic, and behavioral evidence on the distinct contributions of 5αR1 and 5αR2 to steroid signaling across stress, sex, and development. Finally, we outline several open questions in the biology of 5αRs, the resolution of which will be essential to advancing toward mechanistically precise and clinically actionable interventions.