Search Results (4,156)

A naive Bayesian classifier (NBC) combined with principal component analysis (PCA) effectively differentiates the dose-dependent effects of certain groups of psychoactive drugs based on their impact on the amplitude–spectral characteristics of electrocorticograms (ECoG) in rats. This approach has been shown to be useful for pharmacological screening of agents with unknown or poorly understood activity. Despite previously obtained optimistic results, classification determination for some drugs was inaccurate, necessitating the search for possible ways to improve the predictive effectiveness of the proposed algorithm. One possible approach would be to use as input quantitative data not only the impact of the psychoactive drugs studied on the amplitude–spectral characteristics of ECoG but also connectivity changes, including the average coherence power of different pairs of leads. The aim of this study was to compare the accuracy of NBC in classifying the pharmacological mechanism of action of agents with well-known mechanisms (test set) using pharmaco-EEG data on changes in the amplitude–spectral characteristics of ECoG, coherence, and the combined use of two data sets. Materials and methods. Experiments were performed on Wistar rats with chronically implanted ECoG electrodes. The training set, relative to which the effects of the pharmacological agents from the test set were classified, were the matrices of effects of 12 pharmacological agents: the NMDA antagonist dizocilpine, the D2/D3 antagonists haloperidol and sulpiride, the M-anticholinergic tropicamide, the H1/5HT2A receptor blocker hydroxyzine, the acetylcholinesterase inhibitor galantamine, the alpha-2 adrenergic agonist dexmedetomidine, the alpha-2 adrenergic antagonist atipamezole, the adenosine receptor blocker caffeine and the GABA-mimetics aminophenylbutyric acid (phenibut), bromdihydrochlorophenylbenzodiazepine (phenazepam) and 5-ethyl-5-phenyl-2,4,6(1H,3H,5H)-pyrimidinetrione. The test set included various drugs with tropism for the targets of the training set drugs: dopamine receptor antagonists chlorpromazine, droperidol, tiapride and raclopride, H1-histamine blockers diphenhydramine and promethazine, 5-HT2-receptor blockers ritanserin and glemenserin, acetylcholinesterase inhibitor ipidacrine, alpha2-adrenergic receptor antagonist yohimbine, alpha2-adrenergic agonists medetomidine and xylazine, GABA-mimetics 5-ethyl-5-(1-methylbutyl)-2,4,6(1H,3H,5H)-pyrimidinetrione and chloral hydrate. The analysis of the ECoG signal included the calculation of 132 amplitude–spectral characteristics and 75 coherence indicators, which, using the PCA, led to new integrative indicators used for further classification of the NBC. Results and discussion. For each drug in the test set, the median similarity probability with a particular group from the training set was calculated, which was used to assess the classification quality. It was found that, when using the amplitude–spectral characteristics of ECoG, the proposed methodological approach allows for the identification of the ECoG effects of several groups of psychoactive drugs, including D2/D3-dopamine, M-cholinergic, H1-histamine, and 5-HT2-serotonin receptor blockers, AChE inhibitors, GABA-mimetics, and alpha-2-adrenergic receptor agonists and antagonists. This approach enabled the correct classification of 18 of 24 groups in the test set. When using changes in coherence indices as the initial data, the classification accuracy also amounted to 18 of 24 groups. When combining the two data sets, the number of correctly identified NBC groups was 20 of 24 groups. When comparing the classification during training (confusion matrix), it was found that coherence data or adding coherence data to the data based on changes in amplitude–spectral characteristics leads to a statistically significant (p < 0.01 in both cases) increase in accuracy. Conclusions. The obtained data demonstrated high accuracy in classifying the pharmacological activity of the test sample drugs using any of the three compared approaches. Despite the lack of statistically significant differences between them, classification based on the combined dataset demonstrated a higher number of “correct” similarities. This allows us to recommend the approach based on combined data of drug effects on amplitude–spectral characteristics and coherence as the most promising for further studies using pharmaco-EEG screening. Full article

Background and Objectives: Apparent non-response to phosphodiesterase type 5 (PDE5) inhibitors is common, but the label conflates inadequate instruction or drug exposure, partial or absent response, treatment discontinuation, and coexisting clinical contributors. This narrative review presents an author-proposed structured reassessment framework, not a new or validated diagnostic classification. Materials and Methods: PubMed/MEDLINE was searched from database inception to 7 August 2026 using a documented, reproducible search strategy, with targeted checks of guideline, regulatory, clinical, observational, and mechanistic sources; selection was purposive, without a registered protocol, quantitative synthesis, or certainty-of-evidence grading. Results: PDE5 inhibitors preserve nitric oxide-cyclic guanosine monophosphate signaling but require sexual stimulation, adequate exposure, and sufficient erectile physiology. In one specialist-referral cohort, 88 of 250 men (35.2%) responded after structured re-education, being 88 of the 115 (76.5%) who accepted it, which should not be generalized. The framework separates trial and exposure adequacy, observed response documented with validated measures where feasible, targeted evaluation of contributing domains, and shared selection of oral optimization or an established non-oral option. Persistent clinically meaningful oral-PDE5-inhibitor non-response is defined by principle rather than by a fixed number of attempts, agents, or mandatory daily tadalafil. Conclusions: Structured reassessment may clarify why an observed response is inadequate and may support preference-sensitive management; whether it does so better than existing guidance has not been tested. Switching agents or daily tadalafil is not a prerequisite and should not delay vacuum therapy, intracavernosal injection, or penile-prosthesis discussion. Full article

Background: Despite more than 30 licenced antiseizure medications (ASMs), approximately one third of people with epilepsy remain drug-resistant, and developmental and epileptic encephalopathies represent one of the greatest unmet needs in epilepsy therapeutics. The past decade has produced a substantial reorientation of ASM discovery, driven by epilepsy genetics, new disease models, advances in drug screening, and innovative therapeutic modalities. Objective: The objective of this study was to review the contemporary clinical-stage pipeline of ASMs with novel or differentiated mechanisms of action, organized by molecular target, while placing recent regulatory successes and instructive failures within the broader transition toward mechanism-based, precision, and potentially disease-modifying therapies. Findings: A 2024 pipeline analysis identified more than 200 epilepsy therapies in preclinical or clinical development; at the cutoff of the present literature search (30 June 2026), over 40 compounds had reached phase II or III, with the majority directed at DEEs. Functional-state-selective sodium channel modulation has emerged as a leading conceptual advance supported by converging mechanistic and early clinical evidence, exemplified by relutrigine (PRAX-562), a preferential persistent-current inhibitor for which a regulatory decision is pending in SCN2A/SCN8A-DEEs, and vormatrigine (PRAX-628), whose large open-label effect was not reproduced in a controlled (blinded) trial. Several of the efficacy figures summarized here derive from congress presentations, interim analyses, or open-label extensions and await full peer-reviewed publication. Parallel advances include the selective Kv7 opener azetukalner; the dual-mechanism benchmark cenobamate; cholesterol-24-hydroxylase inhibition (soticlestat); selective serotonergic agonism (bexicaserin); glutamatergic precision agents (radiprodil); subtype-selective GABA_A modulators (darigabat, ganaxolone); and gene-directed therapies (zorevunersen, elsunersen). Pre-symptomatic intervention in tuberous sclerosis complex provides an early, single-trial clinical proof of principle for delaying and reducing the incidence of epilepsy in a genetically defined population; this should not yet be equated with established disease prevention. Conclusions: The pipeline reflects an ongoing shift from broad symptomatic agents toward mechanism-led, genotype-matched, and potentially disease-modifying treatments. This shift is tempered by a persistent translational gap between early signals and randomized-trial confirmation, and by the preliminary status of much of the supporting evidence. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

Antimicrobial resistance is a major global health challenge that has created an urgent need for new antibacterial agents capable of overcoming emerging resistance mechanisms. Among nitrogen-containing heterocycles, pyrrolidine has been widely investigated in medicinal chemistry due to its structural versatility, favourable physicochemical properties, and ability to enhance interactions with biological targets. This review provides a comprehensive and critical overview of pyrrolidine-based compounds investigated for antibacterial applications. Relevant studies describing clinically approved antibiotics, natural products, synthetic derivatives, hybrid molecules, and antibacterial adjuvants containing a pyrrolidine scaffold were collected, classified, and critically evaluated, with particular emphasis on structural features, antibacterial activity, and structure–activity relationships. The reviewed evidence demonstrates that the pyrrolidine moiety is present in several antibacterial drug classes, including carbapenems, cephalosporins, fluoroquinolones, lincosamides, streptogramins, and tetracyclines, where it contributes to improved target affinity, antibacterial potency, and pharmacokinetic behaviour. Numerous recently reported pyrrolidine derivatives have shown promising activity against clinically relevant, multidrug-resistant bacterial pathogens. The pyrrolidine scaffold is valuable for the design of next-generation antibacterial agents and resistance-modifying compounds, though further in vivo studies and pharmacological evaluation are required to support their clinical development. Full article

Background: The emergence of antifungal resistance and the limited number of clinically available antifungal drug classes necessitate the development of new agents with improved efficacy and safety. We investigated how linker architecture influences the antifungal activity and lead properties of hybrid triazole-thiazolidine derivatives. Methods: A focused library of triazole-thiazolidine hybrids incorporating alkylamine, amide, cyclic amine, 2-hydroxypropyl, and thiazepane linkers was synthesized and characterized. Antifungal activity was evaluated against reference strains and clinical isolates of Candida spp., Aspergillus fumigatus, dermatophytes, and Cryptococcus neoformans. Structure–activity relationships were analyzed by molecular docking. Selected compounds were further assessed by SCRAPPY profiling, fluorescence microscopy, mammalian-cell cytotoxicity assays, acute oral toxicity studies, and evaluation of microsomal stability and interactions with human CYP450 isoforms. Results: Linker architecture strongly influenced antifungal potency. Amide- and cyclic amine-containing hybrids were generally the most active, whereas simple alkylamide derivatives showed narrower activity profiles. Compound 28 emerged as the most promising lead, exhibiting sub-microgram MIC values against several Candida isolates, particularly C. parapsilosis, and retaining measurable activity against an azole-resistant C. albicans strain. Docking generated putative CYP51-binding models, while SCRAPPY profiling and fluorescence microscopy revealed an azole-like cellular response consistent with perturbation of sterol-associated homeostasis. Compound 28 was tolerated at 300 mg/kg in an acute oral study but showed concentration- and time-dependent cytotoxicity and rapid CYP3A4-mediated microsomal metabolism. Conclusions: Systematic variation of linker architecture identified compound 28 as a promising exploratory antifungal lead. Further optimization should focus on improving metabolic stability and cytotoxicity, together with direct target validation, pharmacokinetic characterization, and in vivo efficacy studies. Full article

Glaucoma is an ocular disease caused by the improper management of elevated intraocular pressure (IOP). IOP-lowering via topical administration is the first choice to prevent further progression. However, patients may forget to administer their medication, compromising IOP control. To address this problem, a prolonged active pharmaceutical ingredient (API) release system is proposed. A new prodrug (latanoprost acid–brimonidine conjugate, LBJ) was designed and expected to achieve potential long-lasting release of APIs. LBJ was synthesized by two methods. First, Steglich esterification without protecting the hydroxyl group led to a yield of 34.24%. However, the integral ratio between LPA and BM obtained from NMR was 1.25:1, indicating a potential side product resulting from further coupling through the unprotected hydroxyl group in LBJ. As an alternative route, Steglich esterification with a protecting agent, tert-butyldimethylchlorosilane (TBDMSCl), resulted in a yield of 39.35%, and the integral ratio between LPA and BM obtained from NMR was 1:1. The hydrolysis time of LBJ was investigated and compared with that of latanoprost (LP). In the presence of esterase (0.4 U/mL), the hydrolysis times of LP and LBJ were 4 h and 28 days, respectively. The prolonged hydrolysis time results in sustained APIs release, which is beneficial for the development of a sustained drug release system. Full article

Cyclin-Dependent Kinase 4/6 inhibitors (CDK 4/6i) represented a paradigm shift in the treatment of patients with metastatic hormone-receptor-positive (HR+), HER2-negative (HER2-) breast cancer patients. When disease progression occurs and further hormonal manipulations or target therapies fail, chemotherapy remains a therapeutic choice. For these reasons, resources should be invested in redesigning the best treatment strategy with the current chemotherapy drugs available. Nevertheless, the preferred strategy typically remains a planned sequence of single chemotherapeutic agents. This approach endeavors to extend overall survival and maintain quality of life. Within this complex and evolving therapeutic scenario, where the necessity for effective and treatment options is crucial, we explore in the present paper a perspective for a hypothetical new role of bevacizumab combined with paclitaxel for patients with metastatic HR+, HER2- breast cancer patients resistant to hormone therapy. Recent findings from our preliminary published pharmacogenetic studies, could suggest the efficacy of bevacizumab as linked to a well-defined genomic profile of genes implicated in the process of neoangiogenesis (e.g., favorable profile: VEGF-A rs833061/VEGFR-2 rs1870377: CT/AT, CT/AA, TT/AA, TT/TT, CC/TT), concluding the present perspective underlying the fact that bevacizumab combined with paclitaxel will be reconsidered with this new potential use only if well-designed prospective trials confirm what has been observed from our retrospective data. Full article

Wound healing is a multifaceted biological process comprising the phases of hemostasis, inflammation, proliferation, and remodeling, all of which require supportive microenvironment for optimal tissue regeneration. Biopolymer-based hydrogels, derived from materials such as cellulose and its derivatives, chitosan, alginate, and hyaluronic acid, have emerged as promising wound dressing materials due to their excellent biocompatibility, biodegradability, moisture-retention capacity, and potential to mimic the native extracellular matrix. The structural characteristics, wound healing functions, and underlying mechanisms of these biopolymers are critically examined and summarized in tabular form. The review further highlights the incorporation of natural and synthetic therapeutic agents, growth factors, stem-cell-derived products, and peptides into biopolymer matrices to enhance therapeutic efficacy. The examined research findings indicate significant increases in fluid intake, moisture retention, antibacterial activity, angiogenesis, collagen deposition, tissue regeneration, and wound healing rates. Translational difficulties, regulatory issues, clinical research, and new patent activity pertaining to advanced wound healing biomaterials are also covered in the review. Despite tremendous improvements, issues still exist in bulk manufacturing, long-term safety, reproducibility, mechanical stability, and clinical validation. Future innovations are anticipated to concentrate on smart, multipurpose, and customized hydrogel systems that can integrate drug delivery, biosensing, and regenerative capabilities while reacting dynamically to wound microenvironments. Overall, biopolymer-based hydrogels are a flexible, rapidly developing platform with significant promise to improve next-generation skin tissue engineering and change the treatment of both acute and chronic wounds. Full article

Antimicrobial resistance in mycobacteria arises from a complex interplay of intrinsic and acquired mechanisms that collectively limit the efficacy of current therapeutic options. Intrinsic resistance is largely driven by the low permeability of the mycobacterial cell envelope, the activity of efflux pumps, and the presence of drug-modifying enzymes, which together restrict intracellular drug accumulation and contribute to broad baseline tolerance. This review integrates resistance mechanisms of both M. tuberculosis and M. abscessus, two clinically relevant mycobacteria that share core molecular pathways while exhibiting species-specific determinants that complicate treatment. Additional intrinsic factors, including biofilm formation and stress-induced adaptive responses, further enhance persistence and reduce susceptibility to multiple drug classes. Acquired resistance predominantly results from chromosomal mutations affecting drug targets or prodrug activation pathways, such as katG, inhA, rpoB, gyrA, and pncA in Mycobacterium tuberculosis, leading to high rates of multidrug-resistant and extensively drug-resistant disease. In nontuberculous mycobacteria, species-specific determinants—including inducible macrolide resistance mediated by erm(41) in M. abscessus, plasmid-mediated erm (55) variants, rrl and rrs mutations, diverse enzymatic inactivation systems, and regulatory alterations in the MarR family that result in inducible resistance to drugs such as ethionamide —generate highly variable resistance profiles that complicate treatment. Recent advances in molecular diagnostics, including PCR-based assays, whole-genome sequencing, CRISPR-based diagnostic platforms, AI-assisted diagnostics, and emerging multi-omics approaches, have improved the detection of resistance-associated mutations and enhanced understanding of mycobacterial pathophysiology. In parallel, new therapeutic agents and optimized regimens offer promising avenues to overcome resistance, although emerging resistance to novel drugs underscores the need for continued surveillance. This review synthesizes current knowledge on the molecular basis of resistance in M. tuberculosis and NTM, highlighting implications for diagnosis, treatment, and future research. Full article

Cridanimod (acridoneacetic acid), the active ingredient of the immunomodulatory drug Cycloferon^®, has a well-characterized antiviral profile, but an unexplored analgesic potential. Bornane monoterpenes, notably (+)-camphor and (−)-fenchone, are established scaffolds for analgesic drug design. We therefore synthesized thirteen cridanimod–monoterpene conjugates—seven amides, three acylhydrazones, and three esters—by EDCI/DMAP-mediated coupling or CDI/DBU-promoted esterification, and evaluated them in mice at an oral dose of 10.0 mg/kg in the acetic acid writhing and hot plate tests, with diclofenac sodium (10.0 mg/kg) as the reference. Acridoneacetic acid and Cycloferon^® were themselves inactive in both assays. By contrast, six of the thirteen conjugates were significantly active (p < 0.05) in at least one test, with distinct leads in each: amide 19 matched diclofenac in the writhing test (−63.7% vs. −64.4%), whereas acylhydrazone 23 exceeded diclofenac in the hot plate test (+43.9% vs. +25.7%). The divergent profiles suggest that different structural subclasses engage peripheral and central antinociceptive mechanisms. Conjugation thus converts an analgesically inactive immunomodulator into a substance yielding analgesics that match or exceed a standard NSAID at the same oral dose, providing a promising starting point for the development of new pain-relieving agents. Full article

The rapid emergence and dissemination of antimicrobial resistance (AMR) among bacterial pathogens, particularly the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), represents one of the most pressing global public health challenges, contributing to increased morbidity, mortality, and healthcare costs. The limited development of new antibiotic classes over the past two decades has intensified the search for structurally novel antimicrobial agents and adjuvants capable of overcoming multidrug resistance. Natural products continue to serve as an invaluable source of anti-infective drug leads owing to their remarkable structural diversity and broad spectrum of biological activities. Mangrove ecosystems, located at the interface of terrestrial and marine environments, harbor highly diverse microbial communities, including fungi that have evolved under extreme environmental conditions and produce a wide range of unique secondary metabolites. Beyond their ecological significance, mangrove-associated fungi have emerged as prolific producers of bioactive compounds with promising antibacterial activity against multidrug-resistant pathogens. This review comprehensively summarizes recent advances (2018–2026) in the discovery of antibacterial metabolites from mangrove-associated fungi active against ESKAPE pathogens, which discusses their structural diversity, reported antimicrobial activities, and emerging strategies for accelerating natural product discovery, including genome mining, metabolomics, OSMAC, adaptive laboratory evolution, and artificial intelligence-assisted approaches. A total of 139 chemically distinct metabolites (Compounds 1–139) isolated from mangrove-associated fungi are critically reviewed, highlighting their potential as promising leads for the development of next-generation antimicrobial agents against ESKAPE pathogens. Full article

Streptococcus pneumoniae is the major causative agent of community-acquired pneumonia, one of the main infectious diseases that causes inflammation in the alveoli and leads to significant morbidity and mortality across various age groups. Current treatments are challenged by multidrug-resistant strains of S. pneumoniae, which has led to the reemergence of pneumonia in recent years; therefore, it is pivotal to identify new drug targets. The enzyme chorismate synthase (CS), involved in the shikimate pathway of S. pneumoniae, aids in the synthesis of vital aromatic amino acids and other metabolites required for bacterial viability. The present study identifies natural compounds that can inhibit CS using an in silico approach, including pharmacophore modeling, virtual screening, molecular docking, ADME analysis, and molecular dynamics (MD) simulations. Our results suggest that the identified compounds can bind effectively to the active site of S. pneumoniae CS (SpCS), exhibiting affinities better than the known inhibitor 1-benzofuran-3-one and close to the enzyme’s natural substrate, 5-enolpyruvylshikimate-3-phosphate (EPSP). This study suggests lead natural compounds as promising candidates for further investigation as potential inhibitors for the treatment of pneumonia, offering a novel strategy to combat this resilient pathogen. Full article

Acinetobacter baumannii is a microorganism of major global clinical importance, whose carbapenem-resistant phenotype is considered a priority target for the development of new antimicrobial agents. Carbapenem-resistant A. baumannii is associated with healthcare-associated infections and exhibits high mortality rates, prolonged hospital stays, and extensive use of intensive care units. As a control strategy, green-synthesized silver nanoparticles have gained increasing attention. Based on this, the aim of this study was to synthesize a novel triphasic silver nanocomposite, characterize it, and evaluate its antibacterial activity against extensively drug-resistant and pan-drug-resistant isolates. The nanocomposite was synthesized using cell-free bacterial supernatant and was physicochemically characterized regarding concentration, size, morphology, and crystallinity. Its antibacterial activity was assessed using broth microdilution and time–kill assays, followed by toxicity assays using human erythrocytes. A nanoscale and stable nanocomposite was obtained and was composed of metallic silver, silver chloride, and silver phosphate, which exhibited antibacterial activity against all tested isolates. In the toxicity assay, the nanocomposite demonstrated low toxicity and a high selectivity index. These findings demonstrate that Ag/AgCl/Ag₃PO₄ nanocomposite exhibits strong activity against resistant phenotypes for which therapeutic options are limited, highlighting its potential as a control strategy against this pathogen. Full article

Background/Objectives: Prostate cancer (PC) exhibits marked disparities in incidence and mortality across ethnicities, with men of Sub-Saharan African (SSA) ancestry experiencing 1.7 and 2.0 times higher values, respectively, than European men (EUR). However, SSA preclinical models remain scarce (just one commercial cell line). In this study, we established and characterized a novel panel of PC cell lines derived from SSA patients using conditional reprogramming (CR), a method that enables efficient propagation of primary cells while maintaining their genotypic and phenotypic features. Methods: CR was applied to five SSA-PC samples, and successfully propagated samples were authenticated by STR and ~1 million SNP profiling, and extensively characterized for proliferative capacity, migratory behaviour, karyotyping and epithelial and prostate tumour lineage markers. To explore drug response profiles, a high-throughput screen (HTS) of 1280 clinically annotated compounds was conducted. Results: Three SSA-PC cell lines were successfully established and authenticated, and five potential drug hits were validated. A new finding was the reduced sensitivity of SSA-derived models (9.0 times difference compared to commercial EUR PC cell lines) to camptothecin, a TOP1 inhibitor, while being equally sensitive to epirubicin hydrochloride, a TOP2 inhibitor. The cardiac glycoside digoxin, anthelmintic pyrvinium pamoate and antirheumatic agent auranofin were also efficient drugs in the in vitro testing. Conclusions: These results support the relevance of SSA-derived PC models for preclinical drug screening and highlight the value of including ancestry-diverse models in oncobiology research. Full article