{"title":"Deguelin Alleviates Renal Tubular Epithelial Cell Injury in Lupus Nephritis by Inhibiting the PI3K/Akt Signaling Pathway.","authors":"Shiling Zhong, Xunwei Liu, Yunyan Li, Wenying Hao, Yuanling Chen, Jika Zheng, Ling Wu","doi":"10.1177/1540658X261494333","DOIUrl":"https://doi.org/10.1177/1540658X261494333","url":null,"abstract":"<p><p>\u0000 <i>Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus. Circadian rhythm disorders are related to the pathogenesis of LN. This study aims to identify the core circadian rhythm-related genes in LN and identify the potential natural active compounds for LN treatment. In the present study, cyclin A2 (CCNA2) and cyclin-dependent kinase inhibitor 3 (CDKN3) were identified as the core targets most related to the circadian rhythm of LN. Both of them were upregulated in blood and kidney tissue samples in LN and had high diagnostic efficacy. Deguelin had strong binding capabilities with CCNA2 and CDKN3 proteins. Deguelin could dose-dependently alleviate lipopolysaccharide-induced human kidney-2 (HK-2) cell damage, inhibit cell apoptosis and the release of inflammatory factors, downregulate the mRNA and protein expression levels of core genes CCNA2 and CDKN3, and inhibit the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The protective effect of deguelin could be reversed by AKT activator SC79 treatment. In summary, CCNA2 and CDKN3 are core genes related to the circadian rhythm in LN. Deguelin probably alleviates renal tubular epithelial cell injury by modulating the expression levels of core genes CCNA2 and CDKN3, inhibiting the activation of the PI3K/Akt signaling pathway, and thus has the potential to become a therapeutic agent for LN.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"1540658X261494333"},"PeriodicalIF":1.8,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Quorum Sensing LsrR Protein in <i>E. coli:</i> A Computational Approach to Screen the Plant Bioactive Compounds as Inhibitors of Biofilm Formation in Urinary Tract Infections.","authors":"Sitrarasu Vijaya Prabhu, Shreya Suman, Alagu Chellapandi, Padmalochani Baskaradoss, Sivan Padma Priya, Thilakavathy Pandurangan, Muniappan Ayyanar, Rengarajan Murugesan, Prabhu Srinivasan","doi":"10.1177/1540658X261429261","DOIUrl":"10.1177/1540658X261429261","url":null,"abstract":"<p><p>\u0000 <i>Antimicrobial resistance (AMR) in <i>Escherichia coli</i>, driven by biofilm formation and quorum sensing (QS), presents a significant challenge in combating infections, particularly urinary tract infections. This study explored the potential of plant bioactive compounds to inhibit LsrR, a key transcriptional regulator of the QS system, in <i>E. coli</i>. The active site of LsrR was identified using the Sitemap module, which demonstrated high druggability, with a D-score of 0.987. Structure-based virtual screening was used to identify plant-derived inhibitors, followed by docking, binding free energy calculations, and induced-fit docking to evaluate ligand interactions and stability. Chebulinic acid, rutin, and vicine have emerged as potent inhibitors with better docking scores and multiple protein-ligand interactions. Molecular dynamics simulations confirmed the stability of these complexes, highlighting their potential to disrupt QS pathways and inhibit bacterial biofilm formation. These findings suggest that plant bioactive compounds are promising novel therapeutic agents for mitigating AMR in <i>E. coli</i> by targeting LsrR.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"517-537"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Integrated <i>In Vivo</i> and <i>In Silico</i> Approaches for Targeting JAK2/STAT3/SOCS3: Repurposing Boeravinone B and Resveratrol as Chemopreventive Agents in Colon Cancer.","authors":"Shabnoor Iqbal, Usman Khan","doi":"10.1177/1540658X261467596","DOIUrl":"10.1177/1540658X261467596","url":null,"abstract":"<p><p>\u0000 <i>Colon cancer ranks among the most prevalent malignancies worldwide and contributes substantially to cancer-related mortality. This study employed an integrated approach to evaluate the chemopreventive effects of Boeravinone B (BB) and Resveratrol (REV), administered individually and in combination, in the azoxymethane (AOM)-induced rat model of colon cancer, with particular emphasis on cytokine signaling pathways and mitochondrial regulation of apoptosis. The combination of BB (15 mg/kg) and REV (8 mg/kg) exhibited greater efficacy than either treatment alone. These combined treatments (BB + REV) significantly reduced pro-inflammatory cytokines (IL-1β, IL-6, tumor necrosis factor-alpha [TNF-α]), nitro-oxidative stress indicators (NO, iNOS), and histological damage, while promoting mitochondria-mediated apoptosis via modulation of BAX and BCL2. Network analysis revealed that centrality metrics (betweenness, closeness, degree, and stress centrality), identified STAT3, SOCS3, JAK2, BAX, and BCL2 as key hub proteins involved in cytokine signaling and apoptotic pathways. These nodes exhibited the highest centrality values (betweenness: 0.046667 for STAT3/SOCS3/JAK2; degree: 10 for all five proteins), indicating their pivotal roles as therapeutic targets. Molecular docking revealed favorable binding affinities of BB for SOCS3 (-9.0 kcal/mol), BAX (-9.0 kcal/mol), JAK2 (-8.1 kcal/mol), and STAT3 (-7.8 kcal/mol). In comparison, REV exhibited its highest binding affinities for SOCS3 (-7.2 kcal/mol) and BAX (-7.0 kcal/mol). These findings identify SOCS3, BAX, JAK2, and STAT3 as potential molecular targets mediating the combined treatment's anti-inflammatory and pro-apoptotic effects. This integrated <i>in vivo</i> and <i>in silico</i> study showed that combined BB and REV exerted a stronger chemopreventive effect against AOM-induced colon cancer via complementary mechanisms: restoring mitochondrial adenosine triphosphate synthase (ATPase) activity, suppressing biomarkers of inflammation, nitro-oxidative stress, and apoptosis, with strong binding affinities. These findings support repurposing BB and REV as a multitargeted combination therapy against colon cancer.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"560-581"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular Mechanisms and Optimization Strategies for the Impact of Antihypertensive, Lipid-Lowering, and Antidiabetic Drugs on Gut Microbiota.","authors":"Ningning Xie, Yahan Zhang","doi":"10.1177/1540658X261438871","DOIUrl":"10.1177/1540658X261438871","url":null,"abstract":"<p><p>\u0000 <i>Patients often suffer from hypertension, hyperlipidemia, and diabetes, requiring long-term polypharmacy. These drugs may alter gut microbiota composition, leading to adverse effects, but the underlying mechanisms are unclear. We selected 23 common drugs from ChEMBL, identified their metabolites via DrugBank, and used TargetNet and GeneCardsSuite to find drug targets and human proteins. Cross-analysis revealed 15 shared human side-effect protein targets. Molecular docking and Structure-activity relationship analyses assessed interactions with human and bacterial proteins. Eight compounds, including metabolites of amlodipine, metoprolol, glipizide, and fenofibrate, showed significant binding to human and gut bacterial proteins. Based on our <i>in silico</i> models, we predict that specific structural modifications could potentially enhance efficacy while minimizing microbial disruption and adverse reactions. Molecular dynamics simulations suggest that these modified drugs might computationally maintain therapeutic interactions while reducing gut microbiota disruption. Our findings highlight the impact of these drugs on gut microbiota and side effects via shared protein targets. Supported by <i>in silico</i> models and preliminary <i>in vitro</i> assays, we think that precision medicine, probiotic co-administration, or drug structure modifications could potentially serve as future strategies to mitigate complications and side effects in elderly patients, warranting further <i>in vivo</i> and clinical validation.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"538-547"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiajun Huang, Chaohong Da, Shengrui Zhai, Xingyan Yao, Meiling Zhang, Tao Zhang
{"title":"Identification of Broad-Spectrum Inhibitors Targeting Multiple Amyloidogenic Proteins Using Functional Group-Based Virtual Screening.","authors":"Jiajun Huang, Chaohong Da, Shengrui Zhai, Xingyan Yao, Meiling Zhang, Tao Zhang","doi":"10.1177/1540658X261460558","DOIUrl":"10.1177/1540658X261460558","url":null,"abstract":"<p><p>\u0000 <i>Amyloidosis comprises a spectrum of protein misfolding disorders characterized by the aggregation of diverse amyloidogenic proteins into cytotoxic fibrillar structures. Due to the conserved β-sheet-rich architecture of fibrils across various amyloid species, pan-amyloid therapeutics present a promising strategy for simultaneously targeting multiple amyloidogenic proteins. In this study, four representative amyloidogenic proteins-amyloid β, serum amyloid A1, islet amyloid polypeptide, and transthyretin-were selected as targets. From a library of 10,272 small molecules, five functional groups were identified as critical contributors to high-affinity binding. Utilizing these functional groups, potential compounds capable of binding to all four amyloidogenic proteins were further screened. This functional group-based screening workflow not only validates the effectiveness of functional group-driven screening in multitarget drug discovery but also facilitates the efficient identification of candidate pan-amyloid binding compounds. Furthermore, these findings provide valuable insights into the development of pan-amyloid therapeutic strategies.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"548-559"},"PeriodicalIF":1.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lovekesh Singh, Ghanshyam Das Gupta, Shamsher Singh
{"title":"Neurobehavioral and Molecular Rescue by Dapagliflozin in Aluminum Chloride-Induced Alzheimer's Model: Possible Relevance of NF-κB and Aβ<sub>(1-42)</sub>.","authors":"Lovekesh Singh, Ghanshyam Das Gupta, Shamsher Singh","doi":"10.1177/1540658X261486541","DOIUrl":"https://doi.org/10.1177/1540658X261486541","url":null,"abstract":"<p><p>\u0000 <i>Alzheimer's disease (AD), a progressive neurodegenerative disorder, characterized by the deposition of amyloid-β plaques in the hippocampus, leading to cognitive and behavioral impairments. This study investigated the neuroprotective outcome of Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor primarily used for glycemic control, which also exhibits notable anti-inflammatory, antioxidant, and neuroprotective properties. Using an aluminum chloride (AlCl<sub>3</sub>)-induced rat model of AD, the research evaluates behavioral, biochemical, and neuroinflammatory changes, particularly focusing on the nuclear factor kappa-B protein (NF-κB) signaling pathway. Rats were orally administered AlCl<sub>3</sub> to induce AD-like pathology, followed by DAPA treatment (1 and 2 mg/kg, p.o.) over a 28-day period. Behavioral assessments, including the Morris water maze and Elevated Plus Maze, were used to evaluate spatial memory and anxiety. On day 29, hippocampal tissues were collected to assess neurotransmitter levels, oxidative stress markers (LPO, GSH, nitrite), and inflammatory cytokines (interleukin-1 beta, interleukin-6), along with the expression of NF-κB. AlCl<sub>3</sub> exposure led to significant alterations in neurotransmitter balance (AChE, GABA, and glutamate), heightened oxidative stress, and increased neuroinflammatory responses. DAPA treatment significantly mitigated these changes, notably downregulating NF-κB, which correlated with decreased amyloid beta and expression in the hippocampus. These findings suggest that beyond its antidiabetic action, DAPA offers promising neuroprotection against AlCl<sub>3</sub>-induced neurotoxicity, potentially via modulation of the NF-κB signaling pathway.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"1540658X261486541"},"PeriodicalIF":1.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maya Cielo Cornejo, Sandy Che-Eun S Lee, Christina Nguyen, Shaya Smith, Cameron Taylor, Robert Damoiseux, Carla M Koehler
{"title":"Yeast-Based High-Throughput Screening Platform for Identifying Modulators of Mitochondrial Protein Import.","authors":"Maya Cielo Cornejo, Sandy Che-Eun S Lee, Christina Nguyen, Shaya Smith, Cameron Taylor, Robert Damoiseux, Carla M Koehler","doi":"10.1177/1540658X261490394","DOIUrl":"https://doi.org/10.1177/1540658X261490394","url":null,"abstract":"<p><p>\u0000 <i>Mitochondrial protein import is essential for overall cellular homeostasis, yet scalable approaches to systematically interrogate mitochondrial protein import and identify modulators of this process remain limited. Here, we describe a yeast-based, gain-of-growth (GoG), high-throughput screening assay for the identification of small-molecule modulators of mitochondrial protein import. In this system, truncated human proteins that contain N-terminal mitochondrial targeting sequences (MTSs) are expressed in <i>S. cerevisiae</i>, where mitochondrial protein import is coupled to an auxotrophic growth readout. Disruption of import leads to cytosolic accessibility of the URA3 reporter, producing a GoG phenotype under selective conditions. As a proof of concept, we applied this model to PTEN-induced kinase 1 (PINK1), a mitochondrial imported regulator of mitochondrial quality control. Using this approach, we demonstrate the ability to monitor PINK1 import and identify candidate compounds that modulate this process. Collectively, this work establishes a scalable and reproducible platform for interrogating mitochondrial protein import and identifying compounds for downstream validation in mammalian systems.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"1540658X261490394"},"PeriodicalIF":1.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Method Development and Validation of Promethazine HCl by Using RP-HPLC and Its Forced Degradation Studies.","authors":"Deepshikha Nirwan, Kandasamy Nagarajan, Parul Grover, Snigdha Bhardwaj, Ashutosh Mishra","doi":"10.1177/1540658X261486549","DOIUrl":"https://doi.org/10.1177/1540658X261486549","url":null,"abstract":"<p><p>\u0000 <i>A simple, rapid, sensitive, and stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantitative determination of promethazine hydrochloride (HCl) in pharmaceutical formulations. Chromatographic separation was achieved using a SunFire® C18 column (4.6 × 250 mm, 5 µm) with a mobile phase consisting of acetonitrile and 0.1% orthophosphoric acid in water (80:20, v/v) at a flow rate of 1.0 mL/min. Detection was performed at 249 nm using a photodiode array detector. The developed method was validated according to the International Council for Harmonisation Q2 guidelines with respect to specificity, linearity, precision, accuracy, robustness, limit of detection, and limit of quantitation.The method exhibited good linearity over the concentration range of 2-64 µg/mL with a correlation coefficient (<i>R</i><sup>2</sup>) of 0.9993. The percentage relative standard deviation for precision studies was below 2%, indicating satisfactory repeatability and reproducibility. Forced degradation studies were performed under acidic, alkaline, neutral, oxidative, and thermal stress conditions to evaluate the stability indicating capability of the method. Additional chromatographic peaks corresponding to degradation products were observed in acid, base, neutral, and oxidative stress conditions, while minimal degradation was observed under thermal stress. Furthermore, liquid chromatography-mass spectrometry (LC-MS) analysis was carried out to characterize the degradation products formed during stress studies. LC-MS results indicated that alkaline stress produced the highest degree of degradation, whereas thermal stress generated only minor residual impurities, confirming the relative stability of promethazine HCl under thermal conditions. The developed RP-HPLC method was found to be suitable for routine quality control analysis and stability assessment of promethazine HCl in pharmaceutical formulations.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"1540658X261486549"},"PeriodicalIF":1.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Thiolated Natural Gum-Based Drug Delivery Techniques and Their Efficiency in Diabetes Mellitus and Associated Carcinoma: Possibilities, Pathways, Applications, and Challenges.","authors":"Diya Zaman Shah, Bani Kumar Jana, Anup Kumar Das, Niva Rani Gogoi, Tumpa Sarkar, Mohini Singh, Bhaskar Mazumder","doi":"10.1177/1540658X261477914","DOIUrl":"https://doi.org/10.1177/1540658X261477914","url":null,"abstract":"<p><p>\u0000 <i>In the last few decades, diabetes mellitus has become an increasingly prevalent global health crisis. Both type 1 and type 2 diabetes are associated with a wide range of complications, including diabetic retinopathy, neuropathy, nephropathy, cardiovascular disease, and a higher risk of gastrointestinal, liver, and pancreatic cancers. In managing such conditions, drug delivery systems with enhanced therapeutic efficacy and specific tissue targets have received significant attention. Development of thiolated natural gums, which are polysaccharides that have been covalently modified with thiol groups, has paved the way for biomaterial-based drug delivery. These modified polymers are also prominent choices for controlled delivery of active pharmaceutical ingredients in topical application, dry powder inhalation, or oral administration. Additionally, they can enclose hydrophilic macromolecular drugs, peptides, RNA, and biomacromolecules, namely insulin, FGF, and siRNA. This article explores the potential of thiolated natural gums in drug delivery for the treatment of diabetes and diabetes-associated carcinoma. The properties of thiolated gums, their mechanisms of drug release, and their advantages over conventional drug delivery systems are also discussed here. Furthermore, the article delves into various applications for diabetes and diabetes-associated breast, liver, and colorectal cancers. The article also discusses the challenges and future prospects of thiolated natural gums in the pharmaceutical arena.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"1540658X261477914"},"PeriodicalIF":1.8,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>In Vitro</i> Interaction of Tacrolimus (FK506) with Conventional and Nanoformulated Antifungal Drugs Against Clinical Dermatophyte Isolates Including <i>Trichophyton indotineae</i>.","authors":"Reihaneh Seiad Ahmadnezhad, Shirin Farahyar, Bita Mehravi, Maryam Roudbary, Romina Ghazi Mirsaid, Sahar Soleymanzadeh, Shahram Mahmoudi","doi":"10.1177/1540658X261480271","DOIUrl":"https://doi.org/10.1177/1540658X261480271","url":null,"abstract":"<p><p>\u0000 <i>Dermatophytosis is a global infection with increasing reports of resistance among its causative agents in recent years. As a result of this issue, new therapeutic options are needed. The calcineurin-calmodulin pathway is critical for fungi. Inhibitors of this pathway, such as tacrolimus in combination with antifungal drugs, may serve as alternative treatments. Nanoformulation is another method to address challenges in dermatophytosis treatment. Thirty dermatophyte isolates were included in this study. Antidermatophyte activities of terbinafine, itraconazole, posaconazole, nanoposaconazole, and tacrolimus were investigated using the third edition of the CLSIM38 protocol. <i>In vitro</i> interactions between tacrolimus and the antifungal drugs were studied using a checkerboard method. The isolates included <i>Trichophyton indotineae</i> (<i>n</i> = 14), <i>Trichophyton tonsurans</i> (<i>n</i> = 9), <i>Trichophyton interdigitale</i> (<i>n</i> = 6), and <i>Microsporum canis</i> (<i>n</i> = 1). Tacrolimus demonstrated moderate inhibitory effects against all species. Itraconazole had the strongest activity; however, based on EUCAST epidemiological cutoff values, one <i>T. indotineae</i> isolate was non-wildtype to this drug. Additionally, 10 out of 14 (71.42%) isolates of this species were non-wild type to terbinafine. Nanoposaconazole showed superior antifungal activity compared to posaconazole. Regarding drug combinations, the highest and lowest synergistic rates were observed for combinations of tacrolimus with nanoposaconazole (15/30, 50%) and itraconazole (4/30, 13.33%), respectively. The high rate of non-wildtype <i>T. indotineae</i> isolates to terbinafine underscores the necessity of precise identification to prevent treatment failure. Itraconazole proved to be the most effective antifungal. Combining tacrolimus with antifungal drugs, particularly nanoposaconazole, shows promise and warrants further investigation.</i>\u0000 </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":" ","pages":"1540658X261480271"},"PeriodicalIF":1.8,"publicationDate":"2026-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}