BMC Pharmacology & Toxicology最新文献

{"title":"Network toxicology integrated with machine learning and SHAP analysis identifies overlapping immune signatures between Di(2-ethylhexyl) phthalate (DEHP) and Sjögren's syndrome.","authors":"Cheng Lili, Tang Zhongfu, Li Ming, Chuanbing Huang","doi":"10.1186/s40360-026-01119-x","DOIUrl":"10.1186/s40360-026-01119-x","url":null,"abstract":"<p><p>BACKGROUND: As a prevalent plasticizer in industrial manufacturing and daily-use products, di(2-ethylhexyl) phthalate (DEHP) has raised growing concerns regarding its safety and potential role in disease pathogenesis. Although direct epidemiological evidence linking DEHP exposure to Sjögren’s syndrome (SS) remains limited, DEHP has been reported to exert immunomodulatory and endocrine-disrupting effects that are highly relevant to the core pathological mechanisms of SS. Therefore, this study aimed to systematically explore the potential links between DEHP and SS using an integrated strategy combining toxicity prediction, network toxicology, machine learning, molecular docking, single-cell atlas interrogation, and in vitro validation. METHODS: The toxicity profile of DEHP was predicted using two complementary online platforms (ProTox 3.0 and ADMETlab 2.0). SS-related transcriptomic datasets were obtained from GEO, and potential DEHP targets were collected from CTD, SwissTargetPrediction, and SEA. Network toxicology analyses (intersection screening, PPI construction, and GO/KEGG enrichment) were performed to identify key genes and pathways. Machine learning models were trained to classify SS versus controls using the DEHP–SS intersect genes, and SHAP was applied to interpret key predictors. Molecular docking (AutoDock Vina) was conducted to estimate the binding propensity between DEHP and prioritized proteins. A single-cell atlas of mouse submandibular gland tissue (PanglaoDB; Mus musculus; SRA693675:SRS3206192) was queried to localize gene expression. Finally, in vitro experiments were performed in human submandibular gland epithelial cells (HSG) to validate STAT1 expression changes following DEHP exposure. RESULTS: In silico toxicity predictions suggested that DEHP may exhibit immunotoxic potential among multiple predicted toxicity endpoints. Network toxicology analysis identified 27 DEHP–SS intersect targets, and the PPI network highlighted STAT1, CCL2, CXCL10, MYD88, and IRF7 as highly connected hub genes. Across 113 machine learning models, Ridge/Elastic Net–based models demonstrated stable classification performance, and SHAP analysis prioritized five core predictors (STAT1, PHGDH, ISG15, CXCL10, and CCL2). Molecular docking suggested favorable binding energies ( ≤ − 5.0 kcal/mol) between DEHP and these five proteins. Single-cell atlas interrogation indicated that STAT1 is expressed in salivary mucous cells. In vitro experiments further demonstrated that DEHP exposure increases STAT1 mRNA and protein expression in HSG cells in a dose-dependent manner. Collectively, these results provide mechanistically plausible—yet non-causal—evidence linking DEHP to SS-relevant immune signatures. CONCLUSION: This study identifies an overlapping immune-response signature between predicted DEHP-associated targets and SS-related transcriptomic features, highlighting STAT1 as a prioritized node within this intersection. In vitro experiments demonstrate th","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective effects of Urolithin A and B in an intracerebroventricular streptozotocin-induced Alzheimer's-like model in rats.","authors":"Mona Taghizade Salari, Kianoush Gholami, Leila Khani, Hananeh Ahmadnia, Milad Iranshahy, Mehrdad Iranshahi, Mohammad Tohidy Majd, Morteza Behnam-Rassouli, Omid Yazarlu, Maede Hasanpour","doi":"10.1186/s40360-026-01118-y","DOIUrl":"10.1186/s40360-026-01118-y","url":null,"abstract":"<p><p>Alzheimer’s disease (AD), a prevalent neurodegenerative disorder, is characterized by amyloid beta and tau protein aggregation, oxidative stress, and neuroinflammation. Urolithin A (Uro A) and Urolithin B (Uro B), known for their anti-inflammatory, antioxidant, and neuroprotective properties, are promising therapeutic candidates for AD. This study evaluated the effects of Uro A and Uro B on memory, anxiety-like behaviors, brain oxidative stress markers, and histopathological changes in male rats subjected to streptozotocin (STZ)-induced AD. Wistar rats were divided into eight groups (n = 7) and treated with Uro A or Uro B (10 or 20 mg/kg), memantine (positive control), or vehicle control for 14 days following intracerebroventricular STZ injection. Behavioral tests, biochemical analyses, and histological evaluations were conducted after six weeks. Modest improvements in memory performance were observed (p < 0.05) in the shuttle box test and reduced anxiety-like behaviors in the elevated plus-maze test. Biochemical analyses revealed decreased oxidative stress markers (malondialdehyde and hydroperoxides) and increased total antioxidant capacity (p < 0.05). Also, it seems that both compounds can reduce necrotic neurons and amyloid-like depositions in the hippocampus and cerebral cortex, and no adverse effects on the histology of the liver, kidney, pancreas, and testis were observed. These findings demonstrate the therapeutic potential of Uro A and Uro B in ameliorating cognitive deficits, oxidative stress, and neuronal damage in AD. Further studies are needed to explore the mechanisms underlying these effects and their applicability in clinical contexts.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13081563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of compound candidates for the treatment of allergic diseases: integration of DFT analyses, molecular docking, molecular dynamics simulations, and ADMET profiling.","authors":"Velid Unsal, Erkan Oner, Reşit Yıldız, Supriyo Saha, Başak Doğru Mert, Mehmet Emrah Aksan, Abdulkerim Hatipoğlu","doi":"10.1186/s40360-026-01104-4","DOIUrl":"10.1186/s40360-026-01104-4","url":null,"abstract":"<p><p>In this study, a combination of computational analyses (drug similarity, physicochemical properties, pharmacokinetic properties, molecular docking, molecular dynamics simulation, principal component analysis (PCA), free energy landscape (FEL), density functional theory (DFT), and absorption, distribution, metabolism, and excretion (ADMET) analysis) was used to evaluate the efficacy of natural compounds (aloe emodin, fisetin, vitamin D3, β-carotene, berberine, and cinnamic acid) against allergic diseases and compare them with pharmaceuticals such as cetirizine and mizolastine. Elementary molecular structures and electronic properties were determined through DFT calculations accounting for reactivity by natural bond orbital (NBO) and nonlinear optical properties (NLO) analyses. Molecular docking studies were performed on critical proteins interleukin-10 (IL-10), filaggrin, thymic stromal lymphopoietin (TSLP), and high-affinity Fc receptor for immunoglobulin E (FcεRI) to elucidate the energetics of binding and to reveal interaction mechanisms facilitated by hydrophobic and hydrogen bonds. Highlighted in molecular docking, molecular dynamics (MD) simulation analysis of beta carotene and mizolastine was performed for IL-10, TSLP, FcεRI, and filaggrin, respectively. MD simulation revealed that the beta carotene-IL-10 complex exhibited higher structural stability. MD simulation showed that both filaggrin apoprotein and the mizolastine-filaggrin complex maintained their structural stability with consistent root mean square standard deviation, root mean square fluctuation, radius of gyration, and solvent accessible surface area (SASA) values. MD simulation revealed that both TSLP apoprotein and the beta carotene-TSLP complex maintained their stable conformations. MD simulation showed that both the FcεRI apoprotein and the beta carotene-FcεRI complex achieved stable structures with consistent radius of gyration and SASA values. PCA and FEL analyses revealed ligand-induced conformational variability. Although some physicochemical properties require further development, β-carotene, exhibiting very strong protein binding, and vitamin D3, particularly displaying good integration, superior drug-like properties, low toxicity, and good binding affinity, have been identified as promising candidates for the treatment of allergic diseases. This comprehensive approach combines structural chemistry, energetics, and drug discovery to create a powerful model for the rational design of allergy medications.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147353801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The anticancer properties of the nanocomposite of low-nanoscale Ag nanoparticles obtained in SiO₂-grafted polyacrylamide carrier.","authors":"Olga V Akopova, Tatyana Zheltonozhskaya, Svitlana Zahorodnia, Dmytro Klymchuk, Yulia Korkach, Mykola Zavgorodniy, Valery Klepko","doi":"10.1186/s40360-026-01115-1","DOIUrl":"10.1186/s40360-026-01115-1","url":null,"abstract":"<p><p>BACKGROUND/AIMS: Silver-based nanomedicine is an ongoing trend in anticancer research. Polymers greatly improve the stability of bare metal silver and improve its interaction with cells. We aimed to evaluate the anticancer efficiency of the synthesized Ag/polymer nanocomposite against B95-8 and Wish cell lines. METHODS: A highly stable low-nanoscale Ag/silica-grafted polyacrylamide nanocomposite (Ag/Hyb) with a mean particle size of 6 nm, estimated by TEM, was obtained. Malignant cell lines: B95-8 (Burkitt lymphoma), Wish (human amniotic with marker chromosomes of HeLa), and the control MDCK cell lines were used. To assess cell viability, the MTT test was applied. To find putative targets of Ag/Hyb, mitochondrial respiration, lipid peroxidation, and NO synthase activity were evaluated in rat tissue homogenates. RESULTS: The half-inhibition (IC50) of B95-8 and Wish cells viability was 6.1 and 7.8 µg/ml, respectively, and was not reached in the control MDCK cells, which indicated high anticancer activity. At the same dilutions, the matrix was similarly toxic to B95-8 cells but safe to Wish and MDCK cells. Dose-dependent suppression of glutamate-driven respiration, strong NO synthases (NOS) stimulation, and the reduction of lipid peroxidation (LPO) within the same concentration range were observed. The correlation was found between NOS activation and mitochondrial CI suppression, which indicated possible involvement of these processes in cytotoxicity mechanisms of Ag/Hyb. CONCLUSIONS: A low-nanoscale Ag/SiO2-g-PAAm nanocomposite with high anticancer activity in vitro in a low micromolar concentration range was obtained. The putative mechanism of Ag/Hyb action was proposed, in which Complex I and NOS activity could be involved in anticancer effects. Based on the experiments, we came to the conclusion that Ag/Hyb is a promising system for the future design of anticancer preparations; however, molecular mechanisms of Ag/Hyb action in different cancer cell types require detailed study in the future. </p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a population pharmacokinetic model for lacosamide in adult patients with epilepsy to inform precision dosing.","authors":"Lingyan Yu, Fengqian Mao, Shunan Chen, Kangzhen Yu, Yani Hu, Jie Chen, Wei Hu, Zhenwei Yu, Haibin Dai","doi":"10.1186/s40360-026-01114-2","DOIUrl":"10.1186/s40360-026-01114-2","url":null,"abstract":"<p><p>BACKGROUND: Lacosamide is a third-generation antiseizure medication that reduces seizures by promoting slow inactivation of voltage-gated sodium channels. There are significant interindividual differences in the pharmacokinetics of this drug. The aim of this study was to explore the pharmacokinetic characteristics of lacosamide in adult patients with epilepsy and to develop a robust population pharmacokinetic model. METHODS: Retrospective data from adult epilepsy patients receiving lacosamide treatment and therapeutic drug monitoring were collected. The population pharmacokinetic model was developed via a nonlinear mixed effects modeling approach. Goodness-of-fit plots (GOF), bootstrap analyses and numerical predictive checks were used to evaluate the final model. RESULTS: A total of 294 plasma concentrations from 180 patients were included. A one-compartment model with first-order absorption and elimination was employed. In the final population pharmacokinetic model for lacosamide, concomitant use of carbamazepine (CBZ), sex and creatine clearance (CLCR) were covariates of drug clearance (CL/F), which can be expressed via the following equation: CL/F = 1.86 × 1.48CBZ×0.875SEX×(CLCR/119)0.311. The estimation of CL/F was 1.86 L/h. The GOF, bootstrap analysis and numerical predictive check indicated that the model was robust. The simulation indicated that the dose of lacosamide should be increased by 40–60% to achieve the original exposure when it is coadministered with CBZ. CONCLUSION: A population pharmacokinetic model for lacosamide in adult patients with epilepsy was successfully established, which will improve model-based precision medication. </p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Integrated network toxicology, machine learning and molecular docking reveal the mechanism of benzopyrene-induced periodontitis.","authors":"Wenjie Wen, Rui Li, Pengpeng Zhuo, Chao Deng, Donglin Zhang","doi":"10.1186/s40360-026-01100-8","DOIUrl":"10.1186/s40360-026-01100-8","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"27 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12958609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crossing ocular barriers with quercetin-SPIONs: modulation of Bax/Bcl-2 balance in normal rat eyes.","authors":"Mahtab Hajiaghajanian, Nazanin Movahedi, Dorsa Pouriaii, Zahra Souri, Azam Rezayat, Abolghasem Esmaeili","doi":"10.1186/s40360-026-01113-3","DOIUrl":"10.1186/s40360-026-01113-3","url":null,"abstract":"<p><p>BACKGROUND: Oxidative stress-induced cell death and injury are pivotal mechanisms in the breakdown of ocular tissue, leading to degenerative diseases. To counter this, we investigated quercetin, a flavonoid with well-documented antioxidant and anti-apoptotic properties, as a potential therapeutic agent. Its clinical translation is hampered by poor stability and ocular bioavailability. The goal was to examine the effectiveness and anti-apoptotic properties of polyethylene glycol-coated superparamagnetic iron oxide nanoparticles conjugated with quercetin (QCSPIONs) in rat eye tissue. METHODS: Male Wistar rats received free quercetin (QC), SPIONs, or QCSPIONs orally via gavage or through intraperitoneal injection once daily for 35 days. HPLC measured serum and ocular quercetin levels; nanoparticle localization was assessed by Prussian blue staining; safety was evaluated by histopathology with H&E staining; and apoptotic signaling was examined by qPCR for Bax and Bcl-2 expression. RESULTS: QCSPIONs demonstrated significantly higher ocular quercetin accumulation than free QC after both oral and intraperitoneal delivery (p < 0.0001). Prussian Blue staining confirmed that nanoparticles crossed the corneal and retinal barriers, with greater deposition following intraperitoneal injection. Additionally, histological analysis showed no structural or inflammatory damage in the retina or cornea. Furthermore, molecular results indicated Bax suppression and Bcl-2 upregulation with QCSPIONs, along with a decreased Bax/Bcl-2 ratio, demonstrating vigorous anti-apoptotic activity. Less pronounced effects were observed with free QC. CONCLUSIONS: Overall, QCSPIONs significantly enhance the ocular bioavailability of quercetin and provide robust anti-apoptotic protection without detectable cytotoxicity. These results support nanoparticle-mediated delivery as a practical approach for overcoming ocular barriers and enhancing preventive antioxidant strategies against oxidative stress-related eye diseases. </p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13059554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147343513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical pharmacist-led prevention of intravenous drug incompatibilities in an adult ICU: a prospective observational study.","authors":"Tülay Kayra, Leyla Ferliçolak, İlker Ateş, Neriman Defne Altıntaş, Arzu Onay-Besikci","doi":"10.1186/s40360-026-01095-2","DOIUrl":"10.1186/s40360-026-01095-2","url":null,"abstract":"<p><p>BACKGROUND: Patients in intensive care units (ICU) usually need multiple intravenous drugs (IV) simultaneously and have a limited number of venous routes. This makes IV incompatibility an important problem in these units. The aims of this study were to identify the frequency of possible drug incompatibilities in the ICU and to prepare specific pharmaceutical guidelines for the unit to the prevent them. METHODS: This cross-sectional and prospective study was conducted in Medical Intensive Care Unit (MICU) at Ankara University. Possible incompatibilities of IV drugs were assessed using the IBM Micromedex® and Stabilis 4.0 databases. RESULTS: Three hundred and thirty-eight drug request lists (DRL) of a total of 67 patients were included. At least one possible incompatibility was detected in 68.3% (95% CI: 63.3%–73.3%) of the drug request lists. First three drug groups that cause the most of incompatibilities belonged to the alimentary tract and metabolism, the anti-infectives for systemic use, systemic hormonal drugs and hormone regulators. The analysis of the type of IV drug administration showed that possible incompatibilities most commonly occurred between the continuously infused and bolus drugs (25%, n = 134/532). There was a moderate positive correlation between the number of anti-infective agents and possible incompatibilities (rho:0.41, p:0.001). Extreme drugs accounted for 40.6% (n = 432/1064) of the drugs that cause possible drug-drug incompatibilities. In terms of compatibility category, a poor degree of agreement was found between Micromedex and Stabilis (Cohen kappa = 0.174; 95% CI: 0.08–0.27; p < 0.001). Excluding “unknown” drug pairs slightly improved agreement between the databases (Cohen kappa increased from 0.174 to 0.293). A total of 567 recommendations were made during the study to prevent possible drug incompatibilities. All of which have been accepted and implemented. Of specific importance, all drug-solution incompatibilities were associated with anti-infective agents. A cross-table containing the Micromedex incompatibility data of the most frequently administered drugs with incompatibilities was prepared based on the data. There was no data for 33% (n = 438/1326) of the analyzed drug pairs in this cross-table. CONCLUSIONS: Interventions performed by clinical pharmacists contribute to preventing and reducing possible drug incompatibilities. CLINICAL TRIAL NUMBER: Not applicable. </p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13041401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adverse events associated with tirzepatide: a focus on subgroup-specific differences.","authors":"Zhongming Yu, Yiming Qi, Qian Gan, Guodong Wu, Xinhao Zhang, Cheng Jiang, Jing Li","doi":"10.1186/s40360-026-01105-3","DOIUrl":"10.1186/s40360-026-01105-3","url":null,"abstract":"<p><p>BACKGROUND: Tirzepatide is anticipated to play a pivotal role in managing overweight/obesity and/or type 2 diabetes. Although prior studies have employed spontaneous reporting databases for large-scale safety monitoring of tirzepatide focusing on novel adverse events, current understanding of potential disparities of the adverse events among subgroups remains unexplored. OBJECTIVE: This study aimed to evaluate the differences of adverse events across subgroups related to tirzepatide. RESEARCH DESIGN AND METHODS: Using the data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases, the differences in adverse events across specific subgroups concerning reporter type, sex, age, dose, indication, report year, onset time, and outcome were investigated using the ROR algorithm and Chi-Square Test/Fisher’s exact test. To further verify the differences, subgroup-based stratified analyses and sensitivity analyses were conducted. RESULTS: The results showed that the adverse events related to tirzepatide showed significant difference across subgroups. Notably, males were significantly more inclined to report “gastrointestinal disorders”. Within indication-based subgroups, tirzepatide used in patients with diabetes mellitus was significantly more frequently associated with “gastrointestinal disorders” compared with patients in weight control purpose. CONCLUSION: This study provides contribution for identification potential difference across subgroups, which can guide future research and more targeted monitoring strategies for tirzepatide in clinical practice. Further studies are required to validate these observations. CLINICAL TRIAL NUMBER: Not applicable. </p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13041219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Penetration and disruption of Salmonella typhimurium biofilm using synthesized citric acid doped zein nanocomposites.","authors":"Venkteshwar Yadav, Dharm Pal, Anil Kumar Poonia","doi":"10.1186/s40360-026-01107-1","DOIUrl":"10.1186/s40360-026-01107-1","url":null,"abstract":"<p><p>In the current global scenario, antimicrobial resistance poses a major challenge and significantly contributes to increasing human mortality. Among resistant pathogens, the Salmonella genus, particularly Salmonella enterica serovar Typhimurium (S. Typhimurium), plays a prominent role, with resistance further intensified under mature biofilm conditions. To address this challenge and mitigate the pathogenicity of this Gram-negative bacterium, various strategies have been explored, among which nanodrug delivery using nanocomposites (NCs) has emerged as a promising approach. In the present study, NCs were developed by incorporating citric acid (CA) into zein nanoparticles (NPs) at defined concentrations. X-ray diffraction analysis confirmed the successful formation of CA@Zein NCs, while field-emission scanning electron microscopy (FE-SEM) verified the effective loading of CA onto the surface of zein NPs. Particle size, zeta potential, and polydispersity index analyses indicated optimal physicochemical properties for stable nanocomposite formation. The synthesised NCs were evaluated against both planktonic and biofilm forms of S. Typhimurium. The minimum inhibitory concentration and minimum biofilm inhibitory concentration of CA@Zein NCs were determined to be 64 µg/mL and 128 µg/mL, respectively. These results demonstrate the superior antibiofilm efficacy of CA@Zein NCs compared with CA and zein NPs alone. Furthermore, FE-SEM analysis provided direct evidence of EPS penetration and bacterial cell disruption by CA@Zein NCs. Overall, CA@Zein NCs exhibits strong potential as an effective antibiofilm agent against S. Typhimurium.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13041060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}