Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Association of 24-hours net positive fluid balance with log-transformed vancomycin trough concentrations in the early phase of therapy among critically ill patients.","authors":"Azfar Athar Ishaqui, Khalid Orayj, Tauqeer Hussain Mallhi, Salman Ashfaq Ahmad, Sultan M Alshahrani, Rayah Asiri, Adnan Iqbal, Asaad Ahmed Asaad Khalil, Mohammed Ali Kaddoura, Muhammad Bilal Maqsood, Javeria Farooq, Narendar Kumar","doi":"10.1007/s00210-026-05974-7","DOIUrl":"https://doi.org/10.1007/s00210-026-05974-7","url":null,"abstract":"<p><p>Early vancomycin troughs are frequently low in critical illness and fluid accumulation may contribute through distribution effects. This study estimated the association between net positive fluid balance and early vancomycin troughs as a hypothesis-generating analysis and explored variation across early-therapy windows and by hypoalbuminemia. A retrospective cohort study used ICU electronic health record data from MIMIC-IV. ICU stays with a timing-validated trough were included. The primary cohort N = 255 required at least 80% EMAR dose capture in the prior 24 h and delta serum creatinine at or below 0.2 mg/dL across the 48 h before trough and trough within 72 h of first IV dose. Net fluid balance in the prior 24 h was modeled per + 5 L. Outcome was log trough. Models adjusted for serum creatinine and administered dose and administration count in the prior 24 h. Sensitivity windows were within 48 h (N = 162) and within 96 h (N = 289). Hypoalbuminemia below 3 g/dL was explored in the measured subset. Median trough was 14.00 mg/L (IQR 10.15 to 18.15) and 62 of 255 were below 10 mg/L (24.3%). The point estimate suggested an 11.7% lower trough concentration per + 5 L net positive balance (β =  - 0.1247; SE = 0.079; p = 0.115), but the 95% CI (- 24.4% to + 3.1%) included no association. Serum creatinine had a positive coefficient (β = 0.2995; p = 0.061). Point estimates were similar across early-therapy windows with all confidence intervals including no association. The exploratory albumin interaction was imprecise and limited by substantial missingness and small subgroup sizes. The point estimate suggested lower early vancomycin troughs with higher net positive fluid balance, but the confidence interval included no association. These hypothesis-generating findings require prospective validation to clarify whether fluid balance is associated with early trough concentrations and area under the curve exposure.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165104","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":"Retraction Note: Cardioprotective role of GTS-21 by attenuating the TLR4/NF-κB pathway in streptozotocin-induced diabetic cardiomyopathy in rats.","authors":"Mahmoud E Youssef, Heba M Abdelrazek, Yasser M Moustafa","doi":"10.1007/s00210-026-05995-2","DOIUrl":"https://doi.org/10.1007/s00210-026-05995-2","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169944","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":"Tirofiban after intravenous thrombolysis in acute ischemic stroke patients: An updated systematic review and meta-analysis of randomized controlled trials.","authors":"Omar Fayez Abbas, Abdullah Almarfadi, Nour Aldin Tarek Ahmed, Aya Magdy Siam, Roaa Haddad, Fatma Aljalawy, Ahmed Harb, Abdelrahman M Hamouda, R Saha, Sherief Ghozy, Adam A Dmytriw","doi":"10.1007/s00210-026-05950-1","DOIUrl":"https://doi.org/10.1007/s00210-026-05950-1","url":null,"abstract":"<p><p>Early antiplatelet therapy after intravenous thrombolysis (IVT) for acute ischemic stroke remains controversial because of concerns regarding hemorrhagic complications. Tirofiban, a reversible glycoprotein IIb/IIIa receptor antagonist, may reduce platelet-mediated rethrombosis and improve reperfusion after thrombolysis. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of early intravenous tirofiban following IVT. PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception through May 2026. RCTs comparing early intravenous tirofiban versus standard care or placebo after IVT were included. Outcomes included functional independence (modified Rankin Scale [mRS] 0-2), excellent outcome (mRS 0-1), symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and 90-day mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Six randomized controlled trials (RCTs) involving 1787 patients were included. Tirofiban significantly increased the likelihood of achieving functional independence at 90 days (RR, 1.14; 95% CI, 1.03-1.25; P = 0.019). Although tirofiban showed a trend toward improving excellent functional outcome, the difference was not statistically significant (RR, 1.21; 95% CI, 0.95-1.56; P = 0.080). No significant differences were observed in symptomatic intracranial hemorrhage (RR, 1.72; 95% CI, 0.57-5.19; P = 0.265), any intracranial hemorrhage (RR, 1.17; 95% CI, 0.72-1.90; P = 0.453), or 90-day mortality (RR, 0.92; 95% CI, 0.59-1.45; P = 0.668). Sensitivity analyses demonstrated robust findings across all outcomes. Early intravenous tirofiban following thrombolysis was associated with improved functional recovery without a significant increase in mortality or intracranial hemorrhage on a relative scale. Although a 1% absolute increase in symptomatic ICH was observed, the difference was not statistically significant. These findings support further investigation of tirofiban as an adjunct to thrombolysis in selected patients with acute ischemic stroke.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170089","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":"Deciphering the mechanisms of resveratrol in knee osteoarthritis treatment: insights from bioinformatics and experimental validation.","authors":"Chenyi Huang, Xiong Ye, Xing Liu, Fei Liu, Yang Li, Xi Chen, Pandeng Hao, Xubing San","doi":"10.1007/s00210-026-05985-4","DOIUrl":"https://doi.org/10.1007/s00210-026-05985-4","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Knee osteoarthritis (KOA) is the most prevalent chronic joint disorder in orthopedics, with its underlying pathogenic genes and effective treatment methods remaining unclear. Resveratrol (RES), a potent bioactive natural polyphenol, has been shown to effectively alleviate KOA; however, its complex regulatory mechanisms require further investigation. This research seeks to clarify the molecular mechanisms by which RES contributes to the treatment of KOA, utilizing a blend of bioinformatics approaches and experimental validation. First, gene expression profiles related to KOA were obtained from the GEO database. Subsequently, differential gene analysis was conducted on the samples, and modular genes linked to KOA were extracted through the application of a weighted gene co-expression network. The LASSO algorithm was utilized to identify crucial pathogenic genes in KOA, which were later confirmed using clinical samples. Targets for RES were sourced from traditional Chinese medicine databases, and the therapeutic targets for KOA treatment were determined by finding the intersection of these sources. An enrichment analysis was carried out based on the therapeutic targets identified. Molecular docking studies were conducted to further assess the binding affinity of key therapeutic genes with RES. Lastly, animal experiments were implemented to substantiate the molecular mechanisms by which RES acts in the treatment of KOA. We identified 460 module genes and 10 key predictive genes through LASSO analysis. The findings from the enrichment analysis concerning potential therapeutic targets for RES in the treatment of KOA reveal that the significant genes implicated include VEGFA, IL6, MAPK3, IL1B, CASP3, and AKT1. Subsequent validation with clinical samples revealed that IL6, MAPK3, IL1B, CASP3, and AKT1 were significantly elevated during the progression of KOA, while VEGFA was markedly reduced in the context of KOA. The outcomes of the GO and KEGG analyses suggest that the primary biological processes implicated encompass apoptosis, the FoxO signaling pathway, the IL-17 signaling pathway, cellular senescence, and the NF-κB signaling pathway. The findings from the immune infiltration analysis indicate that resting CD4 memory T cells, memory B cells, resting mast cells, eosinophils, and activated mast cells may have important functions in the immune mechanisms related to KOA. The results of animal experiments demonstrate that RES effectively inhibits the expression of inflammatory factors such as IL-6, MAPK3, IL-1β, CASP3, and AKT1 during the progression of KOA, promotes the expression of VEGFA, and concurrently suppresses the FoxO signaling pathway and the IL-17 signaling pathway, thereby reducing cartilage damage induced by MIA and delaying the progression of KOA. In summary, RES can regulate the expression of genes including VEGFA, IL-6, MAPK3, IL-1β, CASP3, and AKT1, inhibit the FoxO signaling pathway and the IL-17 signaling pathway, alleviate cart","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167587","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":"Pharmacological features of mesoionic compounds: antitumoral effects and bioenergetic disruption of sydnones and 1,3,4-thiadiazolium derivatives.","authors":"André Felipe Naidek, Mariane Londero Rodrigues, Maria Carolina Stipp, Douglas de Jesus da Silva Claudino, Aurea Echevarria, Silvia Suter Correia Cadena, Alexandra Acco","doi":"10.1007/s00210-026-05970-x","DOIUrl":"https://doi.org/10.1007/s00210-026-05970-x","url":null,"abstract":"<p><p>Mesoionic compounds are five-membered heterocyclic betaines that cannot be satisfactorily represented by a single covalent or polar structure. Because their positive and negative charges are delocalized over separate regions of the ring, they yield a net-neutral molecule with a high dipole moment. This unique electronic configuration confers amphiphilic character and pronounced affinity for biological membranes, including mitochondria, underlying a broad pharmacological profile that includes antitumoral, anti-inflammatory and analgesic activities. Among the several mesoionic scaffolds, sydnones (1,2,3-oxadiazolium-5-olate) and 1,3,4-thiadiazolium derivatives have been the most extensively studied, drawing particular attention to their pronounced antineoplastic activity against melanoma, hepatocellular carcinoma, breast cancer and glioblastoma models. Their anticancer effects are closely linked to mitochondrial bioenergetic disruption, including uncoupling of oxidative phosphorylation, inhibition of respiratory complexes, dissipation of the mitochondrial membrane potential, and stimulation of F1Fo-ATPase activity, which together cause ATP depletion, redox imbalance, and apoptosis induction. This review provides a comprehensive analysis of the structural features that govern these biological properties, the antitumor efficacy of sydnones and thiadiazolium derivatives across various cancer models, and the underlying mitochondrial mechanisms. By integrating chemical, pharmacological, and bioenergetic perspectives, this article highlights the potential of mesoionic compounds as versatile scaffolds for the anticancer drug development, emphasizing their preclinical antitumoral activities, the mechanisms related to cell bioenergetics, and the challenges to improve the bioviability through nanotechnologies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172329","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":"The impact of paroxetine on insulin secretion and sensitivity through AKT/GLUT4 axis.","authors":"Nidal A Qinna, Khaled Al-Khatib, Ghayda' AlDabet, Razan M AbdulHadi, Raghad H Mosleh, Bayan Alkhawaja, Bayan Y Ghanim","doi":"10.1007/s00210-026-05966-7","DOIUrl":"https://doi.org/10.1007/s00210-026-05966-7","url":null,"abstract":"<p><p>Selective serotonin reuptake inhibitors (SSRIs) are reported to be implicated in altering glucose homeostasis and inducing hypoglycemia in diabetic patients and mice. Herein, the effects of paroxetine on glucose homeostasis, insulin secretion, and insulin sensitivity were investigated in both healthy and streptozotocin-induced-insulin deficient mouse model. Mice were administered with paroxetine (1, 10, and 50 mg/kg) and fasting insulin levels and glucose-stimulated insulin secretion were assessed in healthy mice, whereas the glycemic profile in diabetic mice was evaluated after glucose or insulin challenge. Muscle mRNA expression of insulin signaling-relevant genes was analyzed, in addition to protein kinase B (PKB/Akt) activity and glucose transporter 4 (GLUT4) plasma membrane expression assessed in C2C12 myotubes. Paroxetine modulated glucose homeostasis and reduced the spike in blood glucose in diabetic mice in a dose-dependent manner after a glucose tolerance test. On the other hand, a reverse relationship was observed in the insulin tolerance test, with no evidence of acute hypoglycemia, suggesting that paroxetine did not further exacerbate insulin-induced glucose lowering under the tested conditions. Paroxetine (50 mg/kg) significantly increased fasting insulin secretion and upregulated genes involved in insulin receptor and Akt signaling, while reducing Glut4 mRNA expression. At 10 mg/kg, paroxetine significantly elevated Akt phosphorylation (p < 0.01). Paroxetine enhanced GLUT4 translocation and Akt phosphorylation in C2C12 myotubes. These findings suggest that paroxetine influences glucose homeostasis in diabetic conditions without causing acute hypoglycemia. Nevertheless, further preclinical and clinical investigations are warranted to clarify its metabolic effects and to determine the clinical implications for glycemic management in diabetic patients receiving paroxetine.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137770","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":"Dihydroflavonoids outperform their flavonoid counterparts in lipid-lowering efficacy based on pairwise analyses.","authors":"Lie Yuan, Yazhen Zhang, Ao Zhang, Dongmei Chen, Xiandeng Li, Yuheng Wang, Long Chu, Xiaoli Li, Xiao Zhang, Qinjian Zhao","doi":"10.1007/s00210-026-05969-4","DOIUrl":"https://doi.org/10.1007/s00210-026-05969-4","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting approximately 25% of the adult population, yet no approved pharmacotherapy is currently available. Flavonoids have shown promise in improving MASLD, but the structural determinants underlying their lipid-lowering activities remain unclear. This study aimed to systematically investigate whether the presence or absence of the C-2,3 double bond affects the efficacy of flavonoids in ameliorating MASLD. Two pairs of C-2,3 positional isomeric flavonoids-eriodictyol (Compound 1a, dihydro form, C-2,3 single bond)/luteolin (Compound 1b, non-dihydro form, C-2,3 double bond) and dihydromyricetin (Compound 2a, dihydro form, C-2,3 single bond)/myricetin (Compound 2b, non-dihydro form, C-2,3 double bond)-were compared using an FFA-induced HepG2 cell model and an HFD-induced MASLD mouse model. Lipid accumulation, gene expression, target protein thermal stabilization (via CETSA), and compound-target interactions (via molecular docking) were systematically assessed. Both in vitro and in vivo experiments consistently demonstrated that the dihydro forms (C-2,3 single bond) exhibited superior efficacy to their non-dihydro counterparts (C-2,3 double bond) in reducing lipid accumulation and modulating lipid metabolism-related genes. Mechanistically, the dihydro forms showed broader regulatory effects on genes involved in fatty acid oxidation, de novo lipogenesis, and fatty acid uptake. CETSA and molecular docking analyses further suggested that the dihydro forms exhibited greater thermal stabilization of the target proteins and generally lower predicted binding energies across all three targets (PPARγ, ACC1, and FASN). This study provides the first systematic evidence that the C-2,3 single-bond configuration may represent a structural feature associated with enhanced lipid-lowering activity of flavonoids, offering experimental evidence for dietary intervention strategies and flavonoid-based lead compound optimization in MASLD.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137812","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":"Berberine inhibits gastric cancer progression by targeting canonical Wnt/β-catenin signaling in AGS cells.","authors":"Li Xiao, Ren Hui, Bai Jing","doi":"10.1007/s00210-026-05955-w","DOIUrl":"https://doi.org/10.1007/s00210-026-05955-w","url":null,"abstract":"<p><p>Gastric cancer (GC) progression is strongly associated with dysregulated proliferation, apoptosis resistance, epithelial-mesenchymal transition, invasion, and aberrant Wnt/β-catenin signaling. Berberine has shown anti-cancer activity in several tumor models; however, its mechanistic effects on Wnt/β-catenin-driven GC phenotypes require further clarification. This study investigated whether berberine suppresses AGS GC cell progression through inhibition of canonical Wnt/β-catenin signaling. AGS cells were treated with berberine at low, medium, and high concentrations, with CHIR99021 used for Wnt/β-catenin pathway activation and XAV939 as a pathway inhibitory control. Cell viability, proliferation, colony formation, cell cycle distribution, apoptosis, migration, invasion, EMT marker expression, β-catenin localization, TOP/FOP luciferase activity, ROS/RNS production, mitochondrial membrane potential, and glucose uptake were assessed using functional, molecular, and fluorescence-based assays. CTNNB1 knockdown was used to validate β-catenin-dependent mechanisms. Berberine reduced AGS cell viability, EdU incorporation, clonogenic survival, migration, invasion, and glucose uptake while inducing G0/G1 arrest, mitochondrial depolarization, oxidative/nitrosative stress, caspase activation, and apoptosis. Berberine increased E-cadherin and decreased N-cadherin, Vimentin, Snail, Slug, ZEB1, and MMP9, indicating suppression of EMT. Mechanistically, berberine reduced β-catenin expression, nuclear localization, TOP/FOP transcriptional activity, and downstream Wnt targets including CCND1, MYC, BIRC5, AXIN2, and MMP9. CHIR99021 partially reversed berberine-induced anti-tumor effects, whereas XAV939 and CTNNB1 knockdown mimicked or enhanced berberine activity. Berberine suppresses AGS GC cell progression by inhibiting canonical Wnt/β-catenin signaling, thereby reducing proliferation, EMT, invasion, metabolic activity, and survival while promoting cell cycle arrest and apoptosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137832","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":"Formononetin attenuates ethanol-induced gastric ulcer injury by targeting ALDH2 to inhibit oxidative stress.","authors":"Zhihong Liu, Xinjie Yao, Tingting Zhao, Yunhui Wang","doi":"10.1007/s00210-026-05942-1","DOIUrl":"https://doi.org/10.1007/s00210-026-05942-1","url":null,"abstract":"<p><p>Ethanol-induced gastric ulceration is primarily driven by oxidative stress, mitochondrial dysfunction, and gastric epithelial cell injury. Although formononetin (Fmn), a naturally occurring isoflavone, possesses well-documented antioxidant and anti-inflammatory properties, its protective role and underlying molecular mechanisms in ethanol-induced gastric injury remain unclear. In this study, ethanol-treated GES-1 gastric epithelial cells were used as an in vitro model to investigate the cytoprotective effects of Fmn. Cell proliferation, apoptosis, oxidative stress, and mitochondrial function were evaluated using biochemical and cellular assays. Potential molecular targets were identified through SwissTargetPrediction and molecular docking, followed by experimental validation, including ALDH2 knockdown, qRT-PCR, and enzymatic activity assays. Fmn significantly attenuated ethanol-induced cellular injury by restoring cell proliferation, suppressing apoptosis, reducing intracellular and mitochondrial reactive oxygen species, decreasing malondialdehyde levels, and enhancing superoxide dismutase activity. Molecular docking demonstrated a strong binding affinity between Fmn and aldehyde dehydrogenase 2 (ALDH2), which was further confirmed by increased ALDH2 mRNA and protein expression as well as enhanced enzymatic activity following Fmn treatment. Functional studies revealed that ALDH2 upregulation plays a pivotal role in preserving mitochondrial integrity and limiting oxidative damage. Collectively, these findings demonstrate that Fmn protects gastric epithelial cells against ethanol-induced injury through ALDH2-mediated suppression of oxidative stress and mitochondrial dysfunction, highlighting its potential as a promising therapeutic candidate for the prevention and treatment of alcohol-induced gastric ulceration.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127649","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":"Potential targets and mechanisms of Di(2-ethylhexyl) phthalate exposure in inducing chronic kidney disease: a multimodal study integrating epidemiology, network toxicology, and Mendelian randomization.","authors":"Yihan Wang, Qi Liu, Xiaojun Li, Ruizhi Tan, Hong Li, Junming Fan, Jun Zhu, Li Wang","doi":"10.1007/s00210-026-05972-9","DOIUrl":"https://doi.org/10.1007/s00210-026-05972-9","url":null,"abstract":"<p><p>Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer present in numerous consumer and medical products and has been associated with adverse effects in multiple organ systems, including the kidney. Chronic kidney disease (CKD) is an increasing global health burden, yet the molecular targets potentially linking DEHP exposure to CKD remain incompletely understood. This study integrated epidemiological analysis, network toxicology, Mendelian randomization (MR), molecular docking, and molecular dynamics simulations to investigate potential molecular targets associated with DEHP exposure and CKD. Data from the National Health and Nutrition Examination Survey (NHANES) were used to examine the association between urinary DEHP metabolites and CKD. DEHP-related and CKD-related targets were subsequently integrated to identify shared targets, followed by PPI network analysis and expression-based evaluation to prioritize candidate genes. MR analysis was then performed to assess the association between genetically proxied candidate genes and CKD. Molecular docking was used to explore the potential interactions between DEHP and the prioritized proteins, and molecular dynamics simulations were performed to further evaluate the structural stability of the predicted DEHP-CTSK complex. Higher urinary DEHP metabolite levels were associated with a higher prevalence of CKD. Four candidate genes-CTSK, ABL1, BCL2L1, and CCND1-were prioritized based on network and expression-based analyses. Among these genes, genetically proxied CTSK showed a significant positive association with CKD in the primary MR analysis. Molecular docking showed favorable predicted docking scores for DEHP with the four candidate proteins, while molecular dynamics simulations supported the structural stability of the predicted DEHP-CTSK complex over 100 ns. These findings provide convergent epidemiological, genetic, and computational evidence supporting CTSK as a candidate molecular target for further investigation in the context of DEHP-associated renal injury.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137757","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}