BMC Pharmacology & Toxicology最新文献

{"title":"Intratympanic N-acetylcysteine in the prevention of cisplatin-induced ototoxicity: a systematic review and meta-analysis of randomized controlled trials.","authors":"Mohamed Tawalbeh, Rewan M Ibrahim, Taif Al-Saraireh, Lubna Khreesha, Baeth Al Rawashdeh","doi":"10.1186/s40360-024-00829-4","DOIUrl":"10.1186/s40360-024-00829-4","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the efficacy of the otoprotective transtympanic application of N-acetylcysteine in preventing chemotherapy-induced ototoxicity in patients subjected to platinum-based chemotherapy.</p><p><strong>Data sources: </strong>PubMed, Scopus, Web of Science, Cochrane Central, and ClinicalTrials.gov were searched for the following concepts: ((\"Acetylcysteine\" [Mesh]) AND (\"Ototoxicity\" [Mesh]) AND (\"Cisplatin\" [Objective: To evaluate the efficacy of otoprotective transtympanic application of N-acetylcysteine in the prevention of chemotherapy-induced ototoxicity in patients subjected to platinum-based chemotherapy. [Mesh]).</p><p><strong>Study selection: </strong>Inclusion: randomized controlled trials, Exclusion: (1) case reports or case series; (2) thesis; (3) review articles; (4) conference abstracts; (5) animal studies; (6) non-english studies; (7) studies whose population was other than patients on platinum-based chemotherapy.</p><p><strong>Data extraction: </strong>changes in hearing thresholds measured by pure tone tympanometry, covering high and low frequencies: 250, 500, 1000, 2000, 4000, and 8000 Hz. We used RevMan (Review Manager) version 5.3 to conduct the meta-analysis and GRADE to assess the quality of the evidence.</p><p><strong>Data synthesis: </strong>The literature search yielded 277 unique articles. After reviewing six full-text articles, three RCTs provided data available for meta-analysis. A total of 88 cisplatin-based chemotherapy candidates were included for final analysis. Hearing thresholds showed a significant threshold difference between the ear treated with N-acetylcysteine and the control ear (ear not treated with N-acetylcysteine), especially at high frequencies as high as 8000 Hz (pooled effect size - 10.67, 95% CI [-12.33, -9.02], P < 0.00001). The data favored the Nac group in all frequencies as well, at 4000 Hz (pooled effect size - 2.13, 95% CI [-3.49, -0.77], P = 0.002), at 2000 Hz (pooled effect size - 1.38, 95% CI [-2.69, -0.06], P = 0.04), at 1000 Hz (pooled effect size - 1.58, 95% CI [-2.63, -0.53], P = 0.003), at 500 Hz (pooled effect size - 1.58, 95% CI [-2.62, -0.54], P = 0.003), and at the low frequency of 250 after solving the heterogeneity (pooled effect size - 0.96, 95% CI [-2.88, 0.95], P = 0.32).</p><p><strong>Conclusions: </strong>Current data justifies the transtympanic administration of N-acetylcysteine for otoprotection in chemotherapy patients, minimizing the enduring consequences of cisplatin-induced ototoxicity and auditory impairment. Given the results' emphasis on the Sarafraz et al. (2018) study, more randomized controlled trials are necessary with an expanded sample size and standardization of N-acetylcysteine concentration, study population, and assessed outcomes.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"26"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188125","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":"Drug-related macular edema: a real-world FDA Adverse Event Reporting System database study.","authors":"Xiang Li, Yi-Qing Sun, Qiong-Lian Huang, Zhi-Jie Zhang, Li-Qiang Shi, Jia-Feng Tang, Zhan-Yang Luo","doi":"10.1186/s40360-025-00856-9","DOIUrl":"10.1186/s40360-025-00856-9","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to assess the risks associated with drug-induced macular edema and to examine the epidemiological characteristics of this condition.</p><p><strong>Methods: </strong>This study analyzed data from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database from January 2004 to June 2024 to conduct a disproportionality analysis identifying drugs with positive signals of drug-induced ME. Additionally, the onset time of ME associated with these drugs was examined.</p><p><strong>Results: </strong>In the FAERS database, a total of 490 drugs were reported to pose a risk of drug-induced ME. Disproportional analysis and screening further identified 8 drugs that significantly increased this risk. Among these, one is ophthalmic drugs, including Latanoprost (ROR = 5.51), and ten are non-ophthalmic drugs, including Cefuroxime (ROR = 75.93), Fingolimod (ROR = 30.69), and Siponimod (ROR = 20.51).</p><p><strong>Conclusions: </strong>This study utilizes the FAERS database to investigate potential associations between drug use and the occurrence of ME, rapidly identify drugs that may induce the condition, and propose research strategies. These findings hold significant value for guiding clinical medication practices.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"23"},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062823","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":"Systematic review and meta-analysis on the carbapenem-resistant hypervirulent Klebsiella pneumoniae isolates.","authors":"Motahareh Sabaghi Qala Nou, Zahra Amirian, Fatemeh Dehghani, Amir-Kazem Vejdan, Roghayeh Rooin, Sadegh Dehghanmehr","doi":"10.1186/s40360-025-00857-8","DOIUrl":"10.1186/s40360-025-00857-8","url":null,"abstract":"<p><strong>Background: </strong>The global dissemination of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) poses a critical threat to public health. However, comprehensive data on the prevalence and resistance rates of CR-hvKp are limited. This systematic review and meta-analysis aim to estimate the pooled prevalence of carbapenem resistance among hvKp strains and assess the distribution of carbapenemase genes.</p><p><strong>Materials and methods: </strong>A systematic search of ISI Web of Science, PubMed, and Google Scholar was conducted to identify studies reporting carbapenem resistance rates in hvKp strains. The pooled prevalence of carbapenem resistance and carbapenemase genes was calculated using event rates with 95% confidence intervals.</p><p><strong>Results: </strong>A total of 36 studies encompassing 1,098 hvKp strains were included. The pooled resistance rates were 49% for imipenem, 53.2% for meropenem, and 38.2% for ertapenem. Carbapenemase gene prevalence was 19.1% for bla_VIM, 22.0% for bla_NDM, 43.4% for bla_OXA-48, and 58.8% for bla_KPC.</p><p><strong>Conclusion: </strong>The high prevalence of carbapenem resistance and the widespread distribution of carbapenemase genes among hvKp strains underscore their significant threat to global health. These findings highlight the urgent need for enhanced surveillance, rapid diagnostic tools, and stringent infection control measures to mitigate the spread of CR-hvKp. Future research should focus on understanding resistance mechanisms and developing targeted therapeutic strategies to address this critical challenge.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"25"},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062807","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":"An exploratory study evaluating the 20 medications most commonly associated with suicidal ideation and self-injurious behavior in the FAERS database.","authors":"Wen-Long Xie, Dao-Chun Xiang, Yuan-Yuan Li, Meng-Lan Ge, Ai-Ping Deng","doi":"10.1186/s40360-025-00858-7","DOIUrl":"10.1186/s40360-025-00858-7","url":null,"abstract":"<p><strong>Background: </strong>A number of pharmaceuticals, including antidepressants and antiepileptics, have a strong correlation with suicide risk. However, it is not entirely clear which of these medications are more strongly associated with suicide-related behaviors.</p><p><strong>Objective: </strong>This study aims to elucidate the drugs responsible for drug-associated suicidal ideation or self-injurious, recognizing the severe consequences associated with such outcomes. However, it is not entirely clear which specific medications are associated with higher levels of suicide-related behavior. Real-world data from the FDA adverse event reporting system database were analyzed to identify medications correlated with suicidal ideation or self-injurious.</p><p><strong>Methods: </strong>The reporting intensity of the High-Level Term \"suicidal ideation or self-injurious behavior\" and its Preferred Terms across distinct categories was assessed using the Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR).</p><p><strong>Results: </strong>We identified the top 20 drugs with the highest reporting frequencies, spanning sedative-hypnotics, antidepressants, antipsychotics, antiepileptics, antihypertensives, antipyretic/analgesic drugs, and antihyperglycemic drugs. Ranking these medications according to ROR, the top five medications with ROR values related to suicidal ideation or self-injurious were alprazolam, zolpidem, amphetamine, quetiapine, and fluoxetine. Further analysis showed that suicide-related adverse events were more frequently reported in females. Antiepileptics had the highest frequency of reported adverse events in the 51-55 year age group, compared to 16-20 years for antidepressants and 46-50 years for sedative-hypnotics.</p><p><strong>Conclusion: </strong>Our study provides valuable information for clinical drug selection by presenting a potential list of medication classes commonly associated with drug-associated suicidal ideation or self-injurious behavior. We observed a large number of adverse event reports of suicidal ideation with duloxetine and relatively few reports of suicide attempts. Acetaminophen and amlodipine had substantial adverse event reports of completed suicides, but may not be associated with drug-induced suicidal behavior. On the other hand, some drugs mentioned in this study, such as quetiapine, aripiprazole, and lamotrigine, are recommended to be used after assessing the risk level of suicide in patients.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"24"},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062820","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":"Elucidating the role of FBXW4 in osteoporosis: integrating bioinformatics and machine learning for advanced insight.","authors":"Jinxiao Li, Jing Li, Man Zheng, Jinxing Liu, Xinyou Zhao","doi":"10.1186/s40360-025-00844-z","DOIUrl":"10.1186/s40360-025-00844-z","url":null,"abstract":"<p><strong>Background: </strong>Osteoporosis (OP), often termed the \"silent epidemic,\" poses a substantial public health burden. Emerging insights into the molecular functions of FBXW4 have spurred interest in its potential roles across various diseases.</p><p><strong>Methods: </strong>This study explored FBXW4 by integrating DEGs from GEO datasets GSE2208, GSE7158, GSE56815, and GSE35956 with immune-related gene compilations from the ImmPort repository. Gene selection was refined using advanced approaches, including LASSO regression and SVM-RFE. Functional enrichment of FBXW4-associated genes was assessed via GSEA and GSVA, identifying significant immune pathway involvement. Immune-related biological processes linked to FBXW4 expression were further evaluated using CIBERSORT and ESTIMATE algorithms. Validation of FBXW4 expression was performed using GSE35956.</p><p><strong>Results: </strong>A total of 13 hub genes were selected through LASSO and SVM-RFE analyses. Functional assays implicated FBXW4 in antiviral defense, cytokine production, and immune response modulation. Notably, FBXW4 expression correlated positively with several immune cell subsets, including memory B cells, activated memory CD4+ T cells, naive B cells, gamma delta T cells, M0 macrophages, follicular helper T cells, and naive CD4+ T cells, while showing a negative association with neutrophils.</p><p><strong>Conclusions: </strong>This study uncovers a complex interplay between FBXW4 and immune processes in osteoporosis, suggesting its potential utility as a biomarker for OP diagnosis and monitoring. These findings lay the groundwork for future investigations into the therapeutic and diagnostic potential of FBXW4 in OP.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"20"},"PeriodicalIF":2.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062824","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":"λ-cyhalothrin induced sex-specific inflammation, glia activation and GABAergic interneuron disruption in the hippocampus of rats.","authors":"Aminu Imam, Christianah Oyegbola, Maryam Busari, Adewumi Mercy Gbemisola, Laaro Abubakar, Ajala Taofeeqoh Odunayo, Alhassan Godwin Attai, Ajibola Musa Iyiola, Wahab Abdulmajeed Imam, Aalimah Akinosho Akorede, Omamuyovwi Meashack Ijomone, Moyosore Salihu Ajao","doi":"10.1186/s40360-025-00860-z","DOIUrl":"10.1186/s40360-025-00860-z","url":null,"abstract":"<p><strong>Background: </strong>Glia mediated neuroinflammation and degeneration of inhibitory GABAergic interneurons are some of the hall marks of pyrethroid neurotoxicity. Here we investigated the sex specific responses of inflammatory cytokines, microglia, astrocyte and parvalbumin positive inhibitory GABAergic interneurons to λ-cyhalothrin (LCT) exposures in rats.</p><p><strong>Methods: </strong>Equal numbers of male and female rats were given oral corn oil, 2 mg/kg.bw and 4 mg/kg.bw of LCT for fourteen days. They were euthanized on day 15, brains were excised and hippocampus (n = 5/group) isolated for interleukin 1 beta (IL-1β) and tumor necrotic factor alpha (TNF-α) analysis. The remaining brains (n = 3/group) were processed for Ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP) and parvalbumin (PV) distribution in the hippocampus. All quantitative data was subjected to one way analysis of variance (ANOVA).</p><p><strong>Results: </strong>LCT caused sex and dose dependent increase in IL-1β and TNF-α concentrations, distribution of microglia (Iba1+) and astrocytes (GFAP+), and reduction of PV + GABAergic interneurons. These effects were greater in males compared to females, and dose-dependent in both sexes.</p><p><strong>Conclusion: </strong>LCT specifically induced inflammation and disrupted GABAergic interneurons' integrities via activation of microglia and reactive astrogliosis and such effects are dose-dependent and sexually dimorphic.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"22"},"PeriodicalIF":2.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063191","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":"Musculoskeletal adverse events associated with CDK4/6 inhibitors: a real-world study using FDA Adverse Event Reporting System (FAERS) database.","authors":"Zhenlin Chen, Zhiwen Fu, Nu Zhang, Wenbin Zou, Wei Chen","doi":"10.1186/s40360-025-00862-x","DOIUrl":"10.1186/s40360-025-00862-x","url":null,"abstract":"<p><strong>Objective: </strong>Cyclin-dependent kinase (CDK)-4/6 inhibitors have significantly improved outcomes in several cancers but can also induce various organ system toxicities, including musculoskeletal disorders. This study aimed to comprehensively characterize the musculoskeletal adverse events (MSAEs) associated with CDK4/6 inhibitors based on real-world data.</p><p><strong>Methods: </strong>Reports of MSAEs linked to CDK4/6 inhibitors from the first quarter (Q1) of 2015 and 2023 Q4 were extracted from the FAERS. Descriptive analyses evaluated report frequencies over time and patient characteristics. Disproportionality analyses using reporting odds ratios (RORs) identified signals for specific musculoskeletal preferred terms (PTs). Time-to-onset analyses examined the temporal patterns of MSAEs.</p><p><strong>Results: </strong>A total of 10,095 MSAE reports associated with CDK4/6 inhibitors were identified, most involving Palbociclib (n = 7819). The median age of patients was 64 years (IQR: 55-72), predominantly female (97.73%). Most reports were submitted by consumers (47.62%) and the majority of reports were from the United States (71.53%). Disproportionality analyses revealed distinct signals, with Ribociclib showing prominent signals for bone pain and bone lesions, and Abemaciclib for osteonecrosis of the jaw and pathological fractures. Palbociclib demonstrated a consistent but less pronounced signal across musculoskeletal PTs. Time-to-onset analyses demonstrated a significantly longer onset of MSAEs for Palbociclib (median 82 days, IQR[14-311]) compared to Abemaciclib (32.5 days, IQR[12-119]) and Ribociclib (34 days, IQR[8-177]) using the nonparametric Kruskal-Wallis test (P-value = 3.048e-11).</p><p><strong>Conclusion: </strong>Musculoskeletal toxicities is a significant adverse event that affects drug safety. Early identification and proper management of these events are crucial for patients receiving CDK4/6 inhibitors. Further research is warranted to elucidate the underlying mechanisms and improve risk mitigation strategies.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"21"},"PeriodicalIF":2.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062826","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":"Epoetin alfa has a potent anxiolytic effect on naive female rats.","authors":"Hasan Çalışkan, Seda Koçak, Emel Güneş","doi":"10.1186/s40360-025-00845-y","DOIUrl":"10.1186/s40360-025-00845-y","url":null,"abstract":"<p><strong>Background: </strong>Epoetin alfa is a derivative of the erythropoietin hormone. This study aims to investigate the epoetin alfa effect on anxiety-like behaviors.</p><p><strong>Methods: </strong>Adult female Wistar Albino rats were divided into Control (n = 8), 1000 U Epoetien alfa, and 2000 U Epoetien alpha. Epoetin alfa was administered intraperitoneally once a week for 4 weeks. The animals were then subjected to open field test, elevated plus maze, light-dark box, and the behaviors were video recorded.</p><p><strong>Results: </strong>Epoetin alfa significantly reduced anxiety-like behaviors in both low- and high-dose groups in a dose-independent manner. This anxiolytic effect was seen in all three anxiety tests. Further, exploratory behaviors such as unsupported rearing and head-dipping behaviors increased with the application of Epoetin alfa. This protocol did not alter locomotor activity.</p><p><strong>Conclusion: </strong>The present study found beneficial effects of epoetin alfa on behaviors. Further studies on the effect of derivatives of erythropoietin hormone on anxiety-like behaviors are needed.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"18"},"PeriodicalIF":2.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057918","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":"Alzheimer's disease: an integrative bioinformatics and machine learning analysis reveals glutamine metabolism-associated gene biomarkers.","authors":"Naifei Xing, Jingwei Yan, Rong Gao, Aihua Zhang, Huiyan He, Man Zheng, Guojing Li","doi":"10.1186/s40360-025-00852-z","DOIUrl":"10.1186/s40360-025-00852-z","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD), a hallmark of age-related cognitive decline, is defined by its unique neuropathology. Metabolic dysregulation, particularly involving glutamine (Gln) metabolism, has emerged as a critical but underexplored aspect of AD pathophysiology, representing a significant gap in our current understanding of the disease.</p><p><strong>Methods: </strong>To investigate the involvement of GlnMgs in AD, we conducted a comprehensive bioinformatic analysis. We began by identifying differentially expressed GlnMgs from a curated list of 34 candidate genes. Subsequently, we employed GSEA and GSVA to assess the biological significance of these GlnMgs. Advanced techniques such as Lasso regression and SVM-RFE were utilized to identify key hub genes and evaluate the diagnostic potential of 14 central GlnMgs in AD. Additionally, we examined their correlations with clinical parameters and validated their expression across multiple independent AD cohorts (GSE5281, GSE37263, GSE106241, GSE132903, GSE63060).</p><p><strong>Results: </strong>Our rigorous analysis identified 14 GlnMgs-GLS2, GLS, GLUD2, GLUL, GOT1, HAL, AADAT, PFAS, ASNSD1, PPAT, NIT2, ALDH5A1, ASRGL1, and ATCAY-as potential contributors to AD pathogenesis. These genes were implicated in vital biological processes, including lipid transport and the metabolism of purine-containing compounds, in response to nutrient availability. Notably, these GlnMgs demonstrated significant diagnostic potential, highlighting their utility as both diagnostic and prognostic biomarkers for AD.</p><p><strong>Conclusions: </strong>Our study uncovers 14 GlnMgs with potential links to AD, expanding our understanding of the disease's molecular underpinnings and offering promising avenues for biomarker development. These findings not only enhance the molecular landscape of AD but also pave the way for future diagnostic and therapeutic innovations, potentially reshaping AD diagnostics and patient care.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"19"},"PeriodicalIF":2.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057816","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":"Analysis of the potential biological mechanisms of geniposide on renal fibrosis by network pharmacology and experimental verification.","authors":"Mengqian Liu, Wenman Zhao, Rui Shi, Zhijuan Wang, Xunliang Li, Deguang Wang","doi":"10.1186/s40360-025-00855-w","DOIUrl":"10.1186/s40360-025-00855-w","url":null,"abstract":"<p><strong>Background: </strong>Renal fibrosis is crucial in the progression of chronic kidney disease (CKD) to end-stage renal failure. Geniposide, an iridoid glycoside, has shown therapeutic potential in acute kidney injury, diabetic nephropathy, and atherosclerosis. The aim of this study was to investigate the role of geniposide in renal fibrosis and its underlying mechanisms.</p><p><strong>Methods: </strong>The network pharmacology and molecular docking methods were used to identify potential targets and pathways of geniposide for treating renal fibrosis. In vivo, the unilateral ureteral obstruction (UUO) mouse model was treated with geniposide. In vitro, TGF-β1-stimulated human renal tubular epithelial (HK-2) cells were applied for validation. HE, PAS, Masson, and immunohistochemistry staining were performed to evaluate its effects on the kidneys of UUO mice. RT-qPCR and western blotting were used to detect the expression of hub genes and signaling pathways.</p><p><strong>Results: </strong>101 overlapping genes were identified, with the top 10 including AKT1, MMP9, GAPDH, BCL2, TNF, CASP3, SRC, EGFR, IL-1β, and STAT1. GO analysis suggested that these key targets were mainly involved in cell proliferation and apoptosis. KEGG analysis revealed that the PI3K/AKT, MAPK, and Rap1 signaling pathways were associated with geniposide against renal fibrosis. Molecular docking suggested a strong binding affinity of geniposide to the hub genes. In vivo experiments showed that geniposide ameliorated kidney injury and fibrosis, and inhibited the mRNA levels of AKT1, MMP9, BCL2, and TNF. In addition, geniposide inhibited the activation of the PI3K/AKT signaling pathway, thereby suppressing renal fibrosis in UUO mice and TGF-β1-induced HK-2 cells.</p><p><strong>Conclusions: </strong>Geniposide can attenuate renal fibrosis by inhibiting the PI3K/AKT pathway, suggesting its potential as a therapeutic agent for renal fibrosis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"17"},"PeriodicalIF":2.8,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051518","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}