Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"METTL14 Inhibits Human Lung Microvascular Endothelial Cell From Ferroptosis in Septic Lung Injury by Regulating N6-Methyladenosine-Modified ACSL4 Level","authors":"Xiao Gui,&nbsp;Yongyang Tian,&nbsp;Haiyuan Zhu,&nbsp;Lilin Wang,&nbsp;Jinhui Wang,&nbsp;Ruimiao Wu,&nbsp;Fangzhou Gan","doi":"10.1111/1440-1681.70095","DOIUrl":"https://doi.org/10.1111/1440-1681.70095","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>N⁶-methyladenosine (m⁶A) RNA modification is involved in numerous physiological and pathological processes. However, the specific role of m⁶A modification in septic lung injury remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, caecal ligation and puncture (CLP) operation was performed to induce septic lung injury in mice, and the establishment of the animal model was verified by haematoxylin and eosin (H&amp;E) staining of lung tissues. The mRNA levels of m⁶A writers in blood samples from septic lung injury model mice were assessed. The intracellular concentrations of Fe²⁺, glutathione (GSH), malondialdehyde (MDA) and reactive oxygen species (ROS) were quantified to evaluate ferroptosis in HULEC-5a cells. In addition, the mitochondrial ultrastructure of HULEC-5a cells was observed by transmission electron microscopy (TEM). The MeRIP assay was performed to detect the m⁶A modification of ACSL4 mRNA. The binding of ACSL4 to METTL14 was verified using RIP and dual luciferase gene reporter assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, METTL14 was identified as aberrantly downregulated in septic lung injury models. Highly expressed METTL14 significantly protected HULEC-5a cells from LPS-induced ferroptosis. Meanwhile, METTL14 increased m⁶A methylation of ACSL4 mRNA and inhibited ACSL4 mRNA levels by suppressing its stability. Mechanistically, METTL14 mediates the m⁶A modification of ACSL4 in a manner dependent on the m⁶A reader protein YTHDC1. These findings support a role for METTL14-mediated modification of ACSL4 and the subsequent suppression of ferroptosis in the pathogenesis of septic lung injury.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data support that ferroptosis-induced damage is a pathogenic event during septic lung injury and that targeting METTL14 may have therapeutic potential for the treatment of septic lung injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145619281","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":"Apelin-13 Attenuates Right Ventricular Hypertrophy and Pulmonary Fibrosis in a Monocrotaline Model of Pulmonary Hypertension","authors":"Önder Öztürk,&nbsp;Rahime Aslankoc,&nbsp;Mustafa Saygın,&nbsp;Ozlem Ozmen,&nbsp;Yusuf. S. Sirin,&nbsp;Oguzhan Kavrik","doi":"10.1111/1440-1681.70094","DOIUrl":"https://doi.org/10.1111/1440-1681.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary hypertension (PH) is a progressive and fatal disease characterised by pulmonary vascular remodelling, right ventricular hypertrophy, and increased pulmonary arterial pressure. Apelin, an endogenous ligand of the APJ receptor, exerts cardioprotective and vasoprotective effects and has been proposed as a potential therapeutic agent in PH. This study aimed to investigate the therapeutic effects of Apelin-13 on hemodynamic, histomorphological, and molecular alterations in a monocrotaline (MCT)-induced PH rat model. Male Wistar rats were divided into four groups: control, MCT, MCT + Apelin-13, and sham-Apelin. A single intraperitoneal injection of MCT (60 mg/kg) was used to induce PH. Apelin-13 was administered intraperitoneally for 21 days. Hemodynamic parameters (<i>P</i>_max, <i>P</i>_min, mPAP, EDP, <i>dP</i>/<i>dt</i>_max, <i>dP</i>/<i>dt</i>_min, MAP), morphometric indices (RVHI, PAWTR, PAVR), histological and immunohistochemical analyses (Apelin-13, ACE, Caspase-3, IL-1β) were evaluated. MCT administration significantly increased pulmonary arterial pressure, right ventricular hypertrophy, and vascular wall thickness, while reducing Apelin-13 and ACE expression and elevating Caspase-3 and IL-1β levels. Apelin-13 treatment markedly attenuated these pathological alterations by lowering right ventricular overload, improving vascular remodelling, restoring Apelin-13 and ACE expression, and reducing apoptotic and inflammatory markers. Apelin-13 exerts multifaceted protective effects in MCT-induced PH by modulating hemodynamic load, vascular structure, and inflammatory-apoptotic pathways. These findings provide novel evidence supporting Apelin-13 as a promising therapeutic candidate for PH and warrant further studies to explore its long-term efficacy and translational potential.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572275","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":"In Vitro Antibacterial Activity of Myxin Against Mycobacterium abscessus","authors":"Zihao Liu,&nbsp;Xiaoyu Wan,&nbsp;Anqi Li,&nbsp;Zhili Tan,&nbsp;Siyuan He,&nbsp;Yaping Jia,&nbsp;Yani Lin,&nbsp;Rong li,&nbsp;Yuheng Qian,&nbsp;Liyun Xu,&nbsp;Bing Li","doi":"10.1111/1440-1681.70091","DOIUrl":"https://doi.org/10.1111/1440-1681.70091","url":null,"abstract":"<div>\u0000 \u0000 <p>Nontuberculous mycobacteria (NTM) infections, especially those caused by <i>Mycobacterium abscessus</i>, are extremely difficult to treat due to the organisms' intrinsic resistance to many antimicrobials. Myxin is a naturally occurring phenazine-5,10-dioxide antibiotic from <i>Sorangium</i> sp., notable for its broad-spectrum antimicrobial activity. In this study, we determined the susceptibilities of Myxin against 11 NTM reference strains and 194 clinical <i>M. abscessus</i> isolates using microdilution assays. Additionally, time-kill kinetic experiments were performed to distinguish the clearing efficiency of Myxin in broth. We also evaluated the efficacy of Myxin against intracellular <i>M. abscessus</i> in THP-1 macrophages. Checkerboard assays assessed the interactions between Myxin and eight clinically important anti-NTM antibiotics. Myxin demonstrated potent activity against <i>M. abscessus</i> with low MIC values (MIC₅₀ = 0.125 mg/L and MIC₉₀ = 0.5 mg/L). Treatment with 20 × MIC of Myxin in 7H9 broth resulted in up to 10 log₁₀ CFU/mL reduction after 4 days of incubation. An intracellular concentration-dependent bactericidal effect of Myxin was observed in THP-1 macrophages. Myxin exhibited no antagonism in combination with standard anti-NTM drugs. As such, Myxin represents a promising candidate for the treatment of <i>M. abscessus</i> and other NTM infections.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572558","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":"Dexmedetomidine Alleviates Sleep Rhythm Abnormalities in Chronic Sleep-Deprived Mice via Modulation of SIK3/HDAC4/5 Signalling","authors":"Zhengye Wang,&nbsp;Yitong Ding,&nbsp;Yonghong Zhou,&nbsp;Zhouquan Wu","doi":"10.1111/1440-1681.70086","DOIUrl":"https://doi.org/10.1111/1440-1681.70086","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Sleep deprivation (SD) often disrupts normal sleep patterns, leading to anxiety-like behaviours and cognitive impairments. Dexmedetomidine (DEX), a highly selective α-2 adrenergic agonist, has been reported to improve postoperative sleep quality and alleviate cognitive deficits. Evidence indicates that DEX can regulate the expression of histone deacetylase 5 (HDAC5), a substrate of the sleep-regulating molecule salt-inducible kinase 3 (SIK3). However, its specific role and the underlying mechanisms in regulating sleep structure remain unclear. This study aims to examine DEX's effects and potential mechanisms in regulating sleep structure in sleep-deprived mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>C57BL/6J mice were subjected to chronic sleep deprivation (CSD) for 20 h (from 5 to 1 PM the next day), followed by administration of DEX at 1 and 3 PM daily for 7 consecutive days. Emotional behaviours were evaluated using the open-field test. Sleep patterns were assessed during the recovery period using EEG/EMG. Golgi-Cox staining was used to determine neuronal dendritic damage. Western blotting was employed to detect the SIK3/HDAC4/5 pathway-related protein levels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CSD disrupted the sleep structure of mice during the recovery period and induced anxiety-like behaviour and neuronal dendritic damage. DEX administration alleviated the above effects caused by CSD. Mechanistically, DEX activated SIK3/HDAC4/5 signalling in CSD mice, while inhibition of SIK3 with a specific inhibitor attenuated DEX's effects on the pathway activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>DEX can alleviate sleep rhythm disturbances caused by CSD in mice possibly via modulation of the SIK3/HDAC4/5 pathway, thereby improving anxiety-like behaviours and cognitive function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572276","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":"Exploring the Protective Role and Regulation of Prdx6 in Cisplatin-Induced AKI","authors":"Xianzhe Li,&nbsp;Jinbo Yu,&nbsp;Shi Cheng,&nbsp;Yaqiong Wang,&nbsp;Xiaoqiang Ding","doi":"10.1111/1440-1681.70093","DOIUrl":"https://doi.org/10.1111/1440-1681.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>Cisplatin (CDDP) is a widely used chemotherapeutic agent that induces nephrotoxicity by generating excessive reactive oxygen species (ROS), leading to oxidative stress, inflammation and apoptosis in renal proximal tubular cells. Peroxiredoxin 6 (Prdx6), an antioxidant enzyme, plays a crucial role in maintaining ROS homeostasis by degrading hydroperoxides; however, its role in CDDP-induced acute kidney injury (CIAKI) remains unclear. In this study, a CIAKI model was established using CDDP treatment in vivo (C57BL/6 mice) and in vitro (PTECs) with or without Prdx6 overexpression (Prdx6 OE). CDDP treatment significantly increased ROS levels, while Prdx6 OE attenuated oxidative stress, apoptosis and renal tubular damage. Furthermore, we found that Prdx6 expression was regulated by Nuclear factor erythroid 2-related factor 2 (Nrf2), suggesting a mechanistic link between Nrf2 and Prdx6 in CIAKI. These findings indicate that Prdx6 plays a protective role in CDDP-induced nephrotoxicity by modulating oxidative stress and apoptosis, and highlight its potential as a therapeutic target.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145555658","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 ELF1/IGF2BP2/FAM111B Cascade Drives Colorectal Cancer Progression and Ferroptosis Resistance","authors":"Dian Yin,&nbsp;Lili Cao,&nbsp;Mei Hua,&nbsp;Ying Chen","doi":"10.1111/1440-1681.70090","DOIUrl":"10.1111/1440-1681.70090","url":null,"abstract":"<div>\u0000 \u0000 <p>Epigenetic dysregulation plays a critical role in colorectal cancer (CRC) progression. Our study investigated the role of FAM111B in tumorigenic phenotypes and ferroptosis in CRC and the mechanisms by which epigenetic alterations influence FAM111B expression. Bioinformatics analyses revealed FAM111B expression and predicted the association between IGF2BP2 and FAM111B or ELF1. The influence on cell phenotypes was determined by assessing cell proliferation, migration, apoptosis and ferroptosis. Mechanism analyses were performed using luciferase reporter and ChIP assays. Subcutaneous xenografts were used to evaluate the role in vivo. FAM111B, IGF2BP2 and ELF1 were upregulated in CRC tumours and cell lines. FAM111B downregulation inhibited cell proliferation and migration while inducing apoptosis and ferroptosis. IGF2BP2 increased FAM111B expression by stabilising its mRNA, and ELF1 transcriptionally upregulated IGF2BP2. Moreover, ELF1 modulated FAM111B expression through IGF2BP2. ELF1 knockdown suppressed cell proliferation and migration while triggering apoptosis and ferroptosis, which could be abolished by reintroduction of IGF2BP2 or FAM111B. Additionally, ELF1 depletion diminished the in vivo tumorigenicity of HCT116 cells. The ELF1/IGF2BP2/FAM111B cascade drives CRC progression and ferroptosis resistance. Targeting this cascade may provide a therapeutic avenue for CRC treatment.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 12","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480973","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":"Long-Term Anticoagulation and Outcomes of Head and Neck Cancer: Analysis of the US Nationwide Inpatient Sample","authors":"Chun-Feng Wu,&nbsp;Hang Huong Ling,&nbsp;Yun-Cong Zheng,&nbsp;Po-Hsu Su,&nbsp;Hsuan-Jen Shih,&nbsp;Che-Wei Ou,&nbsp;Shih-Ming Chen,&nbsp;Yu-Cheng Chang,&nbsp;Yen-Min Huang","doi":"10.1111/1440-1681.70087","DOIUrl":"https://doi.org/10.1111/1440-1681.70087","url":null,"abstract":"<div>\u0000 \u0000 <p>Venous thromboembolism (VTE) is a complication of head and neck cancer (HNC). However, the effectiveness of routine anticoagulation as a preventive measure and its impact on patient outcomes is unclear. The purpose of this study was to evaluate the association between long-term systemic anticoagulation and in-hospital outcomes of patients with HNC. Data of patients ≥ 20 years old with HNC treated from 2005 to 2018 were extracted from the US Nationwide Inpatient Sample (NIS) database. Associations between long-term systemic anticoagulation and in-hospital outcomes were assessed by the univariate and multivariable regression analyses. The study included 20 312 patients with a mean age of 63 years, and 72% were males. Among them, 5078 (25.0%) were on long-term systemic anticoagulation. After adjustment, the multivariable analysis indicated long-term systemic anticoagulation was significantly associated with decreased odds for in-hospital mortality (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI]: 0.54–0.76, <i>p</i> &lt; 0.001), overall life-threatening events (aOR = 0.84, 95% CI: 0.78–0.92, <i>p</i> &lt; 0.001), acute myocardial infarction (aOR = 0.76, 95% CI: 0.59–0.97, <i>p</i> = 0.026), sepsis (aOR = 0.80, 95% CI: 0.71–0.90, <i>p</i> &lt; 0.001) and acute kidney injury (aOR = 0.86, 95% CI: 0.76–0.97, <i>p</i> = 0.015). Long-term systemic anticoagulation was significantly associated with elevated overall bleeding risk (aOR = 1.34, 95% CI: 1.17–1.54, <i>p</i> &lt; 0.001) but not intracerebral haemorrhage (ICH) (aOR = 1.65, 95% CI: 0.90–3.04, <i>p</i> = 0.107). In conclusion, in patients with HNC, long-term anticoagulation is associated with better in-hospital outcomes, and does not increase the risk of ICH; however, there is an increased risk of overall bleeding.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 12","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470048","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":"Inflammatory Bowel Disease and Novel Cell Death: Bibliometric Analysis and Study Trend Projections Based on Burst Detection","authors":"Hui Ouyang,&nbsp;Jingling Su,&nbsp;Jiawen Lin,&nbsp;Shuping Li,&nbsp;Yuan Sui,&nbsp;Chenxi Xie,&nbsp;Mingcheng Huang","doi":"10.1111/1440-1681.70088","DOIUrl":"10.1111/1440-1681.70088","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a chronic relapsing gastrointestinal inflammatory disorder, whose underlying mechanisms remain elusive. Novel cell death modalities such as ferroptosis and pyroptosis are implicated in its pathogenesis. This study employed bibliometric analysis to elucidate research trends in IBD and novel forms of cell death.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 682 records were retrieved from the Web of Science Core Collection on 20 June 2024, using relevant keywords. Bibliometric analysis and visualisation were conducted with tools including Citespace, VOSviewer, the bibliometrix R package, Scimago Graphica, and an online bibliometric platform. Topic modelling was performed via the latent Dirichlet allocation (LDA) algorithm, and burst detection was applied to forecast emerging research trends.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over the past 20 years, there has been a remarkable increase in research output and influence in this field. The number of publications grew exponentially after 2019, and the median impact factor of highly cited papers also showed an upward trend. China and the United States were the major contributors. Chinese Academy of Sciences and Zhejiang University had the highest publication volumes among institutions. Key authors like Zhang Caiying and Markus F. Neurath were identified. Nature, Cell, and Gastroenterology were the most influential journals. Research focus evolved from traditional inflammatory mechanisms to diverse cell death mechanisms. Ten themes were identified through topic modelling, with their significance changing over time. MeSH and gene/protein/pathway analyses highlighted the importance of necroptosis, ferroptosis, and pyroptosis. Biclustering analysis explored specific research topics, and 22 gene/pathway/protein named entities with significant research potential were identified by burst detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This is the first bibliometric analysis of novel cell death in the context of IBD. It offers a holistic overview of research dynamics, trends, and hotspots in this field, which can enhance the comprehension of the field modalities and offer valuable guidance for future research. Future studies should focus on the interactions between different cell death forms and accelerate the translation of basic research findings into clinical applications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 12","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457717","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":"Safety Evaluation of Nitroimidazole Antibiotics Based on the FAERS Database","authors":"Qian Wu,&nbsp;Fansheng Wu,&nbsp;Han Jiang,&nbsp;Ling Jiang,&nbsp;Xingfei Zhang,&nbsp;Chengjun Guo,&nbsp;Longjian Huang,&nbsp;Junlong Ma,&nbsp;Yun Kuang,&nbsp;Yuxia Xiang,&nbsp;Chengxian Guo","doi":"10.1111/1440-1681.70084","DOIUrl":"10.1111/1440-1681.70084","url":null,"abstract":"<div>\u0000 \u0000 <p>Nitroimidazole antibiotics, including metronidazole, tinidazole, and ornidazole, are widely used to treat anaerobic infections and parasitic diseases. Although their efficacy is well established, comprehensive safety profiles—particularly concerning rare adverse events—remain incompletely elucidated. This study aimed to systematically evaluate the safety signals of these drugs using the FDA adverse event reporting system (FAERS) database from 2014 to 2024. Disproportionality analyses were performed at the system organ class (SOC) and standardised MedDRA queries (SMQ) levels to identify associations between nitroimidazole antibiotics and adverse events. A total of 17,631 adverse event reports were analysed for metronidazole, tinidazole, and ornidazole, respectively. Females comprised the majority of reports (57.35%, 51.70%, and 61.11%, respectively), which may reflect the common use of these agents in gynaecological infections. Metronidazole was associated with the shortest median time to onset of adverse events (2.5 days), while tinidazole had the longest (5.5 days). At the SOC level, all three drugs showed positive associations with gastrointestinal, nervous system, and cardiac disorders. Ornidazole showed strong disproportionality signals for vascular (IC₀₂₅ = 18.46) and skin disorders (IC₀₂₅ = 17.46), while tinidazole was associated with weaker but notable signals for skin and blood disorders. Notably, SMQ-level analysis uncovered significant safety signals not currently emphasised in drug labelling, including acute pancreatitis, hepatic failure, fibrosis/cirrhosis, and tachyarrhythmias for tinidazole and ornidazole. These findings highlight the potential need for intensified clinical monitoring of hepatic and cardiac function during treatment with these antibiotics. Although limited by the nature of spontaneous reporting data, this study offers important insights into both established and emerging risks associated with nitroimidazole antibiotics, reinforcing the value of continuous pharmacovigilance to optimise patient safety.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 12","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387606","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":"PDZK1 Regulates the Stability and Function of ADRB2 to Prevent Vascular Remodelling in Hypertension","authors":"Haoran Zhang,&nbsp;Yan Meng,&nbsp;Dandan Li,&nbsp;Wenjing Zheng,&nbsp;Wenjie Bu,&nbsp;Zhiyu Shi,&nbsp;Chunnan Liu,&nbsp;Meng Zhao,&nbsp;Huiying Wang,&nbsp;Yufeng Bai,&nbsp;Liying Luo,&nbsp;Dechao Zhao,&nbsp;Jinyu Chi","doi":"10.1111/1440-1681.70085","DOIUrl":"10.1111/1440-1681.70085","url":null,"abstract":"<div>\u0000 \u0000 <p>In this study, we found that PDZK1, a scaffold protein, interacts with the β₂-adrenergic receptor (ADRB2) through its PDZ domains, stabilising ADRB2 by inhibiting its ubiquitination and proteasomal degradation. This study explored the PDZK1–ADRB2 interaction and its role in hypertension-induced vascular remodelling. Using PDZK1 knockout mice infused with angiotensin II, we found that PDZK1 deficiency further exacerbates angiotensin II-induced hypertension, vascular dysfunction, and vascular remodelling. Mechanistically, PDZK1 stabilises ADRB2 protein by preventing its ubiquitination and proteasomal degradation, thereby maintaining ADRB2-mediated vasodilation. Additionally, PDZK1 prevents ADRB2 internalisation and its interaction with β-arrestin, thereby inhibiting β-arrestin–mediated ERK activation and suppressing vascular smooth muscle cell (VSMC) phenotypic switching. This mechanism contributes to vascular protection under hypertensive conditions. Targeting the PDZK1/ADRB2 interaction may provide a novel therapeutic strategy for hypertension-related vascular complications.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 12","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145372369","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}