Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"NOTIFICATION: MiR-375-3p/YWHAZ/β-catenin Axis Regulates Migration, Invasion, EMT in Gastric Cancer Cells","authors":"","doi":"10.1111/1440-1681.70045","DOIUrl":"https://doi.org/10.1111/1440-1681.70045","url":null,"abstract":"<p>\u0000 <b>NOTIFICATION:</b> <span>F. Guo</span>, <span>Y. Gao</span>, <span>G. Sui</span>, <span>D. Jiao</span>, <span>L. Sun</span>, <span>Q. Fu</span>, and <span>C. Jin</span>, “ <span>MiR-375-3p/YWHAZ/β-catenin Axis Regulates Migration, Invasion, EMT in Gastric Cancer Cells</span>,” <i>Clinical and Experimental Pharmacology and Physiology</i> <span>46</span>, no. <span>2</span> (<span>2019</span>): <span>144</span>–<span>152</span>, https://doi.org/10.1111/1440-1681.13047.\u0000 </p><p>This notification is for the above article, published online on 24 October 2018 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Yang Yang; and John Wiley &amp; Sons Australia Ltd. This notification has been issued in response to concerns raised by third parties [<span>1</span>]. The article mentions a non-verifiable cell line identifier, “MGC-823” in relation to Figure 1C. Within the figure, the cell line identifier is spelled “MGC-803”, which describes a verified cell line (RRID: CVCL_5334). As the authors could not be reached to clarify this discrepancy, the journal has decided to publish this notification to inform and alert readers.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reliability of Matrix-Assisted Laser Desorption-Ionisation Time-of-Flight Mass Spectrometry as a Method for Drug-Resistant Tuberculosis Gene Identification","authors":"Kaishun Zhao,&nbsp;Wei Wei,&nbsp;Lijia Yang,&nbsp;Wei Chen,&nbsp;Haiying Liang,&nbsp;Ye Jin,&nbsp;Yameng Sun,&nbsp;Jun Xu,&nbsp;Yanfang Yu","doi":"10.1111/1440-1681.70038","DOIUrl":"https://doi.org/10.1111/1440-1681.70038","url":null,"abstract":"<div>\u0000 \u0000 <p>Instances of drug-resistant tuberculosis (TB), particularly multidrug- and extensive drug-resistant TB, are escalating worldwide; therefore, there is an urgent need to explore suitable treatment strategies. This study assessed the precision of matrix-assisted laser desorption-ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in detecting drug-resistant TB. We developed a multiplex MALDI-TOF MS detection assay that concurrently identifies 51 gene mutations for six commonly used medications: rifampicin (RFP), isoniazid (INH), levofloxacin (LVX), moxifloxacin (MOX), capreomycin (CPM) and amikacin (AMK). Subsequently, we evaluated the accuracy of the system by testing clinical sputum samples with known (<i>n</i> = 45) and unknown (<i>n</i> = 254) minimum inhibitory concentrations (MICs), using Sanger-sequenced genes as references. The detection system exhibited a minimum sensitivity of 88.00% and a specificity of 95.24% for the 45 known isolates. Similarly, for the 254 unknown samples, the detection system demonstrated sensitivity and specificity for mutations associated with each medication as follows: RFP—sensitivity: 98.97%, specificity: 99.36%; INH—sensitivity: 97.80%, specificity: 100.00%; LVX and MOX—sensitivity: 97.14%, specificity: 100.00%; AMK and CPM—sensitivity: 100.00%, specificity: 100.00%. The unknown samples also displayed favourable sensitivity and specificity values in the MIC validation as follows: RFP—sensitivity: 92.39%, specificity: 92.59%; INH—sensitivity: 75.21%, specificity: 99.27%; LVX—sensitivity: 75.28%, specificity: 99.39%; MOX—sensitivity: 73.24%, specificity: 91.26%; AMK—sensitivity: 94.87%, specificity: 96.74%; CPM—sensitivity: 89.47%, specificity: 95.83%. Meanwhile, our study allows for the identification of the <i>Mycobacterium tuberculosis</i> complex (MTBC). The MALDI-TOF MS exhibited remarkable accuracy in the detection of drug-resistant TB, making it a potential alternative approach for clinical TB diagnosis.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143871469","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":"Alpha-Linolenic Acid for Mitigating Neuroinflammation and Dopaminergic Neuronal Loss in Parkinson's Disease: Insights From In Vivo and In Silico Studies","authors":"Mahnoor,&nbsp;Sarwat Jahan,&nbsp;Laila Elahi,&nbsp;Muhammad Zakria,&nbsp; Rabia,&nbsp;Muhammad Ikram,&nbsp;Najeeb Ullah","doi":"10.1111/1440-1681.70043","DOIUrl":"https://doi.org/10.1111/1440-1681.70043","url":null,"abstract":"<div>\u0000 \u0000 <p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by dopaminergic neuronal loss and chronic neuroinflammation, leading to significant motor and non-motor deficits. This study explores the therapeutic potential of alpha-linolenic acid (ALA), a known antioxidant and anti-inflammatory agent, in a lipopolysaccharide (LPS)-induced murine model of PD. Male Balb-C mice were divided into control, LPS-treated, LPS + ALA-treated and ALA-only groups. Behavioural assessments, including the pole test, rotarod test and open field test, revealed significant motor impairments in LPS-treated mice. Co-treatment with ALA partially ameliorated motor deficits in LPS-treated mice compared to the healthy control group. However, no direct comparison was made with standard PD treatments such as levodopa. Immunohistochemistry analysis showed a 68% reduction in tyrosine hydroxylase-positive (TH+) neurons in the substantia nigra pars compacta (SNpc) of LPS-treated mice. Notably, ALA co-treatment preserved dopaminergic neurons, demonstrating its neuroprotective effects. Western blotting and ELISA revealed heightened expression of inflammatory mediators, including TNF-α, IL-1β and NF-κB, in LPS-treated mice. ALA treatment significantly reduced these markers, indicating its capacity to mitigate neuroinflammation. Molecular docking analysis revealed moderate binding affinities of ALA to NF-κB (−5.1 kcal/mol), TNF-α (−5.7 kcal/mol) and IL-1β (−3.9 kcal/mol), suggesting possible interactions with key inflammatory pathways. These interactions were comparable to known inhibitors, indicating ALA's potential for neuroprotection. This study highlights the neuroprotective and anti-inflammatory effects of ALA in reducing dopaminergic neuronal loss and mitigating neuroinflammation in an LPS-induced PD model. Although behavioural improvements were moderate, these findings underscore ALA's potential as an adjunct therapeutic candidate for PD and other neurodegenerative diseases. Further research is warranted to explore its translational applications in clinical settings.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865971","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":"Sex Steroid Control of Serotonergic System: Clinical Implications for Psychiatric Disorders and Addiction Treatment","authors":"Lien-Chung Wei,&nbsp;Hsien-Jane Chiu","doi":"10.1111/1440-1681.70044","DOIUrl":"https://doi.org/10.1111/1440-1681.70044","url":null,"abstract":"<div>\u0000 \u0000 <p>The seminal work by Fink et al. on sex steroid regulation of mood, cognition, and memory has profound implications for understanding sex differences in psychiatric disorders and addiction treatment. Their findings that estradiol upregulates serotonin transporter (SERT) and 5-HT2A receptor expression, along with testosterone's reliance on aromatisation for its serotonergic effects, highlight key neurobiological mechanisms underlying psychiatric conditions. These insights are particularly relevant to addiction medicine, given serotonin's modulatory role in reward pathways and substance use disorders. Recent research by Gu et al. has demonstrated that estradiol reduces serotonin reuptake by downregulating the plasma membrane monoamine transporter (PMAT) through oestrogen receptor beta (ERβ) and MAPK/ERK signalling pathways, further elucidating the neurochemical underpinnings of mood disorders. Additionally, testosterone's effects on serotonergic regulation are dependent on its conversion to estradiol via aromatase, which influences the expression of SERT and 5-HT2A receptors in critical brain regions. This process may explain sex differences in psychiatric disorders and treatment responses, particularly in mood disorders and substance use disorders. From a clinical perspective, understanding aromatase activity's role in modulating serotonergic pathways may aid in predicting treatment responses, particularly for male patients undergoing testosterone replacement therapy. Furthermore, targeting ERβ as a potential treatment strategy could provide novel therapeutic avenues for managing depression and substance use disorders in women experiencing hormonal fluctuations. These findings underscore the importance of sex-specific considerations in psychiatric and addiction treatment paradigms.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861962","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 Rough Morphotype of Mycobacterium abscessus Enhances Its Virulence Through ROS/p65/NLRP3/GSDMD-Mediated Macrophage Pyroptosis","authors":"Jingren Li,&nbsp;Juan Li,&nbsp;Anqi Li,&nbsp;Zhili Tan,&nbsp;Junsheng Fan,&nbsp;Siyuan He,&nbsp;Qi Guo,&nbsp;Liyun Xu,&nbsp;Haiqing Chu","doi":"10.1111/1440-1681.70034","DOIUrl":"https://doi.org/10.1111/1440-1681.70034","url":null,"abstract":"<div>\u0000 \u0000 <p>The rough morphotype of <i>Mycobacterium abscessus</i> exhibits significantly higher virulence compared to the smooth morphotype, yet the underlying molecular mechanisms remain incompletely understood. Pyroptosis in macrophages plays a pivotal role in lung tissue damage; however, its specific involvement in <i>Mycobacterium abscessus</i> infection remains to be fully clarified. In this study, we identified that the rough morphotype of <i>Mycobacterium abscessus</i> upregulates the ROS/p65/NLRP3/GSDMD signalling pathway, thereby mediating pyroptosis in THP-1-derived macrophages. This heightened ability to induce macrophage pyroptosis is attributed to the bacterium's capacity to sustain intracellular viability and proliferation. These findings offer valuable insights into the virulence mechanisms of <i>Mycobacterium abscessus</i> and provide a foundation for future therapeutic interventions.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849300","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":"Endothelin System Blockade Extenuates Sepsis-Induced Acute Heart and Kidney Injuries via Modulating ET-1/Klotho/p38-MAPK","authors":"Alaa Al-kadi,&nbsp;Aliaa F. Anter,&nbsp;Remon Roshdy Rofaeil,&nbsp;Mohamed M. Sayed-Ahmed,&nbsp;Sara Mohamed Naguib Abdel Hafez,&nbsp;Al-Shaimaa F. Ahmed","doi":"10.1111/1440-1681.70042","DOIUrl":"https://doi.org/10.1111/1440-1681.70042","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis-induced organ failure is a major health problem, characterised by massive inflammatory and oxidative stress responses. Endothelin-1 (ET-1) is one of the peptides expressed during septicemia with proapoptotic, proinflammatory, and oxidant effects. ET-1 plays a role in heart and kidney injuries in sepsis. Accordingly, the current study was conducted to investigate, on a mechanistic basis, whether inhibition of ET-1 signalling either by blocking its receptors or inhibiting its formation attenuates sepsis-induced acute cardiorenal injuries. To analyse the role of ET-1 in sepsis, we used a cecal ligation and puncture (CLP) model of sepsis. The animals were divided into five groups: CLP non-treated group, CLP-treated groups with bosentan, ambrisentan, and phosphoramidon (30, 5, and 0.5 mg/kg, respectively), and sham-operated group. In addition to the same set of groups, survival analysis was assigned Survival rate, histopathological assessment, and cardiorenal functions were analysed. Oxidant and antioxidant activities, ET-1, IL-6, and lactate were measured. The expression of TNF-α, p38, Klotho, and caspase-3 was evaluated by immunohistochemistry. CLP caused acute cardiorenal damage, high mortality, upregulated levels of ET-1, IL-6, and lactate, as well as an imbalance in oxidant/antioxidant activities, elevated expression of TNF-α, p38, caspase-3 and reduced expression of klotho. Bosentan, ambrisentan, or phosphoramidon improved survival, reduced the levels of inflammatory and oxidative stress parameters, improved cardiorenal functions and structure, elevated the tissue contents of GSH and SOD, raised the expression of klotho protein, and reduced the cardiorenal expression of p38, TNF-α and caspase-3. Endothelin receptor antagonists (ERAs); bosentan and ambrisentan, or endothelin converting enzyme inhibitor (ECE-i) phosphoramidon, are promising agents against sepsis-induced organ damage. This was evident in their cardiorenal protective effects, up-regulation of klotho, suppression of inflammation, oxidation, apoptosis, and enhancement of the antioxidant status.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831234","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":"Plasma IL4 Levels Linked to Pulmonary Hypertension Severity and Outcome","authors":"Yun Li,&nbsp;Yi Liu,&nbsp;Zhanping Liang,&nbsp;Shuying Jia,&nbsp;Yuyan Liu,&nbsp;Jinling Li,&nbsp;Jinming Liu,&nbsp;Jingyun Shi,&nbsp;Ping Yuan,&nbsp;Jie Zhu,&nbsp;Xiaohuan Xia,&nbsp;Jialin C. Zheng","doi":"10.1111/1440-1681.70040","DOIUrl":"https://doi.org/10.1111/1440-1681.70040","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The anti-inflammatory cytokine interleukin-4 (IL4) has been recognised as a protective factor in various cardiovascular events, yet its prognostic value in patients with pulmonary hypertension (PH) remains unclear. The study aimed to measure the levels of plasma IL4 in patients with PH and to explore their potential association with disease risk and outcomes.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this observational study, we analysed the levels of plasma IL4 in 766 PH patients and 191 healthy controls in Shanghai Pulmonary Hospital from October 2009 to January 2024. To establish the correlations between plasma IL4 levels and the risk and outcomes of PH, all patients were followed up from June 2013 to June 2024. The Spearman correlation test was employed to evaluate the relationships between IL4 and right heart catheterisation parameters among patients with PH. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance of IL4 for PH. The Cox proportional hazards models and Kaplan–Meier survival curves were used to assess the prognostic value of IL4 levels. Logistic regression analysis was performed to predict PH incidence. A nomogram was constructed to predict mortality, and its clinical utility was validated using decision curve analysis (DCA).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Plasma IL4 levels were significantly decreased in patients with PH compared with controls (&lt;i&gt;p&lt;/i&gt; &lt; 0.001), as well as in different PH groups (&lt;i&gt;p&lt;/i&gt; &lt; 0.05 for all). The logistic regression analyses indicated that the lower IL4 levels were associated with the high risk of PH (OR = 0.79, 95% CI: 0.716–0.872; &lt;i&gt;p&lt;/i&gt; &lt; 0.001). IL4 levels correlated inversely with NT-proBNP (&lt;i&gt;r&lt;/i&gt; = −0.10, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and mPAP (&lt;i&gt;r&lt;/i&gt; = −0.01, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), and positively with CI (&lt;i&gt;r&lt;/i&gt; = 0.12, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and PaSaO2 (&lt;i&gt;r&lt;/i&gt; = 0.11, &lt;i&gt;p&lt;/i&gt; &lt; 0.05), indicating an association with disease severity. Kaplan–Meier analysis revealed that patients with IL4 ≥ 2.8774 pg/mL had a 3-year cumulative survival rate of 91.28%, compared with 82.83% for those with IL4 &lt; 2.8774 pg/mL (log–rank &lt;i&gt;p&lt;/i&gt; = 0.007). Cox regression confirmed IL4 as an independent predictor of survival (HR = 0.810, 95% CI: 0.660–0.993; &lt;i&gt;p&lt;/i&gt; = 0.043). A diagnostic model combining IL4, 6MWD and NT-proBNP demonstrated good prognostic value (AUC = 0.692, &lt;i&gt;p&lt;/i&gt; &lt; 0.0001).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Plasma IL4 levels were significantly decreased in p","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electroacupuncture Attenuates Cerebral Ischemia–Reperfusion Injury by Inhibiting Ferroptosis via the p53/SLC7A11 Pathway","authors":"Ziwen Hou,&nbsp;Yaoyao Liu,&nbsp;Qi Wang,&nbsp;Peng Li","doi":"10.1111/1440-1681.70036","DOIUrl":"https://doi.org/10.1111/1440-1681.70036","url":null,"abstract":"<p>Acupuncture has demonstrated efficacy in treating post-stroke complications. Electroacupuncture (EA) ameliorates neurological outcomes in cerebral ischemia models, yet its mechanisms remain unclear. This study investigated EA's role in reducing cerebral ischemia–reperfusion injury (CIRI) in a rat model, focusing on ferroptosis. A CIRI model was established via the MCAO/R method. Rats were randomly assigned to five experimental groups: Sham, MCAO/R, MCAO/R + COTI-2, MCAO/R + EA and MCAO/R + COTI-2 + EA. We evaluated neurological function with Zausinger scoring. 2,3,5-Triphenyltetrazolium chloride (TTC) staining assessed infarct size, while haematoxylin–eosin (HE) staining examined neuronal damage. Transmission electron microscopy analysed mitochondrial changes associated with ferroptosis, and Perl staining measured iron levels in neurons. The biomarkers associated with ferroptosis, including glutathione (GSH), reactive oxygen species (ROS) and malondialdehyde (MDA), were measured. The expression of <i>p53</i>, <i>SLC7A11</i> and <i>GPX4</i> was assessed by qRT-PCR and Western blot. EA enhanced neurological function, reduced the infarct size, alleviated excessive serum iron accumulation, increased antioxidant markers (GSH, GPX4) and decreased lipid peroxidation levels (ROS, MDA), attenuating lipid peroxidation. Additionally, it reversed mitochondrial morphological changes associated with ferroptosis. qRT-PCR and Western blot analyses revealed that EA downregulated <i>p53</i> expression while upregulating <i>SLC7A11</i> and <i>GPX4</i> expression. In summary, ferroptosis was activated after CIRI, and EA ameliorated neurological deficits in cerebral ischemia models by modulating the p53/SLC7A11 axis to counteract oxidative stress-induced ferroptosis, ultimately providing neuroprotective benefits.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global, Regional, and National Temporal Trend and Patterns of Change in the Burden of Asthma From 1990 to 2021: An Analysis of the Global Burden of Disease Study 2021","authors":"Shuyi Mu,&nbsp;Yu Wang,&nbsp;Jie Cui,&nbsp;Linjin Chen,&nbsp;Lei Qiu,&nbsp;Cui Li,&nbsp;Yuwei Jiang,&nbsp;Zhenhui Lu,&nbsp;Zifeng Ma","doi":"10.1111/1440-1681.70039","DOIUrl":"https://doi.org/10.1111/1440-1681.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Asthma presents a significant challenge to the global healthcare systems and imposes a heavy socioeconomic burden. Previous studies had geographical limitations and lacked comprehensive global analysis. The study utilises data from the 2021 Global Burden of Disease (GBD) study to assess the global, regional, and national burden of asthma from 1990 to 2021. It examines disease trends, highlights health inequalities and aims to provide scientific evidence for future public health strategies and the optimisation of resource allocation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Data from GBD 2021 were used to estimate the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of asthma across 21 global regions and 204 countries and territories from 1990 to 2021. Temporal trends were analysed, and the relationship between asthma burden and the socio-demographic index (SDI) was examined using a smoothing spline model. Analyses included the slope index of inequality and the concentration index to assess health disparities, frontier analysis to estimate achievable outcomes based on development levels, and decomposition analysis to identify the drivers of changes in DALYs number.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Over the past three decades, the age-standardised burden of asthma has declined, with age-standardised mortality and DALY rates decreasing by 46% and 44%, respectively. However, the absolute number of deaths has increased by 17%, particularly among females, especially in low and low-middle SDI regions. Significant health inequalities persist, with high-SDI regions benefiting from better asthma control, while low-SDI regions face disproportionate burdens due to healthcare disparities. Frontier analysis highlights gaps between current and optimal disease burden levels, while low-SDI regions require increased investment in asthma control. Aging, population growth, and epidemiological changes are key drivers of asthma burden trends. High body mass index (BMI) remains the leading risk factor, while smoking and occupational exposures continue to contribute significantly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The global burden of asthma has declined, yet significant regional disparities persist, with low-SDI regions experiencing higher mortality and DALYs due to limited healthcare access and environmental risks. High BMI, smoking and occupational exposures remain key contributors, requiring targeted public health interventions and lifestyle modifications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778238","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":"Inhibition of Hsp90 Alleviates Necroptosis and Inflammation in Lung Epithelial Cells During Pulmonary Ischemia–Reperfusion Injury","authors":"Xiaofang Xu,&nbsp;Zhiling Lou,&nbsp;Jinsheng Li,&nbsp;Fuxiang Liang,&nbsp;Yifan Yu,&nbsp;Ming Wu","doi":"10.1111/1440-1681.70037","DOIUrl":"https://doi.org/10.1111/1440-1681.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung ischemia–reperfusion injury (LIRI) is a critical pathological process associated with various clinical conditions, characterised by excessive inflammatory responses and cell death, which can lead to severe respiratory dysfunction and even mortality. However, no effective therapeutic strategy is currently available. This study investigates the protective effects and underlying mechanisms of the Hsp90 inhibitor 17-dimethylaminoethylamino (17-DMAG) in LIRI. An in vivo mouse model of LIRI was established by transiently occluding the left pulmonary hilum with a microvascular clamp, followed by reperfusion. In vitro, necroptosis was induced in BEAS-2B cells using TSZ (TNF-α, Smac mimetic and z-VAD-FMK). Our results demonstrate that 17-DMAG significantly attenuates lung injury, inflammation and epithelial cell necroptosis in mice. Additionally, 17-DMAG mitigates TSZ-induced cell death and inflammatory responses in BEAS-2B cells. Mechanistically, 17-DMAG inhibits the phosphorylation of RIPK1, RIPK3 and MLKL—key necroptotic regulators and client proteins of Hsp90—thereby suppressing necroptosis and reducing the associated inflammatory response. In conclusion, 17-DMAG alleviates LIRI by inhibiting necroptosis and its consequent acute inflammatory cascade. These findings suggest that 17-DMAG may serve as a promising therapeutic candidate for LIRI treatment.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143749361","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}