Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Blood–Brain Barrier-Permeable siRNA Nanodrugs With Dual-Gene Knockdown for Alzheimer's Disease Therapy","authors":"Feng Su, Shengnan Lu, Yaoyao Zhang, Yu Zhang, Ling Cheng, Jing Li, Junli Zhang, Ying Li, Yungen Xu, Guangwei He, Lifang Yin","doi":"10.1111/1440-1681.70108","DOIUrl":"10.1111/1440-1681.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The presence of a blood–brain barrier (BBB) prevents the delivery of most drugs to the brain. This characteristic limitation poses a major challenge to effective pharmacological treatment for numerous neurodegenerative diseases, particularly Alzheimer's disease. Delivering small interfering RNA (siRNA) via nanoparticles represents a highly promising approach for treating Alzheimer's disease. Nevertheless, developing a safe and efficient siRNA delivery system remains challenging. To enhance brain targeting and therapeutic efficacy, we developed an siRNA nanocarrier system based on PAH-AM-PEG-ApoE (PAPA) nanoparticles (PAPA/siRNA NPs), which facilitates BBB penetration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, an siRNA nanocarrier delivery system modified with ApoE peptide (PAPA/siRNA NPs) developed by our research team was employed to simultaneously encapsulate BACE1-siRNA and GSK3β-siRNA. The PAPA/siRNA NPs were prepared through self-assembly and electrostatic binding. The particle size distribution profile and zeta potential of the PAPA/siRNA NPs were analysed with dynamic light scattering, while its morphology was examined with transmission electron microscopy. For in vitro assessments, flow cytometry, confocal laser scanning microscopy, PCR, and Western blotting were employed to evaluate the cellular uptake, gene silencing capacity, and endosomal escape. The biodistribution was investigated by in vivo imaging technology, and the therapeutic effect on AD was verified in AD model mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The prepared PAPA/siRNA NPs exhibited a regular spherical appearance with a uniform particle size distribution profile. In in vitro cell experiments, the PAPA/siRNA NPs demonstrated excellent cellular uptake ability and efficient endosomal escape. Meanwhile, the dual-loaded siRNA nanocarrier delivery system effectively inhibited the expression of GSK3β and BACE1 genes. In vivo experimental results showed that the siRNA could successfully cross the BBB and deliver to the brain. It not only significantly prolonged the half-life of siRNA but also greatly reduced the generation of pathological β-amyloid and phosphorylated microtubule-associated protein tau, showing excellent therapeutic effects in the treatment of AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this study, we successfully constructed a brain-targeted siRNA nanocarrier delivery system for double-gene knockdown. This system can efficiently overcome the obstacle of the BBB, markedly alleviating cognitive and memory deficits in AD mice. It paves the way for novel strategies in","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302907","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":"Acepromazine Reduces Airway Contraction in a Murine Model of Asthma","authors":"Alembert Lino-Alvarado,&nbsp;Maria Aparecida de Oliveira,&nbsp;Carmen Silvia Moreno Serra,&nbsp;Isabella Victoria Santana Melhado,&nbsp;Rafael Campos,&nbsp;Yanira Riffo-Vasquez,&nbsp;Henrique Takachi Moriya","doi":"10.1111/1440-1681.70112","DOIUrl":"10.1111/1440-1681.70112","url":null,"abstract":"<p>Acepromazine (ACP) is one of the most used sedatives in veterinary medicine, and its cardiovascular effects are well documented. In contrast, its effects on the respiratory system remain less well understood, particularly in the context of assessment of respiratory mechanics in murine models of asthma, where its use has become more common in recent years. This study aims to investigate the effect of ACP on respiratory mechanics in BALB/c mice, specifically in an ovalbumin (OVA)-induced model of allergic asthma. Mice received ACP (2.5 mg/kg) in combination with standard ketamine (100 mg/kg) and xylazine (10 mg/kg) anaesthesia. Respiratory mechanics were assessed in vivo using forced oscillation technique (FOT) following methacholine (MCh) challenge. Additionally, tracheal rings and lung strips were evaluated in vitro for airway smooth muscle (ASM) responsiveness to MCh. ACP administration significantly reduced Newtonian resistance (Rn) in OVA-sensitised mice following MCh challenge, suggesting an inhibitory effect on ASM contractility. Furthermore, ACP mitigated increases in tissue damping (G) and hysteresivity (<i>η</i>), particularly in the inflamed lungs of OVA-treated mice. In vitro, ACP induced a rightward shift in MCh concentration–response curves in non-inflamed ASM and lung strips. These findings highlight the potential confounding effects of ACP in studies assessing airway hyperresponsiveness and offer insights into how sedative choice can shape the scientific validity of studies involving assessment of respiratory mechanics.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275838","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":"Sympathetic Nerve Activation Drives Cardiac Fibrosis and Arrhythmia in Lean Metabolic Dysfunction-Associated Steatohepatitis Mice Concurrently Exposed to Ethanol and a High-Fat/High-Cholesterol Diet","authors":"Jinyao Liu,&nbsp;Seiko Yamano","doi":"10.1111/1440-1681.70111","DOIUrl":"10.1111/1440-1681.70111","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lean metabolic dysfunction-associated steatohepatitis (MASH) is increasingly recognised in non-obese individuals and is associated with cardiovascular complications, including arrhythmias. Although sympathetic activation and inflammation have been implicated in disease progression, their mechanistic roles in cardiac fibrosis and arrhythmogenesis in lean MASH remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the contribution of sympathetic nerve activation to myocardial fibrosis and arrhythmia in a lean MASH mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Male C57BL/6J mice were fed a high-fat/high-cholesterol diet (STHD-01) with or without ethanol for 12 weeks. Hepatic and cardiac changes were evaluated by histology, immunohistochemistry, reverse transcription–polymerase chain reaction, and plasma biochemistry. Arrhythmias were recorded by electrocardiogram telemetry. Despite reduced body weight, mice receiving STHD-01 plus ethanol developed marked hepatic and cardiac inflammation and fibrosis. Sympathetic activation, indicated by tyrosine hydroxylase co-localization with cluster of differentiation 68-positive macrophages and with α-smooth muscle actin–positive fibroblast-like stromal cells, was associated with increased expression of tumour necrosis factor-α and transforming growth factor-β1, respectively. These mice exhibited a significantly higher incidence of lethal arrhythmias. Expression of inflammatory and fibrotic genes showed moderate to strong correlations between the liver and heart.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Sympathetic nerve–associated activation of macrophages and fibroblast-like stromal cells is linked to myocardial fibrosis and increased arrhythmia susceptibility in lean MASH. Even modest ethanol intake appears to accelerate disease progression and heighten arrhythmia risk when combined with a high-fat/high-cholesterol diet. These findings suggest that targeting sympathetic activation and inflammation may represent a potential therapeutic strategy for cardiovascular prevention in lean MASH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147269839","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":"Gemfibrozil Prevents Myocardial Ischemia–Reperfusion Injury in Mice Through AMPK Activation","authors":"Yilong Jiang,&nbsp;Weijing Wang,&nbsp;Qi Li,&nbsp;Tianchen Xia,&nbsp;Boyu Xia,&nbsp;Chao Huang,&nbsp;Xu Lu,&nbsp;Le Yin,&nbsp;Qingsheng You,&nbsp;Rongrong Yang","doi":"10.1111/1440-1681.70106","DOIUrl":"10.1111/1440-1681.70106","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial ischemia–reperfusion injury (MIRI) causes severe clinical complications in patients. Although gemfibrozil (GEM) has been extensively studied in metabolic diseases, its effects on MIRI remain unknown. In this study, we investigated the pharmacological effects and molecular mechanisms of GEM in alleviating MIRI through adenosine 5′-monophosphate-activated protein kinase (AMPK) modulation. The results showed that pre-administration of GEM (100 mg/kg) provided significant protection against MIRI in mice, as indicated by reduced infarct size, lower cardiac injury markers such as hydrogen peroxide (H₂O₂), lactate dehydrogenase (LDH), and creatine kinase (CK), and improved cardiac function. This cardioprotective effect of GEM was associated with enhanced myocardial antioxidant capacity, as shown by decreased dihydroethidium (DHE) fluorescence density and reduced nitric oxide (NO) and malondialdehyde (MDA) levels in ischemic cardiac tissue. GEM pretreatment also prevented the I/R-induced increase in TUNEL-positive cells and expression of caspase-3, caspase-9, and Bax, as well as the I/R-induced decrease in Bcl-2 expression in ischemic cardiac tissue, indicating an anti-apoptotic effect of GEM in MIRI. In addition, GEM pretreatment prevented the I/R-induced increase in mRNA expression levels of tumour necrosis factor-<i>α</i> (<i>Tnf-α</i>), interleukin-<i>β</i> (<i>Il-1β</i>), and <i>Il-6</i> in ischemic cardiac tissue. Further analysis showed that GEM administration prevented the I/R-induced decrease in phospho-AMPK levels in ischemic cardiac tissue, and pharmacological inhibition of AMPK with dorsomorphin (DSMF) abolished all cardioprotective effects of GEM. Taken together, these results suggest that GEM mitigates MIRI-induced cardiac injury by inhibiting apoptosis and oxidative stress via modulation of AMPK, supporting its potential for reducing MIRI-related cardiac damage.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212406","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 TNF-α–FABP4–Dhhc7 Axis Mediates Olanzapine-Induced Insulin Resistance in Rats and Humans","authors":"Jing Wang,&nbsp;Peiru Chen,&nbsp;Chuyue Tu,&nbsp;Qian Wu,&nbsp;Yahui Deng,&nbsp;Lixiu Yu,&nbsp;Xiaojin Xu,&nbsp;Xiangming Fang,&nbsp;Weiyong Li","doi":"10.1111/1440-1681.70104","DOIUrl":"10.1111/1440-1681.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>A rapid increase in the incidence of insulin resistance (IR) induced by long-term olanzapine treatment has been observed; however, there are no more efficient ways to prevent IR. Our study aimed to demonstrate the mechanism underlying olanzapine-induced insulin resistance. In this study, we first analysed the data of 120 schizophrenia patients who had been taking olanzapine for at least 3 months. Eventually, it was found that an increase in circulating tumour necrosis factor-α (TNF-α, <i>p</i> &lt; 0.05). Subsequently, we verified this finding in a rat model. We detected the expression levels of the target genes fatty acid binding protein 4 (FABP4) and the palmitoyltransferase <i>Dhhc7</i> in both rats and three T3-L1 adipocytes by using Western blotting and polymerase chain reaction (<i>p</i> &lt; 0.05). Exposure to olanzapine increased the expression of FABP4 while decreasing the expression of <i>Dhhc7</i>. Additionally, we demonstrated that it may affect metabolism by inhibiting glucose transporter 4 (GLUT4) membrane transport. Finally, we improved olanzapine-induced insulin resistance by injecting FABP4 adenovirus and elucidating its underlying mechanism. In summary, our study demonstrated that long-term exposure to olanzapine increases circulating plasma levels of TNF-α, thus leading to increased expression of FABP4 protein in white adipose tissue and subsequently inhibiting <i>Dhhc7</i>expression, which correspondingly leads to reduced membrane translocation of GLUT4 and consequent insulin resistance. In conclusion, this study elucidated the signalling pathway through which olanzapine inhibits GLUT4 membrane transport via the TNF-α/FABP4/<i>Dhhc7</i> axis, thus ultimately leading to insulin resistance.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200237","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":"Acupuncture Alleviates Cerebral Ischemia–Reperfusion Injury by Inhibiting Ferroptosis Through the IRP2/IRE Pathway","authors":"Jia Yuan,&nbsp;Litong Chen,&nbsp;Qianjun Li,&nbsp;Rongqi Wei,&nbsp;Xiaoyue Liu,&nbsp;Chutao Chen,&nbsp;Haomei Tian","doi":"10.1111/1440-1681.70109","DOIUrl":"10.1111/1440-1681.70109","url":null,"abstract":"<p>Acupuncture (AC) has been demonstrated to improve outcomes in ischemic stroke. However, its precise mechanism of action remains incompletely understood. This study investigated the effects of AC in a rat model of cerebral ischemia–reperfusion injury (CIRI). A middle cerebral artery occlusion/reperfusion (MCAO/R) model was established to create CIRI rats. Rats were randomly assigned to the Sham, MCAO/R, AC + MCAO/R, IRP2⁽⁺⁾ + MCAO/R, IRP2⁽⁻⁾ + MCAO/R and IRP2⁽⁻⁾ + AC + MCAO/R groups. Neurological function was assessed using the Garcia scores. TTC staining was used to observe cerebral infarction volume ratios. Transmission electron microscopy (TEM) examined mitochondrial structure in neurons within the ischemic penumbra. Colorimetric assays measured Fe²⁺ content in neurons, along with ferroptosis-related biomarkers Reactive oxygen species (ROS), Glutathione peroxidase 4 (GPX4), Malondialdehyde (MDA) and Glutathione (GSH). Immunofluorescence staining detected Transferrin receptor 1 (TFR1), Ferritin (FER), Ferroportin (FPN) and Iron regulatory protein 2 (IRP2) expressions in the ischemic penumbra. RT-qPCR measured IRP2 mRNA expression, whilst RNA immunoprecipitation (RIP) analysis assessed the impact of each group on IRP2 binding to IRE. Our results showed AC improved neurological deficits, reduced infarct volume, decreased Fe²⁺ overload, enhanced antioxidant markers GPX4 and GSH, and lowered lipid peroxidation levels of ROS and MDA. It also attenuated mitochondrial structural damage related to ferroptosis. Immunofluorescence staining and RT-qPCR analyses revealed that AC downregulated TFR1 and FER expression whilst upregulating FPN and IRP2 expression. Furthermore, RNA immunoprecipitation assays revealed enhanced binding affinity between IRP2 and IRE after AC. These findings indicate that AC inhibits neuronal ferroptosis after CIRI and protects brain tissue, possibly by promoting IRP2-IRE binding, modulating neuronal iron metabolism, and reducing lipid peroxidation.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12900629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146178134","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":"Ddx17 Mitigates Sepsis-Induced Cardiomyopathy by Regulating Mitochondrial Dynamics in Cardiomyocytes","authors":"Ya-ting Jiang,&nbsp;Li-ran Su,&nbsp;Fang-jing Ni,&nbsp;Luo-ye Lu,&nbsp;Yu-qiang Gong,&nbsp;Jun Luo,&nbsp;Chen-xi Shen,&nbsp;Yang Cao","doi":"10.1111/1440-1681.70105","DOIUrl":"10.1111/1440-1681.70105","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis-induced cardiomyopathy (SICM) is a severe complication of sepsis, in which mitochondrial dysfunction contributes to poor outcomes. DEAD-box helicase 17 (Ddx17), a member of the DEAD-box RNA helicase family, is known to regulate mitochondrial function, but its role in SICM remains unclear. In this study, mice with cardiomyocyte-specific Ddx17 knockdown (Ddx17-cKD) and overexpression (Ddx17-OE) were generated, and sepsis models were established using cecal ligation and puncture. Mechanistic findings were further validated in vitro using immunoprecipitation and dual-luciferase assays. Ddx17 expression was markedly reduced in the cardiac tissues of septic mice and in lipopolysaccharide-treated cardiomyocytes. Knockdown of Ddx17 increased mitochondrial reactive oxygen species accumulation, enhanced cell death and decreased superoxide dismutase activity. In contrast, Ddx17 overexpression attenuated mitochondrial apoptosis and oxidative stress, restored adenosine triphosphate production and mitochondrial membrane potential and improved cardiac function in septic mice. Mechanistically, Ddx17 interacted with signal transducer and activator of transcription 3 (STAT3) to suppress transcription of the mitochondrial fission protein dynamin-related protein 1 while maintaining the level of the fusion protein mitofusin 1, thereby preserving mitochondrial integrity and cardiomyocyte homeostasis. These findings demonstrate that Ddx17 protects against sepsis-induced cardiomyopathy by regulating mitochondrial dynamics, reducing oxidative stress and preventing apoptosis, thereby highlighting Ddx17 as a potential therapeutic target for septic cardiac dysfunction.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141133","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":"Kruppel-Like Factor 5 Modulates the Nuclear Factor Erythroid-2-Related Factor 2/Heme Oxygenase 1 Signalling Pathway to Regulate Vascular Smooth Muscle Cell Ferroptosis in Abdominal Aortic Aneurysm","authors":"Guangwei Yang,&nbsp;Cong Yu,&nbsp;Chao Weng","doi":"10.1111/1440-1681.70110","DOIUrl":"10.1111/1440-1681.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Abdominal aortic aneurysm (AAA) refers to a disease where the abdominal aorta progressively dilates to 3.0 cm or more, making it prone to rupture. The etiologic and pathophysiological mechanisms underlying the formation and development of AAA are not yet fully understood. A preliminary investigation was conducted into the effects of Kruppel-like factor 5 (KLF5) regulation of the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (NRF2/HO-1) signalling pathway on ferroptosis in AAA vascular smooth muscle cells (VSMCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ApoE^−/− mice or primary VSMCs were induced with angiotensin II (Ang II). KLF5 overexpression was achieved through adenovirus injection in the mouse model, and ML385 (NFR2 inhibitor) was injected to explore the involvement of the NRF2/HO-1 pathway in KLF5-regulated ferroptosis, inflammation, phenotypic switching and calcium deposition. Ang II-treated VSMCs were transiently transfected to overexpress KLF5 and/or incubated with Erastin (ferroptosis inducer) or ML385. The abdominal aorta was sampled from AAA model mice, and VSMC supernatants were collected to perform functional assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>KLF5 expression was downregulated in abdominal aorta tissues from AAA mice. KLF5 overexpression ameliorated inflammatory response by reducing phenotypic switching in VSMCs and inhibited ferroptosis and vascular calcification by reducing oxidative stress. Induction of ferroptosis partially reversed the ameliorative effect of KLF5 on vascular calcification in VSMCs. KLF5 exerted antioxidant effects by increasing NRF2 nuclear translocation and upregulating HO-1. Inhibition of the NRF2/HO-1 pathway partially reversed KLF5 regulation of phenotypic switching and vascular calcification in VSMCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>KLF5 may exert a protective effect by inhibiting ferroptosis and calcium deposition in VSMCs in AAA through regulation of the NRF2/HO-1 signalling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141168","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":"Correction to “Caffeic Acid Phenethyl Ester Ameliorates Colistin-Induced Nephrotoxicity in Rats via Modulation of FOXO1/Nrf2/Sirt1 Axis”","authors":"","doi":"10.1111/1440-1681.70102","DOIUrl":"10.1111/1440-1681.70102","url":null,"abstract":"<p>M. Z. Nasrullah, T. Neamtalllah, M. Alshibani, et al., “Caffeic Acid Phenethyl Ester Ameliorates Colistin-Induced Nephrotoxicity in Rats via Modulation of FOXO1/Nrf2/Sirt1 Axis,” <i>Clinical and Experimental Pharmacology and Physiology</i> 51, no. 12 (2024): e70000, https://doi.org/10.1111/1440-1681.70000.</p><p>In Table 2, the forward sequence of β-Actin 5′AAAGCACATCCAATAAAAAGC was incorrect.</p><p>It should be corrected to the following: 5′TCCGTCGCCGGTCCACACCC.</p><p>In the abstract, under the methods, ‘group 3 received Cst IP’ is incomplete. It should be corrected to ‘group 3 received Cst (1000 000 IU/Kg) IP’.</p><p>The authors apologise for these oversights and for the inconvenience they may have caused.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017624","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":"Effect and Mechanism of Shenqi Lixin Formula on Angiogenesis and Glucose Metabolism in Rats With Heart Failure After Myocardial Infarction","authors":"Jiaqi Liu,&nbsp;Qili Zhao,&nbsp;Hezhan Wang,&nbsp;Yanbo Sui","doi":"10.1111/1440-1681.70100","DOIUrl":"10.1111/1440-1681.70100","url":null,"abstract":"<div>\u0000 \u0000 <p>Post-myocardial infarction (MI) patients remain at high risk for developing heart failure (HF). This study investigated the therapeutic effects and mechanistic basis of Shenqi Lixin Formula (SQLXF) on angiogenesis and glucose metabolism in MI-HF. MI-HF rat models were generated, and myocardial pathology, infarct area, cardiac function, platelet endothelial cell adhesion molecule-1 (CD31), vascular endothelial growth factor A (VEGFA), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), lysine demethylase 5B (KDM5B) and ER degradation enhancing alpha-mannosidase like protein 3 (EDEM3) expressions, glucose consumption, lactate production and extracellular acidification rate (ECAR) were evaluated. Hypoxia-treated human cardiac microvascular endothelial cells (HCMECs) were used as in vitro models to assess angiogenic capacity. SQLXF intervention and subsequent analyses were performed to determine KDM5B and EDEM3 expression levels, as well as the enrichment of KDM5B and trimethylation of lysine 4 on histone H3 protein subunit (H3K4me3) on the EDEM3 promoter. In animal models, infarct area enlargement, impaired cardiac function, increased glucose consumption, lactate production, and upregulation of CD31, VEGFA, HK2, LDHA and KDM5B expressions were observed, accompanied by reduced EDEM3 expression. SQLXF administration improved cardiac function, promoted angiogenesis, normalised glucose metabolism, inhibited KDM5B and restored EDEM3 expression. In HCMECs, hypoxia suppressed EDEM3, angiogenesis and metabolic stability while increasing KDM5B expression; these alterations were reversed by high-dose SQLXF. Mechanistically, KDM5B inhibited EDEM3 transcription by reducing H3K4me3 enrichment, whereas SQLXF enhanced H3K4me3 and relieved KDM5B-mediated repression. KDM5B overexpression or EDEM3 knockdown attenuated the beneficial effects of SQLXF.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 1","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984555","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}