Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"KRIT1 Inhibits TGF-β/Smad-Mediated Endothelial-To-Mesenchymal Transition in Pulmonary Arterial Hypertension","authors":"Debin Ma,&nbsp;Liang Shi,&nbsp;Congcong Li,&nbsp;Di Song,&nbsp;Lei Liu","doi":"10.1111/1440-1681.70161","DOIUrl":"https://doi.org/10.1111/1440-1681.70161","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary arterial hypertension (PAH) is characterized by pulmonary endothelial cell (EC) dysfunction and pulmonary vascular remodelling. Endothelial-to-mesenchymal transition (EndMT) is a key mechanism underlying pulmonary vascular remodelling. Krev interaction trapped protein 1 (KRIT1) plays a crucial role in maintaining vascular endothelial stability, but its association with PAH remains unclear. Analysis of RNA expression microarray data from the GEO database revealed that KRIT1 expression was downregulated in the lung tissues of PAH patients. In the monocrotaline (MCT)-induced PAH rat model, KRIT1 expression in lung tissue was reduced, accompanied by typical PAH phenotypes, including elevated right ventricular systolic pressure, right ventricular hypertrophy, and increased pulmonary artery wall thickness. In vitro, EndMT in primary rat pulmonary artery ECs (rPAECs) was induced by inflammatory cytokines, and KRIT1 expression was suppressed during this process. Overexpression of KRIT1 attenuated the EndMT-associated molecular phenotype, with increased VE-cadherin and reduced α-SMA expression, and inhibited the enhanced migratory activity of rPAECs. Mechanistically, KRIT1 may exert anti-EndMT effects by negatively regulating the TGF-β/Smad signalling pathway, as evidenced by reduced Smad2/3 phosphorylation. This effect was abrogated by a TGF-β/Smad pathway agonist. In addition, KRIT1 overexpression suppressed β-catenin nuclear translocation. This study reveals a role for KRIT1 in maintaining endothelial homeostasis, suggesting its potential involvement in PAH-associated vascular remodelling.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205681","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":"EXPRESSION OF CONCERN: Renoprotective Effect of Hypericum Perforatum against Diabetic Nephropathy in Rats: Insights in the Underlying Mechanisms","authors":"","doi":"10.1111/1440-1681.70160","DOIUrl":"10.1111/1440-1681.70160","url":null,"abstract":"<p>\u0000 <span>EXPRESSION OF CONCERN</span>: <span>D. M. Abd El Motteleb</span>, <span>D. I. Abd El Aleem</span>, “ <span>Renoprotective Effect of <i>Hypericum Perforatum</i> against Diabetic Nephropathy in Rats: Insights in the Underlying Mechanisms</span>,” <i>Clinical and Experimental Pharmacology and Physiology</i> <span>44</span>, no. <span>4</span> (<span>2017</span>): <span>509</span>–<span>521</span>, https://doi.org/10.1111/1440-1681.12729\u0000 </p><p>This Expression of Concern is for the above article, published online on 12 January 2017 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. Concerns were raised by a third party on PubPeer [<span>1</span>] that there was evidence of splicing in the NFkB and beta actin bands in Figure 2. Additional investigation by the publisher found evidence that the DM + HP100 and DM_HP200 beta-actin bands in Figure 2 may have been duplicated and that there was some evidence of duplicated image elements in the III image in Figure 6B.</p><p>The authors responded to an inquiry by the publisher and stated that the bands in figure 2 were composite images and stated that the original data for Figures 2 and 6B were no longer available. The authors supplied original data for Figure 6A.</p><p>Because the original data are no longer available for Figures 2 and 6, the concerns cannot be resolved. The Expression of Concern has been agreed to in order to inform and alert readers.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104999","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":"Targeting RAB27A Enhances Pembrolizumab Sensitivity and Alleviates Immune Escape via Inactivation of the PI3K/Akt/mTOR Pathway in Triple-Negative Breast Cancer","authors":"Tong Sha,&nbsp;Jingjing Fan,&nbsp;Xiaoli Wang,&nbsp;Binlin Ma","doi":"10.1111/1440-1681.70159","DOIUrl":"10.1111/1440-1681.70159","url":null,"abstract":"<div>\u0000 \u0000 <p>Ras-related protein Rab-27A (RAB27A) is involved in tumour progression and immune regulation. This study investigated its role in triple-negative breast cancer (TNBC) progression, immune escape and responsiveness to immune checkpoint inhibitors. RAB27A expression was analysed in TNBC tissues and public datasets. Gain- and loss-of-function experiments were performed in TNBC cells. Peripheral blood mononuclear cell (PBMC)-based tumour coculture systems and xenograft mouse models were used to evaluate antitumor immunity and therapeutic responses. RAB27A was upregulated in TNBC and correlated with chemotherapy resistance, advanced T stage, high Ki-67 expression and CD8⁺ T-cell infiltration. RAB27A overexpression activated PI3K/Akt/mTOR signalling and promoted tumour cell migration and invasion, whereas RAB27A silencing had the opposite effects. Combined RAB27A targeting and PI3K inhibition decreased PD-L1 expression and cell viability while increasing HLA-I expression and apoptosis; these effects were further enhanced by pembrolizumab. In PBMC coculture models, combination treatment promoted T-cell proliferation and CD8⁺ T-cell expansion while suppressing malignant phenotypes. In vivo, RAB27A knockdown inhibited tumour growth, reduced PI3K/Akt/mTOR activation and PD-L1 expression and increased HLA-I expression. Targeting RAB27A enhances antitumor immunity and pembrolizumab sensitivity by blocking the PI3K/Akt/mTOR axis, representing a potential strategy to overcome immune resistance in TNBC.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104984","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":"Mechanistic Study of SRSF1-Mediated Inhibition of Treg Cell Function via the mTORC1/ULK1 Signalling Axis Through Mitophagy in Asthma","authors":"Chunhua Ye,&nbsp;Yifu Chen,&nbsp;Qinjun Yi,&nbsp;Zhu Ming,&nbsp;Tuoyu Gan,&nbsp;Rong Xiang","doi":"10.1111/1440-1681.70157","DOIUrl":"https://doi.org/10.1111/1440-1681.70157","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study examines the role of serine/arginine-rich splicing factor 1 (SRSF1) in airway inflammation in asthma and the molecular mechanisms in mitophagy and metabolic homeostasis in regulatory T cells (Tregs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bronchoalveolar lavage fluid (BALF) was collected from asthma patients and healthy controls to assess SRSF1 expression and autophagy, and to analyse the correlation of SRSF1 with Treg cell functional markers and lung function. The ovalbumin (OVA)-induced asthma mouse model was established, with the OVA, OVA+shSRSF1, OVA+rapamycin, and OVA+shSRSF1+MHY1485 groups established. Additionally, an OVA+PM2.5 group was set up. Treg cells were isolated from lung tissue to evaluate Treg cell mitophagy, glucose metabolism reprogramming, mitochondrial function, and immunosuppressive activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SRSF1 levels in BALF cells from asthma patients were notably elevated and showed negative correlations with FOXP3 expression in Treg cells and FEV₁% pred. In OVA-induced asthmatic mice, SRSF1 was upregulated in Treg cells, accompanied by increased phosphorylation of mTOR and ULK1 at Ser757, leading to defects in mitophagy and metabolic reprogramming. Silencing SRSF1 or rapamycin treatment reversed the aforementioned autophagy inhibition and metabolic dysregulation, restored Treg cell numbers and suppressive function, and alleviated airway inflammation and airway hyperresponsiveness. In contrast, the mTORC1 activator MHY1485 counteracted the protective effects of shSRSF1. PM2.5 exposure further exacerbated these changes, which were dependent on SRSF1 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SRSF1 modulates the mTORC1/ULK1 axis and is associated with impaired Treg mitophagy and metabolic reprogramming in asthma. Targeting SRSF1 or mTORC1 may represent a promising therapeutic strategy for the prevention and treatment of asthma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 10","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149011602","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":"Ferroptosis in Low-Density Neutrophils of Tuberculosis Patients Suppresses Bactericidal Function","authors":"Li Jiaqi,&nbsp;Ji Xuejiao,&nbsp;Sha Wei,&nbsp;Shen Hongbo","doi":"10.1111/1440-1681.70155","DOIUrl":"https://doi.org/10.1111/1440-1681.70155","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To analyse the immunological characteristics of low-density neutrophils (LDNs) in patients with tuberculosis (TB).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study systematically characterized the immunological features of LDNs in active TB patients by comparing the proportion, phenotype and function of peripheral blood LDNs between healthy controls (HCs) and TB patients. Single-cell RNA sequencing analysis and quantitative PCR validation were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The proportion of LDNs was significantly increased in TB patients, exhibiting an enhanced effector phenotype but impaired migration and antibody-dependent functions. The direct bactericidal activity of LDNs against <i>Mycobacterium bovis</i> BCG was compromised. Single-cell sequencing analysis revealed significant upregulation of genes associated with ferroptosis and neutrophil extracellular trap (NETosis) formation pathways in TB patients' LDNs. Key ferroptosis-related genes HMOX1 and ACSL4 were upregulated, while GPX4 and FSP1 were downregulated, indicating increased susceptibility to ferroptosis. Functional intervention experiments demonstrated that treatment with the ferroptosis inhibitor Ferrostatin-1 enhanced the bactericidal capacity of LDNs against BCG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Ferroptosis and NETosis pathway activation in LDNs of TB patients leads to functional exhaustion and exacerbates immunopathology, providing new insights for immune intervention strategies in TB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148943029","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":"18 β-Glycyrrhetinic Acid Inhibits Malignant Progression of Prostate Cancer via Regulation of Autophagy and EMT Induced by PTEN/PI3K/mTOR Pathway","authors":"Dawei Xiong,&nbsp;Hongfeng Dai","doi":"10.1111/1440-1681.70156","DOIUrl":"10.1111/1440-1681.70156","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Prostate cancer (PCa) is one of the most common malignancies in men, and its progression is closely related to epithelial–mesenchymal transition (EMT) and autophagy imbalance. 18β-Glycyrrhetinic acid (18β-GA) has been reported to exhibit various anti-tumour activities. This study aims to systematically evaluate the impact of 18β-GA on the malignant biological behaviours of PCa and explore its potential molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The human PCa cell lines LNCaP and PC-3 were used to evaluate the inhibitory effects of 18β-GA on malignant progression. The potential mechanisms were further explored by assessing EMT markers, autophagy-related proteins and angiogenesis. The role of the PTEN/PI3K/mTOR pathway in 18β-GA's effects was explored through siRNA-mediated PTEN knockdown and Western blot analysis. A PCa xenograft model was established in vivo to assess the impact of 18β-GA on tumour growth.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>18β-GA significantly inhibited the viability, proliferation, migration and invasion of LNCaP and PC-3 cells, while promoting apoptosis, with no significant toxicity to RWPE-1 cells. 18β-GA upregulated E-cadherin and Claudin-1, while downregulating N-cadherin, Vimentin, Snail and MMP2/9, thus inhibiting the EMT process and reducing the angiogenesis capacity and VEGF expression in HUVECs. Additionally, 18β-GA increased the LC3-II/LC3-I ratio, upregulated Beclin1 and ATG7 and downregulated p62, indicating activation of autophagic flux. Mechanistic studies revealed that 18β-GA upregulated PTEN expression and inhibited PI3K and mTOR phosphorylation. PTEN knockdown partially reversed its effects on autophagy, EMT and malignant phenotypes. In vivo experiments further confirmed that 18β-GA significantly suppressed xenograft tumour growth and exhibited anti-tumour effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>18β-GA inhibits the malignant progression of PCa cells and xenograft tumour growth by upregulating PTEN and inhibiting the PI3K/mTOR axis, synergistically activating autophagy and inhibiting EMT and angiogenesis. 18β-GA holds promise as a potential anti-PCa drug targeting the PTEN/PI3K/mTOR pathway, jointly regulating autophagy and EMT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929107","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":"ANGII Initiated HSF2 Trans-Activating HIF-1α Through Induction of ER Stress to Promote Cardiac Hypertrophy","authors":"Renchuang Cao,&nbsp;Qingying Meng,&nbsp;Gengyuan Li,&nbsp;Shumei Yuan,&nbsp;Chunmei Li,&nbsp;Xin Zhao,&nbsp;Dongmei Zhang","doi":"10.1111/1440-1681.70153","DOIUrl":"10.1111/1440-1681.70153","url":null,"abstract":"<div>\u0000 \u0000 <p>Heat shock factor 2 (HSF2) and hypoxia-inducible factor 1α are activated by angiotensin II (ANGII) in cardiomyocytes. The endoplasmic reticulum (ER) stress plays a critical role in cardiac hypertrophy. Moreover, HIF-1α is known to be regulated by HSF2 in tumour cells. In this study, we hypothesised and clarified whether HSF2 trans-activated HIF-1α through initiation of ER stress in hypertrophic cardiomyocytes. Myocardial hypertrophy was induced by the treatment of ANGII. Expression of the gene or protein was assessed by applying RT-PCR, WB, ICC and IHC. Luciferase and CHIP were applied to detect the transcription of HIF-1α by HSF2. Both in vitro and in vivo, the expression of HIF-1α, ER stress markers and HSF2 was increased in ANGII-treated hypertrophic cardiomyocytes. Blocking ER stress suppressed the expression of HSF2 and HIF-1α in ANGII-treated cardiomyocytes. Silencing HSF2 inhibited HIF-1α, thereby reducing hypertrophy but had no effect on ER stress. Similarly, silencing HIF-1α reduced hypertrophy without affecting ER stress or HSF2 expression. HSF2 transcriptionally activated HIF-1α. We concluded that ER stress induced by ANGII activates HSF2, which then trans-activates HIF-1α, promoting cardiac hypertrophy.</p>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860377","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":"Brucea javanica Oil Emulsion Promotes Breast Cancer Cell Autophagy and Apoptosis by Regulating PAX6 mRNA Stability Through the hsa_circ_0001589/G3BP1 Axis","authors":"Ke Li,&nbsp;MeiXia Li,&nbsp;XueQiang Pan,&nbsp;JiaWen Xu,&nbsp;Rui Jiang","doi":"10.1111/1440-1681.70150","DOIUrl":"10.1111/1440-1681.70150","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Objective</h3>\u0000 \u0000 <p><i>Brucea javanica</i> oil emulsion (BJOE), a traditional Chinese medicine extract, has been demonstrated to possess antitumor activity in multiple cancers. However, its molecular mechanisms in breast cancer, particularly those involving circRNAs, remain unclear. This study investigates whether BJOE exerts its anti-breast cancer effects by inducing autophagy and apoptosis through regulating hsa_circ_0001589/G3BP1/PAX6 signalling axis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>After BJOE treatment of MCF-7 cells, cell viability, apoptosis (Annexin V-FITC/PI staining) and autophagy (LC3-II/LC3-I ratio, autophagosome formation) were assessed. qPCR identified hsa_circ_0001589 as a key circRNA downregulated BJOE. RNA immunoprecipitation (RIP) and Western blot confirmed the interaction between hsa_circ_0001589 and G3BP1 and subsequent PAX6 inhibition. This axis was verified via functional rescue experiments (siRNA knockdown/overexpression).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>BJOE markedly inhibited MCF-7 cells proliferation, induced apoptosis and activated autophagy in a dose-dependent manner. Mechanistically, BJOE downregulated hsa_circ_0001589, thereby weakening the interaction between hsa_circ_0001589 and G3BP1 and reducing G3BP1-mediated stabilisation of <i>PAX6</i> mRNA. Silencing hsa_circ_0001589 mimicked the effects of BJOE, whereas overexpression of hsa_circ_0001589 and G3BP1 attenuated BJOE-induced autophagy and apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>BJOE promotes autophagy and apoptosis through the hsa_circ_0001589/G3BP1/PAX6 axis in MCF-7 breast cancer models, offering a novel therapeutic strategy for breast cancer and providing a circRNA-mediated mechanism for natural anticancer drug research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839073","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":"Shengqingjiangzhuo Capsules Alleviates Renal Fibrosis by Targeting Glomerular Endothelial Cells Exosome miR-31-5p/HO-1 to Suppress Tubular Epithelial Cells Ferroptosis","authors":"Feng Pan,&nbsp;Jinhong Lu,&nbsp;Gaxi Ye,&nbsp;Haifeng Zhu,&nbsp;Hongyuan Ma,&nbsp;Jiale Li,&nbsp;Xingyu Yang,&nbsp;Hongtao Yang,&nbsp;Anrong Tong","doi":"10.1111/1440-1681.70151","DOIUrl":"10.1111/1440-1681.70151","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Chronic renal failure (CRF) represents the advanced stage of chronic kidney disease, for which no specific pharmacological treatments are currently available. Traditional Chinese medicine has demonstrated notable efficacy in managing CRF. Shengqingjiangzhuo capsules (SQJZ capsules), a traditional Chinese medicinal formulation, are employed clinically in the treatment of CRF. However, the precise mechanisms underlying its therapeutic effects remain insufficiently understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The SQJZ capsule's chemical components were identified using UPLC-Q-Exactive-Orbitrap-MS. TGFβ1-induced GECs and adenine-induced CRF models in mice were developed. Exosome miRNA sequencing, quantitative polymerase chain reaction (qPCR), Western blot and dual-luciferase reporter assays explored the interaction between miR-31-5p and HO-1, and their effects on ferroptosis markers (ROS, GSH, MDA, Fe²⁺, SLC7A11, GCLC), mitochondrial membrane potential and fibrosis markers α-SMA and collagen I.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This study is the first to employ UPLC-Q-Exactive-Orbitrap-MS technology to analyse SQJZ capsules, identifying 82 active components. It indicates that TGF-β1-stimulated GECs-derived exosomes increase miR-31-5p in TECs, causing HO-1 inhibition and ferroptosis. The active drug in SQJZ capsules serum counteracts these effects, suggesting anti-ferroptosis and anti-fibrosis properties and improving renal function in cell and CRF animal models. Overall, SQJZ capsules reduce renal fibrosis by modulating the miR-31-5p/HO-1 axis and inhibiting ferroptosis in TECs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SQJZ capsules is associated with amelioration of renal fibrosis by suppressing GECs-derived exosomal miR-31-5p, which derepresses HO-1 expression in TECs, thereby inhibiting ferroptosis and subsequent renal fibrosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148839086","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":"Early Cardiotoxic Remodelling Precedes Hepatic Fibrosis and Increases Susceptibility to Lethal Arrhythmias in Wild-Type MASH Mice","authors":"Jinyao Liu,&nbsp;Kohmei Yamashita,&nbsp;Seiko Yamano","doi":"10.1111/1440-1681.70154","DOIUrl":"10.1111/1440-1681.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatohepatitis (MASH) is increasingly linked to cardiovascular complications; however, the mechanisms underlying the association between hepatic injury and cardiotoxicity remain unclear. This study aimed to establish a wild-type mouse model of MASH with cardiac involvement and to characterise the temporal relationship between hepatic and cardiac alterations during disease progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male C57BL/6J mice were fed a standard diet or a low-carbohydrate, high-protein, high-cholesterol (LCHP-HC) diet with or without non-excessive ethanol for 12 or 24 weeks. Arrhythmogenic susceptibility was assessed using provocation testing. Hepatic and cardiac alterations were evaluated by histology, immunofluorescence, and quantitative RT-PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The LCHP-HC diet combined with ethanol induced histological MASH and markedly increased susceptibility to lethal arrhythmias. At 12 weeks, cardiac remodelling characterised by inflammation, mild fibrosis, and connexin-43 dysregulation was evident in the absence of hepatic fibrosis, indicating early cardiotoxic remodelling. At 24 weeks, hepatic fibrosis and hepatic sympathetic activation became evident, whereas local cardiac sympathetic activation remained unchanged, indicating a temporal dissociation in which cardiac remodelling preceded hepatic fibrotic progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Early cardiotoxic remodelling preceded hepatic fibrosis and was associated with increased arrhythmogenic susceptibility during MASH progression. These findings demonstrate that cardiac remodelling develops early in experimental MASH and reveal a stage-dependent temporal association between hepatic disease progression and cardiac vulnerability.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 9","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817485","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}