Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Saikosaponin D Alleviates Atherosclerosis by Regulating Autophagy and Senescence of VSMCs via Inhibiting EPHB2","authors":"Meihua Yan,&nbsp;Tian Tang,&nbsp;Yanxiu Wang,&nbsp;Yuzhen Qin,&nbsp;Qiangwei Hao,&nbsp;Xinri Chen,&nbsp;Xianmin Luo","doi":"10.1111/1440-1681.70131","DOIUrl":"10.1111/1440-1681.70131","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Atherosclerosis (AS) is a major cause of cardiovascular diseases, with OX-LDL-induced VSMC dysfunction being a critical pathogenic driver of AS development. Saikosaponin D (SSD), a bioactive compound, shows therapeutic potential, but its mechanism in AS is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An atherosclerotic cell model was established by treating hVSMCs with OX-LDL. Intracellular ROS was detected via a fluorescent probe, MDA content and SOD activity via biochemical kits. Inflammatory cytokines (IL-6, IL-8 and TNF-α) were quantified by ELISA. Lipid parameters (TG, LDL and HDL) were analysed biochemically, and intracellular lipid accumulation was assessed via Oil Red O staining. Autophagy (LC3B and p62) and senescence-related (p16 and p21) protein expression was detected by WB, with cellular senescence further assessed via SA-β-gal staining. SSD's potential targets were predicted via bioinformatics (CTD, SwissTargetPrediction and GeneCards). SSD-EPHB2 interaction was predicted by AutoDock Vina docking (visualised by PyMOL), and its stability was evaluated by using iMODS-based NMA. EPHB2's functional role was confirmed via its overexpression in hVSMCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SSD significantly attenuated OX-LDL-induced oxidative stress, inflammation, lipid accumulation, autophagic flux impairment and cellular senescence in hVSMCs. Bioinformatics analysis pinpointed EPHB2 as a hub gene. Molecular studies confirmed that SSD directly binds to EPHB2 and downregulates its expression. Crucially, overexpressing EPHB2 abolished all the protective effects of SSD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>SSD alleviates OX-LDL-induced hVSMC dysfunction by inhibiting EPHB2, highlighting the SSD-EPHB2 pathway as a potential therapeutic target for AS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263536","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":"Noninvasively Evaluating the Cerebral Blood Flow Changes After Surgery in Adult Moyamoya Patients Using 3D Pulsed Arterial Spin Labelling MRI","authors":"Zhenfang Zhu,&nbsp;Biaoling Chen,&nbsp;Wei Zhao,&nbsp;Yu Duan,&nbsp;Yu Zheng,&nbsp;Liang Jin,&nbsp;Feng Gao","doi":"10.1111/1440-1681.70141","DOIUrl":"10.1111/1440-1681.70141","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To explore the feasibility of phase contrast (PC) MRI and three-dimensional pulsed arterial spin labelling (3D PASL)-MRI in assessing cerebrovascular blood flow changes after surgical revascularization in patients with moyamoya disease (MMD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study was a prospective study and comprised two sections. In the first section, 43 patients with MMD who never underwent any revascularization surgery and 19 healthy control volunteers were enrolled. In the second section, 51 patients with MMD who underwent revascularization surgery were included. PC-MRI and 3D PASL-MRI were performed. The average blood flow in the internal carotid (ICA), basilar (BA), superficial temporal (STA) arteries and cerebral blood flow (CBF) were compared between the MMD patients and control volunteers (first section) as well as before and after surgery (second section). Then, MMD patients were divided into haemorrhage and non-haemorrhage subgroups and the average blood flow and CBF before and after surgery were compared between the subgroups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The average flow in the ICA, BA, STA was lower in the MMD patients than in the healthy control group (<i>p</i> = 0.000, <i>p</i> = 0.001, <i>p</i> = 0.001). The CBF of the seven clusters was higher in the healthy controls than in the MMD patients' groups. The average flow in the ICA, BA and STA was increased in MMD patients after combined surgery (<i>p</i> = 0.000, <i>p</i> = 0.002, <i>p</i> = 0.000). Fifteen clusters of elevated CBF and one of reduced CBF were postoperatively evident. Eight clusters of elevated CBF were compared with the preoperative status in the patients without haemorrhage. In the haemorrhage group, postoperative CBF did not significantly change after combined surgery (<i>p</i> &gt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Both 3D PASL-MRI and PC-MRI can noninvasively evaluate CBF changes in patients with MMD after surgery. The CBF of the cerebral was significantly improved after surgery. Moreover, the improvement of CBF was more obvious in patients with non-hemorrhagic rather than hemorrhagic MMD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263434","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":"Targeting S100A8/A9 Ameliorates Heart Failure with Preserved Ejection Fraction by Modulating TLR4/NF-κB-Mediated Inflammation","authors":"Yansong Li,&nbsp;Qi Han,&nbsp;Xianling Liu,&nbsp;Kai Wang,&nbsp;Di Xu,&nbsp;Miao Lu","doi":"10.1111/1440-1681.70140","DOIUrl":"10.1111/1440-1681.70140","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Heart failure with preserved ejection fraction (HFpEF) has emerged as one of the most challenging public health issues worldwide, with few effective preventive and therapeutic options available. S100A8/A9 is an inflammatory mediator that contributes to the development of several cardiovascular diseases via the TLR4/NF-κB pathway. This study aimed to investigate the role of S100A8/A9 in HFpEF and unravel potential mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The HFpEF model was established in C57BL6/J mice by administering a high-fat diet combined with NG-nitroarginine methyl ester hydrochloride (L-NAME). From the eighth week, mice were treated with the S100A8/A9 inhibitor paquinimod (ABR 215757) via oral gavage for 8 weeks. Body weight, tibial length, glucose tolerance, and blood lipids were measured following the intervention. Subsequently, cardiac function, myocardial hypertrophy, cardiac fibrosis, inflammatory markers, and oxidative stress were evaluated. AAV9-TLR4-shRNA and the TLR4 inhibitor TAK-242 were employed in vivo and in vitro, respectively, to explore the probable underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that paquinimod improved diastolic dysfunction in HFpEF mice without affecting systolic function. It also mitigated cardiomyocyte hypertrophy, suppressed cardiac fibrosis, decreased myocardial inflammation, and attenuated oxidative stress. Mechanistically, paquinimod inhibited the TLR4/NF-κB signalling pathway, and TLR4 inhibition reversed the effects of S100A8/A9 in vitro and partly alleviated the heart failure phenotype in mice with HFpEF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Inhibition of S100A8/A9-mediated inflammation improved diastolic function and reversed the pathological changes of the heart in mice with HFpEF. The observed effects were potentially mediated via inhibition of the TLR4/NF-κB pathway. The present study identified S100A8/A9 as a possible therapeutic target in HFpEF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148210229","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":"Cynomorium songaricum Rupr. Polysaccharide (CSP) Attenuates Diabetic Nephropathy by Activating AMPK/SIRT1 Signalling","authors":"Cheng Wan,&nbsp;Bingxin Cheng,&nbsp;Jinlei Li,&nbsp;Hongfei Zeng,&nbsp;Jiaojiao Mo,&nbsp;Xinyu Li,&nbsp;Sifeng Fan,&nbsp;Xin Zhang","doi":"10.1111/1440-1681.70138","DOIUrl":"10.1111/1440-1681.70138","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Diabetic nephropathy (DN) represents a significant complication of diabetes and serves as a primary trigger for end-stage renal disease. The study aimed to investigate the renal protective influence of <i>Cynomorium songaricum</i> Rupr. polysaccharide (CSP) on inflammation and oxidative stress in DN and explore its related mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>High glucose (HG)-stimulated podocytes (MPC-5 cells) were used as the cell model for DN. Cell counting kit-8 assay, flow cytometry analysis, and detection of lactate dehydrogenase production were performed to measure cell viability, apoptosis and cell death. A diabetic mouse model was established through streptozotocin induction. Levels of blood urea nitrogen (BUN), serum creatinine and 24-h urine protein were measured to assess renal function. Immunofluorescence staining of kidney samples was conducted to measure the expression of tumour necrosis factor (TNF)-α and interleukin (IL)-6. Oxidative stress markers of catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by corresponding kits. ELISA was performed to assess inflammatory cytokine levels in renal tissue. Western blot was performed to quantify protein levels of factors related to apoptosis, inflammation, oxidative stress and AMPK/SIRT1 pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CSP protected MPC-5 cells from HG-induced injury by inhibiting cell apoptosis and death while increasing cell viability. In addition, CSP notably repressed oxidative stress as manifested by an increase in CAT and SOD activities and a decline in MDA content, NOX2 level and NOX4 level. Meanwhile, the significant downregulation of IL-6, TNF-α, IL-1β, COX-2 and iNOS levels was found in HG-treated MPC-5 cells in the context of CSP administration. More importantly, CSP treatment attenuated inflammation and oxidative stress in the renal tissue of DN mice. CSP activated the AMPK/SIRT1 signalling in the renal tissue of DN mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CSP inhibits DN progression by alleviating inflammatory response and oxidative stress via activation of the AMPK/SIRT1 signalling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197539","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093683","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093681","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093682","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148074762","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148074763","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148068742","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}