Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"HSPB7 Deficiency Drives Aortic Aneurysm Progression in Marfan Syndrome Through Vascular Smooth Muscle Cell Phenotypic Switching.","authors":"Zining An, Tao Yan, Yang Ming, Zhiwei Tang, Zhaohua Yang, Hui Zhang, Kai Zhu, Yongfeng Shao","doi":"10.1111/1440-1681.70128","DOIUrl":"10.1111/1440-1681.70128","url":null,"abstract":"<p><p>Marfan syndrome (Mfs) arises from mutations in FBN1, predisposing individuals to thoracic aortic aneurysm (TAA) through abnormal smooth muscle cell behaviour. The role of HSPB7 in Mfs-related TAA remains poorly understood. By integrating multi-omics analysis with hiPSC-derived VSMCs from patients with Mfs, we elucidated the molecular landscape of Mfs-associated TAA. Analysis revealed immune cell infiltration, a reduced proportion of VSMCs, and altered intercellular communication. Pathway analyses indicated changes in cell adhesion, extracellular matrix (ECM) remodelling, and immune signalling, with downregulated metabolic pathways. Findings suggest structural, immune, and metabolic imbalances in Mfs-TAA pathogenesis. Downregulation of HSPB7 was associated with altered proliferation, migration, and metabolic activity. Overexpression of HSPB7 in patient-specific hiPSC-derived VSMCs attenuated these pathological features and promoted a more contractile phenotype. These findings suggest that HSPB7 may be involved in the regulation of VSMCs' phenotypic modulation in Mfs-TAA and provide mechanistic insight into disease-associated cellular alterations.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":"e70128"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041074","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":"Aurora A-Mediated Exosomal Secretion of miR-644a Promotes T-Lymphocyte Apoptosis Through the NOXA/p4E-BP1/MCL-1 Pathway.","authors":"Ziyi Zhou, Biao Chen, Kaiyue Zheng, Dewen Wan, Peng Kuang","doi":"10.1111/1440-1681.70132","DOIUrl":"10.1111/1440-1681.70132","url":null,"abstract":"<p><p>Lung cancer continues to be the primary contributor to cancer-related mortality worldwide. While immunotherapy markedly improves outcomes for many patients, clinical evidence indicates that non-small-cell lung cancer (NSCLC) patients with elevated Aurora A expression exhibit reduced therapeutic responses to immune checkpoint blockade. Elucidating the underlying mechanisms may unlock novel strategies to enhance the clinical benefits for this subset. In this study, we characterised cellular senescence and tumour microenvironment interactions using lung cancer cell lines with different Aurora A expression levels. H23 (high Aurora A expression) and A549 (low Aurora A expression) cells were selected to model tumour-immune crosstalk. Tumour-infiltrating lymphocytes (TILs) were isolated and activated via anti-CD28 costimulation. Through gain- and loss-of-function experiments, we established the optimal conditions to induce T-lymphocyte apoptosis and identified critical cell ratios and culture durations. In these co-culture systems, immune checkpoint inhibitors more effectively suppressed Aurora A-low tumour growth. Mechanistically, Aurora A overexpression exacerbated T-lymphocyte apoptosis via the NOXA-MCL-1 pathway. Further analysis revealed that Aurora A disrupts the eIF4G:eIF4E complex by suppressing p4E-BP1, thereby up-regulating the pro-apoptotic factor NOXA while down-regulating the anti-apoptotic factor MCL-1. Aurora A-driven T-lymphocyte apoptosis via the NOXA-MCL-1 axis compromises PD-1/PD-L1-mediated immune responses, providing a molecular rationale for immunotherapy resistance in Aurora A-high NSCLC patients. Targeting this pathway may restore T-cell viability and improve therapeutic outcomes.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 6","pages":"e70132"},"PeriodicalIF":2.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148041047","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 Nrf2/HO-1, NF-κB, and Apoptotic Pathways: Mechanistic Evaluation of Phlorizin Nanoparticles in Diabetic Renal Injury.","authors":"Ahmed M S Hegazy, Nasser S Alqahtani, Ayat B Al-Ghafari, Huda A Al Doghaither, Ekramy M Elmorsy, Noha Osama El-Shaer, Dania Abdelhady","doi":"10.1111/1440-1681.70129","DOIUrl":"10.1111/1440-1681.70129","url":null,"abstract":"<p><p>Diabetes mellitus (DM) is a chronic metabolic disorder associated with hyperglycemia, dyslipidemia, oxidative stress, inflammation, apoptosis, and renal dysfunction. Although phlorizin (PHL) possesses well-documented antidiabetic properties, its clinical applicability is limited by poor bioavailability and rapid metabolism, which may restrict its therapeutic efficacy. This study evaluated the therapeutic potential of phlorizin (PHL) and its chitosan nanoparticle formulation (PHL-CSNPs) in streptozotocin (STZ)-induced type 1 diabetic rats. Ninety adult male albino rats were randomly divided into six groups (n = 15 each): non-diabetic control, non-diabetic treated with crude PHL, non-diabetic treated with PHL-CSNPs, diabetic untreated (STZ-induced T1DM), diabetic treated with crude PHL, and diabetic treated with PHL-CSNPs. STZ-induced T1DM caused significant reductions in serum insulin, body weight gain, renal antioxidant defences, and mitochondrial function, accompanied by marked elevations in fasting blood glucose, dyslipidemia, oxidative stress markers, pro-inflammatory cytokines, apoptotic markers, and renal fibrotic mediators, as well as pronounced histopathological and ultrastructural kidney damage. In diabetic rats, treatment with PHL-CSNPs significantly improved insulin levels, glucose homeostasis, and body weight, restored lipid profiles and antioxidant enzyme activities, enhanced mitochondrial respiratory complex activities and ATP production, suppressed NF-κB-mediated inflammation, upregulated Nrf2/HO-1 signalling, decreased Bax and caspase-3 levels, increased Bcl-2 levels, and reduced TGF-β1-mediated fibrosis. Crude PHL provided moderate protective effects but was consistently less effective than the nanoparticle formulation. Importantly, the chitosan nanoparticle formulation markedly enhanced the therapeutic efficacy of PHL, likely by improving its stability, bioavailability, and renal tissue delivery, thereby producing stronger antioxidant, anti-inflammatory, and anti-apoptotic effects than crude PHL. Non-diabetic rats treated with either PHL or PHL-CSNPs maintained normal metabolic and renal parameters, confirming the safety of the treatments. Histopathological and ultrastructural analyses further confirmed the preservation of renal architecture in PHL-CSNP-treated diabetic rats. Collectively, this study demonstrates that nanoencapsulation significantly potentiates the biological activity of PHL, providing a clear therapeutic advantage over the crude compound. Overall, these findings demonstrate that PHL-CSNPs provide superior nephroprotective, antioxidant, anti-inflammatory, and metabolic benefits, highlighting their potential as a promising therapeutic strategy for managing type 1 diabetes-induced metabolic and renal complications.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":"e70129"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834410","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":"Ginsenoside Rg1 Improves Cardiac Function and Ventricular Remodelling by Down-Regulating SH2B Adaptor Protein 1 Expression in Rats With Myocardial Infarction.","authors":"Na Xiang, Jiayun Hu, Xueting Luo","doi":"10.1111/1440-1681.70121","DOIUrl":"10.1111/1440-1681.70121","url":null,"abstract":"<p><strong>Objective: </strong>Acute myocardial infarction (AMI) remains the leading global cause of mortality. This study explored the mechanism by which ginsenoside Rg1 (Rg1) ameliorates cardiac function and ventricular remodelling (VR) in rats with AMI by regulating SH2 domain-containing adapter protein B1 (SH2B1).</p><p><strong>Methods: </strong>An AMI rat model was established by ligating the left anterior descending coronary artery. Gain- and loss-of-function experiments were conducted to explore the role of SH2B1 in mediating cardioprotective effects of Rg1. Cardiac function and VR were evaluated using echocardiography, enzyme-linked immunosorbent assay (ELISA) and histological staining. RT-qPCR and western blot were employed to analyse SH2B1 expression and molecular docking to predict the binding affinity between Rg1 and SH2B1.</p><p><strong>Results: </strong>Rg1 improved echocardiographic parameters, decreased levels of pro-inflammatory cytokines, reduced infarct size, weakened myocardial tissue cell apoptosis, diminished blue collagen fibre deposition and reduced the proportion of α-smooth muscle actin-positive cells in myocardial tissues of rats with AMI in a dose-dependent manner within a certain range. Additionally, SH2B1 mRNA and protein expression was elevated in the myocardial tissue of AMI rats and Rg1 dose-dependently reduced SH2B1 expression. A binding energy of -2.14 kcal/mol was observed between Rg1 and SH2B1, indicating a potential interaction. SH2B1 knockdown improved cardiac function and VR in rats with AMI, and SH2B1 overexpression partially counteracted the beneficial effects of Rg1 in AMI rats.</p><p><strong>Conclusion: </strong>Rg1 improves cardiac function and VR in rats with AMI by down-regulating SH2B1; these effects are partially nullified by SH2B1 overexpression.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":"e70121"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764143","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":"TRMT13 Facilitates SPAST Upregulation Through ceRNA Crosstalk and Modulates G3-YSD-Triggered Energy Metabolic Decline in Cardiomyocytes.","authors":"Liangyong Liu, Hong Wu, Yan Wang, Zeyu Huang, Xiangqi Li, Qingyun Zhu","doi":"10.1111/1440-1681.70127","DOIUrl":"10.1111/1440-1681.70127","url":null,"abstract":"<p><p>Viral infections are a major cause of cardiac metabolic dysfunction, leading to diseases like viral myocarditis and heart failure. In this study, we used G3-YSD, a synthetic DNA mimic from the HIV-1 genome, to model cytoplasmic viral DNA stress and aim to elucidate the mechanistic roles of TRMT13 and SPAST in cardiomyocyte metabolic impairment under conditions mimicking viral infection. Through functional assays such as ATP quantification and Seahorse XF metabolic stress tests on H9C2 and AC16 cells, we found that G3-YSD treatment suppressed cardiomyocyte energy metabolism in a dose- and time-dependent manner, with upregulation of TRMT13 and SPAST. Further analysis revealed a strong positive association between these two genes. Functional knockdown experiments showed that silencing TRMT13 or SPAST alleviated G3-YSD-induced energy metabolic impairment. Mechanistically, miR-409-3p was identified as a key intermediary directly targeting the 3'UTRs of TRMT13 and SPAST, with TRMT13 mRNA acting as a ceRNA to promote SPAST expression. In vivo validation using a G3-YSD-treated mouse model confirmed that knocking down TRMT13 or SPAST, or delivering miR-409-3p mimics, improved cardiac function and systemic metabolic activity, while SPAST overexpression negated these effects. Our study identifies a novel TRMT13-miR-409-3p-SPAST regulatory axis mediating cardiomyocyte energy metabolic decline in response to cytoplasmic viral DNA stress, revealing a nonmethyltransferase, nonimmune, ceRNA-based mechanism of a newly characterised tRNA methyltransferase in viral infection-induced cardiac metabolic dysfunction and proposing new molecular targets for therapeutic intervention.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":"e70127"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926919","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":"Piezo1 Knockdown Attenuates Hypertension-Induced Cardiac Fibrosis by Inhibiting Ca²⁺/β-Catenin Signalling Pathway.","authors":"Lu-An Li, Qing-Rui Wu, Li-Bo Luo, Hui Yang, Hui-Yi Liu, Qian Li, Meng-Zhen Zhang, Chun-Yu Deng, Fang Rao, Qian-Huan Zhang","doi":"10.1111/1440-1681.70130","DOIUrl":"10.1111/1440-1681.70130","url":null,"abstract":"<p><p>Hypertension promotes cardiac fibrosis and ultimately leads to heart failure. Piezo1, a new mechanically sensitive cation channel, can transduce mechanical stress into biochemical signals that are necessary for cellular physiological and pathological functions. Although some studies have shown that Piezo1 is involved in the occurrence of cardiovascular disease, whether Piezo1 participates in hypertension-induced cardiac fibrosis, and the detailed molecular mechanisms are still unclear. Experiments were performed on cardiac tissue from spontaneously hypertensive rats (SHRs) and angiotensin II (Ang II)-treated mice. Rat cardiac fibroblasts (RCFs) were exposed to high hydrostatic pressure (HHP, 120 or 180 mmHg) using a self-developed device. We found that Piezo1 expression and β-catenin activation were markedly elevated in the cardiac tissue of hypertensive animals and in HHP-treated RCFs, accompanied by elevated expression of fibrosis factors, including TGF-β1, collagen I and collagen III. Furthermore, the inhibition or knockdown of Piezo1 (GsMTx4 and siRNA) and β-catenin (XAV939) alleviated TGF-β1, α-SMA and collagen expression in HHP-induced RCFs. Importantly, inhibition of Piezo1 decreased the concentration of intracellular Ca²⁺ and the nuclear translocation of β-catenin. Knockdown of Piezo1 in Ang II-treated mice ameliorated hypertension-induced myocardial fibrosis. Overall, Piezo1 channel activation caused by HHP could result in an increased concentration of intracellular Ca²⁺ and subsequently mediate the nuclear translocation of β-catenin, leading to the synthesis and secretion of collagen by RCFs. This indicates that targeting Piezo1 could be a potential novel approach for treating cardiac fibrosis induced by hypertension.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":"e70130"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873647","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":"Ciliatoside A Improves Klebsiella pneumoniae-Induced Pneumonia by Modulating Mitochondrial Autophagy via the SIRT1/PINK1/Parkin Pathway.","authors":"Jingxuan Zhu, Lingling Zhou, Xiaoqin Li","doi":"10.1111/1440-1681.70125","DOIUrl":"10.1111/1440-1681.70125","url":null,"abstract":"<p><strong>Background: </strong>Klebsiella pneumoniae (KP)-induced pneumonia has a high incidence rate, and current treatment options remain limited. The efficacy and mechanism of the novel natural compound Ciliatoside A (CA) against KP-induced pneumonia remain unclear.</p><p><strong>Aims: </strong>Investigating whether CA improves KP-induced pneumonia through the sirtuin 1 (SIRT1)/PTEN-induced putative kinase 1 (PINK1)/Parkin axis.</p><p><strong>Methods: </strong>KP was used to infect A549 cells, and resistance genes expression was detected using qRT-PCR. To evaluate CA's effect on cell viability, the Cell Counting Kit-8 assay was utilised. Different kits were employed to measure mitochondrial membrane potential, mitochondrial reactive oxygen species (mtROS), and ATP production. Transmission electron microscopy was used to observe autophagosome formation, and cellular autophagy was assessed via Western blot and LC3 fluorescence analysis. Flow cytometry, PI/Hoechst staining, and ELISA were employed to investigate the impacts of CA on A549 cell death and cytokine secretion. A KP mouse pneumonia model was established. Pathological staining was used to observe lung tissue damage and inflammatory infiltration, and Western blot was employed to validate protein expression in vivo. To verify whether CA alleviates KP-induced pneumonia through the SIRT1/PINK1/Parkin axis, intervention with SIRT1 agonists/inhibitors was conducted.</p><p><strong>Results: </strong>CA treatment downregulated drug resistance genes in KP and A549 cells, enhanced the viability of A549 cells following KP infection, and inhibited apoptosis. CA reduced mtROS accumulation, increased mitochondrial membrane potential and ATP production, promoted mitochondrial autophagy, and inhibited NLRP3-mediated inflammasome-mediated cell death. Additionally, CA alleviated pulmonary edema and pathological damage in mice following KP infection, while inhibiting apoptosis and pulmonary inflammation. Following KP infection, the SIRT1/PINK1/Parkin axis was blocked in A549 cells and mouse lung tissue; CA treatment activated this pathway. SIRT1 agonists enhanced the protective impact of CA against KP infection in A549 cells and mouse lung tissue, while SIRT1 inhibitors reduced the protective effect of CA.</p><p><strong>Conclusion: </strong>CA improves KP-induced pneumonia through activating the SIRT1/PINK1/Parkin axis to regulate mitochondrial autophagy.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"53 5","pages":"e70125"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764111","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":"PACAP Inhibits TNF-α- Induced Senescence in Primary Chondrocytes by SIRT3: An Implication in Osteoarthritis.","authors":"Xuewu Zhou, Kangquan Shou, Hao Yao","doi":"10.1111/1440-1681.70062","DOIUrl":"10.1111/1440-1681.70062","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a degenerative joint disease closely associated with aging, in which chondrocyte senescence plays a critical role in cartilage degradation. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its anti-inflammatory and cytoprotective effects; however, its role in chondrocyte senescence remains poorly understood. This study investigated the protective effects of PACAP38 on tumour necrosis factor-α (TNF-α)- induced chondrocyte senescence and the underlying mechanisms. Intracellular reactive oxygen species (ROS) levels were measured using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, oxidative DNA damage was assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) enzyme-linked immunosorbent assay (ELISA), and senescence markers were evaluated by senescence-associated β-galactosidase (SA-β-Gal) staining, telomerase activity assay, and telomere length analysis. Gene and protein expression were examined via real-time polymerase chain reaction (PCR) and Western blotting. We found that PACAP type I receptor (PAC1R), the receptor for PACAP, was expressed in both murine and human chondrocytes and was downregulated by TNF-α stimulation. PACAP38 treatment significantly reduced ROS and 8-OHdG levels, restored telomerase activity and telomere length, and decreased SA-β-Gal activity. Mechanistically, PACAP38 upregulated sirtuin 3 (SIRT3), a mitochondrial deacetylase that regulates oxidative stress and metabolism, while suppressing acetylated p53 (ac-p53) and plasminogen activator inhibitor-1 (PAI-1) expression. Furthermore, PACAP38 reversed TNF-α-induced dephosphorylation of AMP-activated protein kinase alpha (AMPK-α) and its downstream target acetyl-CoA carboxylase (ACC). Importantly, inhibition of AMPK by compound C abolished these protective effects, confirming the essential role of the AMPK-SIRT3 signalling pathway. In conclusion, our findings demonstrate that PACAP38 mitigates TNF-α-induced chondrocyte senescence via activation of the AMPK-SIRT3 signalling axis, suggesting a potential therapeutic strategy for OA.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"52 9","pages":"e70062"},"PeriodicalIF":2.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798331","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":"Epigallocatechin gallate for Parkinson's disease.","authors":"Consolato M Sergi","doi":"10.1111/1440-1681.13691","DOIUrl":"https://doi.org/10.1111/1440-1681.13691","url":null,"abstract":"<p><p>In the last couple of decades, we have experienced increased use of nutraceuticals worldwide with a demand for organic foods, which has been elevated to an extent probably unmatched with other periods of our civilization. One of the nutraceuticals that gained attention is epigallocatechin gallate (EGCG), a polyphenol in green tea. It has been suggested that diseases of the central nervous system can benefit from consuming some antioxidants, despite current results showing little evidence for their use in preventing and treating these diseases. ECGC may be beneficial in delaying the neurodegeneration of the substantia nigra regardless of the origin of Parkinson's disease (PD). This review covers the effect of EGCG on vitro and animal models of PD, the potential mechanisms of neuroprotection involved and summaries recent clinical trials in human PD. This review also aims to provide an investigative analysis of the current knowledge in this field and to identify putative crucial issues. Environmental factors such as dietary habits, drug use and social interaction are all factors that influence the evolution of neurodegenerative diseases. Therefore, the use of nutraceuticals requires further investigation.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":" ","pages":"1029-1041"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40393605","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":"Potential role of cellular senescence in pulmonary arterial hypertension.","authors":"Lumei Liu,&nbsp;Yaqin Wei,&nbsp;Sergio Giunta,&nbsp;Qinghu He,&nbsp;Shijin Xia","doi":"10.1111/1440-1681.13696","DOIUrl":"https://doi.org/10.1111/1440-1681.13696","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a rare and chronic lung vasculature disease characterised by pulmonary vasculature remodelling, including abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional endothelial cells (ECs). Remodelling of the pulmonary vasculature occurs from maturity to senescence, and it has become apparent that cellular senescence plays a central role in the pathogenesis of various degenerative vascular diseases and pulmonary pathologies. Cellular senescence represents a state of stable proliferative arrest accompanied by the senescence-associated secretory phenotype (SASP), which entails the copious secretion of proinflammatory signals in the tissue microenvironment. Evidence shows that in PAH patients, higher levels of cytokines, chemokines and inflammatory mediators can be detected and correlate with clinical outcome. Moreover, senescent cells accrue with age in epithelial, endothelial, fibroblastic and immunological compartments within human lungs, and evidence has shown that ECs and PASMCs in lungs from patients with chronic obstructive pulmonary disease were characterised by a higher number of senescent cells. However, there is little evidence uncovering the molecular pulmonary vasculature senescence in PAH. Herein, we review the cellular senescence in pulmonary vascular remodelling, and emphasise its importance in PAH. We further introduce some signalling pathways which might be involved in vasculature senescence and PAH, with the intent to discuss the possibility of the PAH therapy via targeting cellular senescence and reduce PAH progression and mortality.</p>","PeriodicalId":10259,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":" ","pages":"1042-1049"},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40395182","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}