CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY临床与实验药理学与生理学
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY(英文缩写 CLIN EXP PHARMACOL P),ISSN 0305-1870,eISSN 1440-1681,中文译名:临床与实验药理学与生理学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-10-01 至 2026-09-30，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 2.963 | Q3 |
| 2022 | 2.900 | Q2 |
| 2023 | 2.400 | Q2 |
| 2024 | 2.500 | Q2 |
| 2025 | 2.500 | Q3 |
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY 最新收录文献
-
1. Targeting RAB27A Enhances Pembrolizumab Sensitivity and Alleviates Immune Escape via Inactivation of the PI3K/Akt/mTOR Pathway in Triple-Negative Breast Cancer.
PMID:日期:2026-10Ras-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.
-
2. Mechanistic Study of SRSF1-Mediated Inhibition of Treg Cell Function via the mTORC1/ULK1 Signalling Axis Through Mitophagy in Asthma.
PMID:日期:2026-09-22This 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). 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. SRSF1 levels in BALF cells from asthma patients were notably elevated and showed negative correlations with FOXP3 expression in Treg cells and FEV% 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. 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.
-
3. Ferroptosis in Low-Density Neutrophils of Tuberculosis Patients Suppresses Bactericidal Function.
PMID:日期:2026-09To analyse the immunological characteristics of low-density neutrophils (LDNs) in patients with tuberculosis (TB). 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. 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 Mycobacterium bovis 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. 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.
-
4. 18 β-Glycyrrhetinic Acid Inhibits Malignant Progression of Prostate Cancer via Regulation of Autophagy and EMT Induced by PTEN/PI3K/mTOR Pathway.
4. 18β-甘草次酸通过调控PTEN/PI3K/mTOR通路诱导的自噬和上皮-间质转化抑制前列腺癌恶性进展PMID:日期:2026-09Prostate 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. 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. 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. 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.
-
5. ANGII Initiated HSF2 Trans-Activating HIF-1α Through Induction of ER Stress to Promote Cardiac Hypertrophy.
PMID:日期:2026-08-30Heat 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.
-
6. Brucea javanica Oil Emulsion Promotes Breast Cancer Cell Autophagy and Apoptosis by Regulating PAX6 mRNA Stability Through the hsa_circ_0001589/G3BP1 Axis.
PMID:日期:2026-08-28Brucea javanica 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. 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). 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 PAX6 mRNA. Silencing hsa_circ_0001589 mimicked the effects of BJOE, whereas overexpression of hsa_circ_0001589 and G3BP1 attenuated BJOE-induced autophagy and apoptosis. 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.
-
7. Shengqingjiangzhuo Capsules Alleviates Renal Fibrosis by Targeting Glomerular Endothelial Cells Exosome miR-31-5p/HO-1 to Suppress Tubular Epithelial Cells Ferroptosis.
PMID:日期:2026-08-28Chronic 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. 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, Fe, SLC7A11, GCLC), mitochondrial membrane potential and fibrosis markers α-SMA and collagen I. 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. 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.
-
8. Early Cardiotoxic Remodelling Precedes Hepatic Fibrosis and Increases Susceptibility to Lethal Arrhythmias in Wild-Type MASH Mice.
PMID:日期:2026-08-26Metabolic 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. 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. 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. 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.
-
9. DUSP1 Inhibits Mechanotransduction and MAPK Signalling to Alleviate Myocardial Cell Hypertrophy.
PMID:日期:2026-08-21Hypertrophic Cardiomyopathy (HCM) is one of the significant causes of heart failure. This study aimed to identify and validate potential therapeutic targets for HCM through bioinformatics analysis and in vitro and in vivo experiments. By analysing differentially expressed genes in HCM patients and combining multiple analytical approaches, key genes were screened. The functions of these genes were validated using AC16 cells under different mechanical force environments and Ang-II induction. HCM-like pathological cardiac remodelling mouse model was established to evaluate myocardial hypertrophy, fibrosis and cardiac remodelling. The results demonstrated that DUSP1 expression was downregulated in the myocardium of HCM patients. Mechanical force transduction activated the MAPK pathway and overexpression of DUSP1 suppressed ERK/MAPK activation and attenuated mechanotransduction-associated cardiomyocyte hypertrophy and hypertrophic gene expression. In vivo experiments showed that cardiac-specific restoration of DUSP1 expression alleviated pathological cardiac remodelling and fibrosis. This study suggests that DUSP1 functions as an endogenous regulator of mechanically activated MAPK signalling, thereby limiting pathological myocardial hypertrophy. These findings identify a previously underappreciated role of DUSP1 in linking mechanical stress-induced signalling with MAPK activation and pathological cardiac remodelling, suggesting DUSP1 restoration as a potential therapeutic strategy for HCM-like cardiac remodelling.
-
10. Polyphyllin I Orchestrates Autophagy to Reprogram the Tumour Immune Microenvironment and Abrogate Cisplatin Resistance in Non-Small Cell Lung Cancer.
PMID:日期:2026-08This study aims to elucidate the molecular mechanisms by which Polyphyllin I (PPI), a potent steroidal saponin, attenuates non-small cell lung cancer (NSCLC) progression via mechanistic reprogramming of an autophagy-dependent immunogenic response. Integrated in vitro (A549, H460) and in vivo (LLC xenograft) models were deployed to evaluate PPI's efficacy on autophagic flux and the tumour immune microenvironment. The regulatory role of autophagy in macrophage-mediated antigen presentation was scrutinised via ATG3-mediated genetic silencing or overexpression in tumour-macrophage co-culture systems. Concurrently, the capacity of PPI to sensitise NSCLC cells to cisplatin (DDP) and counteract chemoresistance was evaluated. PPI activated the AMPK/p53/mTOR signalling axis, robustly inducing core autophagic markers (LC3-II and Beclin-1) in a dose-dependent manner. Mechanistically, PPI-induced autophagic flux served as a prerequisite for antitumoural M1 macrophage polarisation, characterised by significant upregulation of iNOS and MHC-II in co-cultured THP-1 cells. Genetic knockdown of ATG3 effectively abrogated these immunostimulatory profiles, whereas ATG3 overexpression potentiated PPI-driven antigen presentation. Furthermore, PPI administration markedly delayed the onset of DDP resistance sustained by functional autophagic flux. In vivo, PPI significantly suppressed tumour burden, accompanied by enhanced CD8+ T-cell infiltration and elevated cytotoxic effector levels (IFN-γ and Granzyme B). Our findings establish PPI as a dual autophagic-immune modulator that re-engineers the immunosuppressive microenvironment. By coupling intracellular autophagic stress with macrophage-mediated antigen presentation, PPI reinstates antitumour immunity and abrogates chemoresistance, offering a compelling therapeutic framework for managing recalcitrant NSCLC.