Clinical and Experimental Pharmacology and Physiology最新文献_第8页

Erythropoietin hyporesponsiveness in non-alcoholic fatty liver disease 非酒精性脂肪肝中的促红细胞生成素低反应性。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-05-09 DOI: 10.1111/1440-1681.13869

Huixi Zou, Raymond S. M. Wong, Xiaoyu Yan

{"title":"Erythropoietin hyporesponsiveness in non-alcoholic fatty liver disease","authors":"Huixi Zou, Raymond S. M. Wong, Xiaoyu Yan","doi":"10.1111/1440-1681.13869","DOIUrl":"10.1111/1440-1681.13869","url":null,"abstract":"Treatment with erythropoietin (EPO) can correct anaemia in chronic kidney disease (CKD) patients; however, up to 10% exhibit resistance or hyporesponsiveness to EPO. Non-alcoholic fatty liver disease (NAFLD), prevalent liver disease in CKD patients, may limit EPO response because of thrombopoietin deficiency, iron homeostasis disorder and inflammation. Therefore, we hypothesized NAFLD is a risk factor for EPO responsiveness. To test our hypothesis, we evaluated the effect of EPO in healthy rats and rats with NAFLD induced by a high-fat, high-carbohydrate (HFHC) diet. After 12 weeks on the HFHC diet, NAFLD rats showed lower erythroid response to EPO treatment than healthy rats. We, then, determined that the primary cause of EPO hyporesponsiveness could be iron deficiency associated with inflammation, which reduces erythroid cell production. Specifically, the concentrations of hepcidin, ferritin, transferrin and white blood cells in NAFLD rats were 12.8-, 16.4-, 2.51- and 1.40-fold higher than those in healthy rats, respectively. However, erythroid cell types in the bone marrow of NAFLD rats were significantly reduced. In conclusion, our data suggest that NAFLD could be a risk factor for EPO responsiveness, which is attributed to functional iron deficiency associated with inflammation.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13869","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897224","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}

引用次数: 0

PM2.5 regulates the progression of lung adenocarcinoma through the axis of HCG18, miR-195 and ATG14 PM2.5 通过 HCG18、miR-195 和 ATG14 轴调控肺腺癌的进展。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-05-09 DOI: 10.1111/1440-1681.13861

Feng Luo, Yinghui Wu, Yao Li, Huaiyang Xu, Lei Wang, Lianyong Jiang, Hongtao Liu

引用次数: 0

Correction to “low-intensity pulsed ultrasound prevents prolonged hypoxia-induced cardiac fibrosis through HIF-1α/DNMT3a pathway via a TRAAK-dependent manner” 更正为 "低强度脉冲超声通过 TRAAK 依赖性方式，通过 HIF-1α/DNMT3a 途径防止长期缺氧诱导的心脏纤维化"。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-05-09 DOI: 10.1111/1440-1681.13870

引用次数: 0

HDAC6 inhibitor promotes reactive oxygen species-meditated clearance of Staphylococcus aureus in macrophage HDAC6 抑制剂可促进巨噬细胞中活性氧介导的金黄色葡萄球菌清除。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-05-08 DOI: 10.1111/1440-1681.13866

Maimaitiaili Yimiti, Xuefeng Fei, Hao Yang, Xiaobao Yang, Shuhui Li, Huxidanmu Tuoheniyazi, Danping Liu, Junrui Ma, Jialing Xie, Juanjuan Zheng, Zhen Song, Qingtian Li, Dakang Xu, Yanan Zhao, Zhidong Gu

{"title":"HDAC6 inhibitor promotes reactive oxygen species-meditated clearance of Staphylococcus aureus in macrophage","authors":"Maimaitiaili Yimiti, Xuefeng Fei, Hao Yang, Xiaobao Yang, Shuhui Li, Huxidanmu Tuoheniyazi, Danping Liu, Junrui Ma, Jialing Xie, Juanjuan Zheng, Zhen Song, Qingtian Li, Dakang Xu, Yanan Zhao, Zhidong Gu","doi":"10.1111/1440-1681.13866","DOIUrl":"10.1111/1440-1681.13866","url":null,"abstract":"Staphylococcus aureus (S. aureus) pneumonia has become an increasingly important public health problem. Recent evidence suggests that epigenetic modifications are critical in the host immune defence against pathogen infection. In this study, we found that S. aureus infection induces the expression of histone deacetylase 6 (HDAC6) in a dose-dependent manner. Furthermore, by using a S. aureus pneumonia mouse model, we showed that the HDAC6 inhibitor, tubastatin A, demonstrates a protective effect in S. aureus pneumonia, decreasing the mortality and destruction of lung architecture, reducing the bacterial burden in the lungs and inhibiting inflammatory responses. Mechanistic studies in primary bone marrow-derived macrophages demonstrated that the HDAC6 inhibitors, tubastatin A and tubacin, reduced the intracellular bacterial load by promoting bacterial clearance rather than regulating phagocytosis. Finally, N-acetyl-L- cysteine, a widely used reactive oxygen species (ROS) scavenger, antagonized ROS production and significantly inhibited tubastatin A-induced S. aureus clearance. These findings demonstrate that HDAC6 inhibitors promote the bactericidal activity of macrophages by inducing ROS, an important host factor for S. aureus clearance and production. Our study identified HDAC6 as a suitable epigenetic modification target for preventing S. aureus infection, and tubastatin A as a useful compound in treating S. aureus pneumonia.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891624","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}

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In vitro effects and mathematical modelling of CTCE-9908 (a chemokine receptor 4 antagonist) on melanoma cell survival CTCE-9908（一种趋化因子受体 4 拮抗剂）对黑色素瘤细胞存活的体外效应和数学建模

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-05-01 DOI: 10.1111/1440-1681.13865

Charlise Basson, Avulundiah Edwin Phiri, Manjunath Gandhi, Roumen Anguelov, June Cheptoo Serem, Priyesh Bipath, Yvette Nkondo Hlophe

{"title":"In vitro effects and mathematical modelling of CTCE-9908 (a chemokine receptor 4 antagonist) on melanoma cell survival","authors":"Charlise Basson, Avulundiah Edwin Phiri, Manjunath Gandhi, Roumen Anguelov, June Cheptoo Serem, Priyesh Bipath, Yvette Nkondo Hlophe","doi":"10.1111/1440-1681.13865","DOIUrl":"https://doi.org/10.1111/1440-1681.13865","url":null,"abstract":"CTCE-9908, a CXC chemokine receptor 4 (CXCR4) antagonist, prevents CXCR4 phosphorylation and inhibits the interaction with chemokine ligand 12 (CXCL12) and downstream signalling pathways associated with metastasis. This study evaluated the in vitro effects of CTCE-9908 on B16 F10 melanoma cells with the use of mathematical modelling. Crystal violet staining was used to construct a mathematical model of CTCE-9908 B16 F10 (melanoma) and RAW 264.7 (non-cancerous macrophage) cell lines on cell viability to predict the half-maximal inhibitory concentration (IC50). Morphological changes were assessed using transmission electron microscopy. Flow cytometry was used to assess changes in cell cycle distribution, apoptosis via caspase-3, cell survival via extracellular signal-regulated kinase1/2 activation, CXCR4 activation and CXCL12 expression. Mathematical modelling predicted IC50 values from 0 to 100 h. At IC50, similar cytotoxicity between the two cell lines and ultrastructural morphological changes indicative of cell death were observed. At a concentration 10 times lower than IC50, CTCE-9908 induced inhibition of cell survival (p = 0.0133) in B16 F10 cells but did not affect caspase-3 or cell cycle distribution in either cell line. This study predicts CTCE-9908 IC50 values at various time points using mathematical modelling, revealing cytotoxicity in melanoma and non-cancerous cells. CTCE-9908 significantly inhibited melanoma cell survival at a concentration 10 times lower than the IC50 in B16 F10 cells but not RAW 264.7 cells. However, CTCE-9908 did not affect CXCR4 phosphorylation, apoptosis, or cell cycle distribution in either cell line.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13865","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140818851","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}

引用次数: 0

Curcumol reduces lower limb arteriosclerosis in rats by inhibiting human arterial smooth muscle cell activity 姜黄醇通过抑制人体动脉平滑肌细胞活性减轻大鼠下肢动脉硬化症

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-29 DOI: 10.1111/1440-1681.13867

Shengzhuang Yang, Gaosheng Huang, Xiangsen Liang, Yu Sun, Lei Xian

{"title":"Curcumol reduces lower limb arteriosclerosis in rats by inhibiting human arterial smooth muscle cell activity","authors":"Shengzhuang Yang, Gaosheng Huang, Xiangsen Liang, Yu Sun, Lei Xian","doi":"10.1111/1440-1681.13867","DOIUrl":"https://doi.org/10.1111/1440-1681.13867","url":null,"abstract":"Cardiovascular diseases, particularly those involving arterial stenosis and smooth muscle cell proliferation, pose significant health risks. This study aimed to investigate the therapeutic potential of curcumol in inhibiting platelet-derived growth factor-BB (PDGF-BB)-induced human aortic smooth muscle cell (HASMC) proliferation, migration and autophagy. Using cell viability assays, 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays and Western Blot analyses, we observed that curcumol effectively attenuated PDGF-BB-induced HASMC proliferation and migration in a concentration-dependent manner. Furthermore, curcumol mitigated PDGF-BB-induced autophagy, as evidenced by the downregulation of LC3-II/LC3-I ratio and upregulation of P62. In vivo experiments using an arteriosclerosis obliterans model demonstrated that curcumol treatment significantly ameliorated arterial morphology and reduced stenosis. Additionally, curcumol inhibited the activity of the KLF5/COX2 axis, a key pathway in vascular diseases. These findings suggest that curcumol has the potential to serve as a multi-target therapeutic agent for vascular diseases.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140814298","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}

引用次数: 0

N6-methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16-infected cervical squamous cell carcinoma 由 METTL14/IGF2BP3 介导的 FSCN1 上的 N6-甲基腺苷甲基化是人类乳头瘤病毒 16 型感染宫颈鳞状细胞癌的诱因之一

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-28 DOI: 10.1111/1440-1681.13864

Qingqing Tian, Juqing Huang, Qin Zhang, Jufen Zhao

{"title":"N6-methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16-infected cervical squamous cell carcinoma","authors":"Qingqing Tian, Juqing Huang, Qin Zhang, Jufen Zhao","doi":"10.1111/1440-1681.13864","DOIUrl":"https://doi.org/10.1111/1440-1681.13864","url":null,"abstract":"Human papillomavirus (HPV) infection has been reported to be associated with N6-methyladenosine (m6A) modification in cancers. However, the underlying mechanism by which m6A methylation participates in HPV-related cervical squamous cell carcinoma (CSCC) remains largely unclear. In this study, we observed that m6A regulators methyltransferase like protein (METTL14) and insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) were upregulated in HPV-positive CSCC tissues and cell lines, and their high expression predicted poor prognosis for HPV-infected CSCC patients. Cellular functional experiments verified that HPV16 oncogenes E6/E7 upregulated the expression of METTL14 and IGF2BP3 to promote cell proliferation and epithelial mesenchymal transition of CSCC cells. Next, we found that E6/E7 stabilized fascin actin-bundling protein 1 (FSCN1) mRNA and elevated FSCN1 expression in CSCC cells through upregulating METTL14/IGF2BP3-mediated m6A modification, and FSCN1 expression was also validated to be positively associated with worse outcomes of HPV-positive CSCC patients. Finally, HPV16-positive CSCC cell lines SiHa and CaSki were transfected with knockdown vector for E6/E7 or METTL14/IGF2BP3 and overexpressing vector for FSCN1, and functional verification experiments were performed through using MTT assay, flow cytometry, wound healing assay and tumour formation assay. Results indicated that knockdown of E6/E7 or METTL14/IGF2BP3 suppressed cell proliferation, migration and tumorigenesis, and accelerated cell apoptosis of HPV-positive CSCC cells. Their tumour-suppressive effects were abolished through overexpressing FSCN1. Overall, HPV E6/E7 advanced CSCC development through upregulating METTL14/IGF2BP3-mediated FSCN1 m6A modification.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808155","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}

引用次数: 0

A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract 一只自发性高血糖猴出现认知障碍、神经功能紊乱和白内障

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-22 DOI: 10.1111/1440-1681.13863

Hongdi Huang, Jianglin Pu, Yufang Zhou, Yang Fan, Yali Zhang, Yanling Li, Yangzhuo Chen, Yun Wang, Xiaomei Yu, Bulgin Dmitry, Zhu Zhou, Jianhong Wang

{"title":"A spontaneous hyperglycaemic cynomolgus monkey presents cognitive deficits, neurological dysfunction and cataract","authors":"Hongdi Huang, Jianglin Pu, Yufang Zhou, Yang Fan, Yali Zhang, Yanling Li, Yangzhuo Chen, Yun Wang, Xiaomei Yu, Bulgin Dmitry, Zhu Zhou, Jianhong Wang","doi":"10.1111/1440-1681.13863","DOIUrl":"https://doi.org/10.1111/1440-1681.13863","url":null,"abstract":"Chronic hyperglycaemia is a chief feature of diabetes mellitus and complicates with many systematic anomalies. Non-human primates (NHPs) are excellent for studying hyperglycaemia or diabetes and associated comorbidities, but lack behavioural observation. In the study, behavioural, brain imaging and histological analysis were performed in a case of spontaneously hyperglycaemic (HGM) Macaca fascicularis. The results were shown that the HGM monkey had persistent body weight loss, long-term hyperglycaemia, insulin resistance, dyslipidemia, but normal concentrations of insulin, C-peptide, insulin autoantibody, islet cell antibody and glutamic acid decarboxylase antibody. Importantly, an impaired working memory in a delayed response task and neurological dysfunctions were found in the HGM monkey. The tendency for atrophy in hippocampus was observed by magnetic resonance imaging. Lenticular opacification, lens fibres disruptions and vacuole formation also occurred to the HGM monkey. The data suggested that the spontaneous HGM monkey might present diabetes-like characteristics and associated neurobehavioral anomalies in this case. This study first reported cognitive deficits in a spontaneous hyperglycaemia NHPs, which might provide evidence to use macaque as a promising model for translational research in diabetes and neurological complications.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140633850","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}

引用次数: 0

Association between dietary inflammation index and inflammatory bowel disease in adults: Results from National Health and Nutrition Examination Survey 2009–2010 成人膳食炎症指数与炎症性肠病之间的关系：2009-2010 年全国健康与营养调查的结果

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-21 DOI: 10.1111/1440-1681.13859

Jing-yi Zhu, Xiao-ru Sun, Mu-yun Liu, Chang Sun

{"title":"Association between dietary inflammation index and inflammatory bowel disease in adults: Results from National Health and Nutrition Examination Survey 2009–2010","authors":"Jing-yi Zhu, Xiao-ru Sun, Mu-yun Liu, Chang Sun","doi":"10.1111/1440-1681.13859","DOIUrl":"https://doi.org/10.1111/1440-1681.13859","url":null,"abstract":"Previous study has demonstrated that the Dietary Inflammation Index (DII) played a role in the risk of inflammatory bowel disease (IBD), however, the prevalence and risk factors for IBD are distinct across locations and groups, and therefore, the findings are debatable and warrant further investigation. A total of 4363 participants were calculated in the National Health and Nutrition Examination Survey (NHANES) 2009 to 2010, of whom 1.21% self-reported a history of IBD. DII values were performed as a good predictor of dietary inflammation based on data from two 24-h dietary reviews in the NHANES database. Comparing the multifarious effects along with variations of the whole population by grouping populations according to DII quartiles, dietary inflammation levels increased progressively from DII quartile 1(Q1) to quartile 4(Q4). The association between DII and IBD was tested with multi-variable logistic regression models, subgroup analyses and weighted generalized additive models. Participants in the Q4 group showed the highest levels of C-reactive protein and reduced haemoglobin and albumin levels. Logistic regression confirmed the odds ratios (95% confidence intervals) of IBD for DII were 0.99 (0.86, 1.15), 0.97 (0.84, 1.13) and 0.80 (0.66, 0.98) in models 1, 2 and 3, respectively. The negative correlation between DII and IBD among United States adults from the NHANES database became increasingly apparent as covariates were adjusted. Subgroup analyses and smoothed curve fitting confirmed the inverse results. The study revealed that DII was correlated with the overall physical well-being of participants. However, there was no significant association between DII and IBD.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140631991","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}

引用次数: 0

Correction to “GSK3β inhibitor TDZD8 ameliorates brain damage through both ROS scavenging and inhibition of apoptosis in hyperglycemic subarachnoid haemorrhage rats” 对 "GSK3β抑制剂TDZD8通过清除高血糖蛛网膜下腔出血大鼠体内的ROS和抑制细胞凋亡改善脑损伤 "的更正

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-04-18 DOI: 10.1111/1440-1681.13853

引用次数: 0