Clinical and Experimental Pharmacology and Physiology最新文献

{"title":"Attenuation of renal fibrosis in mice due to lack of bombesin receptor-activated protein homologue","authors":"Zhi Peng,&nbsp;Hui Wang,&nbsp;Jiaoyun Zheng,&nbsp;Hui Chen,&nbsp;Jie Wang,&nbsp;Horst Christian Weber,&nbsp;Lin Yuan,&nbsp;Xiaoqun Qin,&nbsp;Yang Xiang,&nbsp;Chi Liu,&nbsp;Ming Ji,&nbsp;Huijun Liu,&nbsp;Xiangping Qu","doi":"10.1111/1440-1681.13916","DOIUrl":"10.1111/1440-1681.13916","url":null,"abstract":"<p>Bombesin receptor-activated protein (BRAP), encoded by the <i>C6orf89</i> gene in humans, is expressed in various cells with undefined functions. <i>BC004004</i>, the mouse homologue of <i>C6orf89</i>, has been shown to play a role in bleomycin-induced pulmonary fibrosis through the use of a <i>BC004004</i> gene knockout mouse (<i>BC004004</i>^−/−). In this study, we investigated the potential involvement of BRAP in renal fibrosis using two mouse models: unilateral ureteral obstruction (UUO) and type 2 diabetes mellitus induced by combination of a high-fat diet (HFD) and streptozocin (STZ). BRAP or its homologue was expressed in tubular epithelial cells (TECs) in the kidneys of patients with chronic kidney disease (CKD) and in <i>BC004004</i>^+/+ mice. Compared to control mice, <i>BC004004</i>^−/− mice exhibited attenuated renal injury and renal fibrosis after UUO or after HFD/STZ treatment. Immunohistochemistry and immunoblot analyses of the kidneys of <i>BC004004</i>^+/+ mice after UUO surgery showed a more significant decrease in E-cadherin expression and a more significant increase in both α smooth muscle actin (α-SMA) and vimentin expression compared to <i>BC004004</i>^−/− mice. Additionally, stimulation with transforming growth factor-β1 (TGF-β1) led to a more significant decrease in E-cadherin expression and a more significant increase in α-SMA and vimentin expression in isolated TECs from <i>BC004004</i>^+/+ than in those from <i>BC004004</i>^−/− mice. These results suggest that an enhanced epithelial-mesenchymal transition (EMT) process occurred in TECs in <i>BC004004</i>^+/+ mice during renal injury, which might contribute to renal fibrosis. The loss of the BRAP homologue in <i>BC004004</i>^−/− mice suppressed EMT activation in kidneys and contributed to the suppression of fibrosis during renal injury.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999489","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":"Cancer-associated fibroblast-derived circFARP1 modulates non–small cell lung cancer invasion and metastasis through the circFARP1/miR-338-3p/SOX4 axis","authors":"Wailong Zou,&nbsp;Yulin Li,&nbsp;Jia Zhang,&nbsp;Rui Yang,&nbsp;Yaxin Yan,&nbsp;Xin Zhang,&nbsp;Lei Yan,&nbsp;Zhe Zhang,&nbsp;Xinjun Zhang,&nbsp;Jichao Chen","doi":"10.1111/1440-1681.13914","DOIUrl":"10.1111/1440-1681.13914","url":null,"abstract":"<p>The pleiotropic effect of cancer-associated fibroblasts (CAFs) on tumour progression depends on the environment. circFARP1 is critical for CAFs-induced gemcitabine (GEM) resistance in pancreatic cancer. Its specific role and mechanism in non–small cell lung cancer (NSCLC) have not been reported yet. We prepared a cancer-associated fibroblasts-conditioned medium (CAF-CM) to incubate the A549 cells. Quantitative real-time polymerase chain reaction was used to detect RNA levels. We detected protein expression by immunohistochemistry, immunocytochemistry, western blot and immunofluorescence. We also detected the targeting impact between circFARP1, miR-338-3p and SRY-box transcription factor 4 (SOX4) by using dual-luciferase reporter and RNA pull-down assays. We determined cell proliferation, migration and invasion capabilities through Cell Counting Kit-8 and transwell assays. In addition, we measured tumour volume and weight in vivo by establishing a xenograft tumour model. CircFARP1 levels were remarkably high in the CAFs. The transfection experiments found that circFARP1 downregulation in CAFs caused migration, proliferation and invasion inhibition of CAFs and A549 cells, whereas inhibiting miR-38-3p or overexpressing SOX4 in CAFs could significantly reverse the inhibition. In vivo study in nude mice confirmed that CAFs could promote NSCLC tumour growth and knockdown of circFARP1 could inhibit tumour growth of NSCLC, whereas miR-38-3p downregulation or SOX4 overexpression could significantly reverse the inhibition. circFARP1 promotes NSCLC development by stimulating miR-338-3p/SOX4 signalling axis to regulate CAFs.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 10","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975234","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":"Down-regulation of CYTL1 attenuates bleomycin-induced pulmonary fibrosis in mice by inhibiting M2 macrophage polarization via the TGF-β/CCN2 axis","authors":"Yan Wang,&nbsp;Chenxi Liu,&nbsp;Yi Xie,&nbsp;Xiaomei Li","doi":"10.1111/1440-1681.13913","DOIUrl":"10.1111/1440-1681.13913","url":null,"abstract":"<p>Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by chronic inflammation, lung tissue fibrotic changes and impaired lung function. Pulmonary fibrosis 's pathological process is thought to be influenced by macrophage-associated phenotypes. IPF treatment requires specific targets that target macrophage polarization. Cytokine-like 1(CYTL1) is a secreted protein with multiple biological functions first discovered in CD34⁺ haematopoietic cells. However, its possible effects on IPF progression remain unclear. This study investigated the role of CYTL1 in IPF progression in a bleomycin-induced lung injury and fibrosis model. In bleomycin-induced mice, CYTL1 is highly expressed. Moreover, CYTL1 ablation alleviates lung injury and fibrosis in vivo. Further, downregulating CYTL1 reduces macrophage M2 polarization. Mechanically, CYTL1 regulates transforming growth factor β (TGF-β)/connective tissue growth factor (CCN2) axis and inhibition of TGF-β pathway alleviates bleomycin-induced lung injury and fibrosis. In conclusion, highly expressed CYTL1 inhibits macrophage M2 polarization by regulating TGF-β/CCN2 expression, alleviating bleomycin-induced lung injury and fibrosis. CYTL1 could, therefore, serve as a promising IPF target.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892948","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":"Dihydromyricetin protects sevoflurane-induced mitochondrial dysfunction in HT22 hippocampal cells","authors":"Xinyan Wang,&nbsp;Haoyi Li,&nbsp;Dongchao Qu","doi":"10.1111/1440-1681.13912","DOIUrl":"10.1111/1440-1681.13912","url":null,"abstract":"<p>Sevoflurane (Sev) is a commonly used inhalation anaesthetic that has been shown to cause hippocampus dysfunction through multiple underlying molecular processes, including mitochondrial malfunction, oxidative stress and inflammation. Dihydromyricetin (DHM) is a 2,3-dihydroflavonoid with various biological properties, such as anti-inflammation and anti-oxidative stress. The purpose of this study was to investigate the effect of DHM on Sev-induced neuronal dysfunction. HT22 cells were incubated with 10, 20 and 30 μM of DHM for 24 h, and then stimulated with 4% Sev for 6 h. The effects and mechanism of DHM on inflammation, oxidative stress and mitochondrial dysfunction were explored in Sev-induced HT22 cells by Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, colorimetric detections, detection of the level of reactive oxygen species (ROS), mitochondrial ROS and mitochondrial membrane potential (MMP), immunofluorescence and western blotting. Our results showed that DHM increased Sev-induced cell viability of HT22 cells. Pretreatment with DHM attenuated apoptosis, inflammation, oxidative stress and mitochondrial dysfunction in Sev-elicited HT22 cells by remedying the abnormality of the indicators involved in these progresses, including apoptosis rate, the cleaved-caspase 3 expression, as well as the level of tumour necrosis factor α, interleukin (IL)-1β, IL-6, malondialdehyde, superoxide dismutase, catalase, ROS, mitochondrial ROS and MMP. Mechanically, pretreatment with DHM restored the Sev-induced the expression of SIRT1/FOXO3a pathway in HT22 cells. Blocking of SIRT1 counteracted the mitigatory effect of DHM on apoptosis, inflammation, oxidative stress and mitochondrial dysfunction in Sev-elicited HT22 cells. Collectively, pretreatment with DHM improved inflammation, oxidative stress and mitochondrial dysfunction via SIRT1/FOXO3a pathway in Sev-induced HT22 cells.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892947","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: High glucose facilitates cell cycle arrest of rat bone marrow multipotent adult progenitor cells through TGF-β1 and ERK1/2 signaling without change in Oct-4 expression","authors":"","doi":"10.1111/1440-1681.13908","DOIUrl":"10.1111/1440-1681.13908","url":null,"abstract":"<p>\u0000 <span>M. Luo</span>, <span>Z. Liu</span>, <span>H. Hao</span>, <span>T. Lu</span>, <span>M. Chen</span>, <span>M. Lei</span>, <span>C.M. Verfaillie</span>, and <span>Z. Liu</span>, “ <span>High Glucose Facilitates Cell Cycle Arrest of Rat Bone Marrow Multipotent Adult Progenitor Cells through Transforming Growth Factor-β1 and Extracellular Signal-Regulated Kinase 1/2 Signalling without Changing Oct4 Expression</span>,” <i>Clinical and Experimental Pharmacology and Physiology</i> <span>39</span>, no. <span>10</span> (<span>2012</span>): <span>843</span>-<span>851</span>. https://doi.org/10.1111/j.1440-1681.2012.05747.x\u0000 </p><p>This Expression of Concern is for the above article, published online on 14 July 2012, in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Yang Yang, and the Publisher, John Wiley &amp; Sons Australia, Ltd. The Expression of Concern has been agreed due to concerns raised by a third party after publication regarding the similarity of certain blots in Figures 2 and 3 and the underlying data that they represent. The authors did not respond to multiple requests for the original data. The journal is issuing this Expression of Concern because the concerns regarding the integrity of the data and the results presented cannot be resolved.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792003","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":"Oxycodone attenuates lipopolysaccharide-induced myocardial injury by inhibiting inflammation, oxidation and pyroptosis via Nrf2/HO-1 signalling pathway","authors":"Yanting Wang,&nbsp;Wei Feng,&nbsp;Shaona Li,&nbsp;Cuicui Liu,&nbsp;Lili Jia,&nbsp;Pei Wang,&nbsp;Linlin Li,&nbsp;Hongyin Du,&nbsp;Wenli Yu","doi":"10.1111/1440-1681.13910","DOIUrl":"10.1111/1440-1681.13910","url":null,"abstract":"<p>Myocardial injury and cardiovascular dysfunction are the most common complications of sepsis, and effective therapeutic candidate is still lacking. This study aims to investigate the protective effect of oxycodone in myocardial injury of lipopolysaccharide-induced sepsis and its related signalling pathways. Wild-type and nuclear factor erythroid 2-related factor 2 (Nrf2)-knockout mice, as well as H9c2 cardiomyocytes cultures treated with lipopolysaccharide (LPS) were used as models of septic myocardial injury. H9c2 cardiomyocytes culture showed that oxycodone protected cells from pyroptosis induced by LPS. Mice model confirmed that oxycodone pretreatment significantly attenuated myocardial pathological damage and improved cardiac function demonstrated by increased ejection fraction (EF) and fractional shortening (FS), as well as decreased cardiac troponin I (cTnI) and creatine kinase isoenzymes MB (CK-MB). Oxycodone also reduced the levels of inflammatory factors and oxidative stress damage induced by LPS, which involves pyroptosis-related proteins including: Nod-like receptor protein 3 (NLRP3), Caspase 1, Apoptosis-associated speck-like protein contain a CARD (ASC), and Gasdermin D (GSDMD). These changes were mediated by Nrf2 and heme oxygenase-1 (HO-1) because Nrf2-knockout mice or Nrf2 knockdown in H9c2 cells significantly reversed the beneficial effect of oxycodone on oxidative stress, inflammatory responses and NLRP3-mediated pyroptosis. Our findings yielded that oxycodone therapy reduces LPS-induced myocardial injury by suppressing NLRP3-mediated pyroptosis via the Nrf2/HO-1 signalling pathway in vivo and in vitro.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787418","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":"Quercetin-4′-O-β-D-glucopyranoside inhibits podocyte injury by SIRT5-mediated desuccinylation of NEK7","authors":"Menghua Wu,&nbsp;Xiaoli Ye","doi":"10.1111/1440-1681.13909","DOIUrl":"10.1111/1440-1681.13909","url":null,"abstract":"<p>Diabetic kidney disease (DKD) is a complication of diabetic mellitus. New treatments need to be developed. This study aimed to investigate the effects of quercetin-4′-O-β-D-glucopyranoside (QODG) on podocyte injury. Podocytes were cultured in high glucose (HG) medium, treated with QODG, and overexpressing or knocking down SIRT5. Oxidative stress indicators were assessed using corresponding kits. Pyroptosis was detected by flow cytometry and western blot analysis. Succinylation modification was detected using immunoprecipitation (IP) and western blot analysis. The interaction between NEK7 and NLRP3 was determined by co-IP. The results indicated that QODG inhibited oxidative stress and pyroptosis of podocytes induced by HG. Besides, QODG suppressed succinylation levels in HG-induced podocytes, with the upregulation of SIRT5. Knockdown of SIRT5 reversed the effects of QODG on oxidative stress and pyroptosis. Moreover, SIRT5 inhibited the succinylation of NEK7 and the interaction between NLRP3 and NEK7. In conclusion, QODG upregulates SIRT5 to inhibit the succinylation modification of NEK7, impedes the interaction between NEK7 and NLRP3, and then inhibits the pyroptosis and oxidative stress injury of podocytes under HG conditions. The findings suggested that QODG has the potential to treat DKD and explore a novel underlying mechanism of QODG function.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747493","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":"Exploring the bidirectional causal associations between pain and circulating inflammatory proteins: A Mendelian randomization study","authors":"Yu Wang,&nbsp;Wenyu Zhou,&nbsp;Faqiang Zhang,&nbsp;Juan Wei,&nbsp;Sheng Wang,&nbsp;Keting Min,&nbsp;Yuanli Chen,&nbsp;Hao Yang,&nbsp;Xin Lv","doi":"10.1111/1440-1681.13905","DOIUrl":"10.1111/1440-1681.13905","url":null,"abstract":"<p>Multisite chronic pain (MCP) and site-specific chronic pain (SSCP) may be influenced by circulating inflammatory proteins, but the causal relationship remains unknown. To overcome this limitation, two-sample bidirectional Mendelian randomization (MR) analysis was used to analyse data for 91 circulating inflammatory proteins, MCP and SSCP encompassing headache, back pain, shoulder pain, hip pain, knee pain, stomach abdominal pain and facial pain. The primary MR method used was inverse variance weighting, sensitivity analyses included weighted median, MR pleiotropy residual sum and outlier and the Egger intercept method. Heterogeneity was also detected using Cochrane's Q test and leave-one-out analyses. Finally, a causal relationship between 29 circulating inflammatory proteins and chronic pain was identified. Among these proteins, 14 exhibited a protective effect, including MCP (T-cell surface glycoprotein cluster of differentiation 5), headache (4E-binding protein 1 [4EBP1], cluster of differentiation 40, cluster of differentiation 6 and C-X-C motif chemokine [CXCL] 11), back pain (leukaemia inhibitory factor), shoulder pain (fibroblast growth factor [FGF]-5 and interleukin [IL]-18R1), stomach abdominal pain (tumour necrosis factor [TNF]-α), hip pain (CXCL1, IL-20 and signalling lymphocytic activation molecule 1) and knee pain (IL-7 and TNF-β). Additionally, 15 proteins were identified as risk factors for MCP and SSCP: MCP (colony-stimulating factor 1, human glial cell line-derived neurotrophic factor and IL-17C), headache (fms-related tyrosine kinase 3 ligand, IL-20 receptor subunit α [IL-20RA], neurotrophin-3 and tumour necrosis factor receptor superfamily member 9), facial pain (CXCL1), back pain (TNF), shoulder pain (IL-17C and matrix metalloproteinase-10), stomach abdominal pain (IL-20RA), hip pain (C-C motif chemokine 11/eotaxin-1 and tumour necrosis factor ligand superfamily member 12) and knee pain (4EBP1). Importantly, in the opposite direction, MCP and SSCP did not exhibit a significant causal impact on circulating inflammatory proteins. Our study identified potential causal influences of various circulating inflammatory proteins on MCP and SSCP and provided promising treatments for the clinical management of MCP and SSCP.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533791","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":"Comparison of disease-modifying anti-rheumatic drugs and hyperbaric oxygen therapy in the experimental model of rheumatoid arthritis in rats","authors":"Mohamad Hallak,&nbsp;Ahmet Inal,&nbsp;Mehmet Akif Baktir,&nbsp;Ayhan Atasever","doi":"10.1111/1440-1681.13906","DOIUrl":"10.1111/1440-1681.13906","url":null,"abstract":"<p>In this study, we wanted to investigate the effectiveness of combining disease-modifying anti-rheumatic drugs (DMARD) with hyperbaric oxygen therapy (HBOT) in reducing inflammation in a rheumatoid arthritis (RA) model using rats. We divided 56 male Sprague–Dawley rats into seven groups and induced RA using complete Freund's adjuvant. Some groups received HBOT, whereas others were given etanercept or leflunomide. We started the treatment on the 10th day after inducing RA and continued it for 18 days. To evaluate the effectiveness of the treatments, we measured paw swelling and used X-rays to examine the joints before and after the treatment. We also analysed the levels of two inflammatory markers, tumour necrosis factor (TNF)-α and interleukin (IL)-1β, using an enzyme-linked immunosorbent assay. Additionally, we conducted histological analysis and assessed the expressions of anti-IL-1β and anti-TNF-α antibodies. All the treatment groups showed a significant decrease in arthritis scores, paw swelling and levels of TNF-α and IL-1β. The X-ray images revealed improvements in joint structure, and the histopathological analysis showed reduced inflammation and collagen abnormalities. Combining DMARD with HBOT had similar effects to individual therapies, suggesting a cost-effective and potentially safer approach for improving outcomes in rats with RA.</p>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533769","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":"Establishment of diagnostic model and identification of diagnostic markers between liver cancer and cirrhosis based on multi-chip and machine learning","authors":"Tianpeng Yang,&nbsp;Lu Huang,&nbsp;Jiale He,&nbsp;Lihong Luo,&nbsp;Weiting Guo,&nbsp;Huajian Chen,&nbsp;Xinyue Jiang,&nbsp;Li Huang,&nbsp;Shumei Ma,&nbsp;Xiaodong Liu","doi":"10.1111/1440-1681.13907","DOIUrl":"10.1111/1440-1681.13907","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533770","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}