International Journal of Experimental Pathology最新文献

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Interaction between mitochondrial homeostasis and barrier function in lipopolysaccharide-induced endothelial cell injury 脂多糖诱导的内皮细胞损伤中线粒体稳态与屏障功能的相互作用。
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-10-12 DOI: 10.1111/iep.12495
Weiwei Zhu, Xiaojing Liu, Liqing Luo, Xiao Huang, Xiaozhi Wang
{"title":"Interaction between mitochondrial homeostasis and barrier function in lipopolysaccharide-induced endothelial cell injury","authors":"Weiwei Zhu,&nbsp;Xiaojing Liu,&nbsp;Liqing Luo,&nbsp;Xiao Huang,&nbsp;Xiaozhi Wang","doi":"10.1111/iep.12495","DOIUrl":"10.1111/iep.12495","url":null,"abstract":"<p>This study aimed to investigate the effects of mitochondrial homeostasis on lipopolysaccharide (LPS)-induced endothelial cell barrier function and the mechanisms that underlie these effects. Cells were treated with LPS or oligomycin (mitochondrial adenosine triphosphate synthase inhibitor) and the mitochondrial morphology, mitochondrial reactive oxygen species (mtROS), and mitochondrial membrane potential (ΔΨm) were evaluated. Moreover, the shedding of glycocalyx-heparan sulphate (HS), the levels of HS-specific degrading enzyme heparanase (HPA), and the expression of occludin and zonula occludens (ZO-1) of Tight Junctions (TJ)s, which are mediated by myosin light chain phosphorylation (p-MLC), were assessed. Examining the changes in mitochondrial homeostasis showed that adding heparinase III, which is an exogenous HPA, can destroy the integrity of glycocalyx. LPS simultaneously increased mitochondrial swelling, mtROS, and ΔΨm. Without oligomycin effects, HS, HPA levels, and p-MLC were found to be elevated, and the destruction of occludin and ZO-1 increased. Heparinase III not only damaged the glycocalyx by increasing HS shedding but also increased mitochondrial swelling and mtROS and decreased ΔΨm. Mitochondrial homeostasis is involved in LPS-induced endothelial cell barrier dysfunction by aggravating HPA and p-MLC levels. In turn, the integrated glycocalyx protects mitochondrial homeostasis.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"272-282"},"PeriodicalIF":3.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41201020","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
Histomorphometric lung density evaluation of Immulina treatment using a murine influenza pneumonia model 使用小鼠流感肺炎模型对螺旋藻治疗的组织形态计量学肺密度评估。
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-09-26 DOI: 10.1111/iep.12493
Floyd D. Wilson, Tahir M. Mir, Mohammad K. Ashfaq, Jin Zhang, Nirmal D. Pugh, Ikhlas A. Khan, Lanny W. Pace, Frederic J. Hoerr
{"title":"Histomorphometric lung density evaluation of Immulina treatment using a murine influenza pneumonia model","authors":"Floyd D. Wilson,&nbsp;Tahir M. Mir,&nbsp;Mohammad K. Ashfaq,&nbsp;Jin Zhang,&nbsp;Nirmal D. Pugh,&nbsp;Ikhlas A. Khan,&nbsp;Lanny W. Pace,&nbsp;Frederic J. Hoerr","doi":"10.1111/iep.12493","DOIUrl":"10.1111/iep.12493","url":null,"abstract":"<p>Histomorphometric lung density measurements were used to evaluate the effects of Immulina on mouse pneumonia. Mice were intra-nasally exposed to H1N1 influenza virus at a dose of 5 × 10<sup>4</sup> PFU/50 μL/mouse. Lung density was measured using the NIH ImageJ software program. Density values were compared to semiquantitative pneumonia severity scores. Lung photomicrographs were evaluated at 25-×, 40-× and 400-× magnification. The study included viral inoculated controls (IC) and non-inoculated controls (NC) and mice either treated or not treated with Immulina. Three doses of Immulina were included (25, 50 or 100 mg/kg) and administered using 3 protocols: prophylactic treatment (P), prodromal treatment (PD) and therapeutic treatment (TH) (note that in most of the evaluations of the data for the three treatment protocols were combined). Groups of mice were evaluated on days 3, 5, 7, 10 and 15 following exposure. The occurrence of “digital pneumonia” (DP) was defined as a density measurement above the 95% confidence limit of the corresponding NC values. A significant reduction in the occurrence of DP with Immulina treatment at the higher doses compared to IC was seen as early as day 3 and persisted up to day 15. There were also statistically significant dose-variable reductions in lung density in response to Immulina. The study suggests early administration of Immulina (P or PD protocols) may enhance resistance against influenza-induced viral pneumonia. A moderate correlation between pneumonia severity scores and lung density was observed for the 25-× and 40-× images (<i>R</i> = 0.56 and 0.53 respectively), and a strong correlation (<i>R</i> = 0.68) for 400-× images.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"283-291"},"PeriodicalIF":3.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123718","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
British Society for Matrix Biology Spring Meeting 2023: Vascular Inflammation and the Extracellular Matrix 英国基质生物学学会2023年春季会议:血管炎症和细胞外基质
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-09-13 DOI: 10.1111/iep.12486
{"title":"British Society for Matrix Biology Spring Meeting 2023: Vascular Inflammation and the Extracellular Matrix","authors":"","doi":"10.1111/iep.12486","DOIUrl":"10.1111/iep.12486","url":null,"abstract":"","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 5","pages":"A1-A10"},"PeriodicalIF":3.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264051","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
Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p 通过ATF3/CSF1轴抑制炎症和M2巨噬细胞浸润:miR-27a-3p的作用
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-08-28 DOI: 10.1111/iep.12490
Bin Zhou, Yan Xu, Li Xu, Yi Kong, Kang Li, Bolin Chen, Jia Li
{"title":"Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p","authors":"Bin Zhou,&nbsp;Yan Xu,&nbsp;Li Xu,&nbsp;Yi Kong,&nbsp;Kang Li,&nbsp;Bolin Chen,&nbsp;Jia Li","doi":"10.1111/iep.12490","DOIUrl":"10.1111/iep.12490","url":null,"abstract":"<p>Non-small cell lung cancer (NSCLC) imposes a significant economic burden on patients and society due to its low overall cure and survival rates. Tumour-associated macrophages (TAM) affect tumour development and may be a novel therapeutic target for cancer. We collected NSCLC and tumour-adjacent tissue samples. Compared with the tumour-adjacent tissues, the Activation Transcription Factor 3 (ATF3) and Colony Stimulating Factor 1 (CSF-1) were increased in NSCLC tissues. Levels of ATF3 and CSF-1 were identified in different cell lines (HBE, A549, SPC-A-1, NCI-H1299 and NCI-H1795). Overexpression of ATF3 in A549 cells increased the expression of CD68, CD206 and CSF-1. Moreover, levels of CD206, CD163, IL-10 and TGF-β increased when A549 cells were co-cultured with M0 macrophages under the stimulation of CSF-1. Using the starbase online software prediction and dual-luciferase assays, we identified the targeting between miR-27a-3p and ATF3. Levels of ATF3, CSF-1, CD206, CD163, IL-10 and TGF-β decreased in the miR-27a mimics, and the tumour growth was slowed in the miR-27a mimics compared with the mimics NC group. Overall, the study suggested that miR-27a-3p might inhibit the ATF3/CFS1 axis, regulate the M2 polarization of macrophages and ultimately hinder the progress of NSCLC. This research might provide a new therapeutic strategy for NSCLC.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"292-303"},"PeriodicalIF":3.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10139769","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
Optimization of decellularization methods using human small intestinal submucosa for scaffold generation in regenerative medicine 人小肠粘膜下层脱细胞制备再生医学支架方法的优化。
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-08-25 DOI: 10.1111/iep.12492
Shumei Mineta, Shunji Endo, Tomio Ueno
{"title":"Optimization of decellularization methods using human small intestinal submucosa for scaffold generation in regenerative medicine","authors":"Shumei Mineta,&nbsp;Shunji Endo,&nbsp;Tomio Ueno","doi":"10.1111/iep.12492","DOIUrl":"10.1111/iep.12492","url":null,"abstract":"<p>Porcine small intestinal submucosa, despite its successful use as a scaffold in regenerative medicine, has innate biomechanical heterogeneity. In this study, we hypothesized that human small intestinal submucosa could be a viable alternative bio-scaffold. For the first time, we characterize submucosal extraction from human small intestine and examine appropriate decellularization methods. In total, 16 human small intestinal submucosal samples were obtained and decellularized using three reported methods of porcine decellularization: Abraham, Badylak, and Luo. For each method, four specimens were decellularized. The remaining four specimens were designated as non-decellularized. We measured the amount of residual DNA and growth factors in decellularized human intestinal samples. Additionally, decellularized human small intestinal submucosa was co-cultured with mouse bone marrow-derived mesenchymal stem cells to examine mesenchymal stem cell survival and proliferation. The reference value for the amount of residual DNA deemed appropriate in decellularized tissue was established as 50 ng/mg of extracellular matrix dry weight or less. Abraham's method most successfully met this criterion. Measurement of residual growth factors revealed low levels observed in samples decellularized using the Abraham and Badylak methods. Co-culture of each small intestinal submucosal sample with mouse bone marrow-derived mesenchymal stem cells confirmed viable cell survival and proliferation in samples derived using protocols by Abraham and Badylak. Abraham's method most successfully met the criteria for efficient tissue decellularization and cell viability and proliferation. Thus, we consider this method most suitable for decellularization of human small intestinal submucosa.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"313-320"},"PeriodicalIF":3.0,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10071861","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
Panx1 knockout promotes preneoplastic aberrant crypt foci development in a chemically induced model of mouse colon carcinogenesis 在化学诱导的小鼠结肠癌模型中,Panx1基因敲除促进肿瘤前异常隐窝灶的发展。
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-08-18 DOI: 10.1111/iep.12491
Sara Gomes Espírito Santo, Tereza Cristina Da Silva, Bruno Cogliati, Luís Fernando Barbisan, Guilherme Ribeiro Romualdo
{"title":"Panx1 knockout promotes preneoplastic aberrant crypt foci development in a chemically induced model of mouse colon carcinogenesis","authors":"Sara Gomes Espírito Santo,&nbsp;Tereza Cristina Da Silva,&nbsp;Bruno Cogliati,&nbsp;Luís Fernando Barbisan,&nbsp;Guilherme Ribeiro Romualdo","doi":"10.1111/iep.12491","DOIUrl":"10.1111/iep.12491","url":null,"abstract":"<p>Colorectal cancer, which is the third leading cause of cancer-related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel-forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1<sup>−/−</sup>) on the early events of chemically induced colon carcinogenesis in mouse. Wild type (WT) and Panx1<sup>−/−</sup> female C57BL6J mice were submitted to a chemically induced model of colon carcinogenesis by receiving six intraperitoneal administrations of 1,2-dimethylhydrazine (DMH) carcinogen. Animals were euthanized 8 h (week 7) or 30 weeks (week 37) after the last DMH administration in order to evaluate sub-acute colon toxicity outcomes or the burden of ACF, respectively. At week 7, Panx1 genetic ablation increased DMH-induced genotoxicity in peripheral blood cells, malondialdehyde levels in the colon, and apoptosis (cleaved caspase-3) in colonic crypts. Of note, at week 37, Panx1<sup>−/−</sup> animals showed an increase in aberrant crypts (AC), ACF mean number, and ACF multiplicity (AC per ACF) by 56%, 57% and 20%, respectively. In essence, our findings indicate that Panx1 genetic ablation promotes preneoplastic ACF development during chemically induced mouse colon carcinogenesis, and a protective role of Panx1 is postulated.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"304-312"},"PeriodicalIF":3.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396749","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
Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression 通过抑制STAT3的表达,Nek6敲低极化巨噬细胞进入促炎表型
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-07-10 DOI: 10.1111/iep.12489
Xiaoyan Wu, Ke-Qiong Deng, Huan-Huan Cai, Ziyue Zeng, Jian-Lei Cao, Lin Zhang, Zhibing Lu, Wen-Lin Cheng
{"title":"Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression","authors":"Xiaoyan Wu,&nbsp;Ke-Qiong Deng,&nbsp;Huan-Huan Cai,&nbsp;Ziyue Zeng,&nbsp;Jian-Lei Cao,&nbsp;Lin Zhang,&nbsp;Zhibing Lu,&nbsp;Wen-Lin Cheng","doi":"10.1111/iep.12489","DOIUrl":"10.1111/iep.12489","url":null,"abstract":"<p>Recently macrophage polarization has emerged as playing an essential role in the oathogenesis of atherosclerosis, which is the most important underlying process in many types of cardiovascular diseases. Although Nek6 has been reported to be involved in various cellular processes, the effect of Nek6 on macrophage polarization remains unknown. Macrophages exposed to lipopolysaccharide (LPS) or IL-4 were used to establish an in vitro model for the study of regulation of classically (M1) or alternatively (M2) activated macrophage. Bone marrow-derived macrophages (BMDMs) transfected with short hairpin RNA-targeting Nek6 were then in functional studies. We observed that Nek6 expression was decreased in both peritoneal macrophages (PMs) and BMDMs stimulated by LPS. This effect was seen at both mRNA and protein level. The opposite results were obtained after administration of IL-4. Macrophage-specific Nek6 knockdown significantly exacerbated pro-inflammatory M1 polarized macrophage gene expression in response to LPS challenge, but the anti-inflammatory response gene expression that is related to M2 macrophages was attenuated by Nek6 silencing followed by treatment with IL-4. Mechanistic studies exhibited that Nek6 knockdown inhibited the phosphorylated STAT3 expression that mediated the effect on macrophage polarization regulated by AdshNek6. Moreover, decreased Nek6 expression was also observed in atherosclerotic plaques. Collectively, these evidences suggested that Nek6 acts as a crucial site in macrophage polarization, and that this operates in a STAT3-dependent manner.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 5","pages":"237-246"},"PeriodicalIF":3.0,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256930","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
mRNA expression profile reveals differentially expressed genes in splenocytes of experimental autoimmune encephalomyelitis model mRNA表达谱揭示了实验性自身免疫性脑脊髓炎模型脾细胞中差异表达的基因
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-07-10 DOI: 10.1111/iep.12488
Arshad Mehmood, Shuang Song, Xiaochen Du, Hongjing Yan, Xuan Wang, Li Guo, Bin Li
{"title":"mRNA expression profile reveals differentially expressed genes in splenocytes of experimental autoimmune encephalomyelitis model","authors":"Arshad Mehmood,&nbsp;Shuang Song,&nbsp;Xiaochen Du,&nbsp;Hongjing Yan,&nbsp;Xuan Wang,&nbsp;Li Guo,&nbsp;Bin Li","doi":"10.1111/iep.12488","DOIUrl":"10.1111/iep.12488","url":null,"abstract":"<p>Experimental autoimmune encephalomyelitis (EAE) is a mouse model that can be used to investigate aetiology, pathogenesis, and treatment approaches for multiple sclerosis (MS). A novel integrated bioinformatics approach was used to understand the involvement of differentially expressed genes (DEGs) in the spleen of EAE mice through data mining of existing microarray and RNA-seq datasets. We screened differentially expressed mRNAs using mRNA expression profile data of EAE spleens taken from Gene Expression Omnibus (GEO). Functional and pathway enrichment analyses of DEGs were performed by Database for Annotation, Visualization, and Integrated Discovery (DAVID). Subsequently, the DEGs-encoded protein–protein interaction (PPI) network was constructed. The 784 DEGs in GSE99300 A.SW PP-EAE mice spleen mRNA profiles, 859 DEGs in GSE151701 EAE mice spleen mRNA profiles, and 646 DEGs in GSE99300 SJL/J PP-EAE mice spleen mRNA profiles were explored. Functional enrichment of 55 common DEGs among 3 sub-datasets revealed several immune-related terms, such as neutrophil extravasation, leucocyte migration, antimicrobial humoral immune response mediated by an antimicrobial peptide, toll-like receptor 4 bindings, IL-17 signalling pathway, and TGF-beta signalling pathway. In the screening of 10 hub genes, including <i>MPO</i>, <i>ELANE</i>, <i>CTSG</i>, <i>LTF</i>, <i>LCN2</i>, <i>SELP</i>, <i>CAMP</i>, <i>S100A9</i>, <i>ITGA2B</i>, and <i>PRTN3</i>, and in choosing and validating the 5 DEGs, including <i>ANK1</i>, <i>MBOAT2</i>, <i>SLC25A21</i>, <i>SLC43A1</i>, and <i>SOX6</i>, the results showed that <i>SLC43A1</i> and <i>SOX6</i> were significantly decreased in EAE mice spleen. Thus this study offers a list of genes expressed in the spleen that might play a key role in the pathogenesis of EAE.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 5","pages":"247-257"},"PeriodicalIF":3.0,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256925","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: 1
Mechanism of the HIF-1α/VEGF/VEGFR-2 pathway in the proliferation and apoptosis of human haemangioma endothelial cells HIF-1α/VEGF/VEGFR-2通路在人血管瘤内皮细胞增殖和凋亡中的作用机制
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-06-28 DOI: 10.1111/iep.12485
Wenpei Zhang, Lei Sun, Hongxia Gao, Shengquan Wang
{"title":"Mechanism of the HIF-1α/VEGF/VEGFR-2 pathway in the proliferation and apoptosis of human haemangioma endothelial cells","authors":"Wenpei Zhang,&nbsp;Lei Sun,&nbsp;Hongxia Gao,&nbsp;Shengquan Wang","doi":"10.1111/iep.12485","DOIUrl":"10.1111/iep.12485","url":null,"abstract":"<p>Haemangiomas (HAs) are prevalent vascular endothelial cell tumours. With respect to the possible involvement of HIF-1α in HAs, we have explored its role in haemangioma endothelial cell (HemEC) proliferation and apoptosis. shRNA HIF-1α and pcDNA3.1 HIF-α were manipulated into HemECs. HIF-α, VEGF, and VEGFR-2 mRNA and protein levels were assessed by qRT-PCR and Western blotting. Cell proliferation and viability, cell cycle and apoptosis, migration and invasion, and ability to form tubular structures were assessed by colony formation assay, CCK-8, flow cytometry, Transwell assay, and tube formation assay. Cell cycle-related protein levels, and VEGF and VEGFR-2 protein interaction were detected by Western blot and immunoprecipitation assays. An Haemangioma nude mouse model was established by subcutaneous injection of HemECs. Ki67 expression was determined by immunohistochemical staining. HIF-1α silencing suppressed HemEC neoplastic behaviour and promoted apoptosis. HIF-1α facilitated VEGF/VEGFR-2 expression and the VEGF had interacted with VEGFR-2 at protein - protein level. HIF-1α silencing arrested HemECs at G0/G1 phase, diminished Cyclin D1 protein level, and elevated p53 protein level. VEGF overexpression partially abrogated the effects of HIF-1α knockdown on inhibiting HemEC malignant behaviours. Inhibiting HIF-1α in nude mice with HAs repressed tumour growth and Ki67-positive cells. Briefly, HIF-1α regulated HemEC cell cycle through VEGF/VEGFR-2, thus promoting cell proliferation and inhibiting apoptosis.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 5","pages":"258-268"},"PeriodicalIF":3.0,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12485","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10261853","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
A prognostic model based on regulatory T-cell-related genes in gastric cancer: Systematic construction and validation 基于调节性t细胞相关基因的胃癌预后模型:系统构建与验证
IF 3 4区 医学
International Journal of Experimental Pathology Pub Date : 2023-06-23 DOI: 10.1111/iep.12487
Qin Tong, Yingjie Ling
{"title":"A prognostic model based on regulatory T-cell-related genes in gastric cancer: Systematic construction and validation","authors":"Qin Tong,&nbsp;Yingjie Ling","doi":"10.1111/iep.12487","DOIUrl":"10.1111/iep.12487","url":null,"abstract":"<p>Human gastrointestinal tumours have been shown to contain massive numbers of tumour infiltrating regulatory T cells (Tregs), the presence of which are closely related to tumour immunity. This study was designed to develop new Treg-related prognostic biomarkers to monitor the prognosis of patients with gastric cancer (GC). Treg-related prognostic genes were screened from Treg-related differentially expressed genes in GC patients by using Cox regression analysis, based on which a prognostic model was constructed. Then, combined with RiskScore, survival curve, survival status assessment and ROC analysis, these genes were used to verify the accuracy of the model, whose independent prognostic ability was also evaluated. Six Treg-related prognostic genes (CHRDL1, APOC3, NPTX1, TREML4, MCEMP1, GH2) in GC were identified, and a 6-gene Treg-related prognostic model was constructed. Survival analysis revealed that patients had a higher survival rate in the low-risk group. Combining clinicopathological features, we performed univariate and multivariate regression analyses, with results establishing that the RiskScore was an independent prognostic factor. Predicted 1-, 3- and 5-year survival rates of GC patients had a good fit with the actual survival rates according to nomogram results. In addition patients in the low-risk group had higher tumour mutational burden (TMB) values. Gene Set Enrichment Analysis (GSEA) demonstrated that genes in the high-risk group were significantly enriched in pathways related to immune inflammation, tumour proliferation and migration. In general, we constructed a 6-gene Treg-associated GC prognostic model with good prediction accuracy, where RiskScore could act as an independent prognostic factor. This model is expected to provide a reference for clinicians to estimate the prognosis of GC patients.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 5","pages":"226-236"},"PeriodicalIF":3.0,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256903","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
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