International Journal of Experimental Pathology最新文献_第9页

Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets 针对谷氨酸脱羧酶的自身抗体干扰分散大鼠胰岛中葡萄糖刺激的胰岛素分泌

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-03-04 DOI: 10.1111/iep.12437

Varun Kamat, Jared R. Radtke, Qingxun Hu, Wang Wang, Ian R. Sweet, Christiane S. Hampe

{"title":"Autoantibodies directed against glutamate decarboxylase interfere with glucose-stimulated insulin secretion in dispersed rat islets","authors":"Varun Kamat, Jared R. Radtke, Qingxun Hu, Wang Wang, Ian R. Sweet, Christiane S. Hampe","doi":"10.1111/iep.12437","DOIUrl":"10.1111/iep.12437","url":null,"abstract":"Islet autoantibodies, including autoantibodies directed against the 65kDa isoform of glutamate decarboxylase (GAD65Ab), are present in the majority of patients with newly diagnosed type 1 diabetes (T1D). Whereas these autoantibodies are historically viewed as an epiphenomenon of the autoimmune response with no significant pathogenic function, we consider in this study the possibility that they impact the major islet function, namely glucose-stimulated insulin secretion. Two human monoclonal GAD65Ab (GAD65 mAb) (b78 and b96.11) were investigated for uptake by live rat beta cells, subcellular localization and their effect on glucose-stimulated insulin secretion. The GAD65 mAbs were internalized by live pancreatic beta cells, where they localized to subcellular structures in an epitope-specific manner. Importantly, GAD65 mAb b78 inhibited, while GAD65 mAb b96.11 enhanced, glucose-stimulated insulin secretion (GSIS). These opposite effects on GSIS rule out non-specific effects of the antibodies and suggest that internalization of the antibody leads to epitope-specific interaction with intracellular machinery regulating insulin granule release. The most likely explanation for the alteration of GSIS by GAD65 Abs is via changes in GABA release due to inhibition or change in GAD65 enzyme activity. This is the first report indicating an active role of GAD65Ab in the pathogenesis of T1D.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 4","pages":"140-148"},"PeriodicalIF":3.0,"publicationDate":"2022-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9909919","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

Investigation of the effect of metoclopramide on proliferation signal molecules in breast tissue 甲氧氯普胺对乳腺组织增生信号分子影响的研究

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-03-03 DOI: 10.1111/iep.12433

Nurcan Umur, Selda İldan Çalım, Gülce Naz Yazıcı, Seren Gulsen Gurgen

{"title":"Investigation of the effect of metoclopramide on proliferation signal molecules in breast tissue","authors":"Nurcan Umur, Selda İldan Çalım, Gülce Naz Yazıcı, Seren Gulsen Gurgen","doi":"10.1111/iep.12433","DOIUrl":"10.1111/iep.12433","url":null,"abstract":"Metoclopramide (MCP) is a drug that has been widely used in recent years due to its hyperprolactinaemia effect on mothers during breastfeeding. The aim of this study was to investigate the proliferative changes that MCP may cause in the maternal breast tissue. In this study, 18 Wistar albino young–adult breastfeeding mothers with their offspring were divided into three groups: control group, low-dose MCP-applied group and high-dose MCP-applied group. The experiment was carried out during the lactation period and at the end of 21 days. Prolactin, BrdU and Ki-67 breast tissue distributions were evaluated by immunohistochemistry, and tissue levels were evaluated biochemically by the ELISA method. According to ELISA and immunohistochemistry results in breast tissue, there was no significant difference between Ki-67 and BrdU results in all groups. Metoclopramide did not change the expression of proliferation molecules Ki-67 and BrdU in breast tissue. These results suggested that while metoclopramide increases breast proliferation, it does not have the risk of transforming the tissue into a tumour.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 3","pages":"83-89"},"PeriodicalIF":3.0,"publicationDate":"2022-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9547802","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

High-altitude hypoxia-induced rat alveolar cell injury by increasing autophagy 高原缺氧通过增加自噬诱导大鼠肺泡细胞损伤

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-03-02 DOI: 10.1111/iep.12434

Zhen Zhao, Bin Hou, Li Tang, Yaping Wang, Yueqing Zhang, Zhanzhuan Ying, Jie Duo

{"title":"High-altitude hypoxia-induced rat alveolar cell injury by increasing autophagy","authors":"Zhen Zhao, Bin Hou, Li Tang, Yaping Wang, Yueqing Zhang, Zhanzhuan Ying, Jie Duo","doi":"10.1111/iep.12434","DOIUrl":"10.1111/iep.12434","url":null,"abstract":"Autophagy has been implicated in the pathogenesis of various lung diseases. This study aimed to investigate the role of autophagy in lung injury induced by high-altitude hypoxia. Wistar rats were randomized into four groups for exposure to normal altitude or high altitude for 1, 7, 14 and 21 days with no treatment or with the treatment of 1 mg/kg rapamycin or 2 mg/kg 3-methyladenine (3-MA) for consecutive 21 days respectively. In control rats, the alveolar structure was intact with regularly arranged cells. However, inflammatory cell infiltration and shrunk alveoli were observed in rats exposed to hypoxia. Rapamycin treatment led to many shrunken alveoli with a large number of red blood cells in them. In contrast, 3-MA treatment led to almost intact alveoli or only a few shrunken alveoli. Compared to the control group exposure to high-altitude hypoxia for longer periods resulted in the aggravation of the lung injury, the formation of autophagosomes with a double-membrane structure and increased levels of Beclin-1 and LC3-II in alveolar tissues. Rapamycin treatment resulted in significant increase in Beclin-1 and LC3-II levels and further aggravation of alveolar tissue damage, while 3-MA treatment led to opposite effects. In conclusion, exposure to high-altitude hypoxia can induce autophagy of alveolar cells, which may be an important mechanism of high-altitude hypoxia-induced lung injury. The inhibition of autophagy may be a promising therapy strategy for high-altitude hypoxia-induced lung injury.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 4","pages":"132-139"},"PeriodicalIF":3.0,"publicationDate":"2022-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9913225","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

Angiogenesis in patient-derived xenografts of odontogenic myxoma 牙源性黏液瘤患者异种移植物的血管生成

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-02-28 DOI: 10.1111/iep.12431

Juliana Cristina de Souza, Victor Coutinho Bastos, Núbia Braga Pereira, Adriana Abalen Martins Dias, Gleide Fernandes de Avelar, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes

{"title":"Angiogenesis in patient-derived xenografts of odontogenic myxoma","authors":"Juliana Cristina de Souza, Victor Coutinho Bastos, Núbia Braga Pereira, Adriana Abalen Martins Dias, Gleide Fernandes de Avelar, Ricardo Santiago Gomez, Carolina Cavaliéri Gomes","doi":"10.1111/iep.12431","DOIUrl":"10.1111/iep.12431","url":null,"abstract":"Previously, by employing 3D organotypic tissue culture and patient-derived xenograft (PDX) model, oral myxoma response to a MAPK/MEK inhibitor was observed. Gross examination of the tumour fragments obtained after 55 days of PDX grafting revealed increased capsule vascularization. Microscopic analyses showed blood capillaries intermixed with myxoma cells, but the origin of these capillaries, from mice or humans, was not established. This study aimed to investigate whether the endothelial cells observed in the myxoma PDX model are derived from the mouse or from the primary human tumour. Immunohistochemistry was performed on five tumour fragments from the PDX of myxoma after 55 days of implantation in mice. Immunopositivity for antibodies against human (HLA-ABC) and mouse (H2 Db/H2-D1) major histocompatibility complex class I (MHCI) was assessed in the endothelial cells. The endothelial cells in the PDX fragments revealed a membrane staining for the human MHCI protein in the PDX tumour and adjacent connective tissue capsule, indicating that capillaries were derived from the human tumour fragment. Considering the probable human origin of the endothelial cells from capillary blood vessels in the myxoma PDX, we conclude that this PDX model is an interesting model to study myxoma angiogenesis.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"65-69"},"PeriodicalIF":3.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9226372","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

DNA methylation and miRNA expression in colon adenomas compared with matched normal colon mucosa and carcinomas 结肠腺瘤中DNA甲基化和miRNA表达与匹配的正常结肠粘膜和癌的比较

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-02-28 DOI: 10.1111/iep.12432

Mezgebe Gebrekiristos, Joshua Melson, Alice Jiang, Lela Buckingham

{"title":"DNA methylation and miRNA expression in colon adenomas compared with matched normal colon mucosa and carcinomas","authors":"Mezgebe Gebrekiristos, Joshua Melson, Alice Jiang, Lela Buckingham","doi":"10.1111/iep.12432","DOIUrl":"10.1111/iep.12432","url":null,"abstract":"Dysregulation of DNA methylation patterns and non-coding RNA, including miRNAs, has been implicated in colon cancer, and these changes may occur early in the development of carcinoma. In this study, the role of epigenetics as early changes in colon tumorigenesis was examined through paired sample analysis of patient-matched normal, adenoma and carcinoma samples. Global methylation was assessed by genomic 5-methyl cytosine (5-mC) and long interspersed nuclear element-1 (LINE-1) promoter methylation by pyrosequencing. KRAS mutations were also assessed by pyrosequencing. Expression of miRNA, specifically, two microRNA genes—miR-200a and let-7c—was analysed using RT-qPCR. Differences in global methylation in adenomas were not observed, compared with normal tissue. However, LINE-1 methylation was decreased in adenomas (p = .056) and carcinomas (p = .011) compared with normal tissue. Expressions of miRNA, miR-200a and let-7c were significantly higher in adenomas than normal tissues (p = .008 and p = .045 respectively). Thus the significant changes in LINE-1 methylation and microRNA expression in precancerous lesions support an early role for epigenetic changes in the carcinogenic process. Epigenetic characteristics in adenomas may provide potential diagnostic and prognostic therapeutic targets early in cancer development at the adenoma stage.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 3","pages":"74-82"},"PeriodicalIF":3.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9926939","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: 2

Orchestrated expression of vasculogenic mimicry and laminin-5γ2 is an independent prognostic marker in oral squamous cell carcinoma 血管生成模拟和层粘连蛋白-5γ - 2的精心表达是口腔鳞状细胞癌的独立预后标志物

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-02-16 DOI: 10.1111/iep.12430

Depanwita Saha, Debarpan Mitra, Neyaz Alam, Sagar Sen, Saunak Mitra Mustafi, Syamsundar Mandal, Biswanath Majumder, Nabendu Murmu

{"title":"Orchestrated expression of vasculogenic mimicry and laminin-5γ2 is an independent prognostic marker in oral squamous cell carcinoma","authors":"Depanwita Saha, Debarpan Mitra, Neyaz Alam, Sagar Sen, Saunak Mitra Mustafi, Syamsundar Mandal, Biswanath Majumder, Nabendu Murmu","doi":"10.1111/iep.12430","DOIUrl":"10.1111/iep.12430","url":null,"abstract":"Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin-5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM− cohorts. The expression pattern of laminin-5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan–Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin-5γ2 (p < .001) and MMP2 (p < .001). This pattern was mirrored by the significant upregulation of laminin-5γ2 and MMP2 in VM+ cohorts compared with the VM− ones. Furthermore, co-expression of VM and laminin-5γ2 was significantly associated with tumour grade (p = .010), primary tumour size (p < .001), lymph node metastasis (p = .001) and TNM stages (p < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin-5γ2 double-positive cohort displayed a significantly poorer disease-free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin-5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p = .028] and OS [HR = 21.401, p = .033] in OSCC patients. Together, our findings imply that VM along with laminin-5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin-5γ2 coordination emerges as a critical prognostic biomarker for OSCC.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"54-64"},"PeriodicalIF":3.0,"publicationDate":"2022-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9219510","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: 1

Remifentanil reduces the proliferation, migration and invasion of HCC cells via lncRNA NBR2/miR-650/TIMP3 axis 瑞芬太尼通过lncRNA NBR2/miR-650/TIMP3轴抑制HCC细胞的增殖、迁移和侵袭

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-02-13 DOI: 10.1111/iep.12429

Wei Liang, Jinyuan Ke

{"title":"Remifentanil reduces the proliferation, migration and invasion of HCC cells via lncRNA NBR2/miR-650/TIMP3 axis","authors":"Wei Liang, Jinyuan Ke","doi":"10.1111/iep.12429","DOIUrl":"10.1111/iep.12429","url":null,"abstract":"Cancer cell hyperproliferation and metastasis are major causes of cancer-associated mortality. Although the use of anaesthetics and analgesics may affect cancer cell metastasis, the underlying molecular mechanism remains unclear. This study aimed to explore the mechanisms of action of remifentanil on hepatocellular carcinoma (HCC) progression. Cell viability was measured by the 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay. Quantitative real-time polymerase chain reaction and Western blotting were performed to assess the expression levels of long non-coding RNA (lncRNA) neighbour of BRCA1 gene 2 (NBR2), microRNA (miR)-650 and tissue inhibitor of metalloproteinase-3 (TIMP3) in HCC cells. Wound healing and transwell assays were employed to evaluate the migration and invasion of HCC cells respectively. The target relationships between miR-650 and NBR2/TIMP3 were confirmed by dual luciferase reporter assay. Remifentanil reduced the viability of HCC cells in a dose-dependent manner. Remifentanil treatment significantly increased the expression of lncRNA NBR2 and TIMP3, and repressed miR-650 expression in HCC cells. Decreased lncRNA NBR2 or increased miR-650 promoted the proliferation, migration and invasion of remifentanil-treated HCC cells. LncRNA NBR2 targeted miR-650, and miR-650 further targeted TIMP3. Moreover, miR-650 down-regulation or TIMP3 up-regulation reversed the effects of lncRNA NBR2 knockdown that caused an enhancement of cell viability, migration and invasiveness in remifentanil-treated HCC cells. Thus remifentanil reduces the proliferation, migration and invasion of HCC cells via the lncRNA NBR2/miR-650/TIMP3 axis in vitro.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"44-53"},"PeriodicalIF":3.0,"publicationDate":"2022-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9580323","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

Role of extracellular matrix proteoglycans in immune cell recruitment 细胞外基质蛋白聚糖在免疫细胞募集中的作用

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-01-25 DOI: 10.1111/iep.12428

Anna L. Gray, Nabina Pun, Amanda J. L. Ridley, Douglas P. Dyer

{"title":"Role of extracellular matrix proteoglycans in immune cell recruitment","authors":"Anna L. Gray, Nabina Pun, Amanda J. L. Ridley, Douglas P. Dyer","doi":"10.1111/iep.12428","DOIUrl":"10.1111/iep.12428","url":null,"abstract":"Leucocyte recruitment is a critical component of the immune response and is central to our ability to fight infection. Paradoxically, leucocyte recruitment is also a central component of inflammatory-based diseases such as rheumatoid arthritis, atherosclerosis and cancer. The role of the extracellular matrix, in particular proteoglycans, in this process has been largely overlooked. Proteoglycans consist of protein cores with glycosaminoglycan sugar side chains attached. Proteoglycans have been shown to bind and regulate the function of a number of proteins, for example chemokines, and also play a key structural role in the local tissue environment/niche. Whilst they have been implicated in leucocyte recruitment and inflammatory disease, their mechanistic function has yet to be fully understood, precluding therapeutic targeting. This review summarizes what is currently known about the role of proteoglycans in the different stages of leucocyte recruitment and proposes a number of areas where more research is needed. A better understanding of the mechanistic role of proteoglycans during inflammatory disease will inform the development of next-generation therapeutics.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 2","pages":"34-43"},"PeriodicalIF":3.0,"publicationDate":"2022-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39857078","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: 10

British Society for Matrix Biology Autumn 2021 Autumn Meeting: "Extracellular Matrix and Rare Disease" 英国基质生物学协会2021年秋季会议:“细胞外基质与罕见疾病”

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2022-01-21 DOI: 10.1111/iep.12421

引用次数: 0

Colonoscopy Audit Increases Detection of Sessile Serrated Polyps 结肠镜检查增加无梗锯齿状息肉的检出率

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2021-12-29 DOI: 10.33696/pathology.2.030

A. Fraser

引用次数: 0