International Journal of Experimental Pathology最新文献_第4页

Clinical applications of gene therapy for rare diseases: A review 基因治疗罕见病的临床应用综述

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-05-13 DOI: 10.1111/iep.12478

Ioannis Papaioannou, James S. Owen, Rafael J. Yáñez-Muñoz

{"title":"Clinical applications of gene therapy for rare diseases: A review","authors":"Ioannis Papaioannou, James S. Owen, Rafael J. Yáñez-Muñoz","doi":"10.1111/iep.12478","DOIUrl":"10.1111/iep.12478","url":null,"abstract":"Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In this review, we discuss recent advances in clinical applications of gene therapy for rare diseases, focusing on a variety of viral and non-viral strategies. The use of adeno-associated virus (AAV) vectors is discussed in the context of Luxturna, licenced for the treatment of RPE65 deficiency in the retinal epithelium. Imlygic, a herpes virus vector licenced for the treatment of refractory metastatic melanoma, will be an example of oncolytic vectors developed against rare cancers. Yescarta and Kymriah will showcase the use of retrovirus and lentivirus vectors in the autologous ex vivo production of chimeric antigen receptor T cells (CAR-T), licenced for the treatment of refractory leukaemias and lymphomas. Similar retroviral and lentiviral technology can be applied to autologous haematopoietic stem cells, exemplified by Strimvelis and Zynteglo, licenced treatments for adenosine deaminase-severe combined immunodeficiency (ADA-SCID) and β-thalassaemia respectively. Antisense oligonucleotide technologies will be highlighted through Onpattro and Tegsedi, RNA interference drugs licenced for familial transthyretin (TTR) amyloidosis, and Spinraza, a splice-switching treatment for spinal muscular atrophy (SMA). An initial comparison of the effectiveness of AAV and oligonucleotide therapies in SMA is possible with Zolgensma, an AAV serotype 9 vector, and Spinraza. Through these examples of marketed gene therapies and gene cell therapies, we will discuss the expanding applications of such novel technologies to previously intractable rare diseases.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 4","pages":"154-176"},"PeriodicalIF":3.0,"publicationDate":"2023-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10151230","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: 3

RUNX1 promotes liver fibrosis progression through regulating TGF-β signalling RUNX1通过调节TGF-β信号传导促进肝纤维化进展

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-04-17 DOI: 10.1111/iep.12474

Zhaoyang Guo, Xinxin Liu, Shulei Zhao, Fengkai Sun, Wanhua Ren, Mingze Ma

{"title":"RUNX1 promotes liver fibrosis progression through regulating TGF-β signalling","authors":"Zhaoyang Guo, Xinxin Liu, Shulei Zhao, Fengkai Sun, Wanhua Ren, Mingze Ma","doi":"10.1111/iep.12474","DOIUrl":"10.1111/iep.12474","url":null,"abstract":"Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to identify new potential therapeutic targets. For this study we used the carbon tetrachloride abdominal injection induced liver fibrosis animal model in mice. Primary hepatic stellate cell isolation was performed by a density-gradient separation method, and this was followed by immunofluorescence stain analyses. Signal pathway analysis was performed by dual-luciferase reporter assay and western blotting. Our results showed that RUNX1 was upregulated in cirrhotic liver tissues compared with normal liver tissues. Besides, overexpression of RUNX1 caused more severe liver fibrosis lesions than control group under CCl4-induced conditions. Moreover, α-SMA expression in the RUNX1 overexpression group was significantly higher than in the control group. Interestingly, we found that RUNX1 could promote the activation of TGF-β/Smads in a dual-luciferase reporter assay. Thus we demonstrated that RUNX1 could be considered as a new regulator of hepatic fibrosis by activating TGF-β/Smads signalling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target in the treatment of liver fibrosis in the future. In addition, this study also provides a new insight about the aetiology of liver fibrosis.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 4","pages":"188-198"},"PeriodicalIF":3.0,"publicationDate":"2023-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12474","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10271542","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: 2

Abnormal expression and role of MicroRNA-214-3p/SLC8A1 in neonatal Hypoxic-Ischaemic encephalopathy MicroRNA-214-3p/SLC8A1在新生儿缺氧缺血性脑病中的异常表达及其作用

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-04-09 DOI: 10.1111/iep.12475

Liu Yang, Li Zhang, Jing Zhu, Yuqian Wang, Ning Zou, Zhengjuan Liu, Yingjie Wang

引用次数: 1

High density of FOXP3 predicts better prognosis in germinal and non-germinal centre diffuse large B-cell lymphoma FOXP3的高密度预示着生发和非生发中心弥漫性大b细胞淋巴瘤更好的预后

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-03-28 DOI: 10.1111/iep.12477

Asmaa M. Ahmed, Sally S. Abdel-Hakeem, Maged A. F. Amine, Etemad H. Yassin, Fatma A. M. Badary

引用次数: 0

Arginine vasopressin deficiency and conivaptan (a V1a–V2 receptor antagonist) treatment reverses liver damage and fibrosis in rats with chronic portocaval anastomosis 精氨酸抗利尿激素缺乏和康尼伐坦(一种V1a-V2受体拮抗剂)治疗可逆转慢性门静脉吻合大鼠的肝损伤和纤维化

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-03-25 DOI: 10.1111/iep.12476

Yesenia Danyeli Navarro-Gonzalez, Javier Ventura-Juarez, Martín Humberto Muñoz-Ortega, Daniel González-Blas, Argelia Calvillo-Robedo, Manuel-Enrique Avila-Blanco, Fernando Valdez-Urias, Andrés Quintanar-Stephano

{"title":"Arginine vasopressin deficiency and conivaptan (a V1a–V2 receptor antagonist) treatment reverses liver damage and fibrosis in rats with chronic portocaval anastomosis","authors":"Yesenia Danyeli Navarro-Gonzalez, Javier Ventura-Juarez, Martín Humberto Muñoz-Ortega, Daniel González-Blas, Argelia Calvillo-Robedo, Manuel-Enrique Avila-Blanco, Fernando Valdez-Urias, Andrés Quintanar-Stephano","doi":"10.1111/iep.12476","DOIUrl":"10.1111/iep.12476","url":null,"abstract":"Arginine vasopressin (AVP) is a naturally occurring hormone synthesized in the hypothalamus. AVP demonstrates pro-fibrotic effects as it stimulates hepatic stellate cells to secrete transforming growth factor-β (TGF-β) and collagen. Previous work in liver cirrhotic (CCL4-induced) hamsters demonstrated that AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) can restore liver function. Therefore, we hypothesized that liver fibrosis would decrease in portocaval anastomosis (PCA) rats, which model chronic liver diseases, when they are treated with the V1a–V2 AVP receptor antagonist conivaptan (CV). In this study, changes in liver histology and gene expression were analysed in five experimental groups: control, PCA, NIL, PCA + NIL and PCA + CV, with NIL surgery or CV treatment administered 8 weeks after PCA surgery. Body weight gain was assessed on a weekly basis, and serum liver function, liver weight and liver glycogen content were assessed following euthanasia. Most PCA-induced phenotypes were reverted to normal levels following AVP-modelled deficiency, though hypoglycemia and ammonium levels remained elevated in the PCA + CV group. Liver histopathological findings showed a significant reversal in collagen content, less fibrosis in the triad and liver septa and increased regenerative nodules. Molecular analyses showed that the expression of fibrogenic genes (TGF-β and collagen type I) decreased in the PCA + CV group. Our findings strongly suggest that chronic NIL or CV treatment can induce a favourable microenvironment to decrease liver fibrosis and support CV as an alternative treatment for liver fibrosis.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 4","pages":"209-222"},"PeriodicalIF":3.0,"publicationDate":"2023-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9786553","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

Clinicopathological features and immunophenotype of Silva pattern system in endocervical adenocarcinoma 宫颈内腺癌Silva型系统的临床病理特征及免疫表型分析

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-03-16 DOI: 10.1111/iep.12470

Chao Zeng, Jin-ke Wu, Xiaofang Lu

{"title":"Clinicopathological features and immunophenotype of Silva pattern system in endocervical adenocarcinoma","authors":"Chao Zeng, Jin-ke Wu, Xiaofang Lu","doi":"10.1111/iep.12470","DOIUrl":"10.1111/iep.12470","url":null,"abstract":"The aim of this study was to investigate the correlation between Silva pattern system and clinicopathological features of endocervical adenocarcinoma. Moreover, it was to find molecular markers helpful for Silva classification, and thus we also explored the expression levels of invasion, adhesion and proliferation biomarkers in cases of Silva non-invasive and invasive types. The survival based on Silva pattern system was analysed by Kaplan–Meier survival analysis, Log-rank test and a COX risk proportionality model. Sixty samples were chosen to detect the MMP-2, MMP-9, u-PA, E-cadherin, β-catenin, EGF, TGF-α, HDGF, c-Met and RGN expression by immunohistochemistry. Multivariate analysis showed that pattern A/pattern B/pattern C Silva pattern system provided independent risk factors for prognosis. Our results found the levels of MMP-2, MMP-9 and u-PA were significantly higher in endocervical adenocarcinoma with destructive growth than in the nondestructive group. The levels of E-cadherin and β-catenin were significantly lower in endocervical adenocarcinoma with destructive growth than in the nondestructive group. The levels of EGF, TGF-α and HDGF were significantly higher in endocervical adenocarcinoma with destructive growth than in the nondestructive group. Compared with ‘non-invasive/invasive Silva pattern’, this study suggests ‘pattern A/pattern B/pattern C Silva pattern’ could be a better criteria for predicting the prognosis. Furthermore, the dual-marker combination of ‘MMP-2 and u-PA’ and ‘E-cadherin and β-catenin’ is very important in the diagnosis of Silva pattern classification.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 3","pages":"140-150"},"PeriodicalIF":3.0,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9474506","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

Effect of chronic exposure to fine particulate matter on cardiac tissue of NZBWF1 mice 慢性暴露于细颗粒物对NZBWF1小鼠心脏组织的影响

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-03-14 DOI: 10.1111/iep.12473

Dunia Waked, Ana Clara B. Rodrigues, Thamires Moraes Silva, Victor Yuji Yariwake, Sylvia Costa Lima Farhat, Mariana Matera Veras

{"title":"Effect of chronic exposure to fine particulate matter on cardiac tissue of NZBWF1 mice","authors":"Dunia Waked, Ana Clara B. Rodrigues, Thamires Moraes Silva, Victor Yuji Yariwake, Sylvia Costa Lima Farhat, Mariana Matera Veras","doi":"10.1111/iep.12473","DOIUrl":"10.1111/iep.12473","url":null,"abstract":"Epidemiological and toxicological studies have shown that inhalation of particulate matter (PM) is associated with development of cardiovascular diseases. Long-term exposure to PM may increase the risk of cardiovascular events and reduce life expectancy. Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, autoimmune in nature, that is characterized by the production of autoantibodies that affects several organs, including the heart. Air pollution - which can be caused by several different factors - may be one of the most important points both at the onset and the natural history of SLE. Therefore this study aims to investigate whether exposure to air pollution promotes increased inflammation and cardiac remodelling in animals predisposed to SLE. Female NZBWF1 mice were exposed to an environmental particle concentrator. Aspects related to cardiac remodelling, inflammation and apoptosis were analysed in the myocardium. Body weight gain, cardiac trophism by heart/body weight ratio, relative area of cardiomyocytes and the fibrotic area of cardiac tissue were evaluated during the exposure period. Animals exposed to PM2.5 showed increased area of cardiomyocytes, and area of fibrosis; in addition, we observed an increase in IL-1 and C3 in the cardiac tissue, demonstrating increased inflammation. We suggest that air pollution is capable of promoting cardiac remodelling and increased inflammation in animals predisposed to SLE.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 4","pages":"177-187"},"PeriodicalIF":3.0,"publicationDate":"2023-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9789394","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

British Society for Matrix Biology Autumn Meeting 2022: “Matrix in Development” 英国基质生物学学会2022年秋季会议:“发展中的基质”

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-03-12 DOI: 10.1111/iep.12471

引用次数: 0

Wnt signalling in the articular cartilage: A matter of balance 关节软骨中的Wnt信号:一个平衡问题

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-02-26 DOI: 10.1111/iep.12472

Amandeep Kaur Gill, Peter J. McCormick, David Sochart, Giovanna Nalesso

引用次数: 1

miR-144-3p represses hepatocellular carcinoma progression by affecting cell aerobic glycolysis via FOXK1 miR-144-3p通过FOXK1影响细胞有氧糖酵解抑制肝癌进展

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-02-19 DOI: 10.1111/iep.12468

Binyu Xing, Cunyi Shen, Qinling Yang, Zheng Wang, Wenjun Tan

{"title":"miR-144-3p represses hepatocellular carcinoma progression by affecting cell aerobic glycolysis via FOXK1","authors":"Binyu Xing, Cunyi Shen, Qinling Yang, Zheng Wang, Wenjun Tan","doi":"10.1111/iep.12468","DOIUrl":"10.1111/iep.12468","url":null,"abstract":"Aerobic glycolysis is a unique mark of cancer cells, which enables therapeutic intervention in cancer. Forkhead box K1 (FOXK1) is a transcription factor that facilitates the progression of multiple cancers including hepatocellular carcinoma (HCC). Nevertheless, it is unclear whether or not FOXK1 can affect HCC cell glycolysis. This study attempted to study the effect of FOXK1 on HCC cell glycolysis. Expression of mature miRNAs and mRNAs, as well as clinical data, was downloaded from The Cancer Genome Atlas-Liver hepatocellular carcinoma (TCGA-LIHC) dataset. FOXK1 and miR-144-3p levels were assessed through quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Targeting of the relationship between miR-144-3p and FOXK1 was verified via a dual-luciferase assay. Pathway enrichment analysis of FOXK1 was performed by Gene Set Enrichment Analysis (GSEA). Cell function assays revealed the glycolytic ability, cell viability, migration, invasion, cell cycle, and apoptosis of HCC cells in each treatment group. Bioinformatics analysis suggested that FOXK1 was upregulated in tissues of HCC patients, while the upstream miR-144-3p was downregulated in tumour tissues. Dual-luciferase assay implied a targeting relationship between miR-144-3p and FOXK1. Cellular experiments implied that silencing FOXK1 repressed HCC cell glycolysis, which in turn inhibited the HCC malignant progression. Rescue assay confirmed that miR-144-3p repressed glycolysis in HCC cells by targeting FOXK1, and then repressed HCC malignant progression. miR-144-3p/FOXK1 axis repressed malignant progression of HCC via affecting the aerobic glycolytic process of HCC cells. miR-144-3p and FOXK1 have the potential to become new therapeutic targets for HCC, which provide new insights for HCC treatment.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 3","pages":"117-127"},"PeriodicalIF":3.0,"publicationDate":"2023-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12468","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465963","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: 5