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":"<p>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 (CCL<sub>4</sub>-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.</p>","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}
{"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":"<p>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.</p>","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}
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":"<p>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.</p>","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}
{"title":"British Society for Matrix Biology Autumn Meeting 2022: “Matrix in Development”","authors":"","doi":"10.1111/iep.12471","DOIUrl":"10.1111/iep.12471","url":null,"abstract":"","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 2","pages":"A1-A21"},"PeriodicalIF":3.0,"publicationDate":"2023-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9119316","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}
Amandeep Kaur Gill, Peter J. McCormick, David Sochart, Giovanna Nalesso
{"title":"Wnt signalling in the articular cartilage: A matter of balance","authors":"Amandeep Kaur Gill, Peter J. McCormick, David Sochart, Giovanna Nalesso","doi":"10.1111/iep.12472","DOIUrl":"10.1111/iep.12472","url":null,"abstract":"<p>Degradation of the articular cartilage is a hallmark of osteoarthritis, a progressive and chronic musculoskeletal condition, affecting millions of people worldwide. The activation of several signalling cascades is altered during disease development: among them, the Wnt signalling plays a pivotal role in the maintenance of tissue homeostasis. Increasing evidence is showing that its activation needs to be maintained within a certain range to avoid the triggering of degenerative mechanisms. In this review, we summarise our current knowledge about how a balanced activation of the Wnt signalling is maintained in the articular cartilage, with a particular focus on receptor-mediated mechanisms.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 2","pages":"56-63"},"PeriodicalIF":3.0,"publicationDate":"2023-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12472","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9127475","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}
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":"<p>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.</p>","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}
Cresle Andrei Zacarias, Rosimere Farias de Mendonça Florenziano, Thiago Antonio Moretti de Andrade, Andrea Aparecida de Aro, Maria Esméria Corezola do Amaral, Gláucia Maria Tech dos Santos, Marcelo Augusto Marretto Esquisatto
{"title":"Arnica montana L. associated with microcurrent accelerates the dermis reorganisation of skin lesions","authors":"Cresle Andrei Zacarias, Rosimere Farias de Mendonça Florenziano, Thiago Antonio Moretti de Andrade, Andrea Aparecida de Aro, Maria Esméria Corezola do Amaral, Gláucia Maria Tech dos Santos, Marcelo Augusto Marretto Esquisatto","doi":"10.1111/iep.12469","DOIUrl":"10.1111/iep.12469","url":null,"abstract":"<p>The aim of this study was to test the effect of electrical stimulation in association with topical <i>Arnica montana</i> gel on organisational changes in the dermis during tissue repair. An experimental rat incisional skin lesion was used for the study. This involved making an incisional lesion on the dorsum of the animals using a scalpel. Ninety-six animals were used divided into the following groups: control (C), microcurrent (MC); topical treatment with <i>Arnica montana</i> gel (ARN); the ARN + microcurrent (ARN + MC). Treatments were administered daily, and injured tissue samples were collected and processed on Days 2, 6 and 10 for dermis analyses. Myeloperoxidase levels were greater in control than in treatment groups on Days 2 and 6. F4/80 expression was similar among all treatment groups and greater than that in control on Day 2. On Day 6, the expression of vascular endothelial growth factor was higher in the MC group than that in other groups, whereas transforming growth factor-β expression increased in the MC and ARN + MC groups on Day 10. The expression of matrix metalloproteinase-2 was higher in the ARN + MC group when compared with other groups on Day 10. Expression levels of collagen I were increased in the ARN and ARN + MC groups when compared with control and MC groups on Day 6, while expression of collagen III was enhanced in MC, ARN, and ARN + MC groups when compared with the control. The protocol combining microcurrent with topical application of ARN reduces the inflammatory process, increases myofibroblasts proliferation and decreases the presence of macrophages in the dermis during skin repair in rats.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 2","pages":"81-95"},"PeriodicalIF":3.0,"publicationDate":"2023-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9118991","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}
Carlos A. Rubio, Michael Vieth, Corinna Lang-Schwarz
{"title":"The frequency of dysplastic branching crypts in colorectal polypoid tubular adenomas","authors":"Carlos A. Rubio, Michael Vieth, Corinna Lang-Schwarz","doi":"10.1111/iep.12466","DOIUrl":"10.1111/iep.12466","url":null,"abstract":"<p>Dysplastic crypt branching (DCB) was recently found in ulcerative colitis-associated dysplasia. The aim was to assess the frequency and the branching phenotype of DCB in polypoid colorectal tubular adenomas (TA). A total of 3956 DCB were found in the 139 TA: 98% were in asymmetric branching (DCAB) and the remaining 2% in symmetric branching (DCSB). A linear correlation was found between DCB frequency and the increasing digital size in TA (<i>p</i> < .05). Using a digital ruler, adenomas were divided into small TA (<5 mm) and larger TA (≥5 mm). The difference between the frequency of DCB in small TA (<i>n</i> = 75) vs. larger TA (<i>n</i> = 64), was significant (<i>p</i> < .05). DCB frequency was not influenced by age, gender or TA localization. In the normal colorectal mucosa (≈2 m<sup>2</sup>), only occasional CSB is found and no CAB. And yet, multiple DCB (mean 16.7 DCB), mostly DCAB, was found in small TA, occupying <5 mm of the mucosal area. In larger TA, as many as 42.1 DCB (mean), mostly DCAB, occurred in merely 7.8 mm (mean) of the colon mucosa. Thus it is suggested that DCB is a standard histologic element of TA. The natural expansion of the adenomatous tissue in larger TA appears to be follow on from newly produced, mostly DCAB, by DCSB and by the accumulation of their dysplastic offspring's progenies. The findings strongly suggest that DCB is a central microstructure in the histological events unfolding in polypoid colorectal TA.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 3","pages":"100-106"},"PeriodicalIF":3.0,"publicationDate":"2023-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2c/47/IEP-104-100.PMC10182366.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9472258","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":"MIMT1 and LINC01550 are uncharted lncRNAs down-regulated in colorectal cancer","authors":"Faramarz Vejdandoust, Rahmaneh Moosavi, Nasrin Fattahi Dolatabadi, Atefeh Zamani, Hossein Tabatabaeian","doi":"10.1111/iep.12467","DOIUrl":"10.1111/iep.12467","url":null,"abstract":"<p>Incomplete knowledge of the molecular basis of colorectal cancer, with subsequent limitations in early diagnosis and effective treatment, has contributed to this form of malignancy becoming the second most common cause of cancer-related death worldwide. With the advances in high-throughput profiling techniques and the availability of public data sets such as The Cancer Genome Atlas Program (TCGA), a broad range of coding transcripts have been profiled and their underlying modes of action have been mapped. However, there is still a huge gap in our understanding of noncoding RNA dysregulation. To this end, we used a bioinformatics approach to shortlist and evaluate yet-to be-profiled long noncoding RNAs (lncRNAs) in colorectal cancer. We analysed the TCGA RNA-seq data and followed this by validating the expression patterns using a qPCR technique. Analysing in-house clinical samples, the real-time PCR method revealed that the shortlisted lncRNAs, that is MER1 Repeat Containing Imprinted Transcript 1 (MIMT1) and Non-Protein Coding RNA 1550 (LINC01550), were down-regulated in colorectal cancer tumours compared with the paired adjacent normal tissues. Mechanistically, the in silico results suggest that LINC01550 could form a complex competitive endogenous RNA (ceRNA) network leading to the subsequent regulation of colorectal cancer-related genes, such as CUGBP Elav-Like Family Member (CELF2), Polypyrimidine Tract Binding Protein 1 (PTBP1) and ELAV Like RNA Binding Protein 1 (ELAV1). The findings of this work indicate that MIMT1 and LINC01550 could be novel tumour suppressor genes that can be studied further to assess their roles in regulating the cancer signalling pathway(s).</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 3","pages":"107-116"},"PeriodicalIF":3.0,"publicationDate":"2023-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9484036","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}
Yaron Gil, Asia Zubkov, Jacques Balayla, Aviad Cohen, Ishai Levin
{"title":"Apoptosis versus necrosis in tubal ectopic pregnancies following Methotrexate","authors":"Yaron Gil, Asia Zubkov, Jacques Balayla, Aviad Cohen, Ishai Levin","doi":"10.1111/iep.12465","DOIUrl":"10.1111/iep.12465","url":null,"abstract":"<p>Methotrexate administration for the treatment of tubal ectopic pregnancies has been shown to cause tubal mass enlargement. Our hypothesis was that, by administrating Methotrexate, a local necrotic reaction occurs, leading to hematoma formation and eventually fallopian tube rupture. Salpingectomy specimens were collected, analysed and divided into three equal groups: patients who received Methotrexate but who ultimately failed medical treatment, patients who had a viable ectopic pregnancy and patients with a self-resolving ectopic pregnancy that were operated due to other medical indications. The specimens were dyed using the Cleaved Caspase-3 (Asp175) Rabbit mA. Specimens were divided into three equal groups and analysed. The patients in self-resolving ectopic pregnancy group were older and had more pregnancies. Rates of apoptosis were found to be less than 1% per slide. Necrosis was not evident in any of the pathological specimens. It seems Methotrexate administration does not lead to a significant tubal necrotic reaction. Further studies are required.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 2","pages":"76-80"},"PeriodicalIF":3.0,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9472086","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}