International Journal of Experimental Pathology最新文献

{"title":"Synergistic activation of genes promoting invasiveness by dual deprivation in oxygen and nutrients","authors":"Charly Jehanno,&nbsp;Yann Le Page,&nbsp;Gilles Flouriot,&nbsp;Pascale Le Goff,&nbsp;Denis Michel","doi":"10.1111/iep.12464","DOIUrl":"10.1111/iep.12464","url":null,"abstract":"<p>By depriving cancer cells of blood supplies of oxygen and nutrients, anti-angiogenic therapy is aimed at simultaneously asphyxiating and starving the cells. But in spite of its apparent logic, this strategy is generally counterproductive over the long term as the treatment seems to elicit malignancy. Since a defect of blood supply is expected to deprive tumours simultaneously of oxygen and nutrients naturally, we examine here these two deprivations, alone or in combination, on the phenotype and signalling pathways of moderately aggressive MCF7 cancer cells. Each deprivation induces some aspects of the aggressive and migratory phenotypes through activating several pathways, including HIF1-alpha as expected, but also SRF/MRTFA and TCF4/beta-catenin. Strikingly, the dual deprivation has strong cooperative effects on the upregulation of genes increasing the metastatic potential, such as four and a half LIM domains 2 (FHL2) and HIF1A-AS2 lncRNA, which have response elements for both pathways. Using anti-angiogenic agents as monotherapy is therefore questionable as it may give falsely promising short-term tumour regression, but could ultimately exacerbate aggressive phenotypes.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 2","pages":"64-75"},"PeriodicalIF":3.0,"publicationDate":"2023-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12464","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9125897","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":"KLF13 overexpression protects sepsis-induced myocardial injury and LPS-induced inflammation and apoptosis","authors":"Ni Zeng,&nbsp;Zaijin Jian,&nbsp;Wenxin Zhu,&nbsp;Junmei Xu,&nbsp;Yongmei Fan,&nbsp;Feng Xiao","doi":"10.1111/iep.12459","DOIUrl":"10.1111/iep.12459","url":null,"abstract":"<p>Sepsis remains a worldwide public health problem. This study aims to explore the role and mechanism of transcriptional factors (TFs) in sepsis-induced myocardial injury. Firstly, TF KLF13 was selected to explore its role in sepsis-induced myocardial injury. The caecal ligation and puncture (CLP) -induced sepsis mouse model was established and the septic mice were examined using standard histopathological methods. KLF13 expression was detected in the septic mouse heart and was also seen in a lipoploysaccharide (LPS) -induced cellular inflammation model. To explore this further both pro-apoptotic cleaved-caspase3/caspase3 and Bax levels and anti-apoptotic Bcl2 levels were examined, also in both models, In addition inflammatory cytokine (IL-1β, TNF-α, IL-8 and MCP-1) production and IκB-α protein level and p65 phosphorylation were examined in both septic mice and LPS-induced cells. Thus three parameters - cardiomyocyte apoptosis, inflammatory response and NF-κB pathway activation were evaluated under similar conditions. The septic mice showed significant oedema, disordered myofilament arrangement and degradation and necrosis to varying degrees in the myocardial cells. KLF13 was downregulated in both the septic mouse heart and the LPS-induced cellular inflammation model. Furthermore, both models showed abnormally increased cardiomyocyte apoptosis (increased cleaved-caspase3/caspase and Bax protein levels and decreased Bcl2 level), elevated inflammation (increased production of inflammatory cytokines) and the activated NF-κB pathway (increased p65 phosphorylation and decreased IκB-α protein level). KLF13 overexpression notably ameliorated sepsis-induced myocardial injury in vivo and in vitro<i>.</i> KLF13 overexpression protected against sepsis-induced myocardial injury and LPS-induced cellular inflammation and apoptosis via inhibiting the inflammatory pathways (especially NF-κB signalling) and cardiomyocyte apoptosis.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 1","pages":"23-32"},"PeriodicalIF":3.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10726587","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":"Expression of autocrine motility factor receptor (AMFR) in human breast and lung invasive micropapillary carcinomas","authors":"Jing Xu,&nbsp;Hongfei Ma,&nbsp;Qi Wang,&nbsp;Hui Zhang","doi":"10.1111/iep.12462","DOIUrl":"10.1111/iep.12462","url":null,"abstract":"<p>The aim of this study was to evaluate the clinicopathological significance of autocrine motility factor receptor (AMFR) expression in a variety of human invasive micropapillary carcinomas (IMPC). AMFR expression was compared in 111 samples of a variety of human IMPCs which had intrinsic non-micropapillary components and with 26 cases of control pulmonary adenocarcinoma (CPA, carcinoma without an IMPC component) by immunohistochemistry (IHC). In the 137 cases analysed, AMFR expression was significantly elevated in the IMPC components compared to the non-IMPC components (<i>p</i> = .005) and normal tissues (<i>p</i> &lt; .001). AMFR expression was also higher in the IMPC samples compared to their intrinsic non-IMPC components (<i>p</i> = .0234). Between the 69 cases of lung IMPC and 26 cases of CPA, AMFR expression was notably higher in the IMPC components than in the CPA components (<i>p</i> = .0455). However, there was no significant difference between the non-IMPC components in the lung and the CPA components (<i>p</i> = .4584). Moreover, in breast cancer, elevated AMFR expression was not significantly correlated with mixed type or pure type IMPC (<i>p</i> = .5969) or with age, gender, T stage, or lymph node metastasis (LNM). Between IMPC and CPA of the lung, there was no statistical significance in age, T stage, and LNM, where AMFR expression was higher in IMPC (<i>p</i> = .0071). Thus this study demonstrated that AMFR was overexpressed in a variety of human IMPC components compared with non-micropapillary components. This suggests that AMFR expression is a potential new prognostic indicator for different types of human IMPC, which might thus be a new therapeutic target.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 1","pages":"43-51"},"PeriodicalIF":3.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12462","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280721","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":"Silencing of RhoC induces macrophage M1 polarization to inhibit migration and invasion in colon cancer via regulating the PTEN/FOXO1 pathway","authors":"Bin Yang,&nbsp;Lihua Wang,&nbsp;Zhiying Tian","doi":"10.1111/iep.12460","DOIUrl":"10.1111/iep.12460","url":null,"abstract":"<p>Ras homologue family member C (RhoC) is an oncogene in diverse types of human cancers, whereas its regulatory mechanisms involving macrophage polarization is rarely investigated. This study is designed to explore the regulatory role of RhoC in colon cancer and the underlying molecular mechanisms involving macrophage polarization. We detected RhoC expression by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, and analysed the biological function of RhoC knockdown in CC cells by the MTT, wound healing and transwell assay. Macrophage polarization-associated markers, genes associated with migration, phosphatase and tensin homologue (PTEN) and forkhead box O (FOXO) were determined by qRT-PCR and western blot. The xenograft tumour mouse model was used to assess the role of RhoC in vivo. RhoC is highly expressed in CC cells. The cell viability, invasion and migration abilities of CC cells were reduced by knockdown of RhoC. RhoC knockdown promoted M1 polarization, inhibited M2 polarization and decreased levels of genes associated with migration (matrix metalloproteinase-2 and matrix metalloproteinase-9). Silencing of RhoC inhibited tumour growth and expression of genes associated with migration in the xenografted model. In addition, silencing of RhoC promoted PTEN/FOXO1 expression, and PTEN inhibitor (SF1670) reversed the inhibitory effects of RhoC silencing. We demonstrated that silencing of RhoC reduced CC cells invasion and migration, and tumour growth by suppressing M2 macrophage polarization via regulating the PTEN/FOXO1 pathway.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 1","pages":"33-42"},"PeriodicalIF":3.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12460","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9280723","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":"Cilostazol attenuates oxidative stress and apoptosis in the quadriceps muscle of the dystrophic mouse experimental model","authors":"Túlio de Almeida Hermes,&nbsp;Rafael Dias Mâncio,&nbsp;Daniela Sayuri Mizobutti,&nbsp;Aline Barbosa Macedo,&nbsp;Larissa Akemi Kido,&nbsp;Valéria Helena Alves Cagnon Quitete,&nbsp;Elaine Minatel","doi":"10.1111/iep.12461","DOIUrl":"10.1111/iep.12461","url":null,"abstract":"<p>Duchenne muscular dystrophy (DMD) is the most severe and frequent form of muscular dystrophy. The mdx mouse is one of the most widely used experimental models to understand aspects of the biology of dystrophic skeletal muscles and the mechanisms of DMD. Oxidative stress and apoptosis are present in early stages of the disease in mdx mice. The high production of reactive oxygen species (ROS) causes activation of apoptotic death regulatory proteins due to DNA damage and breakdown of nuclear and mitochondrial membranes. The quadriceps (QUA) muscle of the mdx mouse is a good tool to study oxidative events. Previous studies have demonstrated that cilostazol exerts an anti-oxidant effect by decreasing the production of reactive oxygen species (ROS). The present study aimed to evaluate the ability of cilostazol to modulate oxidative stress and apoptosis in the QUA muscle of mdx mice. Fourteen-day-old mdx mice received cilostazol or saline for 14 days. C57BL/10 mice were used as a control. In the QUA muscle of mdx mice, cilostazol treatment decreased ROS production (−74%), the number of lipofuscin granules (−47%), lipid peroxidation (−11%), and the number of apoptotic cells (−66%). Thus cilostazol showed anti-oxidant and anti-apoptotic action in the QUA muscle of mdx mice.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 1","pages":"13-22"},"PeriodicalIF":3.0,"publicationDate":"2022-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10736136","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":"Protection of dystrophic muscle cells using Idebenone correlates with the interplay between calcium, oxidative stress and inflammation","authors":"Amanda Harduim Valduga,&nbsp;Daniela Sayuri Mizobuti,&nbsp;Fernanda dos Santos Rapucci Moraes,&nbsp;Rafael Dias Mâncio,&nbsp;Luis Henrique Rapucci Moraes,&nbsp;Túlio de Almeida Hermes,&nbsp;Aline Barbosa Macedo,&nbsp;Elaine Minatel","doi":"10.1111/iep.12463","DOIUrl":"10.1111/iep.12463","url":null,"abstract":"<p>There is strong cross-talk between abnormal intracellular calcium concentration, high levels of reactive oxygen species (ROS) and an exacerbated inflammatory process in the dystrophic muscles of mdx mice, the experimental model of Duchenne muscular dystrophy (DMD). In this study, we investigated effects of Idebenone, a potent anti-oxidant, on oxidative stress markers, the anti-oxidant defence system, intracellular calcium concentrations and the inflammatory process in primary dystrophic muscle cells from <i>mdx</i> mice. Dystrophic muscle cells were treated with Idebenone (0.05 μM) for 24 h. The untreated <i>mdx</i> muscle cells were used as controls. The MTT assay showed that Idebenone did not have a cytotoxic effect on the dystrophic muscle cells. The Idebenone treatment was able to reduce the levels of oxidative stress markers, such as H₂O₂ and 4-HNE, as well as decreasing intracellular calcium influx in the dystrophic muscle cells. Regarding Idebenone effects on the anti-oxidant defence system, an up-regulation of catalase levels, glutathione reductase (GR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity was observed in the dystrophic muscle cells. In addition, the Idebenone treatment was also associated with reduction in inflammatory molecules, such as nuclear factor kappa-B (NF-κB) and tumour necrosis factor (TNF) in mdx muscle cells. These outcomes supported the use of Idebenone as a protective agent against oxidative stress and related signalling mechanisms involved in dystrophinopathies, such as DMD.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 1","pages":"4-12"},"PeriodicalIF":3.0,"publicationDate":"2022-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12463","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10736137","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":"Differential Expression of Long Non-coding Ribonucleic Acid (RNA) Genes in Endometriosis-associated Ovarian Cancer (EAOC): A Pilot Meta-analysis for Pathological Insights and Potential Diagnostic Biomarker Identification","authors":"A. Finall, D. James, M. Quintela-Vazquez, RS Conlan","doi":"10.33696/pathology.3.039","DOIUrl":"https://doi.org/10.33696/pathology.3.039","url":null,"abstract":"Introduction: Endometrioid and clear cell carcinomas of the ovary are the most common subtypes of epithelial malignancy arising from endometriosis and are often termed endometriosis-associated ovarian carcinomas (EAOCs). There is a paucity of experimental evidence in the medical literature regarding the role of long non-coding ribonucleic acid (RNA) gene expression in the pathogenesis of these carcinomas.\u0000Purpose: There is a need to develop understanding of the pathogenesis of these carcinomas for neoplastic risk stratification in endometriosis and to develop novel diagnostic biomarkers. Clear cell carcinoma of the ovary, in particular, has a poor prognosis as a result of resistance to standard platinum-based chemotherapy.\u0000Methods: RNAseq datasets from EAOCs were downloaded from Gene Expression Omnibus (GEO) and compared with normal ovarian control sequences using a customized bioinformatic pipeline.\u0000Results: We found 88 differentially expressed non-coding RNA molecules present in both endometrioid and clear cell carcinoma types compared with controls. A further 117 were specifically differentially expressed in the endometrioid carcinoma group and 128 in clear cell carcinoma samples alone. Genes of interest for further study from the 88 shared set in both EAOC types include CASC9, RP4-561L24.3, SLC2A1-AS1, LUCAT1, XIST, CASC15, and MIR99AHG. These genes appear to influence ferroptosis as a common pathway.\u0000Conclusions: Alterations in the ferroptosis pathway may be a key event in development of EAOC in ovarian endometriosis patients. Further work is required to elucidate the function of the candidate RNA genes identified in this study by in-vitro, cell line and cultured organoid experiments. These candidate RNA gene biomarkers have potential clinical utility in early diagnosis, risk stratification of endometriosis, and post-surgical monitoring.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"2003 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87051825","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":"The Duration of Mechanical Ventilation is the Main Cause of Bacterial/Fungal Superinfection in Critically Ill Patients with COVID-19 at Altitude","authors":"Daniel Molano Franco, R. Masclans Joan, X. Nuvials, Mario Gómez, Cesar Enciso, M. Villabon, Edgar Beltran, M. Pérez, G. Ramírez, Andres Gomez, Luis Escobar, Andres Villa, Cristian Arias-Reyes, J. Soliz","doi":"10.33696/pathology.3.040","DOIUrl":"https://doi.org/10.33696/pathology.3.040","url":null,"abstract":"Background. COVID-19 patients in intensive care units suffer from bacterial/fungal superinfections. However, the incidence and cause of such superinfections in high-altitude hospitals remain poorly investigated.\u0000\u0000Objectives. The aim of this study was to evaluate the frequency of bacterial/fungal superinfection in patients with COVID-19 hospitalized in the intensive care unit (ICU) of the Hospital Universitario San José de Bogotá, Colombia, located at an altitude of 2,651 meters above sea level (high altitude). The impact of corticosteroids on the development of infection was also evaluated.\u0000\u0000Methods. The cohort included 279 patients, of which 188 (67.4%) were male, 116 (42.3%) were treated with dexamethasone, and 48 (17.2%) were diagnosed with superinfection. A retrospective descriptive cohort study was performed to evaluate the association between bacterial/fungal superinfection frequency, corticosteroid treatment, mechanical ventilation, and mortality rate.\u0000\u0000Results. Our results showed that bacteremia was the most frequent diagnosis (n=20; 41.6%) of patients with superinfection, followed by pulmonary superinfection (n=17; 35.4%). The most frequently identified causative agents of superinfection were K. pneumoniae (n=23; 26.1%), C. albicans (n=10; 11.4%) and P. aeruginosa (n=8; 9.1%). Moreover, our results showed no association between corticosteroid treatment (or the use of empiric antibiotic treatment) and mortality. However, we found a significant association between bacterial/fungal superinfection and the number of days on mechanical ventilation. However, bacterial/fungal superinfection showed no impact on the mortality rate. \u0000\u0000Conclusions. We conclude that bacterial/fungal superinfection in ICU highland patients with SARS-CoV-2 treated at Hospital Universitario San José in Bogotá, Colombia, increases mainly in proportion to the time required for mechanical ventilation.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"22 1","pages":""},"PeriodicalIF":3.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79726177","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":"British Society for Matrix Biology Spring 2022 Meeting","authors":"","doi":"10.1111/iep.12454","DOIUrl":"https://doi.org/10.1111/iep.12454","url":null,"abstract":"","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 6","pages":"A1-A8"},"PeriodicalIF":3.0,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71967045","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":"British Society for Matrix Biology Spring 2022 Meeting.","authors":"","doi":"10.1111/iep.12454","DOIUrl":"https://doi.org/10.1111/iep.12454","url":null,"abstract":"","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"1 1","pages":"A1-A8"},"PeriodicalIF":3.0,"publicationDate":"2022-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75424257","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}