International Journal of Experimental Pathology最新文献

{"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}

{"title":"Non-Interventional Treatment of Post-Dural-Puncture Headache; High-Flow Oxygen and Pro-Serotonin Agents a Safe and Effective Alternative","authors":"A. Tran, C. Roldan","doi":"10.33696/pathology.3.038","DOIUrl":"https://doi.org/10.33696/pathology.3.038","url":null,"abstract":"Lumbar punctures are commonly performed for diagnostic and/or therapeutic purposes by threading a needle through the outermost layer of the meninges, the dura mater, and into the intrathecal space within the lumbar region of the spine [1]. The intrathecal space contains cerebrospinal fluid (CSF), a clear and colorless fluid, which surrounds the brain and spinal cord and can provide information regarding intracranial pressures, presence of diseases involving the central nervous system (CNS) or surrounding meninges [2-4]. A common complication of dural puncture is a postdural puncture headache (PDPH) which is defined by The International Headache Society as a “headache that develops within 5 days of dural puncture and resolves within 1 week spontaneously or within 48 hours after effective treatment of the spinal fluid leak” [5]. Symptoms of PDPH classically include a frontal and/or occipital headache that improves in the supine position, worsened by sitting or standing, and may be associated with nausea, nick stiffness, vertigo, vision changes, dizziness, or auditory disturbances [6]. PDPH has the propensity to cause significant morbidity; among affected patients, 39% report a duration of at least one week of significant impairment of daily activities while severe PDPH may require hospital admission [7]. The gold standard treatment for PDPH is to administer an epidural blood patch (EBP), autologous blood collected in the periphery vessels and delivered in the area of suspected CSF leak within the spinal canal to “mechanically plug the leak” [8]. However, in order to perform this intervention safely, training and specific equipment are necessary but unfortunately not a common part of the armamentarium of most clinical settings. Among cancer patients, access to the intrathecal space for diagnostic or therapeutic purposes may be part of the standard of care and occurrences of headaches associated with dural puncture in these scenarios are not totally unavoidable. Furthermore, many patients with cancer often have clear contraindications to accessing the epidural space to perform a therapeutic blood patch [9]. Under these circumstances, noninvasive alternatives should be considered (Table 1).","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"32 8","pages":""},"PeriodicalIF":3.0,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72411458","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":"Long-term intake of aspartame-induced cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and trigger P53-dependent apoptosis in a mouse model","authors":"Hojat Anbara,&nbsp;Mehdi Kian,&nbsp;Gholam-Hossein Darya,&nbsp;Mohammad Taghi Sheibani","doi":"10.1111/iep.12458","DOIUrl":"10.1111/iep.12458","url":null,"abstract":"<p>Aspartame (ASP) is probably the best known artificial sugar substitute that is used widely in food. Many experimental studies have reported the toxicity of long-term administration of ASP in various organ tissues. However, there is little evidence available about the nature and mechanisms of the adverse effects of long-term consumption of ASP on the cardiovascular system. This study was conducted to evaluate the possible effects of ASP on heart tissue. For this study 36 mature male mice were divided into one control group and three groups which received respectively 40 mg/kg, 80 mg/kg and 160 mg/kg ASP orally, for 90 days. ASP at the doses of 80 and 160 mg/kg increased the serum content of malondialdehyde (MDA), but decreased serum nitric oxide (NO), creatine kinase (CK) and CK-MB, as well as blood superoxide dismutase (SOD) levels. Serum level of total anti-oxidant capacity (TAC) in blood was also reduced in serum at the dose of 80 mg/kg. Histochemical staining, including Periodic acid-Schiff, Masson's trichrome and Verhoeff-van Gieson staining, indicated that ASP at doses of 80 and 160 mg/kg reduced glycogen deposition and decreased the number of collagen and elastic fibres in the cardiac tissue. The cardiac expression of pro-apoptotic genes, including P53, Bax, Bcl-2 and Caspase-3, was modulated at the dose of 160 mg/kg. Moreover, transcription of Caspase-3 was up-regulated at the dose of 80 mg/kg. In conclusion, long-term consumption of ASP any higher than the acceptable daily intake (40 mg/kg) appears to act by promoting oxidative stress, has the potential to alter both histopathological and biochemical parameters, and induces P53-dependent apoptosis in cardiac tissue.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 6","pages":"252-262"},"PeriodicalIF":3.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33518880","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":"Skin fibrosis associated with keloid, scleroderma and Jorge Lobo's disease (lacaziosis): An immuno-histochemical study","authors":"Wagner Luiz Tafuri,&nbsp;Thaise Yumie Tomokane,&nbsp;Ana Maria Gonçalves Silva,&nbsp;Luciane Kanashiro-Galo,&nbsp;David Miichael Mosser,&nbsp;Juarez Antonio Simões Quaresma,&nbsp;Carla Pagliari,&nbsp;Mirian N. Sotto","doi":"10.1111/iep.12456","DOIUrl":"10.1111/iep.12456","url":null,"abstract":"<p>Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of α-smooth muscle actin (α-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-β. Higher expression of vimentin in comparison to α-SMA in all three lesion types was found. CD31- and CD34-positive blood vessel endothelial cells were observed throughout the reticular dermis. Ki67 expression was low and almost absent in scleroderma. p16-positive levels were higher than ki67 and observed in reticular dermis of keloidal collagen in keloids, in collagen bundles in scleroderma and in the external layers of the granulomas in lacaziosis. The presence of α-actin positive cells and rarely CD34 positive cells, observed primarily in keloids, may be related to higher p16 antigen expression, a measure of cell senescence. Low FOXP3 expression was observed in all lesion types. CD105-positive cells were mainly found in perivascular tissue in close contact with the adventitia in keloids and scleroderma, while, in lacaziosis, these cells were chiefly observed in conjunction with collagen deposition in the external granuloma layer. We did not find high involvement of CD163 or CD206-positive cells in the fibrotic process. TGF-β was notable only in keloid and lacaziosis lesions. In conclusion, we have suggested vimentin to be the main myofibroblast general marker of the fibrotic process in all three studied diseases, while endothelial-to-mesenchymal transition (EndoMT) and mesenchymal stem cells (MSCs) and M2 macrophages may not play an important role.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"103 6","pages":"234-244"},"PeriodicalIF":3.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40389107","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}