Experimental and molecular pathology最新文献

{"title":"Amplicon-based NGS test for assessing MLH1 promoter methylation and its correlation with BRAF mutation in colorectal cancer patients","authors":"Sara Iolanda Oliveira da Silva ,&nbsp;Tabata Alves Domingos ,&nbsp;Bruna Elisa Catin Kupper ,&nbsp;Louise De Brot ,&nbsp;Samuel Aguiar Junior ,&nbsp;Dirce Maria Carraro ,&nbsp;Giovana Tardin Torrezan","doi":"10.1016/j.yexmp.2023.104855","DOIUrl":"10.1016/j.yexmp.2023.104855","url":null,"abstract":"<div><p>Detecting <em>MLH1</em> promoter methylation is highly relevant to differentiate between possible Lynch syndrome patients or patients with sporadic causes of MLH1/PMS2 deficiency in colorectal (CRC) and endometrial cancers. Here, we aimed to develop a test for assessing <em>MLH1</em> promoter methylation based in next generation sequencing (NGS), and to evaluate the concordance of <em>MLH1</em> methylation and <em>BRAF</em>-V600 mutation status in CRC. For that, we performed a series of experiments with DNA from tumor, saliva and commercial control samples and our in house developed amplicon-based NGS test. In patients' samples, <em>MLH1</em> methylation above 10% was only observed in tumors with MLH1/PMS2 loss. We confirmed the reproducibility and accuracy of <em>MLH1</em> promoter analysis performing a serial dilution experiment with completely methylated and unmethylated control DNAs and a comparison between two NGS platforms (Ion Proton and Illumina). In MLH1/PMS2 deficient tumors, the <em>MLH1</em> methylation status was concordant with the <em>BRAF</em> mutation status in 90% (18/20) of the cases. Our amplicon-based NGS test showed a great sensitivity and specificity for detecting <em>MLH1</em> methylation in CRC samples, with a high agreement with the evaluation of <em>BRAF</em> mutation. This simple and affordable test could be used as a reflex test to identify patients with sporadic causes of MLH1/PMS2 deficiency in CRC, aiding to genetic test referral and identification of Lynch syndrome patients.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"130 ","pages":"Article 104855"},"PeriodicalIF":3.6,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624437","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":"Retraction notice to “ Probucol via inhibition of NHE1 attenuates LPS-accelerated atherosclerosis and promotes plaque stability in vivo” [Experimental and Molecular Pathology 96/2 (2014) 250–256]","authors":"Li Jian-Fei ,&nbsp;Chen Song ,&nbsp;Feng Jun-Duo ,&nbsp;Zhang Ming-Yu ,&nbsp;Liu Xiao-Xia","doi":"10.1016/j.yexmp.2022.104847","DOIUrl":"10.1016/j.yexmp.2022.104847","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"129 ","pages":"Article 104847"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9170300","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":"Expression analysis of hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in renal cell carcinoma","authors":"Elham Mohammadisoleimani ,&nbsp;Zahra Firoozi ,&nbsp;Mohammad Mehdi Naghizadeh ,&nbsp;Ali Ghanbari Asad ,&nbsp;Anahita Jafari ,&nbsp;Mohammad Hosein Pourjafarian ,&nbsp;Ali Ariafar ,&nbsp;Hosein Mansoori ,&nbsp;Hassan Dastsooz ,&nbsp;Hani Sabaie ,&nbsp;Shahryar Zeighami ,&nbsp;Yaser Mansoori","doi":"10.1016/j.yexmp.2022.104848","DOIUrl":"10.1016/j.yexmp.2022.104848","url":null,"abstract":"<div><p>Renal cell carcinoma (RCC) is a prevalent heterogeneous kidney cancer. So far, different genes have been reported for RCC development. However, its particular molecular mechanism remains unclear. Circular RNAs (circRNAs), a class of non-coding RNAs, are involved in numerous biological processes in different malignancies such as RCC. This study aims to assess the expression and underlying mechanism of four circRNAs (hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, hsa_circ_0006990) with possible new roles in RCC. In the experimental step, we investigated the expression of these four circRNAs in our RCC samples using quantitative real-time polymerase chain reaction. In the bioinformatics step, the differential expressed mRNAs (DEmRNAs), and miRNAs (DEmiRNAs) were obtained from the GEO datasets using the GEO2R tool. A protein-protein interaction network was constructed using the STRING database, and hub genes were identified by Cytoscape. Molecular pathways associated with hub genes were detected using KEGG pathway enrichment analysis. Then, we utilized the ToppGene database to detect the relationships between DEmiRNAs and hub genes. Furthermore, interactions between circRNAs and DEmiRNAs were predicted by the StarBase and circinteractome databases. Finally, a circRNA-DEmiRNA-hub gene triple network was constructed. Our results revealed that the expression of hsa_circ_0020397, hsa_circ_0005986, and hsa_circ_0006990 was downregulated in RCC tissues. Moreover, these circRNAs had a significantly lower expression in patients with a history of kidney disease. Furthermore, hsa_circ_0003028 and hsa_circ_0006990 showed higher expression in the tumor of participants with Lymphovascular/perineural invasion and oncocytoma type, respectively. Based on bioinformatic results, 15 circRNA-DEmiRNA-hub gene ceRNA regulatory axes were predicted, which included three hub genes, five miRNAs, and four selected circRNAs. In conclusion, the current work is the first to emphasize the expression of the hsa_circ_0020397, hsa_circ_0005986, hsa_circ_0003028, and hsa_circ_0006990 in RCC patients presents a novel perspective on the molecular processes underlying the pathogenic mechanisms of RCC.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"129 ","pages":"Article 104848"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10761001","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":"Corrigendum to “Upregulation of immunomodulatory molecules by matrine treatment in experimental autoimmune Encephalomyelitis.” [Experimental and Molecular Pathology. 2014; 97(3):470–6. doi: 10.1016/j.yexmp.2014.10.004.]","authors":"Nan Liu ,&nbsp;Quan-cheng Kan ,&nbsp;Xiao-jian Zhang ,&nbsp;Yu-ming Xv ,&nbsp;Su Zhang ,&nbsp;Guang-Xian Zhang ,&nbsp;Lin Zhu","doi":"10.1016/j.yexmp.2022.104837","DOIUrl":"10.1016/j.yexmp.2022.104837","url":null,"abstract":"","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"129 ","pages":"Article 104837"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9297663","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 PI3K-AKT pathway: A plausible therapeutic target in Parkinson's disease","authors":"Ahsas Goyal (Assistant Professor),&nbsp;Anant Agrawal,&nbsp;Aanchal Verma,&nbsp;Nandini Dubey","doi":"10.1016/j.yexmp.2022.104846","DOIUrl":"10.1016/j.yexmp.2022.104846","url":null,"abstract":"<div><p>Parkinson's disease is a common progressive and multifactorial neurodegenerative disease, characterized by the loss of midbrain dopaminergic neurons. Numerous pathological processes including, inflammation, oxidative stress, mitochondrial dysfunction, neurotransmitter imbalance, and apoptosis as well as genetic factors may lead to neuronal degeneration. With the emergence of aging population, the health problem and economic burden caused by PD also increase. Phosphatidylinositol 3-kinases-protein kinase B (PI3K-AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K-AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. The current review provides an overview of the PI3K-AKT signaling pathway and review the relationship between this signaling pathway and PD.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"129 ","pages":"Article 104846"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9324176","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":"Diversin upregulates the proliferative ability of colorectal cancer by inducing cell cycle proteins","authors":"Lan Luan ,&nbsp;Nanyang Li ,&nbsp;Keyuan Zhang ,&nbsp;Xiaojie Wang ,&nbsp;Hai Pan","doi":"10.1016/j.yexmp.2023.104850","DOIUrl":"10.1016/j.yexmp.2023.104850","url":null,"abstract":"<div><p>Colorectal cancer (CRC) is a common gastrointestinal tumour with increasing incidence worldwide. However, the underlying molecular mechanism of CRC proliferation is not completely clear. Diversin，as an ankyrin repeat-containing protein, is upregulated in various solid tumours and accelerates cancer progression by promoting cell proliferation and increasing S phase fraction of cells. In this study, 71 CRC samples and corresponding adjacent tissue samples were included. The expression of diversin in tissues was verified via immunohistochemical analysis. The MTS assay and flow cytometry (FCM) was used to measure cell proliferation and cell cycle. Results of immunohistochemical analysis revealed that diversin was highly expressed in human CRC tissues and was significantly associated with tumour differentiation, clinical stage and lymph node metastasis. The analysis based on the CRC data from The Cancer Genome Atlas (TCGA) database showed that a high expression of diversin correlated with the poor prognosis of CRC. Results of the MTS assay indicated that the overexpression of diversin promoted the proliferation of CRC cells, while its downregulation had an inhibitory effect on CRC cell proliferation. FCM analysises presented that diversin increased the flux of the CRC cell cycle from G1 to S and regulated cycle-related proteins, namely, P21, P27, cyclin E, CDK2, cyclin D and CDK4. The results suggest that diversin contributes to CRC proliferation that involves the distribution of the cell cycle. In CRC tissues, the expression of diversin has closely related to the prognosis. The higher the expression levels of diversin, the worse the prognosis. In vitro, diversin could increase the proliferative ability of CRC cells through the G1–S checkpoint and JNK signalling pathway, confirming that diversin contributes to CRC development.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"129 ","pages":"Article 104850"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10773084","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":"Docking is not enough: 17-trifluoromethylphenyl trinor PGF2α is only a very weak ligand of neurokinin-1 receptor","authors":"Joanna Matalińska,&nbsp;Piotr F.J. Lipiński","doi":"10.1016/j.yexmp.2022.104849","DOIUrl":"10.1016/j.yexmp.2022.104849","url":null,"abstract":"<div><p>17-trifluoromethylphenyl trinor prostaglandin F_2α (17-CF₃PTPGF_2α) was reported recently to exhibit in vitro and in vivo anticancer activity. Based solely on the results of in silico molecular docking, it was claimed that this compound is NK1 receptor (NK1R) antagonist and that its activity is through this receptor. In this contribution we show that 17-CF₃PTPGF_2α is only a very weak NK1R ligand (IC₅₀ &gt; 200 μM). In connection with that we discuss the issue of this compound's molecular target. Finally, we briefly narrate on the proper use of molecular docking in biomedical research.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"129 ","pages":"Article 104849"},"PeriodicalIF":3.6,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10762241","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":"ST2 and the alteration of cobalt, sodium, potassium and calcium concentration in acute inflammation","authors":"Marija S. Stankovic ,&nbsp;Silvio R. De Luka ,&nbsp;Sasa Jankovic ,&nbsp;Srdjan Stefanovic ,&nbsp;Maja Stojanovic ,&nbsp;Jelena Nesovic-Ostojic ,&nbsp;Nina Japundzic-Zigon ,&nbsp;Alexander M. Trbovich","doi":"10.1016/j.yexmp.2022.104820","DOIUrl":"10.1016/j.yexmp.2022.104820","url":null,"abstract":"<div><h3>Introduction</h3><p>ST2 is the receptor for interleukin (IL)-33, the last discovered member of the IL-1 cytokine family. Acute inflammation is an early response of vascularized tissue to injury, in which alteration of micro- and macro-elements occurs. This study aimed to examine the alteration of cobalt, sodium, potassium, and calcium concentration at the site of acute inflammation and the role of ST2 in these alterations.</p></div><div><h3>Material and methods</h3><p>Wild-type (WT) and ST2 knockout (ST2−/−) mice were divided into groups: WT control group (WT-C), ST2 knockout control group (KO-C), WT inflammatory group (WT-I), and ST2 knockout inflammatory group (KO-I). We induced acute inflammation by intramuscular injection<span> of turpentine oil<span> or saline in the case of the control group. After 12 h, we anesthetized mice and collected treated tissues for histopathological analysis and determination of cobalt, sodium, potassium, and calcium concentration by atomic absorption spectrometer.</span></span></p></div><div><h3>Results</h3><p>Histopathological analysis showed the inflammatory infiltrate<span> and cell necrosis in the treated tissue in WT-I and KO-I. The concentration of sodium was significantly lower in WT-I than in WT-C. The concentration of potassium and cobalt was significantly lower in WT-I and KO-I when compared to WT-C and KO-C, respectively. However, the concentration of potassium and cobalt in the tissue was significantly lower in WT-I than in KO-I. The concentration of calcium in the tissue did not significantly differ between groups.</span></p></div><div><h3>Conclusion</h3><p>We reported, to our knowledge for the first time, that ST2 is involved in decreasing sodium, potassium, and cobalt concentration at the site of acute inflammation.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104820"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10685185","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":"A novel prognostic index of stomach adenocarcinoma based on immunogenomic landscape analysis and immunotherapy options","authors":"Weijie Xue ,&nbsp;Bingzi Dong ,&nbsp;Yixiu Wang ,&nbsp;Yuwei Xie ,&nbsp;Pu Li ,&nbsp;Zhiqi Gong ,&nbsp;Zhaojian Niu","doi":"10.1016/j.yexmp.2022.104832","DOIUrl":"10.1016/j.yexmp.2022.104832","url":null,"abstract":"<div><p>Stomach adenocarcinoma<span><span><span><span> (STAD) is one of the most common malignant tumors worldwide. In this study, we attempted to construct a valid immune-associated gene prognostic index risk model that can predict the survival of patients with STAD and the efficacy of immune checkpoint inhibitors (ICIs) </span>treatment. </span>Transcriptome<span><span>, clinical, and gene mutational data were obtained from the TCGA database. Immune-related genes were downloaded from the ImmPort and InnateDB databases. A total of 493 immune-related genes were identified to be enriched in functions associated with immune response, as well as in immune and tumor-related pathways. Further, 36 candidate genes related to the overall survival (OS) of STAD were obtained by weighted gene co-expression network analysis (WGCNA). Next, based on a </span>Cox regression<span><span><span> analysis, we constructed an immune-associated gene prognostic index (IAGPI) risk model based on eight genes, which was verified using the GEO STAD cohort. The patients were divided into two subsets according to their risk score. Patients in the low-risk group had better OS than those in the high-risk group. In the low-risk group, there were more CD8<span>, activated memory CD4, and follicular helper T cells, and M1 macrophages, whereas </span></span>monocytes, M2 macrophages, </span>eosinophils<span>, and neutrophils<span> were more abundant in the high-risk group. The patients in the low-risk group were more sensitive to ICIs therapy. The IAGPI risk model can precisely predict the prognosis, reflect the tumor immune microenvironment, and predict the efficacy of ICIs therapy </span></span></span></span></span>in patients with STAD.</span></p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104832"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10328775","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":"Microbial community profiling by next-generation DNA sequencing of adenocarcinoma of the prostate with evidence of ochratoxin A producing fungi","authors":"Stephen E. Fry ,&nbsp;Mitchell Kaye ,&nbsp;Dara S. Missan ,&nbsp;Christian Becker ,&nbsp;Matthew Shabilla ,&nbsp;Delyn Martinez ,&nbsp;Erin Bossert ,&nbsp;Jeremy Ellis","doi":"10.1016/j.yexmp.2022.104831","DOIUrl":"10.1016/j.yexmp.2022.104831","url":null,"abstract":"<div><h3>Background</h3><p>Prostatic carcinomas are a leading cancer and leading cause of mortality in the developed world. The etiology is diverse with underlying patient genetics, environmental factors, and microbial associations. Sequencing DNA for microbes allows the detection of potential disease relationships.</p></div><div><h3>Objective</h3><p>Targeted 16S (prokaryotic) and 18S (eukaryotic) rDNA sequencing was performed to map the tumor microbial flora.</p></div><div><h3>Design</h3><p>Twelve patients undergoing elective laparoscopic prostatectomy for biopsy proven adenocarcinoma of the prostate were enrolled. PCR and amplicon based sequencing was conducted; a portion of the sequencing results were confirmed by special stains.</p></div><div><h3>Setting</h3><p>Patients were recruited by the urologist were prospectively scheduled for radical prostatectomy by ‘Da Vinci’ robotically assisted procedure in an outpatient setting. Samples were portioned in the hospital surgical suite at the time of prostatectomy.</p></div><div><h3>Participants</h3><p>Male patients were requested to enter the study on a first come basis. Outcome Measurement and Statistical Analysis: Average age of the 12 participants was 64.3 years.</p></div><div><h3>Results and limitations</h3><p>DNA reads were detected and by ‘best match’ were identified belonging to Perkinsus, Hydrurus, Diversispora and Funneliformis genera, few samples displayed bacteria. Out of the 12 total patients, 11 patients had detectable DNA sequences matching arbuscular mycorrhizal fungi in the Glomeromycetes Class; Funneliformis mosseae and Diversasporum versiformis. Specific PCR for arbuscular mycorrhizal fungi failed to confirm Glomeromycetes Class; in-depth taxonomic analysis suggests a newer fungal grouping, not falling within an accepted Phylum of fungi. Calcoflour white staining of histological sections confirmed potential fungal markers in all 12 cases. Ochratoxin A antigen was identified by immunofluorescence in all 12 patient samples. The study was limited by the low sample volume and disease free normal controls.</p></div><div><h3>Conclusions</h3><p>Fungi may play a significant role in adenocarcinoma of the prostate.</p></div>","PeriodicalId":12176,"journal":{"name":"Experimental and molecular pathology","volume":"128 ","pages":"Article 104831"},"PeriodicalIF":3.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014480022000946/pdfft?md5=e7aa9fd3770a6f4078827dd710806fca&pid=1-s2.0-S0014480022000946-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10397158","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}