Pathobiology : journal of immunopathology, molecular and cellular biology最新文献

{"title":"Microsatellite Instability Is Rare in the Admixed Brazilian Population of Non-Small Cell Lung Cancer: A Cohort of 526 Cases.","authors":"Pedro De Marchi,&nbsp;Gustavo Noriz Berardinelli,&nbsp;Rodrigo de Oliveira Cavagna,&nbsp;Icaro Alves Pinto,&nbsp;Flavio Augusto Ferreira da Silva,&nbsp;Vinicius Duval da Silva,&nbsp;Iara Viana Vidigal Santana,&nbsp;Eduardo Caetano Albino da Silva,&nbsp;Leticia Ferro Leal,&nbsp;Rui Manuel Reis","doi":"10.1159/000520023","DOIUrl":"https://doi.org/10.1159/000520023","url":null,"abstract":"<p><strong>Background: </strong>Microsatellite instability (MSI) in non-small cell lung cancer (NSCLC) is uncommon; however, most studies refer to European and Asian populations. There are currently no data on MSI frequency in highly admixed populations, such as the one represented by Brazilian NSCLC patients.</p><p><strong>Aim: </strong>This study aimed to evaluate the frequency of MSI in Brazilian NSCLC patients.</p><p><strong>Methods: </strong>We evaluated 526 patients diagnosed with NSCLC at the Barretos Cancer Hospital (Brazil). The molecular MSI evaluation was performed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis. The mutation profile of MSI-positive cases was performed using next-generation sequencing.</p><p><strong>Results: </strong>Only 1 patient was MSI positive (0.19%). This patient was a female, white, and active smoker, and she was diagnosed with clinical stage IV lung adenocarcinoma at 75 years old. The molecular profile exhibited 4 Tumor Protein p53 (TP53) mutations and the absence of actionable mutations in the Epidermal Growth Factor Receptor (EGFR), Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), or V-Raf Murine Sarcoma Viral Oncogene Homolog B1 (BRAF) genes.</p><p><strong>Conclusions: </strong>The frequency of MSI in Brazilian NSCLC patients is equally rare, a finding that is consistent with the current literature based on other populations such as Europeans, North Americans, and Asians.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"101-106"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39715156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma: Immunohistochemical Assessment of Markers of Cancer Cell Metabolism.","authors":"Sara Costa Granja,&nbsp;Adhemar Longatto-Filho,&nbsp;Priscila B de Campos,&nbsp;Claudia P Oliveira,&nbsp;José T Stefano,&nbsp;Sebastião N Martins-Filho,&nbsp;Aline L Chagas,&nbsp;Paulo Herman,&nbsp;Luiz C D'Albuquerque,&nbsp;Mário Reis Alvares-da-Silva,&nbsp;Flair José Carrilho,&nbsp;Fátima Baltazar,&nbsp;Venâncio A F Alves","doi":"10.1159/000521034","DOIUrl":"https://doi.org/10.1159/000521034","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) has been associated to non-alcoholic fatty liver disease (NAFLD). We sought to investigate the immunoexpression of several glycolytic metabolism-associated markers in patients with HCC associated to NAFLD and associate these factors to their clinical-pathological characteristics.</p><p><strong>Methods: </strong>We evaluated 35 HCC specimens from 21 patients diagnosed with non-alcoholic steatohepatitis (NASH) undergoing liver resection (12 patients), liver transplantation (8 patients), or both (1 patient). Histological features, clinical aspects, demographic and biochemical data, as well as the immunohistochemical reactivity for monocarboxylate transporters 1, 2, and 4; their chaperone CD147; carbonic anhydrase IX; and glucose transporter-1 (GLUT1) were assessed.</p><p><strong>Results: </strong>Metabolic-associated cirrhosis was present in 12 of the 21 patients (8 child A and 4 child B scores). From 9 patients without cirrhosis, 3 presented NASH F3 and 6 NASH F2. Sixteen (76%) had diabetes mellitus, 17 (81%) arterial hypertension, and 19 (90%) body mass index above 25 kg/m2; 8 (38%) had dyslipidemia. From 35 nodules, steatosis was found in 26, ballooning in 31 nodules, 25 of them diagnosed as steatohepatitic subtype of HCC. MCT4 immunoexpression was associated with extensive intratumoral fibrosis, advanced clinical stages, and shorter overall survival. GLUT1 was noticeable in nodules with extensive intratumoral steatosis, higher intratumoral fibrosis, and advanced clinical stages. Immunohistochemical expression of the metabolic biomarkers MCT4 and GLUT1 was higher in patients with Barcelona-clinic liver cancer B or C. GLUT1 correlated with higher degree of steatosis, marked ballooning, intratumoral fibrosis, and higher parenchymal necroinflammatory activity.</p><p><strong>Conclusion: </strong>Our data indicate that the expression of the glycolytic phenotype of metabolic markers, especially GLUT1 and MCT4, correlates with a more severe course of HCC occurring in NASH patients.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"157-165"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39829861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of Predictive Biomarkers in Breast Cancer: Challenges and Updates.","authors":"Emad A Rakha,&nbsp;Ewa Chmielik,&nbsp;Fernando C Schmitt,&nbsp;Puay Hoon Tan,&nbsp;Cecily M Quinn,&nbsp;Grace Gallagy","doi":"10.1159/000525092","DOIUrl":"https://doi.org/10.1159/000525092","url":null,"abstract":"<p><p>The management of patients with breast cancer (BC) relies on the assessment of a defined set of well-established prognostic and predictive markers. Despite overlap, prognostic markers are used to assess the risk of recurrence and the likely benefit of systemic therapy, whereas predictive markers are used to determine the type of systemic therapy to be offered to an individual patient. In this review, we provide an update and present some challenges in the assessment of the main BC-specific molecular predictive markers, namely hormone receptors (oestrogen receptor [ER] and progesterone receptor [PR]), human epidermal growth factor receptor 2 (HER2), and KI67. As the main platform for assessing these markers in BC is immunohistochemistry (IHC), we address the cut-off values used to define positivity, the ER-low subgroup, the existence and significance of the ER-/PR+ phenotype, the use of PR in routine practice, and the role of hormone receptors in ductal carcinoma in situ. We discuss the newly introduced HER2-low class of BC and the clinical/biological difference between different HER2 groups (e.g., HER2 IHC score 3+ BCs vs. those with a HER2 IHC score 2+ with HER2 gene amplification). The review concludes with an update on the applications of KI67 assessment in BC and observations on the role of immune checkpoint identification in BC.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"263-277"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40150903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Papillary Thyroid Carcinoma with Honeycomb-Like Growth: Clinicopathological Characteristics and Diagnostic Significance as a Novel Variant.","authors":"Mitsuyoshi Hirokawa,&nbsp;Miyoko Higuchi,&nbsp;Ayana Suzuki,&nbsp;Toshitetsu Hayashi,&nbsp;Seiji Kuma,&nbsp;Akira Miyauchi","doi":"10.1159/000520165","DOIUrl":"https://doi.org/10.1159/000520165","url":null,"abstract":"<p><strong>Introduction: </strong>We aimed to clarify the clinical and pathological characteristics of papillary thyroid carcinoma (PTC) with unique honeycomb-like growth (HLG) and discuss its diagnostic significance.</p><p><strong>Methods: </strong>Among the 12,745 PTCs that were resected and histologically diagnosed, 28 PTC cases with HLG components (0.2%) were included.</p><p><strong>Results: </strong>PTC-HLG was subclassified into pure (9 cases), which consisted of only HLG components, and mixed (19 cases), which consisted of conventional PTC and HLG components, types. HLG components were histologically characterized by (1) neoplastic cyst aggregation with intervening normal thyroid follicles, (2) the cyst wall composed of single-layered carcinoma cells, (3) low papillary growth, and (4) ball-like granulation tissues. Compared with the mixed type, the pure type occurred in older people (p < 0.05), had a smaller tumor size (p < 0.0001), was more interpreted as being benign by ultrasound (p < 0.05), and had a lower lymph node metastasis rate (p < 0.005). In the mixed type, 44.4% of conventional PTCs showed a Ki-67 labeling index of >5%. All and 10.5% of the mixed type showed lymph node and lung metastases, respectively.</p><p><strong>Conclusion: </strong>The pure type could be a nonaggressive variant of PTCs with a unique honeycomb growth pattern and tended to be clinically interpreted as benign. The mixed type is pathogenetically different from the pure type and is slightly aggressive compared with conventional PTCs.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"107-115"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39658707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emodin Promotes Autophagy and Prevents Apoptosis in Sepsis-Associated Encephalopathy through Activating BDNF/TrkB Signaling.","authors":"Li-Li Gao,&nbsp;Zhi-Hao Wang,&nbsp;Yu-Hang Mu,&nbsp;Zuo-Long Liu,&nbsp;Li Pang","doi":"10.1159/000520281","DOIUrl":"https://doi.org/10.1159/000520281","url":null,"abstract":"<p><strong>Objective: </strong>Sepsis-associated encephalopathy (SAE) is a severe and common complication of sepsis and can induce cognitive dysfunction and apoptosis of neurons and neuroinflammation. Emodin has been confirmed to have anti-inflammatory effects. Thus, we sought to investigate the role of Emodin in SAE.</p><p><strong>Methods: </strong>The cecal ligation and puncture (CLP) method was used for the establishment of SAE in mice model. For treatment of Emodin, intraperitoneal injection of 20 mg/kg Emodin was performed before the surgery. The Morris water maze and open field tests were carried for measurement of cognitive dysfunction. Hematoxylin and eosin staining was for histological analysis of hippocampus. Cell apoptosis of hippocampus neurons was measured by TUNEL staining. Pro-inflammatory and anti-inflammatory cytokines in hippocampus tissue homogenate were evaluated by ELISA. BDNF/TrkB signaling-related proteins (TrkB, p-TrkB, and BDNF), autophagy-related proteins (LC3 II/I and Beclin-1), and apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) were detected by Western blotting.</p><p><strong>Results: </strong>Emodin significantly inhibited apoptosis and induced autophagy in hippocampal neurons of CLP-treated mice. In addition, Emodin significantly ameliorated CLP-induced cognitive dysfunction and pathological injury in mice. Meanwhile, Emodin notably inhibited CLP-induced inflammatory responses in mice via upregulation of BDNF/TrkB signaling, while the effect of Emodin was partially reversed in the presence of K252a (BDNF/TrkB signaling inhibitor).</p><p><strong>Conclusion: </strong>Emodin significantly inhibited the progression of SAE via mediation of BDNF/TrkB signaling. Thus, Emodin might serve as a new agent for SAE treatment.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"135-145"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39698727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of CD44 and Sox-2 Overexpression as Two Independent Favourable Prognostic Factors in HPV Positive Patients with Oropharyngeal Cancers.","authors":"Marta Kołodziej-Rzepa,&nbsp;Beata Biesaga,&nbsp;Anna Janecka-Widła,&nbsp;Anna Mucha-Małecka","doi":"10.1159/000521292","DOIUrl":"https://doi.org/10.1159/000521292","url":null,"abstract":"<p><strong>Introduction: </strong>In our earlier publications, in the group of 63 patients with oropharyngeal cancer, we have found HPV16 infection (assessed by qPCR) in 25 tumours (39.7%), immunohistochemical overexpression of CD44, CD98, ALDH1/2 and Nanog in, respectively: 43 (68.2%), 30 (47.6%), 33 (52.4%), and 53 (84.1%) cancers. Analysing CD44, CD98, ALDH1/2, we have also shown that lack of CD44 overexpression indicates excellent prognosis in patients with HPV16 positivity. The aim of the present study was to compare prognostic potential of Nanog, Oct3/4, Sox-2 expression in relation to CD44, CD98, ALDH1/2 immunoreactivity (assessed by us earlier) and clinicopathological features in the subgroups of patients: with HPV16 positivity and HPV16 negativity.</p><p><strong>Methods: </strong>Status of Oct3/4 and Sox-2 expression was assessed for 63 patients with oropharyngeal cancers based on immunohistochemistry. In survival analysis, two endpoints were applied: overall survival (OS) and disease-free survival (DFS).</p><p><strong>Results: </strong>Overexpression of Oct3/4 and Sox-2 was found in 0 (0.0%) and 27 (42.9%) of patients. In the subgroup with HPV16 positivity, the DFS for patients with lack of Sox-2 overexpression was significantly (p = 0.003) higher than for patients with Sox-2 overexpression. In the subgroup with HPV16 negativity, Nanog and Sox-2 immunoexpression did not significantly influence OS and DFS. In multivariate analysis performed for the subgroup with HPV16 positivity, lack of CD44 overexpression (p = 0.012) and lack of Sox-2 overexpression (p = 0.027) were positive independent prognostic factors.</p><p><strong>Conclusion: </strong>Based on CD44 and Sox-2 immunoreactivity, it is possible to differentiate the prognosis of HPV16-positive patients with oropharyngeal cancers.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"205-213"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39948676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Inter- and Intratumoral Variability of Ki67 Labeling Index in Newly Diagnosed Prostate Cancer with High Gleason Scores.","authors":"Tatjana Vlajnic,&nbsp;Patrik Brunner,&nbsp;Serenella Eppenberger-Castori,&nbsp;Cyrill A Rentsch,&nbsp;Tobias Zellweger,&nbsp;Lukas Bubendorf","doi":"10.1159/000519007","DOIUrl":"https://doi.org/10.1159/000519007","url":null,"abstract":"<p><strong>Background: </strong>The majority of studies investigating the role of Ki67 labeling index (LI) in prostate carcinoma (PC) focused on localized PC treated radically, where Ki67 LI is regarded as a prognostic marker. The relevance of Ki67 in advanced PC remains largely unexplored. While Gleason score is still one of the best indicators of clinical outcomes in PC, differences in progression-free survival and overall survival in patients with high Gleason scores suggest that additional factors are involved in tumor progression. Understanding the underlying mechanisms could help to optimize treatment strategies for an individual patient. Here, we aimed to determine the inter- and intratumoral distribution of Ki67 LI in patients with PC with high Gleason scores and to correlate Ki67 LI with the status of ERG, PTEN, and Bcl-2.</p><p><strong>Methods: </strong>Immunohistochemistry for Ki67, ERG, PTEN, and Bcl-2 was performed on core needle biopsies from 112 patients with newly diagnosed PC Gleason score 8, 9, and 10.</p><p><strong>Results: </strong>Using a cutoff of ≥10%, 17/112 cases (15%) had a homogeneously low and 95/112 cases (85%) a high Ki67 LI. 41% of cases showed intratumoral heterogeneity containing areas with low and high proliferation. There was no association between Ki67 LI and ERG, PTEN, or Bcl-2 status.</p><p><strong>Conclusions: </strong>Our data demonstrate major inter- and intratumoral variability of Ki67 LI in high-grade PC with a surprisingly low Ki67 LI in a subset of cases. Further studies are necessary to explore the molecular basis and potential clinical implications of a paradoxically low proliferation rate in high-grade PC.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"74-80"},"PeriodicalIF":5.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9153326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39442201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"YAP1 Overexpression Is Associated with Kidney Dysfunction in Lupus Nephritis.","authors":"Ying Xie,&nbsp;Yuanyuan Ruan,&nbsp;Huimei Zou,&nbsp;Yixin Wang,&nbsp;Xin Wu,&nbsp;Xiaoying Li,&nbsp;Jiao Lai,&nbsp;Mingjun Shi,&nbsp;Ying Xiao,&nbsp;Yuanyuan Wang,&nbsp;Yuxia Zhou,&nbsp;Bing Guo,&nbsp;Fan Zhang","doi":"10.1159/000517575","DOIUrl":"https://doi.org/10.1159/000517575","url":null,"abstract":"Objective: The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. Methods: C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. Results: Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. Conclusion: YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"412-423"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517575","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39280421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes of Gastric Juice Microenvironment in Patients with Fundic Gland Polyp and Hyperplastic Polyp.","authors":"He Gao,&nbsp;Lili Chang,&nbsp;Limin Wang,&nbsp;Xiaona Zhou,&nbsp;Ning Wang","doi":"10.1159/000516855","DOIUrl":"https://doi.org/10.1159/000516855","url":null,"abstract":"<p><strong>Introduction: </strong>The aim of this study was to study the relationship between the formation of gastric fundic gland polyp and gastric hyperplastic polyp (HP) and the changes of gastric juice microenvironment.</p><p><strong>Methods: </strong>The proton-pump inhibitor (PPI) applications to patients were recorded. Gastric juices and biopsy polyps were collected for pathological examination, H. pylori tests, biomarkers, and MUC1, MUC2, MUC5AC expression measurement.</p><p><strong>Results: </strong>Among 34,892 patients, the detection rate of gastric fundic gland polyps was significantly higher than that of gastric HPs (p < 0.01). The incidence rate of gastric fundic gland polyp and gastric HP in PPI users (n = 3,886) was higher than that of non-PPI users (p < 0.01). The occurrence of polyp was positively related to the duration of PPI application and the H. pylori-positive rate. The bile reflux rate between fundic gland polys group (17.61%) and HPs (28.67%) was significantly different (p < 0.01). The levels of gastric juice Gastrin-17, epidermal growth factor (EGF) and MUC2 from patients with gastric fundic gland polyps and gastric HPs were higher than those in the control group (p < 0.01). However, patients with gastric fundic gland polyps and HPs had significantly lower gastric juice PGE2 and MUC5AC (p < 0.01).</p><p><strong>Conclusion: </strong>PPI application, H. pylori infection, and bile reflux are the potential risk factors for formation of fundic gland polyps and HPs. The potential mechanism of polyps' formation can be related to the levels of Gastrin-17, EGF, MUC2, PGE2, and MUC5AC in gastric juice.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"383-391"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39398371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-506-3p Promotes the Proliferation and Migration of Vascular Smooth Muscle Cells via Targeting KLF4.","authors":"Hang Dong,&nbsp;Guangyu Jiang,&nbsp;Jiayue Zhang,&nbsp;Yuming Kang","doi":"10.1159/000513506","DOIUrl":"https://doi.org/10.1159/000513506","url":null,"abstract":"<p><strong>Background: </strong>The dysregulation of proliferation and migration of vascular smooth muscle cells (VSMCs) is one of the major causes of atherosclerosis (AS). Accumulating studies confirm that Kruppel-like factor 4 (KLF4) can regulate the proliferation and differentiation of VSMCs through multiple signaling pathways. However, the mechanism of KLF4 dysregulation remains unknown.</p><p><strong>Methods: </strong>Apolipoprotein E-knockout (ApoE-/-) mice and human VSMCs were used to establish AS animal model and cell model, respectively. qRT-PCR was employed to determine the expressions of miR-506-3p and KLF4. Cell Counting Kit -8, Transwell, TUNEL assays, and flow cytometry were performed to measure the proliferation, migration, and apoptosis of VSMCs. The upstream miRNAs of KLF4 were predicted by microT, miRanda, miRmap, and TargetScan databases. The interaction between KLF4 and miR-506-3p was confirmed using qRT-PCR, Western blot, and luciferase reporter gene assay.</p><p><strong>Results: </strong>KLF4 expression was significantly decreased in the VSMCs of ApoE-/- mice fed with high-fat diet and in human VSMCs treated with oxidized low-density lipoprotein in time-dependent and dose-dependent manners. The transfection of miR-506-3p mimics or KLF4 shRNA promoted the proliferation and migration of VSMCs but inhibited the apoptosis while miR-506-3p inhibitors and pcDNA3.1-KLF4 exerted opposite effects. Additionally, KLF4 was confirmed as a target gene of miR-506-3p and could be negatively regulated by miR-506-3p.</p><p><strong>Conclusion: </strong>MiR-506-3p can promote the proliferation and migration of VSMCs via targeting KLF4, which can probably contribute to the pathogenesis of AS.</p>","PeriodicalId":244631,"journal":{"name":"Pathobiology : journal of immunopathology, molecular and cellular biology","volume":" ","pages":"277-288"},"PeriodicalIF":5.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000513506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38894850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}