Analytical Cellular Pathology最新文献

{"title":"Comparative Effect of the Active Substance of Thyme with N-Acetyl Cysteine on Hematological Parameters and Histopathological Changes of Bone Marrow and Liver in Rat Models of Acetaminophen Toxicity.","authors":"Zahra Mokhtari, Mahdieh Raeeszadeh, Loghman Akradi","doi":"10.1155/2023/1714884","DOIUrl":"10.1155/2023/1714884","url":null,"abstract":"<p><p>Acetaminophen has always been at the center of attention as a non-steroidal anti-inflammatory drug, which is generally associated with the serious side effects on liver and the hematological parameters. This study aimed to compare the effect of N-acetyl cysteine (NAC) and thyme extract on rat models of acetaminophen-induced toxicity. The present experimental study was conducted on 48 Wistar rats randomized into six groups, including the control group (no treatment); the Ac group (470 mg/kg of acetaminophen); the Ac + 100Ex, Ac + 200Ex, and Ac + 400Ex groups (acetaminophen + thyme extract at doses of 100, 200, 400 mg/kg); and Ac + NA group (acetaminophen + NAC). After weighing, a blood sample was taken from heart at the end of the period. The measured parameters were hematological, liver biochemical, and oxidative stress profiles. A part of the liver tissue was also fixed for the pathological examinations. The bone marrow was aspirated to check for cellular changes as well. The lowest mean of the final weight and liver weight to body weight ratio was observed in the Ac group. Weight loss was compensated in Ac + NA and Ac + 200Ex groups (<i>P</i> = 0.035). White blood cell (WBC), red blood cell (RBC), Hemoglobin (Hgb), and Hematocrit (HCT) in Ac and Ac + 400Ex groups showed significant differences from those of the other test groups (<i>P</i> < 0.001). Aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) enzymes in Ac + 200Ex and Ac + NA groups showed a significant decrease compared to those of the other treatment groups (<i>P</i> = 0.043). Total antioxidant capacity (TAC) and glutathione peroxidase (GPx) had the lowest levels in Ac and Ac + 400Ex groups, while malondialdehyde (MDA) had the highest content. In this regard, the liver histopathological indices (necrosis, hyperemia, and hemorrhage) in the Ac + 200Ex and Ac + NA groups reached their lowest grades in the treatment groups. The mean number of erythroid and myeloid cells in the Ac group reached the lowest (17.40 ± 3.48). The microscopic appearance of the bone marrow cells was different from normocytosis in the control group to hypocytosis in the Ac and Ac + 400Ex groups. Thymol, as an effective ingredient in thyme extract at a dose of 200 mg/kg compared to NAC, had a unique effect on reducing bone marrow and liver cell-tissue changes due to the acetaminophen toxicity.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2023-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10089780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9310078","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":"Functional Role of RBP in Osteosarcoma: Regulatory Mechanism and Clinical Therapy.","authors":"Ziyuan Que,&nbsp;Kang Yang,&nbsp;Nan Wang,&nbsp;Shuying Li,&nbsp;Tao Li","doi":"10.1155/2023/9849719","DOIUrl":"https://doi.org/10.1155/2023/9849719","url":null,"abstract":"<p><p>Malignant bone neoplasms can be represented by osteosarcoma (OS), which accounts for 36% of all sarcomas. To reduce tumor malignancy, extensive efforts have been devoted to find an ideal target from numerous candidates, among which RNA-binding proteins (RBPs) have shown their unparalleled competitiveness. With the special structure of RNA-binding domains, RBPs have the potential to establish relationships with RNAs or small molecules and are considered regulators of different sections of RNA processes, including splicing, transport, translation, and degradation of RNAs. RBPs have considerable significant roles in various cancers, and experiments revealed that there was a strong association of RBPs with tumorigenesis and tumor cell progression. Regarding OS, RBPs are a new orientation, but achievements in hand are noteworthy. Higher or lower expression of RBPs was first found in tumor cells compared to normal tissue. By binding to different molecules, RBPs are capable of influencing tumor cell phenotypes through different signaling pathways or other axes, and researches on medical treatment have been largely inspired. Exploring the prognostic and therapeutic values of RBPs in OS is a hotspot where diverse avenues on regulating RBPs have achieved dramatical effects. In this review, we briefly summarize the contribution of RBPs and their binding molecules to OS oncogenicity and generally introduce distinctive RBPs as samples. Moreover, we focus on the attempts to differentiate RBP's opposite functions in predicting prognosis and collect possible strategies for treatment. Our review provides forwards insight into improving the understanding of OS and suggests RBPs as potential biomarkers for therapies.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10328736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10168737","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":"Interleukin-6 and Hypoxia Synergistically Promote EMT-Mediated Invasion in Epithelial Ovarian Cancer via the IL-6/STAT3/HIF-1<i>α</i> Feedback Loop.","authors":"Tongshuo Zhang,&nbsp;Jing Yang,&nbsp;Yang Sun,&nbsp;Jiangnan Song,&nbsp;Dandan Gao,&nbsp;Suhui Huang,&nbsp;Aibo Pang,&nbsp;Jianhui Zhang,&nbsp;Junhong Wang,&nbsp;Yue Wang,&nbsp;Yanqiu Li","doi":"10.1155/2023/8334881","DOIUrl":"https://doi.org/10.1155/2023/8334881","url":null,"abstract":"<p><p>Extensive peritoneal spread and capacity for distant metastasis account for the majority of mortality from epithelial ovarian cancer (EOC). Accumulating evidence shows that interleukin-6 (IL-6) promotes tumor invasion and migration in EOC, although the molecular mechanisms remain to be fully elucidated. Meanwhile, the hypoxic microenvironment has been recognized to cause metastasis by triggering epithelial-mesenchymal transition (EMT) in several types of cancers. Here, we studied the synergy between IL-6 and hypoxia in inducing EMT in two EOC cell lines, A2780 cells and SKOV3 cells. Exogenous recombination of IL-6 and autocrine production of IL-6 regulated by plasmids both induced EMT phenotype in EOC cells characterized by downregulated E-cadherin as well as upregulated expression of vimentin and EMT-related transcription factors. The combined effects of IL-6 and hypoxia were more significant than those of either one treatment on EMT. Suppression of hypoxia-inducible factor-1<i>α</i> (HIF-1<i>α</i>) before IL-6 treatment inhibited the EMT phenotype and invasion ability of EOC cells, indicating that HIF-1<i>α</i> occupies a key position in the regulatory pathway of EMT associated with IL-6. EMT score was found positively correlated with mRNA levels of IL-6, signal transducer and activator of transcription 3 (STAT3), and HIF-1<i>α</i>, respectively, in 489 ovarian samples from The Cancer Genome Atlas dataset. Next, blockade of the abovementioned molecules by chemical inhibitors reversed the alteration in the protein levels of EMT markers induced by either exogenous or endogenous IL-6. These findings indicate a positive feedback loop between IL-6 and HIF-1<i>α</i>, and induce and maintain EMT phenotype through STAT3 signaling, which might provide a novel rationale for prognostic prediction and therapeutic targets in EOC.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9940980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10823547","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":"Suppression of lncRNA OIP5-AS1 Attenuates Apoptosis and Inflammation, and Promotes Proliferation by Mediating miR-25-3p Expression in Lipopolysaccharide-Induced Myocardial Injury.","authors":"Jiaju Ma,&nbsp;Hebu Qian,&nbsp;Han Zou","doi":"10.1155/2023/3154223","DOIUrl":"https://doi.org/10.1155/2023/3154223","url":null,"abstract":"<p><strong>Purpose: </strong>Long non-coding RNAs (LncRNAs) OIP5-AS1 and miR-25-3p play important roles in myocardial injury, whereas their roles in lipopolysaccharide (LPS)-induced myocardial injury remain unknown. The purpose of our study was to investigate the functional mechanisms of OIP5-AS1 and miR-25-3p in LPS-induced myocardial injury.</p><p><strong>Methods: </strong>Rats and H9C2 cells were treated with LPS to establish the model of myocardial injury <i>in vivo</i> and <i>in vitro</i>, respectively. The expression levels of OIP5-AS1 and miR-25-3p were determined by quantitative reverse transcriptase-polymerase chain reaction. Enzyme-linked immunosorbent assay was performed to measure the serum levels of IL-6 and TNF-<i>α</i>. The relationship between OIP5-AS1 and miR-25-3p/NOX4 was determined by luciferase reporter assay and/or RNA immunoprecipitation assay. The apoptosis rate was detected by flow cytometry, and cell viability was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Western blot was performed to detect the protein levels of Bax, Bcl-2, caspase3, c-caspase3, NOX4, and p-NF-<i>κ</i>B p65/NF-<i>κ</i>B p65.</p><p><strong>Results: </strong>OIP5-AS1 was up-regulated, and miR-25-3p was down-regulated in myocardial tissues of LPS-induced rats and LPS-treated H9C2 cells. Knockdown of OIP5-AS1 relieved the myocardial injury in LPS-induced rats. Knockdown of OIP5-AS1 also inhibited the inflammation and apoptosis of myocardial cells <i>in vivo</i>, which was subsequently confirmed by <i>in vitro</i> experiments. In addition, OIP5-AS1 targeted miR-25-3p. MiR-25-3p mimics reversed the effects of OIP5-AS1 overexpression on promoting cell apoptosis and inflammation and on inhibiting cell viability. Besides, miR-25-3p mimics blocked the NOX4/NF-<i>κ</i>B signalling pathway in LPS-induced H9C2 cells.</p><p><strong>Conclusion: </strong>Silencing of lncRNA OIP5-AS1 alleviated LPS-induced myocardial injury by regulating miR-25-3p.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10042636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9959032","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":"Diagnostic Accuracy of p16^INK4a/Ki-67 Dual Immunostaining for Detection of High-Grade Cervical Intraepithelial Neoplasia in Women Involved in Cervical Cancer Screening in Georgia.","authors":"Sopio Kakaliashvili-Dzagnidze,&nbsp;Omar Khardzeishvili,&nbsp;Sergo Tabagari","doi":"10.1155/2023/7988323","DOIUrl":"https://doi.org/10.1155/2023/7988323","url":null,"abstract":"<p><strong>Background: </strong>Despite the widespread introduction of primary and secondary preventative measures, death rates for cervical cancer are still significantly high among females, especially in developing countries. Pap cytology and human papillomavirus-based screening often lead to unnecessary additional testing. The aim of this study is to analyze diagnostic accuracy of p16^INK4a/Ki-67 dual immunostaining (DS) in cervical smear for identifying high-grade cervical intraepithelial neoplasia (CIN2+).</p><p><strong>Materials and methods: </strong>We studied the diagnostic performance of p16^INK4a/Ki-67 DS in cervical smear of those women, who enrolled in cervical cancer screening due to abnormal previous screening results and compared it with Pap test results in identifying CIN2+. The reference standard was histopathology results. p16^INK4a/Ki-67 DS and Pap test results for 162 women and histopathology results for 29 women were available, respectively.</p><p><strong>Results: </strong>In our study, sensitivity, specificity, positive predictive value, and negative predictive value of p16^INK4a/Ki-67 DS, irrespective of the morphology of stained cells to detect CIN2+ were 100%, 89%, 85%, and 100% (<i>p</i> < 0.01), respectively. The diagnostic accuracy of p16^INK4a/Ki-67 DS is superior to that of existing cervical screening tests in the detection of CIN2+.</p><p><strong>Conclusion: </strong>The findings of cervical cancer screening based on Pap cytology highlight the importance of assessing the cost-effectiveness of integrating p16^INK4a/Ki-67 biomarkers in cervical cancer cytology. Furthermore, these findings emphasize the need to enhance support for preventive programs for cervical cancer in Georgia.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260307/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9666251","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":"Selenium Donor Inhibited Hepatitis B Virus Associated Hepatotoxicity via the Apoptosis and Ferroptosis Pathways.","authors":"Jingdong Shi,&nbsp;Zhen Liu,&nbsp;Weina Li,&nbsp;Di Wang","doi":"10.1155/2023/6681065","DOIUrl":"https://doi.org/10.1155/2023/6681065","url":null,"abstract":"<p><strong>Methods: </strong>The serum selenium level was determined in 45 patients with HBV-positive HCC (HBV⁺-HCC group), 45 patients with chronic hepatitis B virus infection (CHB group), and 45 healthy cases (HC group). The sodium selenite (Na₂SeO₃)-treated HepG2.2.15 cells were used to observe the regulatory role of selenium on HBV replication. D-GalN/erastin-added HL7702 was used to determine the regulatory roles of Na₂SeO₃ on hepatotoxicity or hepatocyte ferroptosis. The wild-type (WT) C57BL/6 mice and HBx-Tg mice were received lipopolysaccharide (LPS)/D-GalN, together with or without Na₂SeO₃ administration for indicated period. Following euthanasia, the blood and liver tissue samples were collected, and specific markers were evaluated subsequently.</p><p><strong>Results: </strong>The serum selenium level was downregulated in patients with HBV-positive HCC (HBV⁺-HCC group) (57.2 ± 22.5 <i>μ</i>g/L vs. 91.8 ± 43.9 <i>μ</i>g/L, <i>P</i> < 0.001), and its higher level could provide a better prognosis in these patients. The treatment using Na₂SeO₃, a selenium donor, at high concentration (5 <i>μ</i>M), suppressed the HBV replication by about 50% in HepG2.2.15 cells (<i>P</i> < 0.001), through promoting apoptotic cell death and inhibiting cellular inhibitor of apoptosis proteins (cIAPs). In addition, low-dose (500 nM) Na₂SeO₃ could almost totally reversed the hepatotoxicity induced by hepatitis B virus X protein (HBx) (<i>P</i> < 0.001), which were the main causes of HCC in patients. Studies at the cellular levels showed that low-dose Na₂SeO₃ inhibited the HBx-related hepatotoxicity by blocking ferroptosis, and glutathione peroxidase 4 (GPX4) mediated this regulatory role. Mice model results confirmed that the treatment with Na₂SeO₃ could mitigated LPS/D-GalN-induced hepatic injury through ferroptosis pathways.</p><p><strong>Conclusion: </strong>Selenium regulated the dual cell death in different HCC stages via different signaling pathways, which could partly explain the anti-HBV and anti-HCC properties of selenium.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10567286","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":"Nicotine Suppresses Phagocytic Ability of Macrophages by Regulating the miR-296-3p-SIRP<i>α</i> Axis.","authors":"Zhen Liu,&nbsp;Fang Wang,&nbsp;Xiaowu Huang,&nbsp;Zhi Chen,&nbsp;Yicheng Zhao,&nbsp;Yawei Wang,&nbsp;Xiaobo Luo,&nbsp;Guanren Zhao","doi":"10.1155/2023/6306358","DOIUrl":"https://doi.org/10.1155/2023/6306358","url":null,"abstract":"<p><p>Phagocytic ability of macrophage is responsible for tuberculosis infection. Nicotine has been shown to attenuate the phagocytic ability of macrophage; however, the underlying mechanism remains unclear. Here, we demonstrated that nicotine increased the message RNA (mRNA) and protein expression of signal regulatory protein alpha (SIRP<i>α</i>) and enhanced the stability of SIRP<i>α</i> mRNA in macrophage. Nicotine decreased the expression of microRNA (miR)-296-3p, which directly targeted the 3'-untranslated region (3'-UTR) of SIRP<i>α</i> mRNA in macrophage. Furthermore, nicotine inhibited the phagocytic ability of macrophage by regulating the miR-296-3p-SIRP<i>α</i> axis. Moreover, nicotine decreased miR-296-3p expression via increasing c-Myc expression in macrophage. Together, we found that nicotine attenuate the phagocytic ability of macrophage by regulating the c-Myc-miR-296-3p-SIRP<i>α</i> signal.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9946743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10813394","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":"Mechanism of Action of Decitabine in the Treatment of Acute Myeloid Leukemia by Regulating LINC00599.","authors":"Fan Du,&nbsp;Ting Jin,&nbsp;Li Wang","doi":"10.1155/2023/2951519","DOIUrl":"https://doi.org/10.1155/2023/2951519","url":null,"abstract":"<p><strong>Objective: </strong>Acute myeloid leukemia (AML) is a heterogeneous malignancy with a low long-term survival rate. The aim of this study was to investigate the effects of decitabine (DAC) treatment cell proliferation and apoptosis in AML and role of the expression of LINC00599 and, consequently, miR-135a-5p.</p><p><strong>Materials and methods: </strong>Human promyelocytic leukemia cells (HL-60) and human acute lymphatic leukemia (CCRF-CEM) cells were treated with various concentrations of DAC. Cell proliferation in each group was detected using the cell counting kit 8. For each group, apoptosis and reactive oxygen species (ROS) levels were detected using flow cytometry. Reverse transcription polymerase chain reaction (RT-PCR) was performed to examine the expression of lncRNA LINC00599. The expression of apoptosis-related proteins was analyzed using western blotting. The regulatory relationship between miR-135a-5p and LINC00599 was verified by constructing miR-135a-5p mimics, miR-135a-5p inhibit, wild type LINC00599 3'-untranslated region (UTR), and mutant LINC00599 3'-UTR. Ki-67 expression in the tumor tissues of nude mice was detected using immunofluorescent assays.</p><p><strong>Results: </strong>Both DAC and LINC00599 Inhibit groups were able to significantly reduce the proliferation of HL60 and CCRF-CEM cells, increase apoptosis, upregulate the expression of Bad, cleaved caspase-3, and miR-135a-5p, downregulate the expression of Bcl-2, and elevate ROS levels in cells, with these effects being more pronounced after combined treatment with DAC and LINC00599 Inhibit. In comparison to mimic NC, the miR-135a-5p mimic group significantly decreased the relative fluorescence activity ratio of LINC00599 3'-UTR wild-type CCRF-CEM cells. The LINC00599 Inhibit and miR-135a-5p mimic groups exhibited substantially reduced proliferation of HL60 and CCRF-CEM cells, increased apoptosis, upregulated Bad, cleaved caspase-3, and miR-135a-5p expression, along with downregulated Bcl-2 and LINC00599 expression and increased ROS levels in cells; these effects were more pronounced after LINC00599 Inhibit was combined with miR-135a-5p mimics. In vivo experiments revealed that both DAC and LINC00599 Inhibit were able to considerably reduce the long diameter, short meridian, volume, and mass of tumors, increase miR-135a-5p expression, and decrease LINC00599 and ki-67 expression in tumor tissues of nude mice. This effect was more pronounced when the DAC and LINC00599 Inhibit were used in combination.</p><p><strong>Conclusion: </strong>DAC regulates the expression of miR-135a-5p by regulating the expression of LINC00599, which in turn affects cell proliferation, apoptosis, and tumor proliferation. Our findings provide a theoretical basis for improving the clinical outcome of AML.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10854216","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":"<i>PCSK9-</i>D374Y Suppresses Hepatocyte Migration through Downregulating Free Cholesterol Efflux Rate and Activity of Extracellular Signal-Regulated Kinase.","authors":"Lei Huang,&nbsp;Ying Cheng,&nbsp;Yulian Mu,&nbsp;Kui Li","doi":"10.1155/2023/6985808","DOIUrl":"https://doi.org/10.1155/2023/6985808","url":null,"abstract":"<p><p>Proprotein convertase subtilisin/kexin type 9 can mediate the intracellular lysosomal degradation of the low-density lipoprotein receptor protein in hepatocytes and decrease the liver's ability to scavenge low-density lipoprotein cholesterol from circulation, resulting in high levels of cholesterol in the circulatory system. Current studies have primarily focused on the relationship between <i>PCSK9</i> and blood lipid metabolism; however, the biological function of <i>PCSK9</i> in hepatocytes is rarely addressed. In this study, we evaluate its effects in the human hepatoma carcinoma cell line HepG2, including proliferation, migration, and free cholesterol transport. <i>PCSK9-</i>D374Y is a gain-of-function mutation that does not affect proliferation but significantly suppresses the migration and cholesterol efflux capacity of these cells. The suppression of the transmembrane outflow of intracellular-free cholesterol regulates small G proteins and the suppression of extracellular signal-regulated kinase. In summary, <i>PCSK9-</i>D374Y affects hepatocyte features, including their migration and free cholesterol transport capabilities.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9842426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10567304","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":"Effect of COP1 in Promoting the Tumorigenesis of Gastric Cancer by Down-Regulation of CDH18 via PI3K/AKT Signal Pathway.","authors":"Benhuo Zhao,&nbsp;Jiaojiao Wu,&nbsp;Xiuli Cha,&nbsp;Guangtong Mao,&nbsp;Hengliang Shi,&nbsp;Sujuan Fei,&nbsp;Bei Miao","doi":"10.1155/2023/5617875","DOIUrl":"https://doi.org/10.1155/2023/5617875","url":null,"abstract":"<p><p>In recent years, the involvement of E3 ubiquitin ligase constitutive photomorphogenesis 1 (COP1) in the tumorigenesis of gastric cancer (GC) has been elucidated. However, the exact underlying mechanism remains to be clarified. In the present study, the expression profiles of COP1 in GC were derived from the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, followed by verification via immunohistochemical staining (IHC), Western blotting (WB), and quantitative real-time polymerase chain reaction (qRT-PCR) reaction assays on clinical samples. In vitro, the gain- and loss-of-function experiments of COP1 protein were conducted to explore its role in GC cell lines HGC-27 and SGC-7901. Furthermore, we screened the interaction protein of COP1 by yeast two-hybrid experiment and verified their combination by co-immunoprecipitation (co-IP). We preliminary explored the possible underlying mechanisms of COP1 protein in GC cell lines via WB. COP1 was upregulated in GC tissues compared with the corresponding non-carcinoma tissues. In vitro, the upregulation of COP1 protein promoted the proliferation and migration of GC cells. The yeast two-hybrid experiment and co-IP indicated that Cadherin 18 (CDH18) could constitute a complex with COP1. Moreover, cells with COP1 over-expression showed low levels of CDH18 expression, with the intracellular PI3K/AKT pathway activated and the malignancy of GC cell lines enhanced. Our findings demonstrated that COP1 promoted the GC tumorigenesis by downregulated CDH18 with the involvement of PI3K/AKT signaling pathway in cell lines, suggesting the potential of COP1 as a prognostic biomarker and therapeutic target for GC.</p>","PeriodicalId":49326,"journal":{"name":"Analytical Cellular Pathology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10072965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9264102","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}