Genes and Environment最新文献

{"title":"MicroRNA miR-627-5p restrains pulmonary artery smooth muscle cell dysfunction by targeting MAP 2 K4 and PI3K/AKT signaling.","authors":"Ting Li,&nbsp;Xiaoqin Tan,&nbsp;Yuexia Huang,&nbsp;Jun Cui,&nbsp;Fan Chen,&nbsp;Ying Xiong","doi":"10.1186/s41021-022-00251-4","DOIUrl":"https://doi.org/10.1186/s41021-022-00251-4","url":null,"abstract":"<p><strong>Background: </strong>Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary vascular remodeling, which can be caused by abnormal proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Several microRNAs were demonstrated to regulate the PASMC dysfunction. Our study intends to evaluate whether miR-627-5p affects cigarette smoke extract (CSE)-induced aberrant biological behaviors of PASMCs.</p><p><strong>Methods: </strong>PASMCs was treated with CSE to create the in vitro cellular model of COPD. The viability and LDH release of PASMCs was detected by CCK-8 assay and LDH release assay. MiR-627-5p and MAP 2 K4 expression in CSE (2%)-treated PASMCs was detected by qRT-PCR. PASMC proliferation was observed under a microscope, and PASMC migration was assessed by Transwell migration assays. The binding of miR-627-5p on MAP 2 K4 was verified by dual-luciferase reporter assay. Protein levels of MAP2K4 and the PI3K/AKT signaling markers were examined by western blotting.</p><p><strong>Results: </strong>The viability of PASMCs treated with 2% CSE reached a peak. CSE dose-dependently downregulated miR-627-5p expression in PASMCs. MiR-627-5p overexpression attenuated the CSE-induced abnormal proliferation and migration of PASMCs. However, MAP2K4 overexpression antagonized the effects of miR-627-5p on PASMC dysfunction. Importantly, miR-627-5p inhibited CSE-stimulated activation of the PI3K/AKT pathway via downregulating MAP2K4.</p><p><strong>Conclusion: </strong>MiR-627-5p improves CSE-induced abnormal proliferation and migration of PASMCs by inhibiting MAP2K4 expression and the PI3K/AKT pathway.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"23"},"PeriodicalIF":1.7,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9513949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40376034","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":"The effect of aging on the repeated-dose liver micronucleus assay using diethylnitrosamine.","authors":"Kensuke Satomoto,&nbsp;Isamu Suzuki,&nbsp;Koji Mita,&nbsp;Atsushi Wakita,&nbsp;Hiroshi Yamagata,&nbsp;Tatsuya Mitsumoto,&nbsp;Shuichi Hamada","doi":"10.1186/s41021-022-00250-5","DOIUrl":"https://doi.org/10.1186/s41021-022-00250-5","url":null,"abstract":"<p><strong>Background: </strong>The repeated-dose liver micronucleus (RDLMN) assay has been well-developed and applied because of its simplicity and the ease of integration into general toxicity studies which is the preferred method from the 3R's point of view. In this assay, we observed micronucleated hepatocytes which accumulated during a rather long-term dosing period. When considering integration into general toxicity studies, the effects of age of the animals used in the micronucleus assay becomes a major issue. The effect of age on the micronucleus induction rate has been reported in bone marrow micronucleus assays, and it is considered that the decrease in cell proliferation rate due to aging is the cause of the decrease in sensitivity. A decrease in sensitivity due to aging was also reported in a liver micronucleus assay using clofibrate and the cause is considered to be a decrease in hepatocyte proliferation activity due to aging. However, no actual decrease in hepatocyte proliferation rate due to aging has been reported. In addition, there are no reports, so far, on whether similar effects of aging appear when other substances were administered. To investigate the effects of aging in the RDLMN assay, this study focused on the effects of 14-day repeated administration of DEN, a well-known genotoxic hepatocarcinogen with the hepatocyte toxicity which should cause an elevation of cell proliferation rate as a reflective regeneration.</p><p><strong>Results: </strong>The liver micronuclei induced by DEN were equivalent between the two age groups (i.e., six and eight weeks of age at the start of dosing). In the histopathological examination for the liver, single cell necrosis, karyomegaly, and increased mitosis were observed in the hepatocytes, and the frequency and severity were increased dose-dependently. Ki-67 immunohistochemical analysis which can detect all cells in the cell cycle other than those in the G0 phase revealed dose-dependent increase of cell proliferation activity, and the difference between ages was not observed.</p><p><strong>Conclusion: </strong>The effect of aging on the RDLMN assay could not be recognized when DEN was administered for 14 days in rats. Meanwhile, it was supported by the histopathological examination and Ki-67 immunohistochemical analysis that such an effect of aging was masked by the compensatory hepatocyte proliferation which was induced by the hepatocyte toxicity of DEN.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"21"},"PeriodicalIF":1.7,"publicationDate":"2022-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40621777","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":"Bisphenol-A reduces DNA methylation after metabolic activation.","authors":"Kei-Ichi Sugiyama,&nbsp;Mawo Kinoshita,&nbsp;Petr Grúz,&nbsp;Toshio Kasamatsu,&nbsp;Masamitsu Honma","doi":"10.1186/s41021-022-00249-y","DOIUrl":"https://doi.org/10.1186/s41021-022-00249-y","url":null,"abstract":"<p><p>Bisphenol-A (BPA) is an important environmental contaminant with adverse health effects suspected to be mediated through epigenetic mechanisms. We had reported that the FLO1-dependent flocculation of transgenic yeast expressing human DNA methyltransferase (DNMT yeast) is a useful tool in epigenotoxicology studies. In this report, we have investigated the effects of BPA in the presence of metabolic activation (S-9 mix) on the transcription level of the FLO1 gene in the DNMT yeast. In the presence of metabolic activation, BPA inhibited the intensity of green fluorescence reporter protein (GFP) driven by the FLO1 promoter. A metabolite of BPA, 4-methyl-2,4-bis(p-hydroxyphenyl) pent-1-ene (MBP), also exhibited similar inhibitory effect. Furthermore, BPA in the presence of S-9 mix had only a weak while MBP had no inhibitory effects on the expression of modified GFP reporter gene under the control of FLO1 promoter with reduced CpG motifs. Aforementioned behavior was confirmed by the inhibition of flocculation as well as FLO1 gene mRNA expression. In addition, the global DNA methylation level in the human HEK293 cells was also reduced by MBP. These results indicate that BPA metabolites have inhibitory effect on DNA methylation. Our approach offers a novel in vitro method for screening for chemicals that can alter the epigenome by a mechanism dependent on their metabolic activation.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"20"},"PeriodicalIF":1.7,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40539066","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":"SIRT1 mediates nutritional regulation of SREBP-1c-driven hepatic PNPLA3 transcription via modulation of H3k9 acetylation","authors":"Xiao Xu, Xiaojie Deng, Yun-Ting Chen, Wen Xu, Fen Xu, Hua Liang","doi":"10.1186/s41021-022-00246-1","DOIUrl":"https://doi.org/10.1186/s41021-022-00246-1","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48160987","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":"Unique characteristics of G719X and S768I compound double mutations of epidermal growth factor receptor (EGFR) gene in lung cancer of coal-producing areas of East Yunnan in Southwestern China","authors":"Jun-ling Wang, Yuxia Fu, Yanguo Gao, Xiu-Ping Li, Qian Xiong, Rui Li, B. Hou, Ruo-Shan Huang, Jun-feng Wang, Jian-Kun Zhang, Jiajun Lv, Chao-Hua Zhang, Hong-Wei Li","doi":"10.1186/s41021-022-00248-z","DOIUrl":"https://doi.org/10.1186/s41021-022-00248-z","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46236328","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":"NEAT1 can be a diagnostic biomarker in the breast cancer and gastric cancer patients by targeting XIST, hsa-miR-612, and MTRNR2L8: integrated RNA targetome interaction and experimental expression analysis","authors":"M. Azadeh, A. Salehzadeh, K. Ghaedi, S. Talesh Sasani","doi":"10.1186/s41021-022-00244-3","DOIUrl":"https://doi.org/10.1186/s41021-022-00244-3","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44927694","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":"Time-course changes in DNA damage of corneal epithelial cells in rabbits following ocular instillation with genotoxic compounds","authors":"Haruna Tahara, Yoshinori Yamagiwa, Yu Haranosono, M. Kurata","doi":"10.1186/s41021-022-00243-4","DOIUrl":"https://doi.org/10.1186/s41021-022-00243-4","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47492518","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":"Copper-mediated DNA damage caused by purpurin, a natural anthraquinone","authors":"Hatasu Kobayashi, Yurie Mori, R. Iwasa, Yuichiro Hirao, Shinya Kato, S. Kawanishi, M. Murata, S. Oikawa","doi":"10.1186/s41021-022-00245-2","DOIUrl":"https://doi.org/10.1186/s41021-022-00245-2","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42593879","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":"Opinion: regulatory genotoxicity: past, present and future","authors":"M. Hayashi","doi":"10.1186/s41021-022-00242-5","DOIUrl":"https://doi.org/10.1186/s41021-022-00242-5","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44216709","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":"Evaluation of a 4-day repeated-dose micronucleus test in rat glandular stomach and colon using aneugens and non-genotoxic non-carcinogens","authors":"Emiko Okada, Yohei Fujiishi, K. Narumi, W. Ohyama","doi":"10.1186/s41021-022-00241-6","DOIUrl":"https://doi.org/10.1186/s41021-022-00241-6","url":null,"abstract":"","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":""},"PeriodicalIF":1.7,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44007439","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}