Genes and Environment最新文献

{"title":"The critical role of epigenetic mechanism in PM_2.5-induced cardiovascular diseases.","authors":"Qinglin Sun,&nbsp;Xiaoke Ren,&nbsp;Zhiwei Sun,&nbsp;Junchao Duan","doi":"10.1186/s41021-021-00219-w","DOIUrl":"https://doi.org/10.1186/s41021-021-00219-w","url":null,"abstract":"<p><p>Cardiovascular disease (CVD) has become the leading cause of death worldwide, which seriously threatens human life and health. Epidemiological studies have confirmed the occurrence and development of CVD are closely related to air pollution. In particular, fine particulate matter (PM_2.5) is recognized as an important environmental factor contributing to increased morbidity, mortality and hospitalization rates among adults and children. However, the underlying mechanism by which PM_2.5 promotes CVD development remains unclear. With the development of epigenetics, recent studies have shown that PM_2.5 exposure may induce or aggravate CVD through epigenetic changes. In order to better understand the potential mechanisms, this paper reviews the epigenetic changes of CVD caused by PM_2.5. We summarized the epigenetic mechanisms of PM_2.5 causing cardiovascular pathological damage and functional changes, mainly involving DNA methylation, non-coding RNA, histone modification and chromosome remodeling. It will provide important clues for exploring the biological mechanisms affecting cardiovascular health.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"47"},"PeriodicalIF":1.7,"publicationDate":"2021-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39522144","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":"Recent progress and perspectives on the mechanisms underlying Asbestos toxicity.","authors":"Akio Kuroda","doi":"10.1186/s41021-021-00215-0","DOIUrl":"https://doi.org/10.1186/s41021-021-00215-0","url":null,"abstract":"<p><p>Most cases of mesothelioma are known to result from exposure to asbestos fibers in the environment or occupational ambient air. The following questions regarding asbestos toxicity remain partially unanswered: (i) why asbestos entering the alveoli during respiration exerts toxicity in the pleura; and (ii) how asbestos causes mesothelioma, even though human mesothelial cells are easily killed upon exposure to asbestos. As for the latter question, it is now thought that the frustrated phagocytosis of asbestos fibers by macrophages prolongs inflammatory responses and gives rise to a \"mutagenic microenvironment\" around mesothelial cells, resulting in their malignant transformation. Based on epidemiological and genetic studies, a carcinogenic model has been proposed in which BRCA1-associated protein 1 mutations are able to suppress cell death in mesothelial cells and increase genomic instability in the mutagenic microenvironment. This leads to additional mutations, such as CDKN2A [p16], NF2, TP53, LATS2, and SETD2, which are associated with mesothelioma carcinogenesis. Regarding the former question, the receptors involved in the intracellular uptake of asbestos and the mechanism of transfer of inhaled asbestos from the alveoli to the pleura are yet to be elucidated. Further studies using live-cell imaging techniques will be critical to fully understanding the mechanisms underlying asbestos toxicity.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"46"},"PeriodicalIF":1.7,"publicationDate":"2021-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39512452","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":"Comparison of the frequencies of ENU-induced point mutations in male germ cells and inherited germline mutations in their offspring.","authors":"Kenichi Masumura,&nbsp;Tomoko Ando,&nbsp;Naomi Toyoda-Hokaiwado,&nbsp;Akiko Ukai,&nbsp;Takehiko Nohmi,&nbsp;Masamitsu Honma","doi":"10.1186/s41021-021-00216-z","DOIUrl":"https://doi.org/10.1186/s41021-021-00216-z","url":null,"abstract":"<p><strong>Background: </strong>Gene mutations induced in germ cells may be transmitted to the next generation and cause adverse effects such as genetic diseases. Certain mutations may result in infertility or death in early development. Thus, the mutations may not be inheritable. However, the extent to which point mutations in male germ cells are transmitted to the next generation or eliminated during transmission is largely unknown. This study compared mutation frequencies (MFs) in sperm of N-ethyl-N-nitrosourea (ENU)-treated gpt delta mice and de novo MFs in the whole exome/genome of their offspring.</p><p><strong>Results: </strong>Male gpt delta mice were treated with 10, 30, and 85 mg/kg of ENU (i.p., weekly × 2) and mated with untreated females to generate offspring. We previously reported a dose-dependent increase in de novo MFs in the offspring estimated by whole exome sequencing (WES) (Mutat. Res., 810, 30-39, 2016). In this study, gpt MFs in the sperm of ENU-treated mice were estimated, and the MFs per reporter gene were converted to MFs per base pair. The inherited de novo MFs in the offspring (9, 26 and 133 × 10^- 8/bp for 10, 30, and 85 mg/kg ENU-treated groups, respectively) were comparable to those of the converted gpt MFs in the sperm of ENU-treated fathers (6, 16, and 69 × 10^- 8/bp). It indicated that the gpt MFs in the ENU-treated father's sperm were comparable to the inherited de novo MFs in the offspring as estimated by WES. In addition, de novo MFs in the offspring of 10 mg/kg ENU-treated and control fathers were estimated by whole genome sequencing (WGS), because WES was not sufficiently sensitive to detect low background MF. The de novo MF in the offspring of the ENU-treated fathers was 6 × 10^- 8/bp and significantly higher than that of the control (2 × 10^- 8/bp). There were no significant differences in de novo MFs between gene-coding and non-coding regions. WGS analysis was able to detect ENU-induced characteristic de novo base substitutions at a low dose group.</p><p><strong>Conclusions: </strong>Despite a difference between exome/genome and exogenous reporter genes, the results indicated that ENU-induced point mutations in male germ cells could be transmitted to the next generation without severe selection.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"43"},"PeriodicalIF":1.7,"publicationDate":"2021-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39501132","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":"Genetic interaction between RLM1 and F-box motif encoding gene SAF1 contributes to stress response in Saccharomyces cerevisiae.","authors":"Meenu Sharma,&nbsp;V Verma,&nbsp;Narendra K Bairwa","doi":"10.1186/s41021-021-00218-x","DOIUrl":"https://doi.org/10.1186/s41021-021-00218-x","url":null,"abstract":"<p><strong>Background: </strong>Stress response is mediated by the transcription of stress-responsive genes. The F-box motif protein Saf1p is involved in SCF-E3 ligase mediated degradation of the adenine deaminase, Aah1p upon nutrient stress. The four transcription regulators, BUR6, MED6, SPT10, SUA7, are listed for SAF1 in the genome database of Saccharomyces cerevisiae. Here in this study, we carried out an in-silico analysis of gene expression and transcription factor databases to understand the regulation of SAF1 expression during stress for hypothesis and experimental analysis.</p><p><strong>Result: </strong>An analysis of the GEO profile database indicated an increase in SAF1 expression when cells were treated with stress agents such as Clioquinol, Pterostilbene, Gentamicin, Hypoxia, Genotoxic, desiccation, and heat. The increase in expression of SAF1 during stress conditions correlated positively with the expression of RLM1, encoding the Rlm1p transcription factor. The expression of AAH1 encoding Aah1p, a Saf1p substrate for ubiquitination, appeared to be negatively correlated with the expression of RLM1 as revealed by an analysis of the Yeastract expression database. Based on analysis of expression profile and regulatory association of SAF1 and RLM1, we hypothesized that inactivation of both the genes together may contribute to stress tolerance. The experimental analysis of cellular growth response of cells lacking both SAF1 and RLM1 to selected stress agents such as cell wall and osmo-stressors, by spot assay indicated stress tolerance phenotype similar to parental strain however sensitivity to genotoxic and microtubule depolymerizing stress agents.</p><p><strong>Conclusions: </strong>Based on in-silico and experimental data we suggest that SAF1 and RLM1 both interact genetically in differential response to genotoxic and general stressors.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"45"},"PeriodicalIF":1.7,"publicationDate":"2021-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39500517","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":"Folate metabolism modifies chromosomal damage induced by 1,3-butadiene: results from a match-up study in China and in vitro experiments.","authors":"Menglong Xiang,&nbsp;Zhi Wang,&nbsp;Peng Zou,&nbsp;Xi Ling,&nbsp;Guowei Zhang,&nbsp;Ziyuan Zhou,&nbsp;Jia Cao,&nbsp;Lin Ao","doi":"10.1186/s41021-021-00217-y","DOIUrl":"https://doi.org/10.1186/s41021-021-00217-y","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the role of folate metabolism in 1,3-Butadiene (BD)'s genotoxicity, we conducted a match-up study in BD-exposed workers in China to analyze the associations between the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and the chromosomal damage induced by BD exposure, and culture-based experiments in TK-6 cells to examine the global DNA methylation levels and chromosomal damage when exposed both to BD's genotoxic metabolite, 1,2:3,4-diepoxybutane (DEB), and MTHFR's direct catalytic product, 5-methyltetrahydrofolate (5-MTHF).</p><p><strong>Methods: </strong>Cytokinesis block micronucleus assay (CBMN) was used to examine the chromosomal damage induced by BD or DEB. Poisson regression models were produced to quantify the relationship of chromosomal damage and genetic polymorphisms in the BD-exposed workers. Global DNA methylation levels in TK6 cells were examined using DNA Methylation Quantification Kit.</p><p><strong>Results: </strong>We found that BD-exposed workers carrying MTHFR C677T CC (2.00 ± 2.00‰) (FR = 0.36, 95%CI: 0.20-0.67, P < 0.01) or MTHFR C677T CT (2.87 ± 1.98‰) (FR = 0.49, 95%CI: 0.32-0.77, P < 0.01) genotypes had significantly lower nuclear bud (NBUD) frequencies than those carrying genotype MTHFR 677 TT (5.33 ± 2.60‰), respectively. The results in TK6 cells showed that there was a significant increment in frequencies of micronucleus (MN), nucleoplasmic bridge (NPB) and nuclear bud (NBUD) with exposure to DEB at each 5-MTHF dose (ANOVA, P < 0.01). Additionally, there was a significant decrease in frequencies of MN, NPB and NBUD in DEB-exposed cultures with increasing concentration of 5-MTHF (ANOVA, P < 0.05). The levels of global DNA methylation were significantly decreased by DEB treatment in a dose-dependent manner within each 5-MTHF concentration in TK-6 cells (ANOVA, P < 0.01), and were significantly increased by 5-MTHF supplementation within each DEB concentration (ANOVA, P < 0.01).</p><p><strong>Conclusion: </strong>We reported that folate metabolism could modify the association between BD exposure and chromosomal damage, and such effect may be partially mediated by DNA hypomethylation, and 5-MTHF supplementation could rescue it.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"44"},"PeriodicalIF":1.7,"publicationDate":"2021-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39501128","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":"Fc receptor-like 1, 3, and 6 variants are associated with rheumatoid arthritis risk in the Chinese Han population.","authors":"Yonghui Yang,&nbsp;Dandan Li,&nbsp;Chunjuan He,&nbsp;Linna Peng,&nbsp;Shishi Xing,&nbsp;Mei Bai,&nbsp;Hao Rong,&nbsp;Dongya Yuan,&nbsp;Yongjun He,&nbsp;Xue He,&nbsp;Li Wang,&nbsp;Tianbo Jin","doi":"10.1186/s41021-021-00213-2","DOIUrl":"https://doi.org/10.1186/s41021-021-00213-2","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is the most common autoimmune system diseases in our world. More studies in recent years have shown that FCRL gene polymorphisms is closely related to autoimmune diseases. It is suggested that genetic factors play a crucial role in the pathogenesis of this disease. In this study, we aimed to investigate the relationship between FCRL1 rs2050568, FCRL3 rs2317230 and FCRL6 rs58240276 polymorphisms and RA risk in the Chinese Han population. 506 with RA patients and 509 healthy controls were recruited in this study, and the single nucleotide polymorphisms (SNPs) was successfully genotyped using the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (95% CIs) after adjusting for age and gender were conducted to assess these SNPs polymorphisms and RA risk. The multifactor dimensionality reduction (MDR) method was conducted to analyze SNP-SNP interaction.</p><p><strong>Results: </strong>Our results revealed that there no significant association was observed between the allele and genotype frequencies among these SNPs and RA risk (all p > 0.05). Straified analysis by age and gender, the results confirmed that FCRL1 rs2050568 T/T genotype enhanced the risk of RA in females (p = 0.014). The G/T - T/T genotype of FCRL3 rs2317230 was correlated with a decreased RA risk in males (p = 0.021). We also observed that the C/T-T/T genotype of FCRL6 rs58240276 was increased the risk of RA in the group at age >  54 years (p = 0.016). In addition, FCRL1 rs2050568-TT, FCRL6 rs58240276-TT and FCRL1 rs2050568-TT, FCRL3 rs2317230-TT, FCRL6 rs58240276-TT are the best models for multi-site MDR analysis (p < 0.05), and the two best models mentioned above and classes RA have the most significant correlation.</p><p><strong>Conclusions: </strong>Our study demonstrated that FCRL1 rs2050568, FCRL3 rs2317230, and FCRL6 rs58240276 polymorphisms were correlated with RA susceptibility in the Chinese Han population.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"42"},"PeriodicalIF":1.7,"publicationDate":"2021-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39519451","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":"Bacterial mutagenicity test data: collection by the task force of the Japan pharmaceutical manufacturers association.","authors":"Atsushi Hakura,&nbsp;Takumi Awogi,&nbsp;Toshiyuki Shiragiku,&nbsp;Atsushi Ohigashi,&nbsp;Mika Yamamoto,&nbsp;Kayoko Kanasaki,&nbsp;Hiroaki Oka,&nbsp;Yasuaki Dewa,&nbsp;Shunsuke Ozawa,&nbsp;Kouji Sakamoto,&nbsp;Tatsuya Kato,&nbsp;Eiji Yamamura","doi":"10.1186/s41021-021-00206-1","DOIUrl":"https://doi.org/10.1186/s41021-021-00206-1","url":null,"abstract":"<p><strong>Background: </strong>Ames test is used worldwide for detecting the bacterial mutagenicity of chemicals. In silico analyses of bacterial mutagenicity have recently gained acceptance by regulatory agencies; however, current in silico models for prediction remain to be improved. The Japan Pharmaceutical Manufacturers Association (JPMA) organized a task force in 2017 in which eight Japanese pharmaceutical companies had participated. The purpose of this task force was to disclose a piece of pharmaceutical companies' proprietary Ames test data.</p><p><strong>Results: </strong>Ames test data for 99 chemicals of various chemical classes were collected for disclosure in this study. These chemicals are related to the manufacturing process of pharmaceutical drugs, including reagents, synthetic intermediates, and drug substances. The structure-activity (mutagenicity) relationships are discussed in relation to structural alerts for each chemical class. In addition, in silico analyses of these chemicals were conducted using a knowledge-based model of Derek Nexus (Derek) and a statistics-based model (GT1_BMUT module) of CASE Ultra. To calculate the effectiveness of these models, 89 chemicals for Derek and 54 chemicals for CASE Ultra were selected; major exclusions were the salt form of four chemicals that were tested both in the salt and free forms for both models, and 35 chemicals called \"known\" positives or negatives for CASE Ultra. For Derek, the sensitivity, specificity, and accuracy were 65% (15/23), 71% (47/66), and 70% (62/89), respectively. The sensitivity, specificity, and accuracy were 50% (6/12), 60% (25/42), and 57% (31/54) for CASE Ultra, respectively. The ratio of overall disagreement between the CASE Ultra \"known\" positives/negatives and the actual test results was 11% (4/35). In this study, 19 out of 28 mutagens (68%) were detected with TA100 and/or TA98, and 9 out of 28 mutagens (32%) were detected with either TA1535, TA1537, WP2uvrA, or their combination.</p><p><strong>Conclusion: </strong>The Ames test data presented here will help avoid duplicated Ames testing in some cases, support duplicate testing in other cases, improve in silico models, and enhance our understanding of the mechanisms of mutagenesis.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"41"},"PeriodicalIF":1.7,"publicationDate":"2021-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39476610","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":"MTHFR A1298C gene polymorphism on stroke risk: an updated meta-analysis.","authors":"Xiaobo Dong,&nbsp;Jun Wang,&nbsp;Gesheng Wang,&nbsp;Jiayue Wang,&nbsp;Lei Wang,&nbsp;Yong Du","doi":"10.1186/s41021-021-00208-z","DOIUrl":"https://doi.org/10.1186/s41021-021-00208-z","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown the effect of MTHFR A1298C gene polymorphism on stroke risk. But the results of published studies remained inconclusive and controversial. So we conducted a meta-analysis to accurately estimate the potential association between MTHFR A1298C gene polymorphism and stroke susceptibility.</p><p><strong>Methods: </strong>A systematic literature search on Embase, Pubmed, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang electronic database identified 40 articles including 5725 cases and 8655 controls. Strength of association was evaluated by pooled odds ratio (OR), 95% confidence interval (CI) and p value. Funnel plots and Begger's regression test were applied for testing the publication bias. Statistical analysis of all data was performed by Stata 12.0.</p><p><strong>Results: </strong>The meta-analysis results indicated a significant relationship between MTHFR gene A1298C polymorphisms and stoke risk under the C allelic genetic model (OR = 1.19, 95%CI = 1.07-1.32, p = 0.001), dominant genetic model (OR = 1.19, 95%CI = 1.06-1.33, p = 0.004) and recessive genetic model (OR = 1.43, 95%CI =1.15-1.77, p = 0.001). In subgroup analysis, we discovered obvious correlation in three genetic model of Asian, stroke type, adult by ethnicity, population, stroke type, source of control and case size. Additionally, in studies of control from hospital and case size equal 100, obvious correlation was also found in the three genetic model.</p><p><strong>Conclusions: </strong>Our meta-analysis results indicated that there was evidence to support the correlation between MTHFR A1298C polymorphism and stroke susceptibility, especially in adults and ischemic stroke.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"40"},"PeriodicalIF":1.7,"publicationDate":"2021-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39447734","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.","authors":"Miyuki Shigano,&nbsp;Hironao Takasawa,&nbsp;Shuichi Hamada","doi":"10.1186/s41021-021-00212-3","DOIUrl":"https://doi.org/10.1186/s41021-021-00212-3","url":null,"abstract":"<p><strong>Background: </strong>The liver micronucleus (MN) assay is an effective and important in vivo test for detecting genotoxic compounds. In particular, the repeated-dose liver MN (RDLMN) assay which greatly facilitates incorporation of the liver MN assay into the general toxicity study has been developed. Usefulness of the RDLMN assay was appraised highly in the 7th International Workshops on Genotoxicity Testing (2017 in Tokyo) in that sufficient numbers and types of chemicals were studied and easy integration into the general toxicity study is preferred from the 3R's point of view. However, it was pointed out that it is necessary to evaluate the effect of age at the start of 4-week repeated administration, since there are limited data, where only those of rats of 6 week of age at the start of administration are available. In this study, we conducted the 4-week RDLMN assay using rats of 6 and 8 weeks of age (at the start of administration) to investigate the effect of age on the liver MN inducibility. Clofibrate, a weak inducer of liver MN, was used in this study to detect the slight difference in the liver MN induction.</p><p><strong>Results: </strong>The liver MN induced by clofibrate was detected in both rats of 6 and 8 weeks of age at the start of administration. However, the liver MN induction was lower in rats of 8 weeks of age compared to rats of 6 weeks of age at the start of administration.</p><p><strong>Conclusion: </strong>These results suggest that the liver MN inducibility decreases with age. Therefore, we recommend the use of rats of 6 weeks of age at start of administration to reliably detect the liver MN induction in the RDLMN assay.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"37"},"PeriodicalIF":1.7,"publicationDate":"2021-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39401732","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":"High resolution melting analysis and detection of Leishmania resistance: the role of multi drug resistance 1 gene.","authors":"Maryam Fekri Soofi Abadi,&nbsp;Alireza Moradabadi,&nbsp;Reza Vahidi,&nbsp;Saeedeh Shojaeepour,&nbsp;Sara Rostami,&nbsp;Iman Rad,&nbsp;Shahriar Dabiri","doi":"10.1186/s41021-021-00210-5","DOIUrl":"https://doi.org/10.1186/s41021-021-00210-5","url":null,"abstract":"<p><strong>Background: </strong>Pentavalent antimonial compounds are currently used to treat leishmaniasis and resistance to these drugs is a serious problem. Multidrug resistance protein is an efflux pump of the cell membrane that expels foreign compounds. This study designed to evaluate the mutations in the multi-drug resistance 1 (MDR1) gene, in biopsy specimens of Leishmania tropica, with high resolution melting (HRM) method. In this experimental study, genomic DNA was extracted from 130 patients with skin leishmaniasis. Then, nucleotide changes were investigated throughout the gene using HRM and sequencing methods. The samples categorized in 5 groups by differences in the melting temperature (Tm).</p><p><strong>Result: </strong>The nucleotide changes analysis showed that 61% of the samples of different groups that were unresponsive to drug had mutations in the MDR1 gene, which were also confirmed by the sequencing method. These mutations can be one of the factors responsible for non-responsiveness to the treatment.</p><p><strong>Conclusion: </strong>According to the findings, it seems that mutation in MDR1 gene could be responsible for drug resistance to pentavalent antimonial compounds. Furthermore, HRM method can be used to diagnose drug resistance in leishmaniasis. It is also recommended that further studies be done regarding the importance of drug resistance in the leishmania affected patients.</p>","PeriodicalId":12709,"journal":{"name":"Genes and Environment","volume":" ","pages":"36"},"PeriodicalIF":1.7,"publicationDate":"2021-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39302035","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}