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Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

《医学前沿(英文)》 2015年 第9卷 第3期   页码 261-274 doi: 10.1007/s11684-015-0406-y

摘要:

Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

关键词: environmental pollution     DNA methylation     cancer     biomarker     diagnosis     therapy     prevention    

Mutant DNA methylation regulators endow hematopoietic stem cells with the preleukemic stem cell property

null

《医学前沿(英文)》 2015年 第9卷 第4期   页码 412-420 doi: 10.1007/s11684-015-0423-x

摘要:

Genetic mutations are considered to drive the development of acute myeloid leukemia (AML). With the rapid progress in sequencing technologies, many newly reported genes that are recurrently mutated in AML have been found to govern the initiation and relapse of AML. These findings suggest the need to distinguish the driver mutations, especially the most primitive single mutation, from the subsequent passenger mutations. Recent research on DNA methyltransferase 3A (DNMT3A) mutations provides the first proof-of-principle investigation on the identification of preleukemic stem cells (pre-LSCs) in AML patients. Although DNMT3A mutations alone may only transform hematopoietic stem cells into pre-LSCs without causing the full-blown leukemia, the function of this driver mutation appear to persist from AML initiation up to relapse. Therefore, identifying and targeting preleukemic mutations, such as DNMT3A mutations, in AML is a promising strategy for treatment and reduction of relapse risk.

关键词: preleukemic stem cell     acute myeloid leukemia     relapse     DNMT3A    

DNA methylation-based subclassification of psoriasis in the Chinese Han population

Fusheng Zhou, Changbing Shen, Yi-Hsiang Hsu, Jing Gao, Jinfa Dou, Randy Ko, Xiaodong Zheng, Liangdan Sun, Yong Cui, Xuejun Zhang

《医学前沿(英文)》 2018年 第12卷 第6期   页码 717-725 doi: 10.1007/s11684-017-0588-6

摘要: Psoriasis (Ps) is an inflammatory skin disease caused by genetic and environmental factors. Previous studies on DNA methylation (DNAm) found genetic markers that are closely associated with Ps, and evidence has shown that DNAm mediates genetic risk in Ps. In this study, Consensus Clustering was used to analyze DNAm data, and 114 Ps patients were divided into three subclassifications. Investigation of the clinical characteristics and copy number variations (CNVs) of , , and in the three subclassifications revealed no significant differences in gender ratio and in Ps area and severity index (PASI) score. The proportion of late-onset (≥40 years) Ps patients was significantly higher in type I than in types II and III ( = 0.035). Type III contained the smallest proportion of smokers and the largest proportion of non-smoking Ps patients ( = 0.086). The CNVs of and showed no significant differences but the CNV of significantly differed among the three subclassifications ( = 0.044). This study is the first to profile Ps subclassifications based on DNAm data in the Chinese Han population. These results are useful in the treatment and management of Ps from the molecular and genetic perspectives.

关键词: psoriasis     DNA methylation     subclassification    

The value of epigenetic markers in esophageal cancer

Xiao-Mei ZHANG, Ming-Zhou GUO,

《医学前沿(英文)》 2010年 第4卷 第4期   页码 378-384 doi: 10.1007/s11684-010-0230-3

摘要: Developing esophageal cancer is a multi-step process that begins with the accumulation of genetic and epigenetic alterations, and leads to the activation of oncogenes and the inactivation or loss of tumor suppressor genes (TSG). In addition to genetic alteration, epigenetic modifications, and in particular DNA methylation, are recognized as a common molecular alteration in human tumors. In esophageal cancer, aberrant methylation of promoter regions occurs not only in advanced cancer, but also in premalignant lesions. DNA methylation is related to survival time and sensitivity of chemoradiotherapy. This review is mainly focused on epigenetic changes in esophageal cancer and the value of early detection for patient prognosis, treatment choices, and potential targeting therapy.

关键词: epigenetics     DNA methylation     esophageal cancer     dysplasia    

The critical importance of epigenetics in autoimmune-related skin diseases

《医学前沿(英文)》 2023年 第17卷 第1期   页码 43-57 doi: 10.1007/s11684-022-0980-8

摘要: Autoimmune-related skin diseases are a group of disorders with diverse etiology and pathophysiology involved in autoimmunity. Genetics and environmental factors may contribute to the development of these autoimmune disorders. Although the etiology and pathogenesis of these disorders are poorly understood, environmental variables that induce aberrant epigenetic regulations may provide some insights. Epigenetics is the study of heritable mechanisms that regulate gene expression without changing DNA sequences. The most important epigenetic mechanisms are DNA methylation, histone modification, and noncoding RNAs. In this review, we discuss the most recent findings regarding the function of epigenetic mechanisms in autoimmune-related skin disorders, including systemic lupus erythematosus, bullous skin diseases, psoriasis, and systemic sclerosis. These findings will expand our understanding and highlight the possible clinical applications of precision epigenetics approaches.

关键词: epigenetics     autoimmune-related skin diseases     DNA methylation     histone modifications     noncoding RNAs    

Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation in acute myeloid leukemia

《医学前沿(英文)》 2022年 第16卷 第4期   页码 627-636 doi: 10.1007/s11684-020-0815-4

摘要: Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

关键词: RUNX1     gene mutation     acute myeloid leukemia     transcriptional repression     DNA methylation    

Effects of the

Yi FANG,Xiangwei FU,Junjie LI,Ming DU,Baoyu JIA,Jinlong ZHANG,Xiaosheng ZHANG,Shien ZHU

《农业科学与工程前沿(英文)》 2014年 第1卷 第4期   页码 314-320 doi: 10.15302/J-FASE-2014038

摘要: This study was conducted to systematically assess the reproductive performance of transgenic ewes. In the transgenic founders (F ) and their positive offspring (F ), hematological and reproductive parameters and the global DNA methylation level in oocytes at various stages were analyzed. The values of the physiological and biochemical parameters determined from the blood samples did not differ significantly between the transgenic and wild-type ewes. Moreover, the transgenic ewes showed reproductive traits similar to the wild-type ewes. These traits included characteristics of puberty, the estrus cycle, estrus duration, gestation, the pregnancy rate and the superovulation response. Additionally, no significant differences were found between transgenic and wild-type ewes in the DNA methylation level of the oocytes at various stages. In summary, the preliminary evidence presented in this paper demonstrates that the presence of the transgene did not affect the reproductive performance in sheep.

关键词: TLR4 transgenic ewe     safety assessment     reproductive trait     oocyte     DNA methylation    

Effects of hydralazine and valproate on the expression of E-cadherin gene and the invasiveness of QBC

Hong LI, Shaoqin CHEN, Yi SHU, Yongjun CHEN, Ying SU, Xin WANG, Shengquan ZOU

《医学前沿(英文)》 2009年 第3卷 第2期   页码 153-157 doi: 10.1007/s11684-009-0034-5

摘要: To clarify the effect of DNA methylation and histone deacetylase inhibitors on the expression of the E-cadherin gene and the invasiveness of the QBC cells, the QBC cells were separately treated with hydralazine, valproate, or combination of the two drugs. The mRNA expression of E-cadherin was examined with reverse transcription-polymerase chain reaction (RT-PCR), the protein of the gene with Western blotting. The methylation status of the promoter region of the gene was detected with methylation-specific PCR (MSP). The invasiveness of QBC cells was detected with transwell assay. It was found that the promoter region of the E-cadherin gene of QBC cells was hypermethylated. Valproate alone could not contribute to demethylation of the gene, whereas hydralazine could make them to be partly demethylated. However, the methylation status of the gene could be thoroughly reversed by using valproate and hydralazine in combination. What’s more, it was confirmed that the E-cadherin gene of QBC cells could not be transcriptionally reactivated by Valproate alone, whereas hydralazine alone could induce moderate reexpression of the gene. However, using valproate and hydralazine in combination could result in robust reexpression of the E-cadherin gene ( =0.000). Likewise, the invasiveness of the QBC939 cells was sharply decreased by treatment with two drugs in combination and slightly decreased with one drug alone. It could be concluded that the two drugs have synergistic effect on the demethylation and reexpression of the E-cadherin gene of QBC cells, and also on the reduction of the invasiveness of the QBC939 cells.

关键词: DNA methylation inhibitor     histone deacetylase inhibitor     bile duct carcinoma     E-cadherin    

Shape selective catalysis in methylation of toluene: Development, challenges and perspectives

Jian Zhou, Zhicheng Liu, Yangdong Wang, Dejin Kong, Zaiku Xie

《化学科学与工程前沿(英文)》 2018年 第12卷 第1期   页码 103-112 doi: 10.1007/s11705-017-1671-x

摘要: Toluene methylation with methanol offers an alternative method to produce -xylene by gathering methyl group directly from C1 chemical sources. It supplies a “molecular engineering” process to realize directional conversion of toluene/methanol molecules by selective catalysis in complicated methylation system. In this review, we introduce the synthesis method of -xylene, the development history of methylation catalysts and reaction mechanism, and the effect of reaction condition in -selective technical process. If constructing -xylene as the single target product, the major challenge to develop -selective toluene methylation is to improve the -xylene selectivity without, or as little as possible, losing the fraction of methanol for methylation. To reach higher yield of -xylene and more methanol usage in methylation, zeolite catalyst design should consider improving mass transfer and afterwards covering external acid sites by surface modification to get short “micro-tunnels” with shape selectivity. A solid understanding of mass transfer will benefit realizing the aim of converting more methanol feedstock into -methyl group.

关键词: shape selective catalysis     methylation of toluene    

工程化DNA材料构建DNA活字系统实现可持续的数据存储 Article

巩子祎, 宋理富, 裴广胜, 董雨菲, 李炳志, 元英进

《工程(英文)》 2023年 第29卷 第10期   页码 130-136 doi: 10.1016/j.eng.2022.05.023

摘要:

DNA分子作为一种具有潜力的数据存储绿色材料,具有密度高和保存期长的优势。然而,目前DNA数据存储的数据写入依赖于DNA从头合成,写入成本高昂,且产生有害物,限制了其实际应用。在本研究中,我们开发了一种DNA活字存储系统,该系统可以利用由细胞工厂预生产的DNA活字片段进行数据写入。在这个系统中,这些预先生成的DNA片段,在这里称为“DNA活字”,是可重复使用的基本数据单元。通过这些DNA活字的快速组装来实现数据写入,从而避免了昂贵且对环境有害的DNA化学合成过程。通过DNA活字片段的反复使用和生物组装,该系统在降低写入成本方面的潜力非常突出,为经济和可持续的DNA数据存储技术开辟了一条新颖路线。

关键词: 合成生物学     DNA信息存储     DNA活字存储系统     经济性DNA数据存储    

The role of PARP1 in the DNA damage response and its application in tumor therapy

null

《医学前沿(英文)》 2012年 第6卷 第2期   页码 156-164 doi: 10.1007/s11684-012-0197-3

摘要:

Single-strand break repair protein poly(ADP-ribose) polymerase 1 (PARP1) catalyzes the poly(ADP-ribosyl)ation of many key proteins in vivo and thus plays important roles in multiple DNA damage response pathways, rendering it a promising target in cancer therapy. The tumor-suppressor effects of PARP inhibitors have attracted significant interest for development of novel cancer therapies. However, recent evidence indicated that the underlying mechanism of PARP inhibitors in tumor therapy is more complex than previously expected. The present review will focus on recent progress on the role of PARP1 in the DNA damage response and PARP inhibitors in cancer therapy. The emerging resistance of BRCA-deficient tumors to PARP inhibitors is also briefly discussed from the perspective of DNA damage and repair. These recent research advances will inform the selection of patient populations who can benefit from the PARP inhibitor treatment and development of effective drug combination strategies.

关键词: PARP1     synthetic lethality     PARP inhibitor     DNA repair     cancer     NHEJ    

Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

《化学科学与工程前沿(英文)》 2011年 第5卷 第2期   页码 179-187 doi: 10.1007/s11705-009-0268-4

摘要: Ataxia-telangiectasia mutated (ATM) plays a key role in regulating the cellular response to ionizing radiation. The tumor-suppressor gene ATM, mutations in which cause the human genetic disease ataxia telangiectasia, encodes a key protein kinase that controls the cellular response to double-stranded breaks. Activation of ATM results in phosphorylation of many downstream targets that modulate numerous damage response pathways, most notably cell cycle checkpoints. Here, we highlight some of the new developments in the field in our understanding of the mechanism of activation of ATM and its signaling pathways, explore whether DNA double-strand breaks are the sole activators of ATM and ATM-dependent signaling pathways, and address some of the prominent, unanswered questions related to ATM and its function. The scope of this article is to provide a brief overview of the recent literature on this subject and to raise questions that could be addressed in future studies.

关键词: ataxia-telangiectasia mutated (ATM)     cell cycle checkpoint     DNA damage     signalling transduction    

Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

《医学前沿(英文)》 2014年 第8卷 第2期   页码 201-216 doi: 10.1007/s11684-014-0324-4

摘要:

Activation-induced deaminase (AID) initiates the secondary antibody diversification process in B lymphocytes. In mammalian B cells, this process includes somatic hypermutation (SHM) and class switch recombination (CSR), both of which require AID. AID induces U:G mismatch lesions in DNA that are subsequently converted into point mutations or DNA double stranded breaks during SHM/CSR. In a physiological context, AID targets immunoglobulin (Ig) loci to mediate SHM/CSR. However, recent studies reveal genome-wide access of AID to numerous non-Ig loci. Thus, AID poses a threat to the genome of B cells if AID-initiated DNA lesions cannot be properly repaired. In this review, we focus on the molecular mechanisms that regulate the specificity of AID targeting and the repair pathways responsible for processing AID-initiated DNA lesions.

关键词: class switch recombination     somatic hypermutation     activation-induced deaminase     DNA repair     genomic instability    

Molecular simulation of the interaction mechanism between CodY protein and DNA in

Linchen Yuan, Hao Wu, Yue Zhao, Xiaoyu Qin, Yanni Li

《化学科学与工程前沿(英文)》 2019年 第13卷 第1期   页码 133-139 doi: 10.1007/s11705-018-1737-4

摘要: In , the global transcriptional regulatory factor CodY can interact with the promoter DNA to regulate the growth, metabolism, environmental adaptation and other biological activities of the strains. In order to study the mechanism of interaction between CodY and its target DNA, molecular docking and molecular dynamics simulations were used to explore the binding process at molecular level. Through the calculations of the free energy of binding, hydrogen bonding and energy decomposition, nine key residues of CodY were identified, corresponding to SER184, SER186, SER208, THR217, ARG218, SER219, ASN223, LYS242 and GLY243, among which SER186, ARG218 and LYS242 play a vital role in DNA binding. Our research results provide important theoretical guidance for using wet-lab methods to study and optimize the metabolic network regulated by CodY.

关键词: CodY     DNA     molecular docking     molecular dynamics    

Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

《农业科学与工程前沿(英文)》 2014年 第1卷 第3期   页码 185-190 doi: 10.15302/J-FASE-2014035

摘要: DNA damage is one of the most common threats to meiotic cells. It has the potential to induce infertility and genetic abnormalities that may be passed to the embryo. Here, we reviewed exogenous factors which could induce DNA damage. Specially, we addressed the different effects of DNA damage on mouse oocytes and embryonic development. Complex DNA damage, double-strand breaks, represents a more difficult repair process and involves various repair pathways. Understanding the mechanisms involved in DNA damage responses may improve therapeutic strategies for ovarian cancer and fertility preservation.

关键词: DNA damage     double-strand breaks (DSBs)     oocyte     embryo    

标题 作者 时间 类型 操作

Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications

null

期刊论文

Mutant DNA methylation regulators endow hematopoietic stem cells with the preleukemic stem cell property

null

期刊论文

DNA methylation-based subclassification of psoriasis in the Chinese Han population

Fusheng Zhou, Changbing Shen, Yi-Hsiang Hsu, Jing Gao, Jinfa Dou, Randy Ko, Xiaodong Zheng, Liangdan Sun, Yong Cui, Xuejun Zhang

期刊论文

The value of epigenetic markers in esophageal cancer

Xiao-Mei ZHANG, Ming-Zhou GUO,

期刊论文

The critical importance of epigenetics in autoimmune-related skin diseases

期刊论文

Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation in acute myeloid leukemia

期刊论文

Effects of the

Yi FANG,Xiangwei FU,Junjie LI,Ming DU,Baoyu JIA,Jinlong ZHANG,Xiaosheng ZHANG,Shien ZHU

期刊论文

Effects of hydralazine and valproate on the expression of E-cadherin gene and the invasiveness of QBC

Hong LI, Shaoqin CHEN, Yi SHU, Yongjun CHEN, Ying SU, Xin WANG, Shengquan ZOU

期刊论文

Shape selective catalysis in methylation of toluene: Development, challenges and perspectives

Jian Zhou, Zhicheng Liu, Yangdong Wang, Dejin Kong, Zaiku Xie

期刊论文

工程化DNA材料构建DNA活字系统实现可持续的数据存储

巩子祎, 宋理富, 裴广胜, 董雨菲, 李炳志, 元英进

期刊论文

The role of PARP1 in the DNA damage response and its application in tumor therapy

null

期刊论文

Functional role of ATM in the cellular response to DNA damage

Ming LIU, Wenxiang HU

期刊论文

Generation and repair of AID-initiated DNA lesions in B lymphocytes

null

期刊论文

Molecular simulation of the interaction mechanism between CodY protein and DNA in

Linchen Yuan, Hao Wu, Yue Zhao, Xiaoyu Qin, Yanni Li

期刊论文

Effects of DNA damage on oocyte meiotic maturation and early embryonic development

Shen YIN,Junyu MA,Wei SHEN

期刊论文