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| 1 | Epigenetic regulation: methylation of histone and non-histone proteins显示文摘Histone methylation is believed to play important roles in epigenetic memory in various biological processes. However, questions like whether the methylation marks themselves are faithfully transmit- ted into daughter cells and through what mechanisms are currently under active investigation. Previ- ously, methylation was considered to be irreversible, but the recent discovery of histone lysine de- methylases revealed a dynamic nature of histone methylation regulation on four of the main sites of methylation on histone H3 and H4 tails (H3K4, H3K9, H3K27 and H3K36). Even so, it is still unclear whether demethylases specific for the remaining two sites, H3K79 and H4K20, exist. Furthermore, be- sides histone proteins, the lysine methylation and demethylation also occur on non-histone proteins, which are probably subjected to similar regulation as histones. This review discusses recent pro- gresses in protein lysine methylation regulation focusing on the above topics, while referring readers to a number of recent reviews for the biochemistry and biology of these enzymes. | LAN Fei1 & SHI Yang 2 1 Department of Biology, Constellation Pharmaceuticals, 148 Sidney Street, Cambridge, MA 02139, USA 2 Department of Pathology, Harvard Medical School, 77 Ave Louise Pasteur, Boston MA, 02115, USA | 2009 | Science China(Life Sciences)2009，52，4： | 27 |
| 2 | QSAR Studies on the Inhibitory Activityof Levofloxacin-thiadiazole HDACi Conjugates to Histone Deacetylases显示文摘A molecular electronegativity distance vector(M_t)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH_i,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH_i)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M_t.The correlation coefficients(R^2)and the leave-one-out(LOO)cross validation R_(cv)^(2 )for the pH_1,pH_(2 )and pH_(6 )models were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R^2,F,R^2_(cv),A_(IC),F_(IT )and V_(IF )tests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH_g–(g=1,2),–NH_2,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH_1,pH_(2 )as well as pH_(6 )bioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Zn^(2+)to form compounds,which is consistent with the results in reports. | 王超 冯长君 | 2018 | Chinese Journal of Structural Chemistry2018，37，11： | 23 |
| 3 | Reversibility and heritability of liver fibrosis:Implications for research and therapy显示文摘Liver fibrosis continues to be a major health problem worldwide due to lack of effective therapy.If the etiology cannot be eliminated,liver fibrosis progresses to cirrhosis and eventually to liver failure or malignancy;both are associated with a fatal outcome.Liver transplantation,the only curative therapy,is still mostly unavailable.Liver fibrosis was shown to be a reversible process;however,complete reversibility remains debatable.Recently,the molecular markers of liver fibrosis were shown to be transmitted across generations.Epigenetic mechanisms including DNA methylation,histone posttranslational modifications and noncoding RNA have emerged as major determinants of gene expression during liver fibrogenesis and carcinogenesis.Furthermore,epigenetic mechanisms have been shown to be transmitted through mitosis and meiosis to daughter cells and subsequent generations.However,the exact epigenetic regulation of complete liver fibrosis resolution and inheritance has not been fully elucidated.This communication will highlight the recent advances in the search for delineating the mechanisms governing resolution of liver fibrosis and the potential for multigenerational and transgenerational transmission of fibrosis markers.The fact that epigenetic changes,unlike genetic mutations,are reversible and can be modulated pharmacologically underscores the unique opportunity to develop effective therapy to completely reverse liver fibrosis,to prevent the development of malignancy and to regulate heritability of fibrosis phenotype. | Hussein M Atta | 2015 | World Journal of Gastroenterology2015，21，17： | 23 |
| 4 | Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer显示文摘尽管有最近的进展, oncogenic K 地岬驾驶的胰腺的 ductal 腺癌(PDAC ) 在最致命的人的癌症之中留在现代医学。PDAC 的致病对内在的染色体不稳定性和外来的发炎激活部分可归因。然而,在在胰腺的 tumorigenesis 的这二个事件之间的分子的连接充分还没被建立了。这里,我们证明(HMGB1 ) 细胞内部的高活动性组盒子 1 显著地压制 oncogenic 由禁止染色体的 K-Ras-driven 胰腺的 tumorigenesis 调停不稳定性的支持 inflammatory nucleosome 版本。任何一个单身者的有条件的基因脱离或在胰的 HMGB1 的两等位基因在出生使老鼠变为极其敏感到先锋损害的 oncogenic K-Ras-driven 开始,包括胰腺的 intraepithelial 瘤, intraductal 乳突的 mucinous 瘤,和 mucinous 膀胱的瘤。在胰的 HMGB1 的损失与染色体重新整理和 telomere 畸形描绘的氧化 DNA 损坏和 chromosomal 不稳定性被联系。这些导致煽动性的 nucleosome 版本并且宣传 K-Ras-driven 胰腺的 tumorigenesis。细胞外的 nucleosomes 支持 interleukin 6 (IL-6 ) 由渗入 macrophages/neutrophils 的分泌物并且提高在胰腺的损害表明激活的 oncogenic K 地岬。到 IL-6 或 histone H3 或为先进 glycation 的受体的大美人的抵销的抗体结束产品都限制表明激活的 K 地岬,阻止癌症开发和转移 / 侵略,并且延长在 Pdx1-Cre 的动物幸存; K 地岬 G12D/+;Hmgb1/ 鼠标。由 glycyrrhizin 的 HMGB1 损失的药理学抑制在煽动性的条件下面在老鼠限制 oncogenic K-Ras-driven tumorigenesis。减少在 PDAC 病人的 HMGB1 的原子、全部的细胞的表示与差的全面幸存相关,在 PDAC 与预示、治疗学的关联作为新奇肿瘤 suppressor 支持细胞内部的 HMGB1。 | Rui Kang Yangchun Xie Qiuhong Zhang Wen Hou Qingping Jiang Shan Zhu Jinbao Liu Dexing Zeng Haichao Wang David L Bartlet Timothy R Billiar Herbert J Zeh III Michael T Lotze Daolin Tang | 2017 | Cell Research2017，27，7： | 22 |
| 5 | Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis显示文摘Although thousands of DNA damaging events occur in each cell every day,efficient DNA repair pathways have evolved to counteract them. The DNA repair machinery plays a key role in maintaining genomic stability by avoiding the maintenance of mutations. The DNA repair enzymes continuously monitor the chromosomes to correct any damage that is caused by exogenous and endogenous mutagens. If DNA damage in proliferating cells is not repaired because of an inadequate expression of DNA repair genes,it might increase the risk of cancer. In addition to mutations,which can be either inherited or somatically acquired,epigenetic silencing of DNA repair genes has been associated with carcinogenesis. Gastric cancer represents the second highest cause of cancer mortality worldwide. The disease develops from the accumulation of several genetic and epigenetic changes during the lifetime. Among the risk factors,Helicobacter pylori(H. pylori) infection is considered the main driving factor to gastric cancer development. Thus,in this review,we summarize the current knowledge of the role of H. pylori infection on the epigenetic regulation of DNA repair machinery in gastric carcinogenesis. | Juliana Carvalho Santos Marcelo Lima Ribeiro | 2015 | World Journal of Gastroenterology2015，21，30： | 19 |
| 6 | 露蜂房提取物对H22肝癌小鼠防治作用及其机制的实验研究显示文摘目的观察露蜂房提取物对H22荷瘤小鼠的抑瘤作用及对腹水瘤小鼠生存期的影响,并探讨其抗肿瘤作用机制。方法将80只小鼠随机分为2批次,每批次40只,分别于右腋下及腹腔接种H22肝癌细胞制作实体瘤和腹水瘤模型。各批次随机分为四组,盐水对照组、5-FU组、露蜂房提取物高剂量组(简称露峰房高剂量组)、露蜂房提取物低剂量组(简称露峰房低剂量组),每组10只。实体瘤模型组连续用药14 d,次日处死取瘤称重,计算抑瘤率,免疫组化技术检测Histone H1、Cy-clin B1的表达。腹水瘤模型组连续用药14 d,记录各组小鼠生存天数,计算生命延长率。结果露蜂房高剂量组对小鼠肝癌细胞的生长抑制率为38.06%,Histone H1表达增加,而Cyclin B1表达降低,与盐水对照组比较差异有统计学意义(P<0.01)。并可明显延长腹水瘤小鼠生存期。结论露蜂房提取物对肝癌细胞有抑制作用,其抑瘤作用机制可能与Histone H1、Cyclin B1调控有关。 | 贾爱明 胡文梅 张红 刘耘 王朝晖 | 2012 | 世界中西医结合杂志2012，7，12： | 16 |
| 7 | Inhibition of autophagy significantly enhances combination therapy with sorafenib and HDAC inhibitors for human hepatoma cells显示文摘AIM:To clarify whether histone deacetylase inhibitors histone deacetylase inhibitors(HDACIs)can sensitize hepatocellular carcinoma(HCC)cells to sorafenib treatment.METHODS:Bax,Bcl-2,ATG5-ATG12,p21,and p27protein levels in Hep3B,HepG2,and PLC/PRF/5 cells were examined by Western blot.CCK8 and a fluorometric caspase-3 assay were used to examine cellular viability and apoptosis levels.The effect of Beclin-1 on sensitization of HCC cells to sorafenib was examined by transfecting Beclin-1 siRNA into Hep3B,HepG2,and PLC/PRF/5 cells.RESULTS:Autophagy inhibition enhances the inhibitory effects of vorinostat and sorafenib alone or in combination on HCC cell growth.Vorinostat and sorafenib synergistically induced apoptosis and cell cycle alterations.Western blot data indicated that HDACIs and Beclin-1 knockdown increased the p53 acetylation level.The knockdown of Beclin-1 enhanced the synergistic effect of the combination of vorinostat with sorafenib.CONCLUSION:HDACIs can sensitize HCC cells to sorafenib treatment by regulating the acetylation level of Beclin-1. | Hang Yuan Ai-Jun Li Sen-Lin Ma Long-Jiu Cui Bin Wu Lei Yin Meng-Chao Wu | 2014 | World Journal of Gastroenterology2014，20，17： | 15 |
| 8 | DNA and histone methylation in gastric carcinogenesis显示文摘Epigenetic alterations contribute significantly to the development and progression of gastric cancer,one of the leading causes of cancer death worldwide.Epigenetics refers to the number of modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA,and these changes lead to transcriptional activation or silencing of the gene.Over the years,the study of epigenetic processes has increased,and novel therapeutic approaches that target DNA methylation and histone modifications have emerged.A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment.Here,we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome. | Danielle Queiroz Calcagno Carolina Oliveira Gigek Elizabeth Suchi Chen Rommel Rodriguez Burbano Marília de Arruda Cardoso Smith | 2013 | World Journal of Gastroenterology2013，19，8： | 14 |
| 9 | Retrospective and perspective of plant epigenetics in China显示文摘Epigenetics refers to the study of heritable changes in gene function that do not involve changes in the DNA sequence. Such effects on cellular and physiological phenotypic traits may result from external or environmental factors or be part of normal developmental program. In eukaryotes, DNA wraps on a histone octamer(two copies of H2A, H2B, H3 and H4) to form nucleosome, the fundamental unit of chromatin. The structure of chromatin is subjected to a dynamic regulation through multiple epigenetic mechanisms, including DNA methylation, histone posttranslational modifications(PTMs), chromatin remodeling and noncoding RNAs. As conserved regulatory mechanisms in gene expression, epigenetic mechanisms participate in almost all the important biological processes ranging from basal development to environmental response. Importantly, all of the major epigenetic mechanisms in mammalians also occur in plants. Plant studies have provided numerous important contributions to the epigenetic research. For example, gene imprinting, a mechanism of parental allele-specific gene expression, was firstly observed in maize; evidence of paramutation, an epigenetic phenomenon that one allele acts in a single locus to induce a heritable change in the other allele, was firstly reported in maize and tomato.Moreover, some unique epigenetic mechanisms have been evolved in plants. For example, the 24-nt siRNA-involved RNA-directed DNA methylation(RdDM) pathway is plant-specific because of the involvements of two plant-specific DNA-dependent RNA polymerases, Pol IV and Pol V. A thorough study of epigenetic mechanisms is of great significance to improve crop agronomic traits and environmental adaptability. In this review, we make a brief summary of important progress achieved in plant epigenetics field in China over the past several decades and give a brief outlook on future research prospects.We focus our review on DNA methylation and histone PTMs, the two most important aspects of epigenetic mechanisms. | Cheng-Guo Duan Jian-Kang Zhu Xiaofeng Cao | 2018 | Journal of Genetics and Genomics2018，45，11： | 14 |
| 10 | Functions and mechanisms of plant histone deacetylases显示文摘Lysine acetylation, one of the major types of post-translational modifications, plays critical roles in regulating gene expression and protein function. Histone deacetylases(HDACs) are responsible for removing acetyl groups from lysines of both histone and non-histone proteins. While tremendous progress has been made in understanding the function and mechanism of HDACs in animals in the past two decades, nearly half of the HDAC studies in plants were reported within the past five years. In this review,we summarize the major findings on plant HDACs, with a focus on the model plant Arabidopsis thaliana, and highlight the components, regulatory mechanisms, and biological functions of HDAC complexes. | Xiangsong Chen Adeline BDing Xuehua Zhong | 2020 | Science China(Life Sciences)2020，63，2： | 11 |
| 11 | Deacetylase inhibitors-focus on non-histone targets and effects显示文摘Inhibitors of protein deacetylases have recently been established as a novel therapeutic principle for several human diseases,including cancer.The original notion of the mechanism of action of these compounds focused on the epigenetic control of transcriptional processes, especially of tumor suppressor genes,by interfering with the acetylation status of nuclear histone proteins,hence the name histone deacetylase inhibitors was coined.Yet,this view could not explain the high specificity for tumor cells and recent evidence now suggests that non-histone proteins represent major targets for protein deacetylase inhibitors and that the post-translational modification of the acetylome is involved in various cellular processes of differentiation,survival and cell death induction. | Matthias Ocker | 2010 | World Journal of Biological Chemistry2010，1，5： | 11 |
| 12 | Current evidence for histone deacetylase inhibitors in pancreatic cancer显示文摘Pancreatic cancer is one of the most aggressive human cancers,with more than 200 000 deaths worldwide every year.Despite recent efforts,conventional treatment approaches,such as surgery and classic chemotherapy,have only slightly improved patient outcomes.More effective and well-tolerated therapies are required to reverse the current poor prognosis of this type of neoplasm.Among new agents,histone deacetylase inhibitors (HDACIs) are now being tested.HDACIs have multiple biological effects related to acetylation of histones and many non-histone proteins that are involved in regulation of gene expression,apoptosis,cell cycle progression and angiogenesis.HDACIs induce cell cycle arrest and can activate the extrinsic and intrinsic pathways of apoptosis in different cancer cell lines.In the present review,the main mechanisms by which HDACIs act in pancreatic cancer cells in vitro,as well as their antiproliferative effects in animal models are presented.HDACIs constitute a promising treatment for pancreatic cancer with encouraging anti-tumor ef-fects,at well-tolerated doses. | Ioannis Koutsounas Constantinos Giaginis Efstratios Patsouris Stamatios Theocharis | 2013 | World Journal of Gastroenterology2013，19，6： | 9 |
| 13 | Epigenetic regulation and epigenomic landscape in rice显示文摘Epigenetic regulation has been implicated in the control of complex agronomic traits in rice(Oryza sativa),a staple food crop and model monocot plant. Recent advances in high-throughput sequencing and the moderately complex genome of rice have made it possible to study epigenetic regulation in rice on a genome-wide scale. This review discusses recent advances in our understanding of epigenetic regulation in rice, with an emphasis on the roles of key epigenetic regulators, the epigenomic landscape, epigenetic variation, transposon repression, and plant development. | Xian Deng Xianwei Song Liya Wei Chunyan Liu Xiaofeng Cao | 2016 | National Science Review2016，3，3： | 8 |
| 14 | Effect of Modified Wuzi Yanzong Pill(五子衍宗丸) on Tip60-Mediated Apoptosis in Testis of Male Rats after Microwave Radiation显示文摘Objective: To investigate the effect of a modi?ed Wuzi Yanzong Pill(五子衍宗丸, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism. Methods: Forty-?ve male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation. The rats in the WZYZP group were given a modi?ed of WZYZP by gavage daily for 7 days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay. Histopathological alterations of the testis were observed by haematoxylin-eosin(HE) staining. Tat-interactive protein, 60 kD(Tip60) and p53 expressions were determined by Western blotting. Results: The apoptosis index(AI) in the radiation group was higher than that of the WZYZP group and control group on day 1(D1), day 7(D7) day 14(D14) after radiation(P<0.05). The seminiferous tubules were of normal morphology in the control group. In the radiation group, the partial seminiferous tubules were collapsed, basement membranes of the seminiferous epithelia became detached. WZYZP could restore the morphological changes. There was no expression of Tip60 among the three groups on D7 and D14. The expression of p53 was higher in the radiation group than in the control group(P<0.05). WZYZP could down-regulate the rising p53 induced by radiation on D7 and D14(P<0.05). Conclusion: A modified WZYZP may affect germ cells, and its protective effects may partly result from its ability to intervene in Tip60 mediated apoptosis. | HU Hai-xiang SUN Jing GAO Ya-jing FANG Hong XU Shao-qiang DONG Jing WEI Li-zhao LUO Shao-bo SHEN Chuan-yun ZHANG Qi-long XIE Ya-lan | 2019 | Chinese Journal of Integrative Medicine2019，0，5： | 8 |
| 15 | Reversible Histone H2B Monoubiquitination Fine-Tunes Abscisic Acid Signaling and Drought Response in Rice显示文摘Histone H2B monoubiquitination (H2Bub1) plays important roles in several physiological and developmental processes, but its roles in the regulation of plant stress responses remain elusive. Here, we report that H2Bub1 is crucially involved in abscisic acid (ABA) signaling and drought response in rice. We found that rice HISTONE MONOUBIQUITINATION2 (OsHUB2), an E3 ligase for H2Bub1, in teracted with OsbZIP46, a key transcription factor regulating ABA signaling and drought response in rice. Genetic analyses suggest that OsHUB2, upregulated by drought and ABA, positively modulates ABA sensitivity and drought resistance. The H2Bub1 levels were in creased in the target genes of OsbZIP46 under the drought stress and ABA treat- merits, which were positively correlated with their increased expression levels. Interestingly, MODD, a reported suppressor of ABA signaling and drought resistance by mediating OsbZIP46 deactivation and degradation, could reduce the H2Bub1 levels in the target genes of OsbZIP46 by recruiting a putative deubiquitinase OsOTLD1 . Suppression of OsOTLD1in vivo resulted in increased H2Bub1 levels and expression of OsbZIP46 target genes. Collectively, these fin dings established an elaborate mecha nism of histone monoubiquitination in the fine-turning of ABA signaling and drought response by balancing H2Bub1 deposition and removal. | Siqi Ma Ning Tang Xu Li Yongjun Xie Denghao Xiang Jie Fu Jianqiang Shen Jun Yang Haifu Tu Xianghua Li Honghong Hu Lizhong Xiong | 2019 | Molecular Plant2019，12，2： | 7 |
| 16 | Cathelicidin LL-37 restoring glucocorticoid function in smoking and lipopolysaccharide-induced airway inflammation in rats显示文摘Background Glucocorticoids have been widely used to treat patients with chronic obstructive pulmonary disease (COPD). Nevertheless, corticosteroid insensitivity is a major barrier to the effective treatment of COPD and its mechanism remains unclear. This study aimed to evaluate the effect of cathelicidin LL-37 on corticosteroid insensitivity in COPD rat model, and to explore the involved mechanisms. Methods COPD model was established by exposing male Wistar rats to cigarette smoke combined with intratracheal instillation of lipopolysaccharide (LPS). Inhaled budesonide and LL-37 were consequently applied to COPD models separately or collectively to confirm the effects on inflammatory cytokines (tumor necrosis factor [TNF]-α and transforming growth factor [TGF]-β)by enzymelinked immunosorbent assay (ELISA) and lung tissue histopathological morphology. Expression of histone deacetylase-2 (HDAC2) and phosphorylation of Akt (p-AKT) in lung were also measured. Results Briefly, COPD model rats showed an increased basal release of inflammatory cytokines (lung TNF-α:45.7±6.1 vs. 20.1 ± 3.8pg/mL, P<0.01;serum TNF-α:8.9±1.2 vs. 6.7±0.5pg/mL, P = 0.01;lung TGF-β:122.4±20.8 vs. 81.9±10.8pg/mL, P<0.01;serum TGF-β:38.9±8.5 vs. 20.6±2.3 pg/mL, P<0.01) and COPD related lung tissue histopathological changes, as well as corticosteroid resistance molecular profile characterized by an increase in phosphoinositide 3-kinase (PI3K)/Akt (0.5±0.1 fold of control vs. 0.2±0.1 fold of control, P = 0.04) and a decrease in HDAC2 expression and activity (expression: 13.1 ±0.4 μmol/μg vs. 17.4± 1.1 μmol/μg, P<0.01;activity: 1.1 ±0.1 unit vs. 1.4±0.1 unit, P< 0.01), compared with control group. In addition, LL-37 enhanced the anti-inflammatory effect of budesonide in an additive manner. Treatment with combination of inhaled corticosteroids (ICS) and LL-37 led to a significant increase of HDAC2 expression and activity (expression: 15.7±0.4 μmol/μg vs. 14.1 ±0.9 μmol/μg, P<0.01;activity: 1.3±0.1 unit vs.1.0±0.1 unit, P<0.01), along with decrease of p-AKT compared to budesonide monotherapy (0.1±0.0 fold of control vs.0.3±0.1 fold of control, P<0.01). Conclusions This study suggested that LL-37 could improve the anti-inflammatory activity of budesonide in cigarette smoke and LPS-induced COPD rat model by enhancing the expression and activity of HDAC2. The mechanism of this function of LL-37 might involve the inhibition of PI3K/Akt pathway. | Jian-Zhen Weng Yan Wang Tie-Ying Sun | 2019 | Chinese Medical Journal2019，，5： | 7 |
| 17 | Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression显示文摘Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain damages.To investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial irradiation.Cognitive impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after irradiation.We also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor.Radiation-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.Sodium butyrate pretreatment reversed these changes.These findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor expression.The study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval No.KIRAMS16-0002)on December 30,2016. | Hae June Lee Yeonghoon Son Minyoung Lee Changjong Moon Sung Ho Kim In Sik Shin Miyoung Yang Sangwoo Bae Joong Sun Kim | 2019 | Neural Regeneration Research2019，14，9： | 7 |
| 18 | Epigenetic therapies in acute myeloid leukemia: the role of hypomethylating agents, histone deacetylase inhibitors and the combination of hypomethylating agents with histone deacetylase inhibitors显示文摘Epigenetic regulation includes changes of DNA methylation and modifications of histone proteins and is essential for normal physiologic functions,especially for controlling gene expression.Epigenetic dysregulation plays a key role in disease pathogenesis and progression of some malignancies,including acute myeloid leukemia(AML).Epigenetic therapies,including hypomethylating agents(HMAs)and histone deacetylase(HDAC)inhibitors,were developed to reprogram the epigenetic abnormalities in AML.However,the molecular mechanisms and therapeutic effects of the two agents alone or their combination remain unknown.An overview of these epigenetic therapies is given here.A literature search was conducted through PubMed database,looking for important biological or clinical studies related to the epigenetic regimens in the treatment of AML until October 15th,2019.Various types of articles,including original research and reviews,were assessed,identified,and eventually summarized as a collection of data pertaining the mechanisms and clinical effects of HMAs and HDAC inhibitors in AML patients.We provided here an overview of the current understanding of the mechanisms and clinical therapeutic effects involved in the treatment with HMAs and HDAC inhibitors alone,the combination of epigenetic therapies with intensive chemotherapy,and the combination of both types of epigenetic therapies.Relevant clinical trials were also discussed.Generally speaking,the large number of studies and their varied outcomes demonstrate that effects of epigenetic therapies are heterogeneous,and that HMAs combination regimens probably contribute to significant response rates.However,more research is needed to explore therapeutic effects of HDAC inhibitors and various combinations of HMAs and HDAC inhibitors. | Qing-Yu Xu Li Yu | 2020 | Chinese Medical Journal2020，，6： | 6 |
| 19 | Development of the triazole-fused pyrimidine derivatives as highly potent and reversible inhibitors of histone lysine specific demethylase1(LSD1/KDM1A)显示文摘Histone lysine specific demethylase 1(LSD1) has been recognized as an important modulator in post-translational process in epigenetics. Dysregulation of LSD1 has been implicated in the development of various cancers. Herein, we report the discovery of the hit compound 8 a(IC50=3.93 μmol/L) and further medicinal chemistry efforts, leading to the generation of compound 15 u(IC50=49 nmol/L, and Ki= 16 nmol/L), which inhibited LSD1 reversibly and competitively with H3 K4 me2, and was selective to LSD1 over MAO-A/B. Docking studies were performed to rationalize the potency ofcompound 15 u. Compound 15 u also showed strong antiproliferative activity against four leukemia cell lines(OCL-AML3, K562, THP-1 and U937) as well as the lymphoma cell line Raji with the IC50 values of 1.79, 1.30, 0.45, 1.22 and 1.40 μmol/L, respectively. In THP-1 cell line, 15 u significantly inhibited colony formation and caused remarkable morphological changes. Compound 15 u induced expression of CD86 and CD11 b in THP-1 cells, confirming its cellular activity and ability of inducing differentiation.The findings further indicate that targeting LSD1 is a promising strategy for AML treatment, the triazolefused pyrimidine derivatives are new scaffolds for the development of LSD1/KDM1 A inhibitors. | Zhonghua Li Lina Ding Zhongrui Li Zhizheng Wang Fengzhi Suo Dandan Shen Taoqian Zhao Xudong Sun Junwei Wang Ying Liu Liying Ma Bing Zhao Pengfei Geng Bin Yu Yichao Zheng Hongmin Liu | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 6 |
| 20 | Role of epigenetics in transformation of inflammation into colorectal cancer显示文摘Molecular mechanisms associated with inflammation-promoted tumorigenesis have become an important topic in cancer research. Various abnormal epigenetic changes, including DNA methylation, histone modification, chromatin remodeling, and noncoding RNA regulation, occur during the transformation of chronic inflammation into colorectal cancer(CRC). These changes not only accelerate transformation but also lead to cancer progression and metastasis by activating carcinogenic signaling pathways. The NF-κB and STAT3 signaling pathways play a particularly important role in the transformation of inflammation into CRC, and both are critical to cellular signal transduction and constantly activated in cancer by various abnormal changes including epigenetics. The NF-κB and STAT3 signals contribute to the microenvironment for tumorigenesis through secretion of a large number of pro-inflammatory cytokines and their crosstalk in the nucleus makes it even more difficult to treat CRC. Compared with gene mutation that is irreversible, epigenetic inheritance is reversible or can be altered by the intervention. Therefore, understanding the role of epigenetic inheritance in the inflammation-cancer transformation may elucidate the pathogenesis of CRC and promote the development of innovative drugs targeting transformation to prevent and treat this malignancy. This review summarizes the literature on the roles of epigenetic mechanisms in the occurrence and development of inflammation-induced CRC. Exploring the role of epigenetics in the transformation of inflammation into CRC may help stimulate futures studies on the role of molecular therapy in CRC. | Zhen-Hua Yang Yan-Qi Dang Guang Ji | 2019 | World Journal of Gastroenterology2019，25，23： | 6 |
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