Alcoholic liver disease （ALD） is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes...Alcoholic liver disease （ALD） is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and phosphorylation, hypomethylation of DNA, and alterations in miRNAs. These modifications can be induced by alcoholnduced oxidative stress that results in altered recruitment of transcriptional machinery and abnormal gene expression. Delineating these mechanisms in initiation and progression of ALD is becoming a major area of interest. This review summarizes key epigenetic mechanisms that are dysregulated by alcohol in the liver. Alterations by alcohol in histone and DNA modifications, enzymes related to histone acetylation such as histone acetyltransferases, his-tone deacetylases and sirtuins, and methylation enzymes such as DNA methyltransferases are discussed. Chromatin modifications and miRNA alterations that result in immune cell dysfunction contributing to inflammatory cytokine production in ALD is reviewed. Finally, the role of alcohol-mediated oxidative stress in epigenetic regulation in ALD is described. A better understanding of these mechanisms is crucial for designing novel epigenetic based therapies to ameliorate ALD.展开更多
Genomic sequences have been determined for a number of strains of Helicobacter pylori （H pylori） and related bacteria. With the development of microarray analysis and the wide use of subtractive hybridization techni...Genomic sequences have been determined for a number of strains of Helicobacter pylori （H pylori） and related bacteria. With the development of microarray analysis and the wide use of subtractive hybridization techniques, comparative studies have been carried out with respect to the interstrain differences between H pylori and inter-species differences in the genome of related bacteria. It was found that the core genome of H pylori constitutes 1111 genes that are determinants of the species properties. A great pool of auxiliary genes are mainly from the categories of cag pathogenicity islands, outer membrane proteins, restriction-modification system and hypothetical proteins of unknown function. Persistence of H pylori in the human stomach leads to the diversification of the genome. Comparative genomics suggest that a host jump has occurs from humans to felines. Candidate genes specific for the development of the gastric diseases were identified. With the aid of proteomics, population genetics and other molecular methods, future comparative genomic studies would dramatically promote our understanding of the evolution, pathogenesis and microbiology of Hpylori.展开更多
Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite...Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite of cutting edge research in the field, how retina and its vasculature are damaged by the diabetic milieu remains ambiguous. The environmental factors, life style or disease process can also bring in modifications in the DNA, and these epigenetic modifications either silence or activate a gene without altering the DNA sequence. Diabetic environment up- or downregulates a number of genes in the retina, and emerging research has shown that it also facilitates epigenetic modifications. In the pathogenesis of diabetic retinopathy, the genes associated with important enzymes(e.g., mitochondrial superoxide dismutase, matrix metalloproteinase-9 and thioredoxin interacting protein) and transcriptional factors are epigenetically modified, the enzymes responsible for these epigenetic modifications are either activated or inhibited, and the levels of micro RNAs are altered. With epigenetic modifications taking an important place in diabetic retinopathy, it is now becoming critical to evaluate these modifications, and understand their impact on this slow progressing blinding disease.展开更多
基金Supported by PHS Grant # AA017545 (to Mandrekar P) and AA017986 (to Mandrekar P) from the National Institute of Al-cohol Abuse and Alcoholism, National Institutes of Health
文摘Alcoholic liver disease （ALD） is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and phosphorylation, hypomethylation of DNA, and alterations in miRNAs. These modifications can be induced by alcoholnduced oxidative stress that results in altered recruitment of transcriptional machinery and abnormal gene expression. Delineating these mechanisms in initiation and progression of ALD is becoming a major area of interest. This review summarizes key epigenetic mechanisms that are dysregulated by alcohol in the liver. Alterations by alcohol in histone and DNA modifications, enzymes related to histone acetylation such as histone acetyltransferases, his-tone deacetylases and sirtuins, and methylation enzymes such as DNA methyltransferases are discussed. Chromatin modifications and miRNA alterations that result in immune cell dysfunction contributing to inflammatory cytokine production in ALD is reviewed. Finally, the role of alcohol-mediated oxidative stress in epigenetic regulation in ALD is described. A better understanding of these mechanisms is crucial for designing novel epigenetic based therapies to ameliorate ALD.
文摘Genomic sequences have been determined for a number of strains of Helicobacter pylori （H pylori） and related bacteria. With the development of microarray analysis and the wide use of subtractive hybridization techniques, comparative studies have been carried out with respect to the interstrain differences between H pylori and inter-species differences in the genome of related bacteria. It was found that the core genome of H pylori constitutes 1111 genes that are determinants of the species properties. A great pool of auxiliary genes are mainly from the categories of cag pathogenicity islands, outer membrane proteins, restriction-modification system and hypothetical proteins of unknown function. Persistence of H pylori in the human stomach leads to the diversification of the genome. Comparative genomics suggest that a host jump has occurs from humans to felines. Candidate genes specific for the development of the gastric diseases were identified. With the aid of proteomics, population genetics and other molecular methods, future comparative genomic studies would dramatically promote our understanding of the evolution, pathogenesis and microbiology of Hpylori.
文摘Diabetes has become the epidemic of the 21 st century, and with over 90% patients with diabetes becoming at a risk of developing retinopathy, diabetic retinopathy has emerged as a major public health concern. In spite of cutting edge research in the field, how retina and its vasculature are damaged by the diabetic milieu remains ambiguous. The environmental factors, life style or disease process can also bring in modifications in the DNA, and these epigenetic modifications either silence or activate a gene without altering the DNA sequence. Diabetic environment up- or downregulates a number of genes in the retina, and emerging research has shown that it also facilitates epigenetic modifications. In the pathogenesis of diabetic retinopathy, the genes associated with important enzymes(e.g., mitochondrial superoxide dismutase, matrix metalloproteinase-9 and thioredoxin interacting protein) and transcriptional factors are epigenetically modified, the enzymes responsible for these epigenetic modifications are either activated or inhibited, and the levels of micro RNAs are altered. With epigenetic modifications taking an important place in diabetic retinopathy, it is now becoming critical to evaluate these modifications, and understand their impact on this slow progressing blinding disease.
