Mutyh deficiency downregulates mitochondrial fusion proteins and causes cardiac dysfunction via α-ketoglutaric acid reduction with oxidative stress.

MutY homolog (MUTYH), an important protein in base excision repair (BER) system, excises adenine in the nascent strand opposite 8-oxoguanine in template DNA and restores G:C base-pair to maintain the fidelity of DNA replication. The loss of MUTYH causes oxidative stress and influences cardiac function, but the mechanism remains to be addressed. Here we demonstrate that Mutyh deficiency alters mitochondrial structure and impairs mitochondrial function through downregulation of mitochondrial fusion protein Mfn2 and alteration of the ratio of L-Opa1/S-Opa1 accompanied by reduction of α-ketoglutaric acid (α-KG) under oxidative stress condition.

Studies on the local structure and spin Hamiltonian parameters for V in Na O-PbO-Bi O -SiO glass ceramics.

The local structure, d-d transition band, and spin Hamiltonian parameters (SHPs) are theoretically studied for the V probe in Na O-PbO-Bi O -SiO (NPBS) glass ceramics containing V O dopant with various concentration x (0 ≤ x ≤ 5 mol%) by using the perturbation formulas of the SHPs for tetragonally compressed octahedral 3d clusters. The first decreasing (or increasing) and then increasing (or decreasing) d-d transition band (= 10 D ) and hyperfine structure constants A and A (or g factors g and g ) with x can be suitably simulated with the similarly varying Fourier type concentration functions of cubic field parameter D , covalence factor N, core polarization constant κ, and reduction factor H (or relative tetragonal compression ratio ρ), with the minima (or maxima) at the middle concentration x = 3 mol%, respectively. The above concentration variations of SHPs and the related quantities may originate from the modifications of local crystal field strength, tetragonal compression, and electron cloud distribution near the impurity V with x, corresponding to the highest [V ]/[V ] ratio at 3 mol%.

[Mitochondrial metabolism's effect on epigenetic change and aging].

Mitochondrion is the metabolic center and powerhouse of cells producing cellular energy which plays an important role in various physiological and pathophysiological processes. Recent research demonstrates that mitochondrial energy metabolism mediates the transmission of mitochondrial-nuclear signals through intermediate products which regulates epigenetic presentation of the chromatin and thereby affects gene expression. Epigenetic modification, a genetic regulatory model, is independent of DNA sequence and plays a major role in establishing and maintaining a specific gene's expression profile.

Oxidative stress induces different tissue dependent effects on Mutyh-deficient mice.

8-oxoguanine (8-oxoG) is one of the most prevalent genotoxic lesions, and it is generated in DNA attacked by reactive oxygen species (ROS). Adenine misincorporated opposite to 8-oxoG during replication is excised by MutY homolog (MUTYH), an important protein of the base excision repair (BER) system. Mutyh plays an important role in the maintenance of genomic integrity, but the functional consequences of Mutyh deficiency are not fully understood.

Serum miR-20a and miR-486 are potential biomarkers for discriminating colorectal neoplasia: A pilot study.

Aim: Recent advances in circulating microRNAs (miRNAs) as noninvasive biomarkers have provided promising prospect in detecting colorectal cancer (CRC). However, the capability of miRNAs for detecting colorectal neoplasia (CRN, including precancerous lesions and curable stage CRCs) remains unclear. This study aimed to identify the potential of serum miRNAs (miR-20a, miR-486, miR-92a, and miR-135b) selected from the literature for discriminating CRN patients.

Effect of histone modifications on hMLH1 alternative splicing in gastric cancer.

hMLH1 is one of the mismatch genes closely related to the occurrence of gastric cancer. Epigenetic regulation may play more important roles than gene mutations in DNA damage repair genes to drive carcinogenesis. In this article, we discuss the role of epigenetic changes, especially histone modifications in the regulation of hMLH1 alternative splicing.

An Epigenetic Compound Library Screen Identifies BET Inhibitors That Promote HSV-1 and -2 Replication by Bridging P-TEFb to Viral Gene Promoters through BRD4.

The human HSV-1 and -2 are common pathogens of human diseases. Both host and viral factors are involved in HSV lytic infection, although detailed mechanisms remain elusive. By screening a chemical library of epigenetic regulation, we identified bromodomain-containing protein 4 (BRD4) as a critical player in HSV infection.

[Application of a novel method to collect large amount of fecal mucosa in screening colorectal cancer].

Objective: To explore the application of a novel device of collecting large amount of fecal mucosa for detecting the DNA methylation and screening colorectal cancer.

Methods: Preoperative complete fecal sample and surgical specimen of 10 patients with colorectal cancer, and complete fecal sample and normal bowel mucosal samples confirmed by colonoscopy of 6 hospitalization cases at The Third Affiliated Hospital, Nanjing University of TCM from March to April 2014 were collected. A self-made bowel mucosa collector (consisting of upper, middle, lower three containers of 1 000 ml volume, with filter screen in each bottom whose pore diameter is 100, 200 and 300 mesh.

Epigenetic regulation of CDH1 exon 8 alternative splicing in gastric cancer.

Background: The tumor suppressor gene CDH1 is critical for intercellular adhesion. In our previous work, we reported a nonfunctional CDH1 transcript that lacks the final 83 base pairs of exon 8 (1054del83). In this work, we probed the role of histone epigenetic modifications as well as DNA methylation in selection of this isoform.

[Screening and diagnostic value of the molecular markers of DNA methylation in colorectal neoplasma].

Objective: To screen the molecular markers of DNA methylation with potential diagnostic value, and to explore their methylation features in Chinese colorectal neoplasma in order to find out ones with higher diagnostic value.

Methods: Tissue samples of colorectal cancer and normal adjacent mucosa(>10 cm distance to tumors) from 10 colorectal cancer patients undergoing operation, and tissue samples of colorectal adenoma from 10 patients undergoing endoscopic resection in our center from June to August 2013 were collected respectively. Methylation status of 8 genes, such as SNCA, MAL, INA, SPG20, FBN1, CNRIP1, TFPI2, OSMR, was detected by BSP and qMSP to screen genes with potential diagnostic valua.

Mucin 5B promoter polymorphism is associated with susceptibility to interstitial lung diseases in Chinese males.

The variation of G>T in the MUC5B promoter (rs35705950) has been associated with idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia (FIP) in Caucasians, but no information is available regarding this variant in the Chinese population. We recruited 405 patients with interstitial lung diseases (ILD), including 165 IPF patients and 2043 healthy controls, for genotyping the MUC5B gene in the Chinese population. One hundred three patients with pneumonia and 360 patients with autoimmune diseases (ADs) were recruited as disease controls.

The specific methylation characteristics of cancer related genes in Chinese colorectal cancer patients.

Aberrant DNA methylation at CpG islands has been implicated as a critical player in colorectal cancer (CRC). However, its biological role and clinical significance in carcinogenesis have not been clearly clarified in Chinese CRC patients. In order to examine the methylation status of cancer-related genes in CRC progression, 184 tumor tissues were collected from Chinese patients diagnosed with CRC during 2008-2011.

[The epigenetic effect on pre-mRNA alternative splicing].

Alternative splicing is a crucial step of the gene expression process in eukaryotes. It is a major cause for protein diversity and plays critical roles in differentiation, development, and disease. The studies on the mechanism of alternative splicing have traditionally focused on RNA sequence elements and their related splicing factors, but recent groundbreaking studies have shown that epigenetic factors play a key role in alternative splicing regulation.

[Establishment of a hMSH2/hMSH6 protein interaction system and functional evaluation of hMSH2 gene missense mutations].

Objective: To construct a hMSH2/hMSH6 protein interaction system, and to use it for evaluating missense mutations detected in hMSH2 gene.

Methods: Recombinant plasmids pGADT7-hMSH2, pGBKT7-hMSH6 and 7 recombinant pGBKT7 plasmids with different hMSH6 domains were constructed through genetic engineering. Subsequently, site-directed mutagenesis was used to construct 10 mutant pGADT7-hMSH2 plasmids, which were transformed into yeast AH109.

Mutation screen and RNA analysis disclose the changed splicing of the E-cadherin transcription in gastric cancer.

Gastric cancer (GC) is considered to be one of the leading cancers in East Asians, and mutations in the CDH1 gene and the reduced expression of E-cadherin are the most frequent genetic alterations in gastric cancer. In this paper, we reported two novel germline CDH1 nonsynonymous mutations, c.1296 C>G (N432 K) and c.

Novel CDH1 germline mutations identified in Chinese gastric cancer patients.

Aim: To give a comprehensive report of E-cadherin gene (CDH1) variations in a population at a high risk for gastric cancer (GC).

Methods: The samples consisted of 178 men and 58 women with a mean age of 62.3 ± 9.

Germline promoter hypermethylation of tumor suppressor genes in gastric cancer.

Aim: To explore germline hypermethylation of the tumor suppressor genes MLH1, CDH1 and P16(INK4a) in suspected cases of hereditary gastric cancer (GC).

Methods: A group of 140 Chinese GC patients in whom the primary cancer had developed before the age of 60 or who had a familial history of cancer were screened for germline hypermethylation of the MLH1, CDH1 and P16(INK4a) tumor suppressor genes. Genomic DNA was extracted from peripheral blood leukocytes and modified by sodium bisulfite.

The MLH1 2101C>A (Q701K) variant increases the risk of gastric cancer in Chinese males.

Background: Gastric cancer is one of the most common cancers affecting East Asians, and MLH1 could play a critical role during tumorigenesis in this condition.

Methods: Samples from 236 Chinese patients suffering from gastric cancer were screened for MLH1 germline mutations. Carrier frequencies of the mutations were compared between gastric cancer patients and 240 cancer-free controls.

Influence of eight unclassified missense variants of the MLH1 gene on Lynch syndrome susceptibility.

Missense mutations in MLH1 have frequently been detected in patients with Lynch syndrome, but their genetic significance has not been extensively assessed. In this study, we attempt to evaluate the etiological role of eight MLH1 missense variants. The variants were analyzed for their ability to affect MLH1 protein interaction with its partner PMS2 in vivo employing a yeast two-hybrid system.

Two functional variations in 5'-UTR of hoGG1 gene associated with the risk of breast cancer in Chinese.

8-Hydroxy-2'-deoxyguanine (8-OHdG) is produced by the oxidative stress-induced damage in DNA, which could pair with adenine (A) during DNA replication, leading to G-T transversion mutations. Glycosylase hOGG1 can recognize and excise oxidized guanines from duplex DNA. This work aims to investigate the relationship between the functional variations in 5-untranslated region (5'-UTR) of hOGG1 gene and the risk of breast cancer.

[Germ-line epimutations and human cancer].

Epimutations are errors in the normal process of epigenetic regulation which can result in aberrant transcriptional silencing of a normally active gene or reactivation of a normally silent gene. Epimutations are generally considered to be somatic events and to be confined in affected tissues. However, recent studies of patients with hereditary nonpolyposis colorectal cancer (HNPCC) have showed that allele-specific hypermethylation of CpG islands in the promoter region of the MLH1 gene, one of the causes of the tumor, existed in all the tissues examined.

Analysis of hMLH1 missense mutations in East Asian patients with suspected hereditary nonpolyposis colorectal cancer.

Purpose: Germ line mutations in the DNA mismatch repair gene hMLH1 are a frequent cause of hereditary nonpolyposis colorectal cancer and about one-third of these are missense mutations. Several missense mutations in hMLH1 have frequently been detected in East Asian patients with suspected hereditary nonpolyposis colorectal cancer, but their pathogenic role has not been extensively assessed. The aim of this study was to perform functional analyses of these variants and their association with gastrointestinal cancer in East Asians.

Variations in exon 7 of the MSH2 gene and susceptibility to gastrointestinal cancer in a Chinese population.

Epidemiologic, structural, and bioinformatic analyses were used to evaluate variants in the MSH2 and MLH1 genes in 187 subjects with suspected hereditary gastrointestinal cancer in China. An increased frequency of variants was observed in exon 7 of the MSH2 gene; there was a statistical difference (P < 0.05) between the colorectal cancer (CRC) group (6/82, or 7.

Germline mutations and polymorphic variants in MMR, E-cadherin and MYH genes associated with familial gastric cancer in Jiangsu of China.

Germline mutations in MSH2, MLH1, E-cadherin and MutY (MYH) genes have been implicated in the occurrence of gastric cancer (GC). Epidemiological investigation was performed by recruiting patients with GC onset during 2002 in Jiangsu province, China. We identified suspected hereditary GC patients based on either the GC family history or GC onset at early ages.

Effective protection of Terminalia catappa L. leaves from damage induced by carbon tetrachloride in liver mitochondria.

The protective effects of chloroform extracts of Terminalia catappa L. leaves (TCCE) on carbon tetrachloride (CCl4)-induced liver damage and the possible mechanisms involved in the protection were investigated in mice. We found that increases in the activity of serum aspartate aminotransferase and alanine aminotransferase and the level of liver lipid peroxidation (2.