Mechanisms and clinical landscape of N6-methyladenosine (m6A) RNA modification in gastrointestinal tract cancers.

Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation.

A promising new cancer marker: Long noncoding RNA EGFR-AS1.

Cancer consists of a group of diseases with the salient properties of an uncontrolled cell cycle, metastasis, and evasion of the immune response, mainly driven by the genomic instability of somatic cells and the physicochemical environment. Long noncoding RNAs (lncRNAs) are defined as noncoding RNAs with a length of more than 200 nucleotides. LncRNA dysregulation participates in diverse disease types and is tightly associated with patient clinical features, such as age, disease stage, and prognosis.

Expression, Prognostic Value, and Functional Mechanism of Polarity-Related Genes in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high mortality and poor prognoses around the world. Within-cell polarity is crucial to cell development and function maintenance, and some studies have found that it is closely related to cancer initiation, metastasis, and prognosis. The aim of our research was to find polarity-related biomarkers which improve the treatment and prognosis of HCC.

Identification and Verification of a Novel MAGI2-AS3/miRNA-374-5p/FOXO1 Network Associated with HBV-Related HCC.

Background: Hepatocellular carcinoma (HCC) is a very common neoplasm worldwide, and competitive endogenous RNA (ceRNA) plays an important role in the development of HCC. The purpose of this study is to investigate the molecular mechanisms of ceRNAs in HCC.

Methods: This study detects potential ceRNAs from HCC through whole genome analysis of lncRNA, miRNA and mRNA expression.

Five-lipoxygenase-activating protein-mediated CYLD attenuation is a candidate driver in hepatic malignant lesion.

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer. However, the lipid pro-inflammatory mediators have only been seldom investigated in HCC pathogenesis. Cylindromatosis (CYLD) attenuation is involved in hepatocarcinogenesis.

Association of Vitamin D Receptor Gene Polymorphisms with Metabolic Syndrome in Chinese Children.

Purpose: To investigate the association between vitamin D receptor (VDR) gene polymorphisms and vitamin D deficiency, overweightness/obesity, and metabolic syndrome (MetS) in a cohort of Han children residing in Hangzhou, China.

Patients And Methods: This study assessed 106 overweight/obese and 86 healthy (control) children. Five single-nucleotide polymorphisms (SNPs) in the VDR gene, namely, TaqI (rs731236 T > C), ApaI (rs7975232 C > A), BsmI (rs1544410 G > A), FokI (rs2228570 G >A), and Cdx2 (rs11568820 G > A), were genotyped by sequencing the total polymerase chain reaction products.

Transcriptomics Curation of SARS-CoV-2 Related Host Genes in Mice With COVID-19 Comorbidity: A Pilot Study.

The pandemic of coronavirus disease 2019 (COVID-19), a respiratory disease caused by a novel severe acute respiratory syndrome coronavirus-2, is causing substantial morbidity and mortality. Along with the respiratory symptoms, underlying diseases in senior patients, such as diabetes, hypertension, and coronary heart disease, are the most common comorbidities, which cause more severe outcomes and even death. During cellular attachment and entry of severe acute respiratory syndrome coronavirus-2, the key protein involved is the angiotensin I converting enzyme 2 (ACE2), which is located on the membrane of host cells.

Identification and characterization of SEC24D as a susceptibility gene for hepatitis B virus infection.

Single nucleotide polymorphisms (SNPs) and genes associated with susceptibility to hepatitis B virus (HBV) infection that have been identified by genome-wide association studies explain only a limited portion of the known heritability, indicating more genetic variants remain to be discovered. In this study, we adopted a new research strategy to identify more susceptibility genes and variants for HBV infection. We first performed genetic association analysis of 300 sib-pairs and 3,087 case-control samples, which revealed that 36 SNPs located in 31 genes showed nominal associations with HBV infection in both samples.

A Review on the Receptor-ligand Molecular Interactions in the Nicotinic Receptor Signaling Systems.

Nicotine is regarded as the main active addictive ingredient in tobacco products driving continued tobacco abuse behavior (smoking) to the addiction behavior, whereas nicotinic acetylcholine receptors (nAChR) is the crucial effective apparatus or molecular effector of nicotine and acetylcholine and other similar ligands. Many nAChR subunits have been revealed to bind to either neurotransmitters or exogenous ligands, such as nicotine and acetylcholine, being involved in the nicotinic receptor signal transduction. Therefore, the nicotinic receptor signalling molecules and the receptor-ligand molecular interactions between nAChRs and their ligands are universally regarded as crucial mediators of cellular functions and drug targets in medical treatment and clinical diagnosis.

Detection of Significant Association Between Variants in Cannabinoid Receptor 1 Gene () and Personality in African-American Population.

Several studies have revealed significant associations between single nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 () gene and a broad spectrum of psychiatric disorders such as major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), and schizophrenia. Personality traits that are highly related to susceptibility to these conditions have been associated with the variants in subjects of Caucasian origin. However, there are no reported studies regarding the effects of polymorphisms on personality traits in the African-American (AA) population.

Association and cis-mQTL analysis of variants in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 in relation to nicotine dependence in a Chinese Han population.

Nicotine dependence (ND) is a worldwide health problem. Numerous genetic studies have demonstrated a significant association of variants in nicotinic acetylcholine receptors (nAChRs) with smoking behaviors. However, most of these studies enrolled only subjects of European or African ancestry.

Prevalence of Cigarette Smoking and Nicotine Dependence in Men and Women Residing in Two Provinces in China.

Aims: Although it is known that there is a high smoking prevalence among Chinese, key issues such as social and environmental factors impacting smoking initiation and persistence, the percentage of smokers considered nicotine dependence (ND), and the availability and use of ND treatments have rarely been investigated.

Methods: To address these issues, from 2012 to 2014, we conducted a large-scale study in the Zhejiang and Shanxi provinces of China using the Fagerström Test for Nicotine Dependence and other validated questionnaires.

Results: Of the 17,057 subjects, consisting of 13,476 males and 3,581 females aged 15 years or older, the prevalence of male smoking was 66.

An Exome-Wide Association Study Identifies New Susceptibility Loci for Age of Smoking Initiation in African- and European-American Populations.

Introduction: Cigarette smoking is one of the largest causes of preventable death worldwide. This study aimed to identify susceptibility loci for age at smoking initiation (ASI) by performing an exome-wide association analysis.

Methods: A total of 2510 smokers of either African-American (AA) or European-American (EA) origin were genotyped and analyzed at both the single nucleotide polymorphism (SNP) and gene levels.

Profiling, clinicopathological correlation and functional validation of specific long non-coding RNAs for hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent and aggressive malignancies worldwide. Studies seeking to advance the overall understanding of lncRNA profiling in HCC remain rare.

Methods: The transcriptomic profiling of 12 HCC tissues and paired adjacent normal tissues was determined using high-throughput RNA sequencing.

Significant association of the CHRNB3-CHRNA6 gene cluster with nicotine dependence in the Chinese Han population.

Although numerous studies have revealed significant associations between variants in the nicotinic acetylcholine receptors (nAChR) subunits and nicotine dependence (ND), only few studies were performed in Chinese subjects. Here, we performed association and interaction analysis for 20 single nucleotide polymorphisms (SNPs) in the CHRNB3-CHRNA6 gene cluster with ND in a Chinese Han population (N = 5,055). We found nominally significant associations for all tested SNPs with ND measured by the Fagerström Test for Nicotine Dependence score; of these, 11 SNPs remained significant after Bonferroni correction for multiple tests (p = 9 × 10~2 × 10).

Association of STAT4 polymorphisms with hepatitis B virus infection and clearance in Chinese Han population.

Genome-wide association study indicates that STAT4 is a plausible candidate for an association study with HBV-related liver diseases. We aimed to examine the roles of STAT4 polymorphisms on HBV-related liver diseases in a Chinese Han population. We selected 13 SNPs in STAT4 based on the HapMap database to investigate their associations in 3,033 participants.

Premalignant alteration assessment in liver-like tissue derived from embryonic stem cells by aristolochic acid I exposure.

The in vitro predictive evaluation of chemical carcinogenicity based on hepatic premalignance has so far not been established. Here, we report a novel approach to investigate the premalignant events triggered by human carcinogen aristolochic acid I (AAI) in the liver-like tissue derived from mouse embryonic stem cells. By AAI exposure, the liver-like tissue exhibited the paracrine interleukin-6 phenotypic characteristics.

MicroRNA-674-5p/5-LO axis involved in autoimmune reaction of Concanavalin A-induced acute mouse liver injury.

Autoimmune hepatitis is characterized, in part, by the pathways involving cysteinyl-leukotriene metabolites of arachidonic acid, the dynamics of which remain unclear. Here, we explored post-transcriptional regulation in the 5-lipoxygenase (5-LO) pathway of arachidonic acid in a Concanavalin A (Con A) induced mouse model. We found that Con A administration lead to 5-LO overexpression and cysteinyl-leukotriene release in early hepatic injury, which was attenuated by cyclosporin A pretreatment.

Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines.

Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day).

Meta-Analysis of the COMT Val158Met Polymorphism in Major Depressive Disorder: Effect of Ethnicity.

The COMT (catechol-O-methyltransferase) Val158Met polymorphism (rs4680) is a potential susceptibility variant for major depressive disorder (MDD). Although many genetic studies have examined the association between MDD and this polymorphism, the results were inconclusive. In the present study, we conducted a series of meta-analyses of samples consisting of 2905 MDD cases and 2403 controls with the goal of determining whether this variant indeed has any effect on MDD.

Fine mapping analysis of HLA-DP/DQ gene clusters on chromosome 6 reveals multiple susceptibility loci for HBV infection.

Recent genome-wide association studies have revealed the HLA region on chromosome 6p21 as a susceptibility locus for hepatitis B virus (HBV) infection, a finding subsequently replicated in independent samples. However, only limited single nucleotide polymorphisms (SNPs) were analyzed in most of these studies, and it remains to be determined which SNPs contribute to the detected association. After genotyping 140 SNPs within this genomic region in a total of 1657 HBV-positive patients and 1456 HBV-negative controls, we conducted a series of genetic epidemiological and bioinformatics analysis, including individual SNP-based association analysis, haplotype-based association analysis, and conditional analysis.

The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes.

The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis.