Investigation of the causal relationship between Interleukin-6 signaling and gastrointestinal tract cancers: A Mendelian randomization study.

BACKGROUND: Observational studies indicate that interleukin-6(IL-6) has been associated with gastrointestinal tract cancers. However, the causal association is still confusing. Thus, we aimed to putative the causality between IL-6 signaling and gastrointestinal tract cancers. METHODS: We conducted a two-sample Mendelian randomization analysis to assess the causal effects. Two groups of IL-6 signaling-related single nucleotide polymorphisms were chosen from two Genome-wide association studies. Summary-level data for gastrointestinal tract cancers including esophageal, gastric, and colorectal cancer, were obtained from the FinnGen consortium and UK Biobank study. We also performed survival analysis to explore the prognostic value of IL-6 in gastrointestinal tract cancers. RESULTS: Genetically predicted plasma sIL6R level, which inhibits IL-6 Signaling, was associated with a reduced risk of gastric cancer in FinnGen. In the combined analysis of the two sources, genetically predicted sIL6R was associated with a decreased risk of gastric cancer (OR = 0.943, 95%CI: 0.904,0.983, p = 0.006). Survival analysis results indicated the prognostic value of IL-6 in gastric cancer. CONCLUSIONS: These results present evidence indicating that genetically-determined reduced IL-6 signaling lowers the risk of gastric cancer, which may provide potential prevention and therapeutic strategies for gastric cancer. Additionally, IL-6 may be a prognostic biomarker for gastric cancer.

New Era of Mapping and Understanding Common Fragile Sites: An Updated Review on Origin of Chromosome Fragility.

Common fragile sites (CFSs) are specific genomic loci prone to forming gaps or breakages upon replication perturbation, which correlate well with chromosomal rearrangement and copy number variation. CFSs have been actively studied due to their important pathophysiological relevance in different diseases such as cancer and neurological disorders. The genetic locations and sequences of CFSs are crucial to understanding the origin of such unstable sites, which require reliable mapping and characterizing approaches. In this review, we will inspect the evolving techniques for CFSs mapping, especially genome-wide mapping and sequencing of CFSs based on current knowledge of CFSs. We will also revisit the well-established hypotheses on the origin of CFSs fragility, incorporating novel findings from the comprehensive analysis of finely mapped CFSs regarding their locations, sequences, and replication/transcription, etc. This review will present the most up-to-date picture of CFSs and, potentially, a new framework for future research of CFSs.

Whole-genome sequencing revealed genetic diversity and selection of Guangxi indigenous chickens.

Guangxi chickens play a crucial role in promoting the high-quality development of the broiler industry in China, but their value and potential are yet to be discovered. To determine the genetic diversity and population structure of Guangxi indigenous chicken, we analyzed the whole genomes of 185 chickens from 8 phenotypically and geographically representative Guangxi chicken breeds, together with 12 RJFt, 12 BRA and 12 WL genomes available from previous studies. Calculation of heterozygosity (Hp), nucleotide diversity (π), and LD level indicated that Guangxi populations were characterized by higher genetic diversity and lower differentiation than RJFt and commercial breeds except for HGFC. Population structure analysis also confirmed the introgression from commercial broiler breeds. Each population clustered together while the overall differentiation was slight. MA has the richest genetic diversity among all varieties. Selective sweep analysis revealed BCO2, EDN3 and other candidate genes had received strong selection in local breeds. These also provided novel breeding visual and data basis for future breeding.

Effects of homocysteine on nonalcoholic fatty liver related disease: A mendelian randomization study.

Background: Since the association of homocysteine and clinical results of observational studies are controversial on non-alcoholic fatty liver related disease, we compute the two-sample Mendelian Randomization (MR) study. Objective: To evaluate whether the plasma level of homocysteine has an effect on the risk of Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and Cirrhosis after its progress, we investigated the causal relationships between plasma homocysteine and the three non-alcoholic fatty liver related diseases mentioned above. Design and methods: Summary estimates were elicited from the inverse-variance weighted (IVW) method through 12 single nucleotide polymorphisms (SNPs) which related to the plasma homocysteine, the SNPs were obtained from a large genome-wide association studies (GWAS) of 44,147 European participants. And the summary statistics for the latest and largest GWAS datasets for NAFLD (307576 in total and 1,578 cases), NASH (309055 in total and 99 cases) and Cirrhosis (306145 in total and 826 cases) were collected from Ristey FinnGen website where the association of genetic variations with blood metabolite levels was conducted using comprehensive metabolite profiling. The study was performed through two-sample MR method. Results: The result indicated that the plasma homocysteine is not significantly associated with NAFLD, and its progression, NASH and Cirrhosis. Conclusion: The evidence in this study is quite deficient to support the causal association of the individual plasma homocysteine with NAFLD, NASH and Cirrhosis, the putative of associations is not exist.

Whole-genome resequencing reveals diversity and selective signals in Longlin goat.

The Longlin goat is one of the most valuable livestock species in Guangxi Autonomous Region of China, but its genomic diversity and selective signals are not clearly elucidated. Here we compared 20 genomes of Longlin goat to 66 genomes of other seven goat breeds worldwide to analyze patterns of Longlin goat genetic variation. We found the lowest linkage disequilibrium at the large distances between SNPs associated with the highest effective population size in the recent generations ago in Longlin goat. The eight goat breeds could be divided into Euro-African and East Asian goat population. Interestingly, like East Asian taurine, the same two migration phases might have occurred in the history of East Asian goat. More importantly, we identified selective signals implicated in immune resistance to disease, especially for skin disease, in Longlin goat. Our findings will not only help understand the evolutionary history and breed characteristic but can provide valuable resources for conservation of germplasm resources and implementation of crossbreeding programs.

Whole-genome resequencing reveals genetic characteristics of different duck breeds from the Guangxi region in China.

Distinctive indigenous duck (Anas platyrhynchos) populations of Guangxi, China, evolved due to the geographical, cultural, and environmental variability of this region. To investigate the genetic diversity and population structure of the indigenous ducks of Guangxi, 78 individuals from eight populations were collected and sequenced by whole-genome resequencing with an average depth of ∼9.40×. The eight indigenous duck populations included four breeds and four resource populations. Moreover, the genome data of 47 individuals from two typical meat-type breeds and two native egg-type breeds were obtained from a public database. Calculation of heterozygosity, nucleotide diversity (π), Tajima's D, and FST indicated that the Guangxi populations were characterized by higher genetic diversity and lower differentiation than meat-type breeds. The highest diversity was observed in the Xilin-Ma ducks. Principal component, structure, and phylogenetic tree analyses revealed the relationship between the indigenous duck populations of Guangxi. A mild degree of differentiation was observed among the Guangxi populations, although three populations were closer to the meat or egg breeds. Indigenous populations are famous for their special flavor, small body size, and slow growth rates. Selective sweep analysis revealed the candidate genes and pathways associated with these growth traits. Our findings provide a valuable source of information regarding genetic diversity, population conservation, and genome-associated breeding of ducks.

Identification of Genomic Characteristics and Selective Signals in a Du'an Goat Flock.

The Du'an goat is one of the most important farm animals in the Guangxi Autonomous Region of China, but the genetic basis underlying its adaptive traits has still not been investigated. Firstly, in this study, the genomes of 15 Du'an goats from a breeding farm were sequenced (mean depth: 9.50X) to analyze the patterns of genetic variation. A comparable diversity (17.3 million single nucleotide polymorphisms and 2.1 million indels) was observed to be associated with a lower runs of homozygosity-based inbreeding coefficient and smaller effective population size in comparison with other breeds. From selective sweep and gene set enrichment analyses, we revealed selective signals related to adaptive traits, including immune resistance (serpin cluster, INFGR1, TLR2, and immune-related pathways), body size (HMGA2, LCOR, ESR1, and cancer-related pathways) and heat tolerance (MTOR, ABCG2, PDE10A, and purine metabolism pathway). Our findings uncovered the unique diversity at the genomic level and will provide the opportunities for improvement of productivity in the Du'an goat.

Wogonoside promotes apoptosis in gastric cancer AGS and SGC-7901 cells through induction of mitochondrial dysfunction and endoplasmic reticulum stress.

Wogonoside (Wg), a natural flavonoid, has anticancer effects against several human cancers. The purpose of the present study was to investigate the antitumor effects and underlying mechanisms of Wg on gastric cancer (GC) cell lines. We report that Wg treatment inhibited cell viability and induced apoptosis in human GC cell lines AGS and SGC-7901, and also retarded GC tumor growth in xenograft mice in vivo. We also found that the Wg exerted its antitumor effects against GC cells via induction of reaction oxygen species accumulation, mitochondrial dysfunction, and endoplasmic reticulum stress. Furthermore, C/EBP homologous protein knockdown inhibited apoptosis and increased the viability of Wg-treated GC cells. Our findings may facilitate the development of novel therapeutic agents for the treatment of GC.