Combining Context and Knowledge Representations for Chemical-Disease Relation Extraction

Automatically extracting the relationships between chemicals and diseases is significantly important to various areas of biomedical research and health care. Biomedical experts have built many large-scale knowledge bases (KBs) to advance the development of biomedical research. KBs contain huge amounts of structured information about entities and relationships, therefore plays a pivotal role in chemical-disease relation (CDR) extraction. However, previous researches pay less attention to the prior knowledge existing in KBs. This paper proposes a neural network-based attention model (NAM) for CDR extraction, which makes full use of context information in documents and prior knowledge in KBs. For a pair of entities in a document, an attention mechanism is employed to select important context words with respect to the relation representations learned from KBs. Experiments on the BioCreative V CDR dataset show that combining context and knowledge representations through the attention mechanism, could significantly improve the CDR extraction performance while achieve comparable results with state-of-the-art systems.Comment: Published on IEEE/ACM Transactions on Computational Biology and Bioinformatics, 11 pages, 5 figure

Candidate Regulators of Dyslipidemia in Chromosome 1 Substitution Lines Using Liver Co-Expression Profiling Analysis

Dyslipidemia is a major risk factor for cardiovascular disease. Although many genetic factors have been unveiled, a large fraction of the phenotypic variance still needs further investigation. Chromosome 1 (Chr 1) harbors multiple gene loci that regulate blood lipid levels, and identifying functional genes in these loci has proved challenging. We constructed a mouse population, Chr 1 substitution lines (C1SLs), where only Chr 1 differs from the recipient strain C57BL/6J (B6), while the remaining chromosomes are unchanged. Therefore, any phenotypic variance between C1SLs and B6 can be attributed to the differences in Chr 1. In this study, we assayed plasma lipid and glucose levels in 13 C1SLs and their recipient strain B6. Through weighted gene co-expression network analysis of liver transcriptome and "guilty-by-association" study, eight associated modules of plasma lipid and glucose were identified. Further joint analysis of human genome wide association studies revealed 48 candidate genes. In addition, 38 genes located on Chr 1 were also uncovered, and 13 of which have been functionally validated in mouse models. These results suggest that C1SLs are ideal mouse models to identify functional genes on Chr 1 associated with complex traits, like dyslipidemia, by using gene co-expression network analysis

Novel HLA-DRB1 alleles contribute risk for disease susceptibility in primary biliary cholangitis

Background: Primary biliary cholangitis (PBC) is a complex disease with high heritability. We investigated the association between human leukocyte antigen (HLA)-DRB1 alleles and PBC in families and sporadic cases to evaluate the genetic components of the disease. Methods: We performed whole exome sequencing in three PBC families. We genotyped HLA-DRB1 and calculated the association between HLA-DRB1 alleles and the encoding amino acid sequences with the clinical features. Results: Ten variants harboured the HLA-DRB1 gene associated with PBC. DRB1 x07:01, 14:01 and 14:05 were highly increased in PBC. Ten coding region polymorphisms were associated with PBC that encode the amino acid variants of HLA-DR beta 54, beta 59 and beta 66 located in the peptide-binding site of the MHC molecule. Glutamine at position 54 was confirmed as a risk amino acid, verifying the results of familial aggregation analysis of PBC families. Discussion: Familial aggregation analysis indicated that HLA-DRB1 is a candidate gene for the risk of disease course. Considering that amino acid variations are critical to peptide-binding properties, they underlie the major component of MHC association with PBC. (c) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved

Gut microbial DL-endopeptidase alleviates Crohn's disease via the NOD2 pathway

The pattern-recognition receptor NOD2 senses bacterial muropeptides to regulate host immunity and maintain homeostasis. Loss-of-function mutations in NOD2 are associated with Crohn's disease (CD), but how the variations in microbial factors influence NOD2 signaling and host pathology is elusive. We demonstrate that the Firmicutes peptidoglycan remodeling enzyme, DL-endopeptidase, increased the NOD2 ligand level in the gut and impacted colitis outcomes. Metagenomic analyses of global cohorts (n = 857) revealed that DL-endopeptidase gene abundance decreased globally in CD patients and negatively correlated with colitis. Fecal microbiota from CD patients with low DL-endopeptidase activity predisposed mice to colitis. Administering DL-endopeptidase, but not an active site mutant, alleviated colitis via the NOD2 pathway. Therapeutically restoring NOD2 ligands with a DL-endopeptidase-producing Lactobacillus salivarius strain or mifamurtide, a clinical analog of muramyl dipeptide, exerted potent anti-colitis effects. Our study suggests that the depletion of DL-endopeptidase contributes to CD pathogenesis through NOD2 signaling, providing a therapeutically modifiable target

Biodegradable double-network GelMA-ACNM hydrogel microneedles for transdermal drug delivery

As a minimally invasive drug delivery platform, microneedles (MNs) overcome many drawbacks of the conventional transdermal drug delivery systems, therefore are favorable in biomedical applications. Microneedles with a combined burst and sustained release profile and maintained therapeutic molecular bioactivity could further broaden its applications as therapeutics. Here, we developed a double-network microneedles (DN MNs) based on gelatin methacrylate and acellular neural matrix (GelMA-ACNM). ACNM could function as an early drug release matrix, whereas the addition of GelMA facilitates sustained drug release. In particular, the double-network microneedles comprising GelMA-ACNM hydrogel has distinctive biological features in maintaining drug activity to meet the needs of application in treating different diseases. In this study, we prepared the double-network microneedles and evaluated its morphology, mechanical properties, drug release properties and biocompatibility, which shows great potential for delivery of therapeutic molecules that needs different release profiles in transdermal treatment

A comprehensive review on the colorless carotenoids phytoene and phytofluene

Carotenoids and their derivatives are versatile isoprenoids involved in many varied actions, hence their importance in the agri-food industry, nutrition, health and other fields. All carotenoids are derived from the colorless carotenes phytoene and phytofluene, which are oddities among carotenoids due to their distinct chemical structure. They occur together with lycopene in tomato and other lycopene-containing foods. Furthermore, they are also present in frequently consumed products like oranges and carrots, among others. The intake of phytoene plus phytofluene has been shown to be higher than that of lycopene and other carotenoids in Luxembourg. This is likely to be common in other countries. However, they are not included in food carotenoid databases, hence they have not been linked to health benefits in epidemiological studies. Interestingly, there are evidences in vitro, animal models and humans indicating that they may provide health benefits. In this sense, the study of these colorless carotenes in the context of food science, nutrition and health should be further encouraged. In this work, we review much of the existing knowledge concerning their chemical characteristics, physico-chemical properties, analysis, distribution in foods, bioavailability and likely biological activities