Drug-induced liver injury (DILI) remains an adverse event of significant concern for drug development and marketed drugs, and the field would benefit from better tools to identify liver liabilities early in development and/or to mitigate potential DILI risk in otherwise promising drugs. DILIsym software takes a quantitative systems toxicology approach to represent DILI in pre-clinical species and in humans for the mechanistic investigation of liver toxicity. In addition to multiple intrinsic mechanisms of hepatocyte toxicity (ie, oxidative stress, bile acid accumulation, mitochondrial dysfunction), DILIsym includes the interaction between hepatocytes and cells of the innate immune response in the amplification of liver injury and in liver regeneration. The representation of innate immune responses, detailed here, consolidates much of the available data on the innate immune response in DILI within a single framework and affords the opportunity to systematically investigate the contribution of the innate response to DILI.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459514PMC
http://dx.doi.org/10.1177/1177625017696074DOI Listing

Publication Analysis

Top Keywords

innate immune
16
liver injury
12
drug-induced liver
8
immune responses
8
immune response
8
response dili
8
liver
6
innate
5
dili
5
mechanistic modelling
4

Similar Publications

Background: Cholangiocarcinoma is a challenging malignancy with limited responses to conventional therapies, particularly immune checkpoint inhibitor therapy. Tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLSs) are key components of the tumor microenvironment (TME) and have been implicated in the immune response to cancer. However, the role and difference of TLSs and TILs in patients with cholangiocarcinoma remains unclear.

View Article and Find Full Text PDF

Adenosine-to-inosine (A-to-I) editing, catalyzed by adenosine deaminases acting on RNA (ADARs), is a prevalent post-transcriptional modification that is vital for numerous biological functions. Given that this modification impacts global gene expression, RNA localization, and innate cellular immunity, dysregulation of A-to-I editing has unsurprisingly been linked to a variety of cancers and other diseases. However, our current understanding of the underpinning mechanisms that connect dysregulated A-to-I editing and disease processes remains limited.

View Article and Find Full Text PDF

Structural analysis of human ADAR2-RNA complexes by X-ray crystallography.

Methods Enzymol

January 2025

Department of Chemistry, University of California, Davis, CA, United States; Department of Molecular and Cellular Biology, University of California, Davis, CA, United States. Electronic address:

Adenosine deaminases acting on RNAs (ADARs) are a class of RNA editing enzymes found in metazoa that catalyze the hydrolytic deamination of adenosine to inosine in duplexed RNA. Inosine is a nucleotide that can base pair with cytidine, therefore, inosine is interpreted by cellular processes as guanosine. ADARs are functionally important in RNA recoding events, RNA structure modulation, innate immunity, and can be harnessed for therapeutically-driven base editing to treat genetic disorders.

View Article and Find Full Text PDF

Mouse models for understanding physiological functions of ADARs.

Methods Enzymol

January 2025

St.Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; Department of Medicine, St. Vincent's Hospital, Melbourne Medical School, University of Melbourne, Fitzroy, Victoria, Australia; Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia. Electronic address:

Adenosine-to-inosine (A-to-I) editing, is a highly prevalent posttranscriptional modification of RNA, mediated by the adenosine deaminases acting on RNA (ADAR) proteins. Mammalian transcriptomes contain tens of thousands to millions of A-to-I editing events. Mutations in ADAR can result in rare autoinflammatory disorders such as Aicardi-Goutières syndrome (AGS) through to irreversible conditions such as motor neuron disease, amyotrophic lateral sclerosis (ALS).

View Article and Find Full Text PDF

Isolation and identification of pigeon adenovirus 1 and analysis of its pathogenicity in pigeons and chickens.

Microb Pathog

January 2025

College of Animal Science and Technology, Shandong Agricultural University, 61 Daizong Street, Tai'an, Shandong Province, 271018, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, 271018, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, 271018, China. Electronic address:

Pigeon adenovirus type 1 predominantly infects pigeons under 12 months of age (mainly 3-5 months old), causing major clinical symptoms such as vomiting, dehydration, and discharge of thin yellow feces. In February 2023, an outbreak of a pathogen with symptoms similar to pigeon adenovirus infections occurred on a pigeon farm in Shandong Province, which was eventually identified as pigeon adenovirus type 1. In this study, a strain of PiAdV-1 was isolated from naturally infected pigeons and named pigeon-adenovirus-1-isolate-CH-SD-2023, and the hexon gene sequence as amplified and analyzed using polymerase chain reaction (PCR).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!