AI Article Synopsis
Article Abstract
Although peroxisome proliferator-activated receptor α (PPARα) agonists are obviously hepatocarcinogenic in rodents, they have been widely used for dyslipidemia and proven to be safe for clinical use without respect to the species difference. It is established that PPARα acts as a part of the transcription factor complex, but its precise mechanism is still unknown. Using the data of Toxicogenomics Database, reliable genes responsive to PPARα agonists, clofibrate, fenofibrate and WY-14,643, in rat liver, were extracted from both in vivo and in vitro data, and sorted by their fold increase. It was found that there were many genes responding to fibrates exclusively in vivo. Most of the in vivo specific genes appear to be unrelated to lipid metabolism and are not upregulated in the kidney. Fifty-seven genes directly related to cell proliferation were extracted from in vivo data, but they were not induced in vitro at all. Analysis of PPAR-responsive elements could not explain the observed difference in induction. To evaluate possible interaction between neighboring genes in gene expression, the correlation of the fold changes of neighboring genes for 22 drugs with various PPARα agonistic potencies were calculated for the genes showing more than 2.5 fold induction by 3 fibrates in vivo, and their genomic location was compared with that of the human orthologue. In the present study, many candidates of genes other than lipid metabolism were selected, and these could be good starting points to elucidate the mechanism of PPARα agonist-induced rodent-specific toxicity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2131/jts.45.449 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nuclear respiratory factor-1 (NRF1) induction as a powerful strategy to deter mitochondrial dysfunction and senescence in mesenchymal stem cells.
Aging Cell
December 2024
Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas, USA.
Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies due to their self-renewal and differentiation capabilities. Pathological microenvironments expose MSCs to senescence-inducing factors such as reactive oxygen species (ROS), resulting in MSC functional decline and loss of stemness. Oxidative stress leads to mitochondrial dysfunction, a hallmark of senescence, and is prevalent in aging tissues characterized by elevated ROS levels.
View Article and Find Full Text PDFNanoCMSer: a consensus molecular subtype stratification tool for fresh-frozen and paraffin-embedded colorectal cancer samples.
Mol Oncol
December 2024
Amsterdam UMC, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam, University of Amsterdam, The Netherlands.
Colorectal cancer (CRC) is a significant contributor to cancer-related mortality, emphasizing the need for advanced biomarkers to guide treatment. As part of an international consortium, we previously categorized CRCs into four consensus molecular subtypes (CMS1-CMS4), showing promise for outcome prediction. To facilitate clinical integration of CMS classification in settings where formalin-fixed paraffin-embedded (FFPE) samples are routinely used, we developed NanoCMSer, a NanoString-based CMS classifier using 55 genes.
View Article and Find Full Text PDFThe Spatial Distribution of Brain Metastasis Is Determined by the Heterogeneity of the Brain Microenvironment.
Hum Brain Mapp
December 2024
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
It is now understood that brain metastases do not occur randomly but have distinct spatial patterns depending on the origin of the cancer. According to the "seed and soil" hypothesis, the final colonization of metastatic cells is the result of their adaptation to the altered environment. To investigate the most favorable microenvironment for brain metastasis, we analyzed neuroimaging data from 177 patients with breast cancer brain metastasis and 548 patients with lung cancer brain metastasis to create a replicable probabilistic map of metastatic locations.
View Article and Find Full Text PDFAntibiotic susceptibility testing and molecular characterization based on whole-genome sequencing of isolates from pediatric infections at the National Regional Medical Center of Southwest China during the COVID-19 pandemic.
Front Public Health
December 2024
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu, China.
Background: is a transmitted respiratory pathogen that causes high morbidity and mortality in children, especially those under 5 years of age. During the implementation of population control measures for COVID-19 in mainland China, the detection rate in pediatric patients decreased. However, with the second wave of the COVID-19 pandemic (2022), the incidence of pneumococcal disease (PD) and even invasive pneumococcal disease (IPD) began to rise again.
View Article and Find Full Text PDFInferring strain-level mutational drivers of phage-bacteria interaction phenotypes arising during coevolutionary dynamics.
Virus Evol
November 2024
Department of Biology, University of Maryland, College Park, MD 20742, USA.
The enormous diversity of bacteriophages and their bacterial hosts presents a significant challenge to predict which phages infect a focal set of bacteria. Infection is largely determined by complementary-and largely uncharacterized-genetics of adsorption, injection, cell take-over, and lysis. Here we present a machine learning approach to predict phage-bacteria interactions trained on genome sequences of and phenotypic interactions among 51 strains and 45 phage λ strains that coevolved in laboratory conditions for 37 days.
View Article and Find Full Text PDFWant 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!