MiRNA-based liquid biopsy provides early prediction of lethal acetaminophene poisoning: a case study
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE111258 | GEO | 2020/01/03
REPOSITORIES: GEO
Similar Datasets
Project description:miRNA-based liquid biopsy provides early prediction of lethal acetaminophene poisoning: a case study
| PRJNA436462 | ENA
Project description:Overdose of acetaminophen (APAP) is the major cause of acute liver failure in the Western world with very limited treatment options. Previous studies from our groups and others have shown that timely activation of liver regeneration is a critical determinant of transplant-free survival of APAP-induced acute liver failure (ALF) patients. We used affy microarrays to explore the mechanisms of transcriptional expression in YAP-KO mice after 300mg/kg APAP overdose.
2021-10-04 | GSE183119 | GEO
Project description:Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available singlenuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as Cxcl14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, Cxcl14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or Cxcl14 with a neutralizing antibody. We found that targeting Cxcl14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting the senescent hepatocyte had no effect. This data supports that the sustained induction of p21 in hepatocytes with persistent Cxcl14 secretion are critical mechanistic events leading to ALF in mice and human patients.
2024-04-15 | GSE255834 | GEO
Project description:Fifty percent of all acute liver failure (ALF) cases in the United States are due to acetaminophen (APAP) overdose. Assessment of canonical features of liver injury, such as plasma alanine aminotransferase activities are poor predictors of acute liver failure (ALF), suggesting the involvement of additional mechanisms independent of hepatocyte death. Previous work demonstrated a severe overdose of APAP results in impaired regeneration, the induction of senescence by p21, and increased mortality. We hypothesized that a discrete population of p21+ hepatocytes acquired a secretory phenotype that directly impedes liver recovery after a severe APAP overdose. Leveraging in-house human APAP explant liver and publicly available singlenuclei RNAseq data, we identified a subpopulation of p21+ hepatocytes enriched in a unique secretome of factors, such as Cxcl14. Spatial transcriptomics in the mouse model of APAP overdose confirmed the presence of a p21+ hepatocyte population that directly surrounded the necrotic areas. In both male and female mice, we found a dose-dependent induction of p21 and persistent circulating levels of the p21-specific constituent, Cxcl14, in the plasma after a severe APAP overdose. In parallel experiments, we targeted either the putative senescent hepatocytes with the senolytic drugs, dasatinib and quercetin, or Cxcl14 with a neutralizing antibody. We found that targeting Cxcl14 greatly enhanced liver recovery after APAP-induced liver injury, while targeting the senescent hepatocyte had no effect. This data supports that the sustained induction of p21 in hepatocytes with persistent Cxcl14 secretion are critical mechanistic events leading to ALF in mice and human patients.
2024-04-15 | GSE255777 | GEO
Project description:The dataset comprises of circulating miRNAs in human subjects with various types of liver impairments. In our study, we analyzed a total 48 serum samples from a group of 42 subjects that included subjects with accidental acetaminophen overdose (APAP), hepatitis B infection (HBV), liver cirrhosis (LC) and type 2 diabetes mellitus (T2DM) subjects with alanine amino transference (ALT) elevation. As a control 16 sex and age matched healthy controls from subjects with no evidence of liver disease were analyzed. The miRNA profiles were measured using next-generation sequencing platform.
2017-06-09 | GSE90028 | GEO
Project description:Liquid biopsies have great promise for precision medicine as they provide information about primary and metastatic tumors via a minimally invasive method. In gastric cancer patients, a large number of blood-based biomarkers have been reported for their potential role in clinical practice for screening, early diagnosis, prognostic evaluation, recurrence monitoring and therapeutic efficiency follow-up. This current review focuses on blood liquid biopsies' role and their clinical implications in gastric cancer patients, with an emphasis on circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) and circulating non-coding RNAs (ncRNAs). We also provide a brief discussion of the potential and limitations of liquid biopsies use and their future use in the routine clinical care of gastric cancer.
| S-EPMC5871105 | biostudies-literature
Project description:There is a paucity of data on how protease-activated receptors (PARs) regulate transcriptional reprogramming. We sought to determine how the expression of two members of the PAR family (PAR1 and PAR4) on hepatic endothelial cells (ECs) influence transcription in the liver after acetaminophen (APAP) overdose. We combined EC-specific translating ribosome affinity purification with next-generation sequencing (EC-TRAPseq) in endothelial-specific Par1 and Par4 knockout mice. This allowed us to gain an in vivo snapshot of how EC gene expression profiles change with APAP overdose and how the loss of endothelial PARs impacts transcriptional reprogramming in hepatic ECs. This approach also provided a high degree of sensitivity for detecting low-expressing transcripts. We found distinct transcriptional changes in APAP-overdosed ECs between endothelial Par1 and Par4 knockout mice.
2024-06-10 | GSE266395 | GEO
Project description:Acetaminophen (APAP) is the major cause of drug-induced liver injury, with limited treatment options. APAP overdose invokes excessive oxidative stress that triggers mitochondria-to-nucleus retrograde pathways, contributing to APAP-induced liver injury (AILI). Mesenchymal stem cell therapy is a promising tool for acute liver failure. Therefore, the purpose of this study is to investigate the beneficial effects of adipose-derived mesenchymal stem cell (AMSC) therapy on AILI and reveal the potential therapeutic mechanisms. C57BL/6 mice are used as the animal model and AML12 normal murine hepatocytes as the cellular model of APAP overdose. Immunohistochemical staining, western blotting, immunofluorescence staining, and RNA sequencing assay are used for assessing the efficacy and validating mechanisms of AMSC therapy. We found AMSC therapy effectively ameliorated AILI, while delayed AMSC injection lost its efficacy related to the c-Jun N-terminal kinase (JNK)-mediated mitochondrial retrograde pathways. We further found that AMSC therapy inhibited JNK activation and mitochondrial translocation, reducing APAP-induced mitochondrial damage. The down-regulation of activated Ataxia telangiectasia mutated (ATM) and DNA damage response proteins in AMSC treated mice liver indicated AMSC blocked the JNK-ATM pathway. Overall, AMSC may be an effective treatment for AILI by inhibiting JNK-ATM mitochondrial retrograde pathway, which improves APAP-induced mitochondrial dysfunction and liver injury.
2022-12-17 | GSE218879 | GEO
Project description:Acetaminophen (APAP) is the most widely used analgesic in the United States. Its acute overdose causes liver damage by inducing localized centrilobular cell death. Because of widespread use, APAP toxicity has become the most frequent cause of acute liver failure. Many factors have been associated with the susceptibility of APAP-induced liver injuries, however, few of them have been confirmed and used in the clinical setting. We tried to identify the subset of factors that could affect susceptibility to APAP-induced liver injury by an integrative genetic, transcriptional and 2-D-NMR-based metabolomic analysis across a panel of inbred mouse strains.
2009-08-14 | GSE17649 | GEO