Drug-induced liver injury (DILI) is the leading cause of acute liver failure (ALF). Continuous and prolonged hepatic cellular oxidative stress and liver inflammatory stimuli are key signatures of DILI. DEAD-box helicase 3, X-linked (DDX3X) is a central regulator in pro-survival stress granule (SG) assembly in response to stress signals. However, the role of DDX3X in DILI remains unknown. Herein, we characterized the hepatocyte-specific role of DDX3X in DILI. Human liver tissues of DILI patients and control subjects were used to evaluate DDX3X expression. APAP, CCl4 and TAA models of DILI were established and compared between hepatocyte-specific DDX3X knockout (DDX3X) and wild-type control (DDX3X) mice. Hepatic expression of DDX3X was significantly decreased in the pathogenesis of DILI compared with controls in human and mice. Compared to DDX3X mice, DDX3X mice developed significant liver injury in multiple DILI models. DDX3X deficiency aggravates APAP induced oxidative stress and hepatocyte death by affecting the pro-survival stress granule (SG) assembly. Moreover, DDX3X deficiency induces inflammatory responses and causes pronounced macrophage infiltration. The use of targeted DDX3X drug maybe promising for the treatment of DILI in human.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322869 | PMC |
| http://dx.doi.org/10.1038/s41419-023-05913-x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adaptive functioning in children and young adults with monogenic neurodevelopmental disorders.
Dev Med Child Neurol
January 2025
Speech and Language, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Aim: To examine the adaptive behaviour profiles of children with monogenic neurodevelopmental disorders (NDDs) to determine whether syndrome-specific or transdiagnostic approaches provide a better understanding of the adaptive behavioural phenotypes of these NDDs.
Method: This cross-sectional study included parents and caregivers of 243 (48% female) individuals (age range = 1-25 years; mean = 8 years 10 months, SD = 5 years 8 months) with genetically confirmed monogenic NDDs (CDK13, DYRK1A, FOXP2, KAT6A, KANSL1, SETBP1, BRPF1, and DDX3X). Parents and caregivers completed the Vineland Adaptive Behavior Scales, Third Edition to assess communication, daily living, socialization, and motor skills.
An exploratory study on the differential diagnostic indicators between adult systemic EBV-positive T-cell lymphoproliferative disorders and angioimmunoblastic T-cell lymphoma with multiple EBV infections.
Infect Agent Cancer
January 2025
Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Background: The differential diagnosis between adult systemic EBV-positive T-cell lymphoproliferative disorders (EBV T-LPD) and angioimmunoblastic T-cell lymphoma (AITL) with multiple EBV infections is difficult, and distinguishing between the two has become a diagnostic challenge for pathologists. Given that the clinical treatment plans are different, an accurate diagnosis is a prerequisite to ensure effective treatment, therefore, it is extremely necessary and meaningful to find effective pathological indicators for distinguishing between two diseases.
Methods: We present a retrospective study comparing 7 cases of adult EBV T-LPD and 16 cases of AITL with multiple EBV infections diagnosed at our institution from 2017 to 2022.
Multi-modal investigation reveals pathogenic features of diverse DDX3X missense mutations.
PLoS Genet
January 2025
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, North Carolina, United States of America.
De novo mutations in the RNA binding protein DDX3X cause neurodevelopmental disorders including DDX3X syndrome and autism spectrum disorder. Amongst ~200 mutations identified to date, half are missense. While DDX3X loss of function is known to impair neural cell fate, how the landscape of missense mutations impacts neurodevelopment is almost entirely unknown.
View Article and Find Full Text PDFModulation of DAPK1 expression by its alternative splice variant DAPK1-215 in cancer.
J Transl Med
January 2025
Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350001, China.
Background: Death-Associated Protein Kinase 1 (DAPK1) family members are calcium/calmodulin-regulated serine/threonine kinases implicated in cell death, normal development, and human diseases. However, the regulation of DAPK1 expression in cancer remains unclear.
Methods: We examined the expression and functional impact of a DAPK1 splice variant, DAPK1-215, in multiple cancer cell lines.
Diagnostic Power of MicroRNAs in Melanoma: Integrating Machine Learning for Enhanced Accuracy and Pathway Analysis.
J Cell Mol Med
January 2025
Cancer Biology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.
This study identifies microRNAs (miRNAs) with significant discriminatory power in distinguishing melanoma from nevus, notably hsa-miR-26a and hsa-miR-211, which have exhibited diagnostic potential with accuracy of 81% and 78% respectively. To enhance diagnostic accuracy, we integrated miRNAs into various machine-learning (ML) models. Incorporating miRNAs with AUC scores above 0.
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!