Machine Learning and Experimental Validation Identified Ferroptosis Signature and Innovative Biomarkers (ESR1 and GSTZ1) in Liver Fibrosis DOI Creative Commons
Wen Luo,

Hong-Wen Wu,

Zhijie Yang

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 10313 - 10332

Published: Dec. 1, 2024

Background: Targeting ferroptosis is an effective approach to mitigate hepatic fibrosis, yet no reports exist on the signature in liver fibrosis. This study aimed explore characteristics this disease. Methods: RNAseq data from GSE6764, GSE188604 and Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) were downloaded. Multiple machine learning methods, including Weighted Gene Co-expression Network Analysis (WGCNA), Random Forest (RF) Support Vector Machine (SVM), used identify core genes fibrosis ferroptosis. WGCNA can pinpoint modules linked clinical traits, aiding discovering diagnostic progression molecules complex diseases. RF SVM are often utilized for validation boost result accuracy. Carbon tetrachloride (CCl4) was establish a mouse model validate gene expression, which also assessed test GEO datasets. Finally, role of hepatocellular carcinoma (HCC) investigated using ROC analysis. Results: methods screened nine genes, IL1B, GSTZ1, LIFR, SLC25A37, PTGS2, MT1G, HSPB1, ESR1, PHGDH. In vivo experimental validation, RT-PCR showed ESR1 GSTZ1 significantly under-expressed group compared normal group. Simultaneously, GSE6764 GSE188604, identified as protective More in-depth research found that exhibited good performance both HCC, suggesting persistent decrease patients might signal HCC. Conclusion: The present first report identifies two novel biomarkers, providing new insights diagnosis treatment future. Keywords: ferroptosis, biomarker

Language: Английский

Epigenetic remodeling by sex hormone receptors and implications for gender affirming hormone therapy DOI Creative Commons

Den Celestra,

Ngan K. Nguyen, Camille Laberthonnìère

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 8, 2025

Sex differences in immune system development and response to pathogens has been well documented, with females exhibiting more favorable outcomes for certain infections but a higher incidence of autoimmune disease compared males. At least some these sex are mediated by hormones, which signal through hormone receptors remodel the regulatory chromatin landscape cells. Here, we summarize current knowledge how structure epigenetic marks different contexts humans. As epigenome is fundamental specifying cell identity function, reflects past exposures, variation can influence cellular responses future stimuli. This implications susceptibility infection complex inflammatory range therapy settings, including gender-affirming transgender people. Therefore, profiling context an important unexplored field research.

Language: Английский

Citations

0
17β-Estradiol (E2) Upregulates the ERα/SIRT1/PGC-1α Signaling Pathway and Protects Mitochondrial Function to Prevent Bilateral Oophorectomy (OVX)-Induced Nonalcoholic Fatty Liver Disease (NAFLD) DOI Creative Commons
Ying Tian, Xinyu Hong, Yuan Xie

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(12), P. 2100 - 2100

Published: Dec. 12, 2023

Premature menopause is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). Menopausal hormone therapy (MHT) has been widely used in clinical practice and the potential to protect mitochondrial function alleviate NAFLD. After bilateral oophorectomy (OVX), female rats without 17β-estradiol (E2) intervention developed NAFLD, whereas E2 supplementation was effective preventing NAFLD rats. The altered pathways cellular events from both comparison pairs, namely, OVX vs. sham group group, were assessed using transcriptomic analysis. KEGG enriched by metabolomic analyses strongly suggest that oxidative phosphorylation a vital pathway changes during development remains unchanged when applied. Liver tissue OVX-induced exhibited lipid peroxidation, impaired mitochondria, downregulated ERα/SIRT1/PGC-1α expression. An vitro study indicated protective effect treatment on hepatic steatosis could be abolished ERα or SIRT1 selectively inhibited. This damage accompanied reduced complex activity peroxidation. current research indicates upregulates signaling protects prevent

Language: Английский

Citations

5
Exploring the active ingredients and mechanisms of Liujunzi decoction in treating hepatitis B: a study based on network pharmacology, molecular docking, and molecular dynamics simulations DOI

Qing Ma,

Wenjun Li,

Wenying Wu

et al.

Computer Methods in Biomechanics & Biomedical Engineering, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 25

Published: Nov. 13, 2024

Liujunzi decoction (LJZD) is commonly used to treat hepatitis B virus (HBV), though its active ingredients and mechanisms are not fully known. This study identified core targets components of LJZD for treating (HB) through network pharmacology, molecular docking, dynamics simulation. Screening from databases yielded 533 components, 2619 LJZD, 2910 HB, with 891 intersecting targets. STRING CytoHubba analyses AR VDR as targets, key pathways including PI3K-Akt MAPK. The findings clarify LJZD's multicomponent, multitarget mechanisms, supporting clinical application HB treatment.

Language: Английский

Citations

1
HLA-DR genetic polymorphisms and hepatitis B virus mutations affect the risk of hepatocellular carcinoma in Han Chinese population DOI Creative Commons
Yubao Zhao, Kun Chen, Hui Yang

et al.

Virology Journal, Journal Year: 2023, Volume and Issue: 20(1)

Published: Nov. 30, 2023

Abstract Background Human leucocyte antigen ( HLA ) -DR plays a crucial role in the immune response against hepatitis B virus (HBV). We aimed to investigate associations of HLA-DR single nucleotide polymorphisms (SNPs) with generation hepatocellular carcinoma (HCC)-related HBV mutations. The effects SNPs and their interactions mutations on HCC risks were also determined. Methods Five (rs3135363, rs9268644, rs35445101, rs24755213, rs984778) genotyped 792 healthy controls, 586 chronic (CHB) patients, 536 liver cirrhosis (LC) 1500 patients using quantitative PCR. Sanger sequencing was used identify Logistic regression model performed evaluate association risk frequencies HCC-related Results variant genotypes at rs3135363, rs984778 associated decreased risks. In genotype C HBV-infected subjects, these such as C1653T, T1674C/G, G1719T, T1753A/C, A1762T/G1764A, A1846T, G1896A, G1899A, preS deletion. AG CA rs24755213 reduced T1753A/C G1896A respectively. addition, HCC. Conclusions genetic might predispose host immunoselection affect possibly through interacting

Language: Английский

Citations

2
Machine Learning and Experimental Validation Identified Ferroptosis Signature and Innovative Biomarkers (ESR1 and GSTZ1) in Liver Fibrosis DOI Creative Commons
Wen Luo,

Hong-Wen Wu,

Zhijie Yang

et al.

Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 10313 - 10332

Published: Dec. 1, 2024

Background: Targeting ferroptosis is an effective approach to mitigate hepatic fibrosis, yet no reports exist on the signature in liver fibrosis. This study aimed explore characteristics this disease. Methods: RNAseq data from GSE6764, GSE188604 and Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) were downloaded. Multiple machine learning methods, including Weighted Gene Co-expression Network Analysis (WGCNA), Random Forest (RF) Support Vector Machine (SVM), used identify core genes fibrosis ferroptosis. WGCNA can pinpoint modules linked clinical traits, aiding discovering diagnostic progression molecules complex diseases. RF SVM are often utilized for validation boost result accuracy. Carbon tetrachloride (CCl4) was establish a mouse model validate gene expression, which also assessed test GEO datasets. Finally, role of hepatocellular carcinoma (HCC) investigated using ROC analysis. Results: methods screened nine genes, IL1B, GSTZ1, LIFR, SLC25A37, PTGS2, MT1G, HSPB1, ESR1, PHGDH. In vivo experimental validation, RT-PCR showed ESR1 GSTZ1 significantly under-expressed group compared normal group. Simultaneously, GSE6764 GSE188604, identified as protective More in-depth research found that exhibited good performance both HCC, suggesting persistent decrease patients might signal HCC. Conclusion: The present first report identifies two novel biomarkers, providing new insights diagnosis treatment future. Keywords: ferroptosis, biomarker

Language: Английский

Citations

0