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1.
Heliyon ; 10(11): e31712, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38845983

ABSTRACT

Background: Tuberculosis (TB) is a complex disease with a spectrum of outcomes for more than six decades; however, the genomic and epigenetic mechanisms underlying the highly heritable susceptibility to TB remain unclear. Methods: Integrated sequence-based genomic, transcriptomic, and methylation analyses were conducted to identity the genetic factors associated with susceptibility to TB in two pairs of Mongolian monozygous twins. In this study, whole-genome sequencing was employed to analyze single nucleotide polymorphisms (SNPs), insertions and deletions (InDels), and copy number variations (CNVs). Gene expression was assessed through RNA sequencing, and methylation patterns were examined using the Illumina Infinium Methylation EPIC BeadChip. The gene-gene interaction network was analyzed using differentially expressed genes. Results: Our study revealed no significant difference in SNP and InDel profiles between participants with and without TB. Genes with CNVs were involved in human immunity (human leukocyte antigen [HLA] family and interferon [IFN] pathway) and the inflammatory response. Different DNA methylation patterns and mRNA expression profiles were observed in genes participating in immunity (HLA family) and inflammatory responses (IFNA, interleukin 10 receptor [IL-10R], IL-12B, Toll-like receptor, and IL-1B). Conclusions: The results of this study suggested that susceptibility to TB is associated with transcriptional and epigenetic alternations of genes involved in immune and inflammatory responses. The genes in the HLA family (HLA-A, HLA-B, and HLA-DRB1) and IFN pathway (IFN-α and IFN-γ) may play major roles in susceptibility to TB.

2.
Kaohsiung J Med Sci ; 39(8): 801-810, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37265208

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome with a rapidly increasing prevalence globally. Plantamajoside (PMS), a phenylethanoid glycoside component extracted from Plantago asiatica, has various biological properties. However, its effect on NAFLD remains unknown. The study aimed to explore the effect and mechanism of PMS on NAFLD in the high-fat diet (HFD)-feeding rats. PMS induced a decrease in body and liver weight, and the amelioration in the blood lipid parameters and pathological symptoms in HFD-feeding rats. The increase in the serum concentrations and the relative protein expressions of proinflammatory factors was decreased by the PMS treatment in HFD-induced NAFLD rats. Additionally, PMS reduced the excessive lipid vacuoles, and modified the relative expressions of proteins involved in the fatty acid synthesis and uptake in HFD-feeding rats. Mechanically, the downregulation of AMPK/Nrf2 pathway in HFD-feeding rats was restored by the PMS treatment. Inhibition of AMPK pathway reversed the PMS-induced the increase in the level of inflammatory factors, pathological symptoms, excessive lipid vacuoles, and the relative expression of proteins involved in the fatty acid synthesis and uptake. Collectively, PMS ameliorated immune dysregulation and abnormal hepatic lipid metabolism by activating AMPK/Nrf2 pathway in rats with NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Rats , AMP-Activated Protein Kinases/genetics , AMP-Activated Protein Kinases/metabolism , Fatty Acids/metabolism , Lipid Metabolism , Lipids/blood , Liver/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism
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