Search

AA, advanced adenoma; CRC, colorectal carcinoma; 5mC, 5-methylcytosine; 5hmC, 5-hydroxymethylcytosine. gl In summary, 5mC and 5hmC showed dynamic changes in the progression of AA-CRC transformation. CRC, colorectal carcinoma; DMGs, differentially methylated genes; 5mC, 5-methylcytosine; 5hmC, 5-hydroxymethylcytosine; RT-qPCR, real-time quantitative polymerase chain reaction. gl To elucidate the mechanism of AA-CRC transformation, the levels of DNA methylases and demethylases were measured. Globally, colorectal carcinoma (CRC) ranks third in terms of prevalence according to the latest Global Cancer Statistics.[1] Studies have shown that most CRCs begin as preexisting adenomas,[2] among which advanced adenomas (AAs) have been demonstrated to be a more intense risk factor.[3] Exploring the underlying mechanism of AA-CRC transformation is helpful in providing a basis for the precise treatment of CRC. [Extracted from the article]

Jiangzhi Granule is a commonly used traditional Chinese medicine for treating non-alcoholic fatty liver disease. However, its key ingredients and underlying mechanisms for attenuating nonalcoholic steatohepatitis (NASH) remain unclear. To address this issue, UPLC-TOF-MS based chemical profiling, network pharmacology and animal experimental validation were employed. First, a total of 56 main ingredients of Jiangzhi Granule and 38 ingredients in the blood and liver (after oral administration) were identified. Then, 170 potential targets of the absorbed ingredients and 50 targets of NASH were identified, and 10 overlapped genes were identified as candidate targets of Jiangzhi Granule for NASH treatment. A Jiangzhi Granule-ingredients-targets-disease network was constructed using Cytoscape software, which included eight main ingredients (such as emodin, resveratrol and quercetin) and 10 candidate targets (such as TNF, IL6 and CCL2). Functional enrichment indicated that the candidate targets were enriched in multiple pathways (such as the TNF signaling pathway). Furthermore, a NASH mice model was constructed and intervened with Jiangzhi Granule. The results revealed that Jiangzhi Granule could ameliorate NASH characteristics, such as histopathological changes and liver cholesterol level. Meanwhile, Jiangzhi Granule significantly decreased the mRNA and protein expression of TNFα in NASH mice liver, suppressed NFκB activation, and inhibited the expression of macrophage activation marker F4/80 and M1-type polarization marker CD11b/CD11c. ELISA assay indicated that Jiangzhi Granule reduced pro-inflammatory cytokines (including TNFα, IL-1β and IL-6) in the liver. Collectively, our results suggested that Jiangzhi Granule could attenuate NASH by suppressing TNF/NFκB signaling mediated macrophage M1-type polarization. [Display omitted] • Jiangzhi Granule attenuated NASH efficiently. • Combination of UPLC-TOF-MS, network pharmacology and animal model was employed. • The active compounds and therapeutic mechanisms of Jiangzhi Granule on NASH were uncovered. [ABSTRACT FROM AUTHOR]

Qiang-Gan formula is a traditional Chinese medicine formula, which has been widely used in treating liver diseases in China. To investigate the effect of Qiang-Gan formula extract (QGE) on non-alcoholic steatohepatitis (NASH) and its underlying possible mechanisms. The high-performance liquid chromatography finger-print method was used for the quality control of chemical components in QGE. Methionine- and choline-deficient diet-induced NASH mice were administrated with QGE via gavage for four weeks. Phenotypic parameters including liver histological change as well as serum levels of alanine transaminase (ALT), aspartate transaminase (AST) were detected. Bile acid profile in the serum, liver and fecal samples was analyzed by gas chromatography-mass spectrometer technique, and fecal microbiota was detected by 16S rDNA sequencing. Expression of liver G protein-coupled bile acid receptor 1 (TGR5), farnesiod X receptor (FXR), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) as well as molecules in nuclear factor kappa B (NF-κB) pathway was assayed by immunohistochemistry staining, RT-qPCR, or Western blot, respectively. QGE alleviated liver inflammation, reduced serum ALT and AST levels and liver TNF-α and IL-1β expression in NASH mice. It also decreased liver and serum BA concentration and increased fecal lithocholicacid (LCA) production in this animal model. QGE altered the structure of gut microbiota, predominantly increased LCA-producing bacteria Bacteroides and Clostridium in NASH mice. In addition, the expression of liver TGR5 but not FXR was increased, and the molecules in NF-κB pathway were decreased in QGE-treated NASH mice. QGE was effective in preventing NASH, possibly by regulation of gut microbiota-mediated LCA production, promotion of TGR5 expression and suppression of the NF-κB activation. Image 1 [ABSTRACT FROM AUTHOR]