Baicalein Alleviates Acute-on-Chronic Liver Failure by Promoting TREM2-dependent Macrophage Polarization
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE248293 | GEO | 2025/12/31
REPOSITORIES: GEO
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Project description:Effects of baicalein in C. elegans gene expression is studied, as our results indicate a lifespan extension effect produced by this molecule. Microarrays were used to detail the global programme of gene expression underlying the lifespan extension and identified distinct classes of up/down-regulated genes in animals treated with baicalein.
2021-03-11 | GSE134775 | GEO
Project description:Baicalein, a purified flavonoid compound with defined chemical structure extracted from the dry roots of Scutellaria radix that is a broadly used herb in China, has been proved to possess significant anti-hepatoma activity by inhibiting cell proliferation, invasion, metastasis and inducing apoptosis, autophagy via several cancer-related signaling molecules. In recent years, emerging studies have demonstrated that Chinese medicinal herbs can exert their anti-tumor effects through targeting lncRNAs，such as curcumin, camptothecin, resveratrol，paclitaxel. However, there is still no related report about the effects of baicalein on lncRNA expression profile when it exerts its inhibition on hepatoma tumor growth. To investigate whether the antitumor effect of baicalein is related to its modulation of lncRNA expression in hepatocellular carcinoma (HCC), we profiled the lncRNA expression in HCC cell line Bel-7402 treated with baicalein (0, 40, 80μM) for 24 hours using lncRNA microarray and detected the changes by comparing the lncRNA expression profile of HCC cell line Bel-7402 treated with baicalein (40 and 80 μM) and its DMSO control (0 μM). These findings suggest that modulation of lncRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein and lay the groundwork for further investigations. To investigate whether the antitumor effect of baicalein is related to its modulation of lncRNA expression in hepatocellular carcinoma (HCC), we profiled the miRNA expression in HCC cell line Bel-7402 treated with baicalein (0, 40, 80μM) for 24 hours using miRNA microarray and detected the changes by comparing the lncRNA expression profile of HCC cell line Bel-7402 treated with baicalein (40 and 80 μM) and its DMSO control (0 μM). These findings suggest that modulation of lncRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein and lay the groundwork for further investigations.
2018-03-01 | GSE95504 | GEO
Project description:Baicalein, a purified flavonoid compound with defined chemical structure extracted from the dry roots of Scutellaria radix that is a broadly used herb in China, has been proved to possess significant anti-hepatoma activity by inhibiting cell proliferation, invasion, metastasis and inducing apoptosis, autophagy via several cancer-related signaling molecules. In recent years, emerging studies have demonstrated that Chinese medicinal herbs can exert their anti-tumor effects through targeting miRNAs，such as curcumin, camptothecin, resveratrol. However, there is still no related report about the effects of baicalein on miRNA expression profile when it exerts its inhibition on hepatoma tumor growth. To investigate whether the antitumor effect of baicalein is related to its modulation of miRNA expression in hepatocellular carcinoma (HCC), we profiled the miRNA expression in HCC cell line Bel-7402 treated with baicalein (0, 40, 80μM) for 24 hours using miRNA microarray and detected the changes by comparing the miRNA expression profile of HCC cell line Bel-7402 treated with baicalein (40 and 80 μM) and its DMSO control (0 μM). These findings suggest that modulation of miRNA expression may be an important mechanism underlying the anti-hepatoma effects of baicalein and lay the groundwork for further investigations.
2017-08-15 | GSE85511 | GEO
Project description:Hepatitis B virus (HBV)-associated acute on chronic liver failure (HBV-ACLF), characterized by an acute deterioration of liver function in the patients with chronic hepatitis B (CHB), is lack of predicting biomarkers for prognosis. To explore potential biomarkers of HBV-ACLF for clinical applications, immuno-depletion of high-abundance plasma proteins followed by iTRAQ-based quantitative proteomic approach was employed to analyze plasma samples from 20 healthy control people, 20 CHB patients and 20 HBV-ACLF patients, respectively. As a result, a total of 427 proteins were identified and quantified from these samples, and 42 proteins were differentially expressed in HBV-ACLF patients as compared to both CHB patients and healthy controls. According to bioinformatics analysis results, 6 proteins related to immune response (MMR), inflammatory response (OPN, HPX), blood coagulation (ATIII) and lipid metabolism (APO-CII, GP73) were selected as biomarker candidates. Further ELISA analysis confirmed the significant up-regulation of GP73, MMR, OPN and down-regulation of ATIII, HPX, APO-CII in HBV-ACLF plasma samples (p<0.01). Moreover, receiver operating characteristic (ROC) curve analysis revealed high diagnostic value of these candidates in assessing HBV-ACLF. In conclusion, present quantitative proteomic study identified 6 novel HBV-ACLF biomarker candidates and might provide fundamental information for development of HBV-ACLF biomarker.
2018-10-23 | PXD007975 | Pride
Project description:Here, we showed that baicalein suppressed transforming growth factor β1 (TGF β1)-stimulated the production of type I collagen in lung fibroblast MRC-5 cells. By applying SILAC-based proteomic technology, 158 proteins were identified as baicalein-modulated proteins in TGF β1-stimulated the accumulation of type I collagen in MRC-5 cells. Our proteomic and biochemical analysis demonstrated that baicalein could decrease the expression levels of connective tissue growth factor (CTGF) in TGF β1-stimulated MRC-5 cells. In addition, CTGF overexpression elevated the levels of type I collagen in baicalein-treated fibroblasts. Moreover, our results demonstrated that baicalein-downregulated CTGF expression might be related with the decrease of Smad2 phosphorylation, but not SP1.
2020-09-21 | PXD016167 | Pride
Project description:Background and aims: Acute-on-chronic liver failure (ACLF) is characterized by rapid deterioration of liver function and organ failure, whereby immunoparesis and susceptibility to infections often precipitate this syndrome. Here we characterized the events triggering immune dysfunction in monocytes within alcoholic liver disease. Methods: We evaluated the frequency of monocyte subsets, their intracellular IL10 production, surface HLA-DR expression, and phagocytic and oxidative burst capacity in patients with decompensated cirrhosis, -alcoholic hepatitis or ACLF. RNAsequencing of ACLF patient-derived CD14+ monocytes were performed either immediately or after 12-hour culture in the presence or absence of plasma from ACLF patients. In this in vitro model of ACLF induction in CD14+ monocytes we characterized the early molecular, immunological and functional changes. Results: Besides a redistribution of monocyte subset composition, ACLF patient-derived monocytes featured elevated frequencies of IL-10-producing cells, reduced HLA-DR expression and impaired phagocytic- and oxidative burst capacity. RNAsequencing revealed a reprogramming of ACLF monocytes, whereby they undergo a transition from a pro-inflammatory to an immunosuppressive- and altered metabolic status. Culturing healthy monocytes in the presence of ACLF plasma, blunted their phagocytic capacity and triggered a gene expression pattern comparable to ACLF patients. Conversely, culturing patient monocytes in normal plasma restored their phagocytic capacity. Finally, plasma IL-10 levels correlated with patient survival. Conclusion: ACLF monocytes featured a defective immunosuppressive and -glycolytic profile, an attribute which could be mimicked by culturing healthy monocytes in the presence of ACLF patient plasma. Our data implicate a role for IL-10 signaling pathways in triggering monocytes dysfunction and opens up new avenues for therapeutic targeting.
2019-02-06 | GSE93265 | GEO
Project description:BACKGROUND: The molecular mechanisms driving the progression from early chronic liver disease (eCLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Thus, the aim of this work is to develop a network-based approach to investigate molecular pathways driving progression from eCLD to ACLF. We created 9 liver-specific biological networks capturing key pathophysiological processes potentially related to CLD. We used these networks as framework to perform gene set enrichment analyses(GSEA) and create dynamic profiles of disease progression. RESULTS: Principal component analyses revealed that samples clustered according to the disease stage. GSEA analyses of the defined processes showed an up-regulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between CC and DC, while ACLF showed acute expression changes in all the defined liver-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated to ACLF onset. Functional analyses showed that ascending profiles were associated to inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the up-regulation of 4 genes of the ascending profile CXCL-6, KRT-18, SPINK-1, and ITGA2, and validated our findings on an independent patient’s cohort. CONCLUSION: ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis processes. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting thus the hypothesis that ACLF should be considered a distinct entity.
2021-09-11 | GSE139602 | GEO
Project description:To comprehensively study the intracellular signaling changes and explore the underlying mechanisms of baicalein-mediated microglial responses, we employed systemic proteomic approach, using target-free SWATH mass spectra (SWATH-MS), focusing on intracellular proteins. BV2 cells were treated with LPS followed by the addition of vehicle or baicalein and they were cultured for a total of 48 hours before being collected for proteomic analysis.
2022-02-14 | PXD030447 | Pride
Project description:BACKGROUND/ AIMS: Severe forms of alcoholic liver disease are associated with increased susceptibility to infections largely due to immune dysfunction. In this study, we analyze the phenotypic, molecular and functional profiles of the mononuclear phagocyte system of patients with cirrhosis, severe alcoholic hepatitis (sAH) or acute-on-chronic liver failure (ACLF). RESULTS: sAH and ACLF patients display a severe impairment of the TH1-promoting IL-12p70/IFNgamma/CXCL10 axis. Furthermore, the CD14+ monocytes and classical dendritic cells of these patients are unable to mount an appropriate pro-inflammatory response after stimulation with PAMPs associated with gram-negative bacteria or fungal pathogens. These cells also have reduced polyfunctionality, which is associated with a higher risk of subsequent infection. Finally, we show that CD14+ monocytes of sAH and ACLF patients display a similar transcriptional profile characterized by immunosuppressive features. This was accompanied with changes in chromatin accessibility in enhancer regions of key immune and metabolic genes. CONCLUSIONS: Altered transcriptional program and functional properties of monocytes from sAH and ACLF patients has strong epigenetic determinants.
2020-08-02 | GSE135285 | GEO
Project description:BACKGROUND/ AIMS: Severe forms of alcoholic liver disease are associated with increased susceptibility to infections largely due to immune dysfunction. In this study, we analyze the phenotypic, molecular and functional profiles of the mononuclear phagocyte system of patients with cirrhosis, severe alcoholic hepatitis (sAH) or acute-on-chronic liver failure (ACLF). RESULTS: sAH and ACLF patients display a severe impairment of the TH1-promoting IL-12p70/IFNgamma/CXCL10 axis. Furthermore, the CD14+ monocytes and classical dendritic cells of these patients are unable to mount an appropriate pro-inflammatory response after stimulation with PAMPs associated with gram-negative bacteria or fungal pathogens. These cells also have reduced polyfunctionality, which is associated with a higher risk of subsequent infection. Finally, we show that CD14+ monocytes of sAH and ACLF patients display a similar transcriptional profile characterized by immunosuppressive features. This was accompanied with changes in chromatin accessibility in enhancer regions of key immune and metabolic genes. CONCLUSIONS: Altered transcriptional program and functional properties of monocytes from sAH and ACLF patients has strong epigenetic determinants.
2020-08-02 | GSE135284 | GEO