scholarly journals Differences in MicroRNA Expression in Chronic Hepatitis B Patients with Early Liver Fibrosis Based on Traditional Chinese Medicine Syndromes

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Mei-Jie Shi ◽  
Huan-Ming Xiao ◽  
Yu-Bao Xie ◽  
Jun-Min Jiang ◽  
Peng-Tao Zhao ◽  
...  

The aim of this study was to determine if microRNA (miRNA) expression is different among chronic hepatitis B (CHB) patients with early liver fibrosis classified according to traditional Chinese medicine (TCM) syndromes. Eighteen CHB-fibrosis patients and 12 CHB patients without fibrosis were enrolled. The CHB-fibrosis group included 9 patients with the TCM syndrome of Ganyu Pixu Xueyu (GYPXXY), characterized by liver stagnation, spleen deficiency, and blood stasis, and 9 patients with the TCM syndrome of Qixu Xueyu (QXXY), characterized by deficiency of qi, blood, and blood stasis. Agilent miRNA microarray was performed first in liver specimens to determine whether miRNA expression is different in patients with these two TCM syndromes of CHB-fibrosis. Gene Ontology (GO) analysis and KEGG analysis were applied to determine the roles of the differentially expressed miRNAs. QRT-PCR was performed to validate the Agilent miRNA microarray results. Compared with GYPXXY patients, 6 differentially expressed miRNAs were upregulated (miR-144-5p, miR-18a-5p, miR-148b-3p, miR-654-3p, miR-139-3p, and miR-24-1-5p) and 1 was downregulated (miR-6834-3p) in QXXY patients. According to qRT-PCR data, miR-144-5p and miR-654-3p were confirmed as upregulated in CHB-liver fibrosis patients compared to CHB patients without fibrosis, whereas the other 4 miRNAs were not significantly different. More importantly, miR-654-3p was confirmed to be significantly upregulated in QXXY patients compared with values in GYPXXY patients, whereas no significant difference was found in miR-144-5p. Moreover, the pathways of central carbon metabolism in cancer and cell cycle related to miR-654-3p and the target genes of PTEN and ATM were found to be different between QXXY patients and GYPXXY patients. These results indicate that there are different miRNAs, pathways, and target genes between QXXY patients and GYPXXY patients. However, due to the limited sample, whether miR-654-3p and the target genes PTEN and ATM could be molecular markers to differentiate TCM syndromes could not be established.

2020 ◽  
Vol 2020 ◽  
pp. 1-13 ◽  
Author(s):  
Chang Fan ◽  
Fu Rong Wu ◽  
Jia Fu Zhang ◽  
Hui Jiang

Purpose. We explored the mechanism of Shugan Jianpi Formula (SGJPF) and its effective components for the treatment of liver fibrosis (LF). Materials and Methods. We collected the active ingredients in SGJPF through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and screened the effective components by absorption, distribution, metabolism, and excretion. Herb-associated target proteins were predicted and screened based on the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine and Search Tool for Interactions of Chemicals databases. LF-associated target proteins were predicted and screened based on the Online Mendelian Inheritance in Man® Database and Comparative Toxicogenomics Database. Common genes with LF and herbs were selected, and Cytoscape 3.5.1 software was used to construct an herb pathway and component-LF common target network. The Search Tool for the Retrieval of Interacting Genes/Proteins was used to build a protein-protein interaction, and quantitative PCR was used to verify the related target genes. Finally, clusterProfiler was applied for the analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results. The pharmacological network contained 252 active compounds (e.g., Astragaloside A, saikosaponin, linoleic acid, and Poria acid A), 84 common target genes, and 94 significant signaling pathways. Among them, interleukin 6 (IL-6), tumor protein 53 p53 (TP53), prostaglandin-endoperoxide synthase 2 (PTGS2), AKT1, IL-1β, and the nucleotide-binding and oligomerization domain-like receptor and Janus kinase-signal transducer and activator of transcription signaling pathways were selected as the critical target gene and critical signal pathway, respectively. Conclusion. The mechanisms of SGJPF in protecting against LF include the regulation of multiple targets such as IL-6, TP53, PTGS2, and AKT1. These target proteins affect LF through various signal transduction pathways.


2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Tao Wang ◽  
Wei Jin ◽  
Qianqian Huang ◽  
Haotian Li ◽  
Yun Zhu ◽  
...  

Background. Traditional Chinese medicine (TCM) is used as an adjuvant drug for the treatment of chronic hepatitis B liver fibrosis and is used frequently. We still do not know which TCM has the best curative effect as an adjuvant drug. Therefore, we decided to use network meta-analysis to solve this problem. Methods. We used the RevMan software (5.3) and Stata software (13.0) to achieve this network meta-analysis (NMA). The primary outcomes of this study were HA, LN, PCIII, and IV-C; the secondary outcomes of this study were AST, ALT, and HBV-DNA negative conversion rate, and the Cochrane risk-of-bias tool was used to assess the quality of the included studies. For all outcomes, the scissors funnel plot, Egger test, and Begg test were used to detect publication bias, and sensitivity analysis was used to investigate the stability of the results. And the meta-regression was used to explore the source of heterogeneity. Results. A total of 34 articles were included in this study. The study involved a total of 3199 patients, of which 1578 were assigned to the control group and 1621 patients were assigned to the experimental group. The number of men and women is roughly equal, and the average age is about 43 years old. In addition, nine treatment strategies were involved in this study. The combination of TCM and entecavir can significantly improve the patients’ HA, LN, PCIII, IV-C, AST, ALT, and HBV-DNA negative conversion rates. The comprehensive evaluation results showed that FHC combined with entecavir has more advantages than other treatment strategies. Conclusion. For improving the HBV-DNA negative conversion rates, adding TCM to the therapeutic strategies does not seem to show absolute superiority. Finally, FHC combined with entecavir is the best therapeutic strategy.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Yiyu Lu ◽  
Zhaoyuan Fang ◽  
Tao Zeng ◽  
Meiyi Li ◽  
Qilong Chen ◽  
...  

Abstract Background In traditional Chinese medicine (TCM) clinical practice, TCM syndromes help to understand human homeostasis and guide individualized treatment. However, the TCM syndrome changes with disease progression, of which the scientific basis and mechanism remain unclear. Methods To demonstrate the underlying mechanism of dynamic changes in the TCM syndrome, we applied a dynamic network biomarker (DNB) algorithm to obtain the DNBs of changes in the TCM syndrome, based on the transcriptomic data of patients with chronic hepatitis B and typical TCM syndromes, including healthy controls and patients with liver-gallbladder dampness-heat syndrome (LGDHS), liver-depression spleen-deficiency syndrome (LDSDS), and liver-kidney yin-deficiency syndrome (LKYDS). The DNB model exploits collective fluctuations and correlations of the observed genes, then diagnoses the critical state. Results Our results showed that the DNBs of TCM syndromes were comprised of 52 genes and the tipping point occurred at the LDSDS stage. Meanwhile, there were numerous differentially expressed genes between LGDHS and LKYDS, which highlighted the drastic changes before and after the tipping point, implying the 52 DNBs could serve as early-warning signals of the upcoming change in the TCM syndrome. Next, we validated DNBs by cytokine profiling and isobaric tags for relative and absolute quantitation (iTRAQ). The results showed that PLG (plasminogen) and coagulation factor XII (F12) were significantly expressed during the progression of TCM syndrome from LGDHS to LKYDS. Conclusions This study provides a scientific understanding of changes in the TCM syndrome. During this process, the cytokine system was involved all the time. The DNBs PLG and F12 were confirmed to significantly change during TCM-syndrome progression and indicated a potential value of DNBs in auxiliary diagnosis of TCM syndrome in CHB. Trial registration Identifier: NCT03189992. Registered on June 4, 2017. Retrospectively registered (http://www.clinicaltrials.gov)


2011 ◽  
Vol 39 (06) ◽  
pp. 1061-1074 ◽  
Author(s):  
Xiao-Xi Zeng ◽  
Zhao-Xiang Bian ◽  
Tai-Xiang Wu ◽  
Shu-Fei Fu ◽  
Eric Ziea ◽  
...  

Many patients with chronic hepatitis B (CHB) seek help from traditional Chinese medicine (TCM). TCM treatment is based on syndrome differentiation. This study aimed to investigate the syndrome distribution in populations of CHB patients. The pre-specific search strategy was set, and 93 studies (20,106 participants) were identified by electronic and hand searches. The methodological quality of included studies was assessed. Data on syndrome distribution and correlations between syndromes and severity of CHB, were extracted and analyzed. Forty-seven syndromes were identified under 24 different syndrome diagnosis systems for CHB. The majority of included studies reported Liver Depression and Spleen Deficiency (LDSD) (52.54% of studies) or Liver-Gallbladder Dampness Heat (LGDH)/Dampness-Heat Obstructing Middle Energizer (DHME) (32.20%) as the major syndromes in CHB patients without cirrhosis. Pooled analysis revealed that LDSD and LGDH/DHME accounted for 61.19% of participants without cirrhosis. In addition, Liver-Kidney Yin Deficiency (LKYinD) (40.99%) and Spleen-Kidney Yang Deficiency (SKYangD) (40.43%) syndromes were common in patients with severe CHB. The percentage of patients with Blood Stasis syndrome increased as the disease progressed to cirrhosis (32.09%). To conclude, LDSD and LGDH/DHME syndromes are found in a significant majority of CHB patients, particularly in the early stages. LKYinD, SKYangD and Blood Stasis dominate in patients at more advanced stages. More epidemiological studies of high methodological quality on syndrome distribution in CHB and standardization of syndrome differentiation for CHB are required to confirm the trends indicated by the studies reviewed here; confirming these trends can increase the efficacy of treatment and give guidance to doctors.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ya-Nan Song ◽  
Hui Zhang ◽  
Yan Guan ◽  
Jing-Hua Peng ◽  
Yi-Yu Lu ◽  
...  

Traditional Chinese medicine (TCM) syndrome, also called ZHENG, is the basis concept of TCM theory. It plays an important role in TCM practice. There are excess and deficiency syndromes in TCM syndrome. They are the common syndromes in chronic hepatitis B (CHB) patients. Here we aim to explore serum protein profiles and potential biomarkers for classification of TCM syndromes in CHB patients. 24 healthy controls and two cohorts of CHB patients of excess syndrome (n=25) or deficiency syndrome (n=19) were involved in this study. Protein profiles were obtained by surface-enhanced laser desorption ionization time-flight mass spectrometry (SELDI-TOF/MS) and multiple analyses were performed. Based on SELDI ProteinChip data, healthy controls and CHB patients or excess and deficiency syndromes in CHB patients were obviously differentiated by orthogonal partial least square (OPLS) analysis. Two significant serum proteins (m/z 4187 and m/z 5032) for classifying excess and deficiency syndromes were found. Moreover, the area under the receiver operating characteristic (ROC) curve was 0.887 for classifying excess and nonexcess syndrome, and 0.700 for classifying deficiency and nondeficiency syndrome, respectively. Therefore, the present study provided the possibility of TCM syndrome classification in CHB patients using a universally acceptable scientific approach.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Asi He ◽  
Wei Wang ◽  
Yang Xia ◽  
Xiaoping Niu

Background. As a traditional Chinese medicine, Artemisiae scopariae Herba (ASH) is used to treat various liver diseases. The purpose of this study was to explore the mechanisms of ASH for treating chronic hepatitis B (CHB) using a network pharmacological method. Methods. Bioactive ingredients and related targets of ASH were obtained from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Gene names of targets were extracted from UniProt database. Differentially expressed genes (DEGs) of CHB were obtained from microarray dataset GSE83148. The intersect genes between DEGs and target genes were annotated using clusterProfiler package. The STRING database was used to obtain a network of protein-protein interactions. Cytoscape 3.7.2 was used to construct the “ingredient-gene-pathway” (IGP) network. Molecular docking studies were performed using Autodock vina. Results. A total of 13 active components were extracted from TCMSP database. Fifteen intersect genes were obtained between 183 target genes and 403 DEGs of GSE83148. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that ASH against CHB mainly involved in toll-like receptor signaling pathway, cellular senescence, hepatitis B, and chemokine signaling pathway. We screened one hub compound, five core targets, and four key pathways from constructed networks. The docking results indicated the strong binding activity between quercetin and AKT1. Conclusions. This study provides potential molecular mechanisms of ASH against CHB based on exploration of network pharmacology.


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