Study of ZHENG differentiation in Hepatitis B-caused cirrhosis: a transcriptional profiling analysis

Lu, Yi‐Yu; Chen, Qilong; Guan, Yan; Guo, Zhixin; Zhang, Hui; Zhang, Wei; Hu, Yiyang; Su, Shi‐Bing

doi:10.1186/1472-6882-14-371

Cited by 16 publications

(11 citation statements)

References 25 publications

(27 reference statements)

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“…TCM is widely used to treat CHB disease, with an advantage in early intervention and combined therapies [26]. However, TCM syndromes lack objective assessment and heavily rely on physician experience.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies have also shown that several biomolecules may be potential markers for TCM syndrome differentiation in CHB [21–23]. Similarly, most potential biomarkers for TCM syndrome are selected from differentially expressed molecules [21, 24–26]. However, with the characteristics of “internal and external deficiency, dynamic space–time change, and multi-dimensional interface” [27], the complexity of dynamic changes mechanism of TCM syndromes have rarely been reported.…”

Section: Introductionmentioning

confidence: 99%

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Chronic hepatitis B: dynamic change in Traditional Chinese Medicine syndrome by dynamic network biomarkers

Fang

Zeng

et al. 2019

Chin Med

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BackgroundIn 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.MethodsTo 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.ResultsOur 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.ConclusionsThis 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)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic hepatitis B: dynamic change in Traditional Chinese Medicine syndrome by dynamic network biomarkers

Fang

Zeng

et al. 2019

Chin Med

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“…During the past decades, clinically lacks the effective strategy for the therapy of HBC, fortunately, as a complementary and alternative medicine, Chinese Traditional Medicine (TCM) has special therapeutic effects for HBC treatment 5 . In previous study, we found that PNP, AQP7, and PSMD2 may be involved in TCM syndromes differentiation of HBC 6 . However, the characteristics of HBC TCM syndromes are unclear, especially, the development mechanism from Excessive (Liver-Gallbladder Dampness Heat Syndrome, LGDHS) to Excessive-Deficient (Liver-Depression and Spleen-Deficiency Syndrome, LDSDS) syndrome, and/or Excessive-Deficient (Liver Depression and Spleen Deficiency Syndrome, LDSDS) develop to Deficient (Liver-Kidney Deficiency Syndrome, LKYDS) syndrome still rigorously lacks in HBC progression.…”

Section: Introductionmentioning

confidence: 84%

MiRNA-target network analysis identifies potential biomarkers for Traditional Chinese Medicine (TCM) syndrome development evaluation in hepatitis B caused liver cirrhosis

Liu

Wang

Luo

et al. 2017

Sci Rep

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Hepatitis B is one of most etiologies of Liver cirrhosis in China, and clinically lacks the effective strategy for Hepatitis B caused cirrhosis (HBC) therapy. As a complementary and alternative medicine, Chinese Traditional Medicine (TCM) has special therapeutic effects for HBC. Here, we focus on the evolution process of HBC TCM syndromes, which was from Excessive (Liver-Gallbladder Dampness-Heat Syndrome, LGDHS) to Deficient (Liver-Kidney Deficiency Syndrome, LKYDS) via Excessive-Deficient syndrome (Liver-Depression and Spleen-Deficiency Syndrome, LDSDS). Using R package, 16 miRNAs in LGDHS/Normal, 48 miRNAs in LDSDS/LGDHS, and 16 miRNAs in LKYDS/LDSDS were identified, respectively. The miRNA-target networks show that the LDSDS was most stability and complicated. Subsequently, 4 kernel miRNAs with LGDHS-LDSDS process, and 5 kernel miRNAs with LDSDS-LKYDS process were screened. Using RT-qPCR data, p1 (hsa-miR-17-3p, -377-3p, -410-3p and -495) and p2 miRNA panel (hsa-miR-377-3p, -410-3p, -27a-3p, 149-5p and 940) were identified by Logistic Regression Model, which clearly improve the accuracy of TCM syndrome classification. The rebuilt miRNA-target network shows that the LDSDS is a critical point and might determine the evolution directions of HBC TCM syndrome. This study suggests that the identified kernel miRNAs act as potential biomarkers and benefit to evaluate the evolution tendency of HBC TCM syndromes.

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“…The microarray data concerning the leukocyte samples obtained from three CHB patients with LKYDS and three healthy donors were provided by the Research Center for TCM Complexity System, Shanghai University of TCM [22]. The differentially expressed genes were identified under the conditions of a fold-change >2 and a p value <0.05.…”

Section: Methodsmentioning

confidence: 99%

Active Ingredients and Action Mechanisms of Yi Guan Jian Decoction in Chronic Hepatitis B Patients with Liver Fibrosis

Zhou

Liu

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Background and Aim. The progression of liver fibrosis in chronic hepatitis B (CHB) patients is currently insufficiently controlled worldwide. The Yi Guan Jian decoction (YGJD) has been widely used in the treatment of liver fibrosis in CHB cases. Although animal studies have reported the antifibrotic effects of the decoction, the active ingredients of the YGJD remain unknown. This study aimed at identifying the potential active ingredients and exploring the mechanisms of action (MOA) of the decoction when treating CHB patients with fibrosis. Methods. Using data mining techniques and a structural clustering analysis, the potential active ingredients were determined. A network analysis of the differentially expressed genes was conducted to identify the potential targets. Selected compounds were docked to the potential targets for the compound-target interaction simulation. In vitro validation, including a cell proliferation assay and Western blot analysis, was conducted to evaluate the prediction results. Results. In the microarray data, 224 differentially expressed genes related to liver fibrosis were considered to be potential targets. Thirty active ingredients of the YGJD and 15 main targets and relevant pathways were identified. Among them, two active ingredients, methylophiopogonone A and 8-geranyloxypsoralen, were validated as exhibiting antifibrotic effects on hepatic stellate cells. Conclusions. We identified the potential active ingredients of the YGJD and proposed the possible explanation for the MOA in the treatment of CHB patients with liver fibrosis. Moreover, this study provides a methodological reference for the systematic investigation of the bioactive compounds and related MOA of a traditional Chinese medicine formula in a clinical context.

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Study of ZHENG differentiation in Hepatitis B-caused cirrhosis: a transcriptional profiling analysis

Cited by 16 publications

References 25 publications

Chronic hepatitis B: dynamic change in Traditional Chinese Medicine syndrome by dynamic network biomarkers

Chronic hepatitis B: dynamic change in Traditional Chinese Medicine syndrome by dynamic network biomarkers

MiRNA-target network analysis identifies potential biomarkers for Traditional Chinese Medicine (TCM) syndrome development evaluation in hepatitis B caused liver cirrhosis

Active Ingredients and Action Mechanisms of Yi Guan Jian Decoction in Chronic Hepatitis B Patients with Liver Fibrosis

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