scholarly journals The mechanism of TiaoGanYiPi formula for treating chronic hepatitis B by network pharmacology and molecular docking verification

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xu Cao ◽  
Xiaobin Zao ◽  
Baiquan Xue ◽  
Hening Chen ◽  
Jiaxin Zhang ◽  
...  

AbstractThe Chinese herbal formula TiaoGanYiPi (TGYP) showed effective against chronic hepatitis B (CHB) caused by hepatitis B virus (HBV) infection. Hence, we aimed to clarify the mechanisms and potential targets between TGYP and CHB. The active compounds and related putative targets of TGYP, and disease targets of CHB were obtained from the public databases. The key targets between TGYP and CHB were identified through the network construction and module analysis. The expression of the key targets was detected in Gene Expression Omnibus (GEO) dataset and normal hepatocyte cell line LO2. We first obtained 11 key targets which were predominantly enriched in the Cancer, Cell cycle and HBV-related pathways. And the expression of the key targets was related to HBV infection and liver inflammation verified in GSE83148 database. Furthermore, the results of real-time quantitative PCR and CCK-8 assay indicated that TGYP could regulate the expression of key targets including CCNA2, ABL1, CDK4, CDKN1A, IGFR and MAP2K1, and promote proliferation of LO2 cells. In coclusion, we identified the active compounds and key targets btween TGYP and CHB, and found that the TGYP might exhibite curative effect on CHB via promoting hepatocyte proliferation and inhibiting the liver inflammatory processes.

2019 ◽  
Vol 20 (10) ◽  
pp. 785-798 ◽  
Author(s):  
Yigan Zhang ◽  
Huaze Xi ◽  
Xin Nie ◽  
Peng Zhang ◽  
Ning Lan ◽  
...  

Objective: Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers. Methods: We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients’ clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction. Results: Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBVinfection liver cancer group (P<0.05). The expression of miR-212 was increased in patients’ Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein. Conclusion: There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker used for the diagnosis and assessment of patients with HBV-infection-related liver diseases.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Magdalena Świderska ◽  
Jerzy Jaroszewicz ◽  
Anna Parfieniuk-Kowerda ◽  
Magdalena Rogalska-Płońska ◽  
Agnieszka Stawicka ◽  
...  

Chronic hepatitis B has highly a dynamic course with significant fluctuations of HBV-DNA and ALT impeding assessment of disease activity. New biomarkers of inflammatory versus noninflammatory stages of HBV infection are urgently needed. Cytokeratin 18 epitope M30 (M30 CK-18) is a sensitive marker of cell death. We aimed to investigate an association between serum M30 CK-18 and histological activity and phase of HBV infection. 150 Caucasian patients with HBV-infection were included in the study. Serum M30 CK-18 levels reflected phase of disease, being significantly higher in both HBeAg(+) and HBeAg(−) hepatitis B in comparison to HBsAg(+) carrier groups. The highest serum M30 CK-18 levels were observed in subjects with the most advanced stages of HBV. Moreover, its serum concentrations correlated with both inflammatory activity and fibrosis advancement (ANOVA P<0.001). Importantly, serum M30 CK-18 levels were able to discriminate patients with mild versus moderate-advanced fibrosis (AUC: 0.86) and mild versus active liver inflammation (AUC: 0.79). M30 CK-18 serum concentration has good sensitivity and specificity in discriminating mild versus moderate/severe fibrosis and inflammation even in patients with normal ALT activity. This study suggests M30 CK-18 as a potential noninvasive marker of disease activity and also a marker of phase of persistent HBV infection.


Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2273
Author(s):  
Katrin Manske ◽  
Annika Schneider ◽  
Chunkyu Ko ◽  
Percy A. Knolle ◽  
Katja Steiger ◽  
...  

Immunity against hepatitis B virus (HBV) infection is complex and not entirely understood so far, including the decisive factors leading to the development of chronic hepatitis B. This lack of a mechanistic understanding of HBV-specific immunity is also caused by a limited number of suitable animal models. Here, we describe the generation of a recombinant adenovirus expressing an HBV 1.3-overlength genome linked to luciferase (Ad-HBV-Luc) allowing for precise analysis of the quantity of infected hepatocytes. This enables sensitive and close-meshed monitoring of HBV-specific CD8 T cells and the onset of anti-viral immunity in mice. A high dose of Ad-HBV-Luc developed into chronic hepatitis B accompanied by dysfunctional CD8 T cells characterized by high expression of PD1 and TOX and low expression of KLRG1 and GzmB. In contrast, a low dose of Ad-HBV-Luc infection resulted in acute hepatitis with CD8 T cell-mediated elimination of HBV-replicating hepatocytes associated with elevated sALT levels and increased numbers of cytotoxic HBV-specific CD8 T cells. Thus, the infectious dose was a critical factor to induce either acute self-limited or chronic HBV infection in mice. Taken together, the new Ad-HBV-Luc vector will allow for highly sensitive and time-resolved analysis of HBV-specific immune responses during acute and chronic infection.


Author(s):  
Jonathan S. Mellen ◽  
Victor W. Xia ◽  
Mehrtash Hashemzadeh ◽  
David Imagawa ◽  
Mazen Jamal ◽  
...  

2019 ◽  
Vol 5 (3) ◽  
pp. 207-211
Author(s):  
Muayad A Merza ◽  
Sagvan Kareem Taha ◽  
Sara Muhsin Ibrahim ◽  
Ahmed Tayar Sadeeq ◽  
Mahabad R Abdulrahman

Thrombocytopenia is a relatively uncommon extra-hepatic manifestation of uncomplicated chronic hepatitis B virus (HBV) infection. This study has two aims: to assess the prevalence of thrombocytopenia in non-cirrhotic patients with chronic hepatitis B (CHB); and to determine the association of certain variables with thrombocytopenia in Duhok province. It is a case control study conducted in Azadi Teaching Hospital during June 2016 - May 2019. Chronic active hepatitis B was defined according to the following parameters: the presence of detectable hepatitis B surface antigen (HBsAg) in the blood longer than six months, positive or negative HBeAg, HBV-DNA level >2000 IU/ml, elevated ALT, and/or at least moderate histopathological fibrosis. Thrombocytopenia was defined as platelet counts below 150,000/μl. The obtained results were analyzed by entering data into Microsoft Excel 2010. A total of 379 CHB patients and 200 cases as control were enrolled in this study. Their mean ages were 33.62 ± 14.48 and 40.72 ± 18.56 for HBV and control cases, respectively. There were 236 (62.27%) males in the HBV patients and 109 (54.50%) males in the control group. Comparing both groups, significant association was found between HBV and younger age, cigarette smoking, and alcohol consumption. Chronic active hepatitis B without liver cirrhosis was strongly associated with an increased rate of thrombocytopenia. This finding is paramount as it is statistically significant (P = 0.042). Significant association with younger age and Syrian nationality was found more in CHB patients with thrombocytopenia compared to non-thrombocytopenic. In conclusion, chronic active hepatitis B is strongly associated with thrombocytopenia. As hypersplenism resulting from liver cirrhosis was excluded in our patients, the cause of thrombocytopenia is due to other mechanisms. Therefore, it is important to consider CHB in the differential diagnosis of patients presenting with isolated thrombocytopenia. Older age and Syrian nationality were predictors for developing thrombocytopenia in chronic active HBV infection. Asian J. Med. Biol. Res. June 2019, 5(3): 207-211


2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Han Shi ◽  
Hongyan He ◽  
Suvash Chandra Ojha ◽  
Changfeng Sun ◽  
Juan Fu ◽  
...  

Abstract Background: It has been reported that polymorphisms of signal transducer and activator of transcription (STAT) 3 and STAT4 might be associated with susceptibility to hepatitis B virus (HBV) infection and risk of chronic hepatocellular carcinoma (HCC). Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. Methods: We identified relevant studies by a systematic search of Medline/PubMed, Embase, Web of Science and the Cochrane Library up to 20 February 2019. The strength of the association measured by odds ratios (OR) with 95% confidence intervals (CIs) was studied. All the statistical analyses were conducted based on Review Manager 5.3 software. Results: A total of 5242 cases and 2717 controls from five studies were included for the STAT3 polymorphism, 5902 cases and 7867 controls from nine studies for the STAT4 polymorphism. Our results suggested that STAT3 rs1053004 polymorphism was a significant risk factor of chronic HBV infection (C vs. T: OR = 1.17, 95% CI: 1.07–1.29, PA=0.0007; CC + CT vs. TT: OR = 1.38, 95% CI: 1.09–1.76, PA=0.008). Validation with all the genetic models revealed that rs7574865 polymorphism of STAT4 gene was closely associated with chronic HBV infection (PA<0.01) and chronic hepatitis B (CHB)-related HCC (PA<0.05). Meanwhile, the authenticity of the above meta-analysis results was confirmed by trial sequential analysis (TSA). Conclusions: The meta-analysis showed that STAT3 rs1053004 polymorphism may be the risk for developing chronic HBV infection but not associated with HCC. The present study also indicates that STAT4 rs7574865 polymorphism increased the risk of chronic HBV infection and HCC.


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