scholarly journals Progression from Excessive to Deficient Syndromes in Chronic Hepatitis B: A Dynamical Network Analysis of miRNA Array Data

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Qi-Long Chen ◽  
Yi-Yu Lu ◽  
Gui-Biao Zhang ◽  
Ya-Nan Song ◽  
Qian-Mei Zhou ◽  
...  

Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for chronic hepatitis B (CHB), which requires a traditional diagnosis method to distinguish the TCM syndrome. In this study, we study the differences and similarities among excessive, excessive-deficient, and deficient syndromes, by an integrative and comparative analysis of weighted miRNA expression or miRNA-target network in CHB patients. We first calculated the differential expressed miRNAs based on random modulet-test and classified three CHB TCM syndromes using SVM method. Then, miRNA target genes were obtained by validated database and predicted programs subsequently, the weighted miRNA-target networks were constructed for different TCM syndromes. Furthermore, prioritize target genes of networks of CHB TCM syndromes progression analyzed using DAVID online analysis. The results have shown that the difference between TCM syndromes is distinctly based on hierarchical cluster and network structure. GO and pathway analysis implicated that three CHB syndromes more likely have different molecular mechanisms, while the excessive-deficient and deficient syndromes are more dangerous than excessive syndrome in the process of tumorigenesis. This study suggested that miRNAs are important mediators for TCM syndromes classification as well as CHB development progression and therefore could be potential diagnosis and therapeutic molecular markers.

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Qi-Long Chen ◽  
Yi-Yu Lu ◽  
Gui-Biao Zhang ◽  
Ya-Nan Song ◽  
Qian-Mei Zhou ◽  
...  

Traditional Chinese medicine (TCM) treatment is regarded as a safe and effective method for many diseases. In this study, the characteristics among excessive, excessive-deficient, and deficient syndromes of Hepatocellular carcinoma (HCC) were studied using miRNA array data. We first calculated the differentially expressed miRNAs based on random modulet-test and classified three TCM syndromes of HCC using SVM method. Then, the weighted miRNA-target networks were constructed for different TCM syndromes using predicted miRNA targets. Subsequently, the prioritized target genes of upexpression network of TCM syndromes were analyzed using DAVID online analysis. The results showed that there are distinctly different hierarchical cluster and network structure of TCM syndromes in HCC, but the excessive-deficient combination syndrome is extrinsically close to deficient syndrome. GO and pathway analysis revealed that the molecular mechanisms of excessive-deficient and deficient syndromes of HCC are more complex than excessive syndrome. Furthermore, although excessive-deficient and deficient syndromes have similar complex mechanisms, excessive-deficient syndrome is more involved than deficient syndrome in development of cancer process. This study suggested that miRNAs might be important mediators involved in the changing process from excessive to deficient syndromes and could be potential molecular markers for the diagnosis of TCM syndromes in HCC.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Zhizhong Guo ◽  
Shuhao Yu ◽  
Yan Guan ◽  
Ying-Ya Li ◽  
Yi-Yu Lu ◽  
...  

Traditional Chinese medicine (TCM) treatment is based on the traditional diagnose method to distinguish the TCM syndrome, not the disease. So there is a phenomenon in the relationship between TCM syndrome and disease, called Same TCM Syndrome for Different Diseases and Different TCM Syndrome for Same Disease. In this study, we demonstrated the molecular mechanisms of this phenomenon using the microarray samples of liver-gallbladder dampness-heat syndrome (LGDHS) and liver depression and spleen deficiency syndrome (LDSDS) in the chronic hepatitis B (CHB) and liver cirrhosis (LC). The results showed that the difference between CHB and LC was gene expression level and the difference between LGDHS and LDSDS was gene coexpression in the G-protein-coupled receptor protein-signaling pathway. Therein genes GPER, PTHR1, GPR173, and SSTR1 were coexpressed in LDSDS, but not in LGDHS. Either CHB or LC was divided into the alternative LGDHS and LDSDS by the gene correlation, which reveals the molecular feature of Different TCM Syndrome for Same Disease. The alternatives LGDHS and LDSDS were divided into either CHB or LC by the gene expression level, which reveals the molecular feature of Same TCM Syndrome for Different Diseases.


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.


2020 ◽  
Vol 20 (5) ◽  
pp. 748-751
Author(s):  
Seyed Ali Dehghan Manshadi ◽  
Neda Alijani ◽  
Mohammadreza Salehi ◽  
Omid Dadras ◽  
SeyedAhmad SeyedAlinaghi ◽  
...  

Introduction: The aim of this study was to determine the prevalence of exposure to hepatitis A by means of serologic markers in chronic hepatitis B patients, with the secondary aim of finding the best prevention method for hepatitis A infection in susceptible groups of our setting. Methods: During the period between 2016 and 2017, we recruited 403 hepatitis B patients aged more than 14 years and regularly attending the infectious diseases clinic at a referral university hospital, Tehran, Iran. A blood sample was collected from all the patients and tested for hepatitis A IgG. The data was analyzed by SPSS v.19. Results: Although none of the patients had previously received hepatitis A vaccine, the results for serologic level of hepatitis A IgG, demonstrated positive results in 379 (94%) cases. The mean age of patients with negative and positive IgG was 29.17 and 42.46 years, respectively; the difference was statistically significant (P≤0.001). The majority of seronegative patients were young adults aged < 25 years and 25 to 35 years (P <0.001). Conclusion: Seroprevalence of hepatitis A in chronic HBV patients in Iran is high. As HBV infected patients younger than 35 years could be seronagative for HAV infection, evaluation of these patients for HAV infection and vaccination of seronegative patients would be a reasonable approach.


Author(s):  
Yostila Derosa ◽  
Nasrul Zubir ◽  
Raveinal Arnelis

Background: Hepatitis B is acute or chronic liver inflammation caused by hepatitis B viral and can progress to hepatic chirrosis or liver cancer. Chronic hepatitis B has a high risk for liver fibrosis. Chronic inflammation and liver fibrosis are interrelated processes. This study aimed to determine the differences in T-regulator cells, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) between chronic hepatitis B patients with and without liver fibrosis.Method: This study used a cross-sectional method for patients diagnosed with chronic hepatitis B in the Inpatient and Outpatient Department of the Internal Medicine Department  DR. M. Djamil Padang and other hospitals in Padang city for 6 months. Samples were selected by consecutive sampling according to inclusion and exclusion criteria. Liver fibrosis is identified by fibroscan. Data were analyzed by SPSS 21.0.Results: thirty-two patients were diagnosed with chronic hepatitis B and 50% had liver fibrosis. The levels of T-regulator cells in chronic hepatitis B patients without liver fibrosis were 2.08% and liver fibrosis 2.25%, but this difference was not statistically significant (p 0.05). Mean ALT levels in the group without fibrosis were 19 IU/L (7IU/L-71IU/L) and liver fibrosis 61 IU / L (13IU/L-625IU/L). The mean AST level in the group without fibrosis were 15.5 IU/L (10IU/L-32IU/L) and liver fibrosis 35.5 IU/L (10IU/L-476IU/L). The difference between ALT and AST in the two groups was significant (p 0.05). Hepatitis B patients with liver fibrosis had higher ALT and AST levels than without fibrosis.Conclusion: There were differences levels of T-regulator cells in the two groups, but it was not statistically significant. ALT and AST levels were higher in the liver fibrosis group and statistically significant.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hui Zhang ◽  
Yan Guan ◽  
Yi-Yu Lu ◽  
Yi-Yang Hu ◽  
Shuang Huang ◽  
...  

Traditional Chinese medicine (TCM) ZHENG as the key pathological principle is to understand the human homeostasis and guide TCM treatment. Here, circulating microRNAs (miRNAs) were utilized to differentiate between ZHENGs including liver-gallbladder dampness-heat syndrome (LGDHS) and liver-kidney yin deficiency syndrome (LKYDS) in chronic hepatitis B (CHB). Sera samples of CHB patients with LGDHS (n=35), LKYDS (n=24), and healthy controls (Ctrls,n=21) were analyzed by microarray and real-time RT-PCR. Receiver-operator characteristic (ROC) curves were established to evaluate the levels of serum miRNA for discriminating LGDHS and LKYDS. The target genes of miRNAs were predicted by TargetScan. Gene Ontology (GO) and pathways were analyzed using DAVID tool. The results showed that 22 miRNAs were differentially expressed between LGDHS and LKYDS (fold change>2.0 andP<0.01). Circulating miR-583 and miR-663 were significantly higher (P<0.001) in CHB patients with LGDHS than those with LKYDS and Ctrls. ROC curve analysis revealed that miR-583 and miR-663 were sensitive and specific enough to distinguish LGDHS from LKYDS. Pathway enrichment analysis indicated that 354 putative targets for miR-583 and 68 putative targets for miR-663 were mainly involved in Axon guidance, Neurotrophin, and MAPK signaling pathway. miR-583 and miR-663 may be potential markers for ZHENG differentiation in CHB.


2006 ◽  
Vol 81 (1) ◽  
pp. 159-165 ◽  
Author(s):  
Verena Christen ◽  
Francois Duong ◽  
Christine Bernsmeier ◽  
Dianxing Sun ◽  
Michael Nassal ◽  
...  

ABSTRACT Alpha interferon (IFN-α) and pegylated IFN-α (pegIFN-α) are used for the treatment of chronic hepatitis B (CHB). Unfortunately, only a minority of patients can be cured. The mechanisms responsible for hepatitis B virus (HBV) resistance to pegIFN-α treatment are not known. pegIFN-α is also used to treat patients with chronic hepatitis C (CHC). As with chronic hepatitis B, many patients with chronic hepatitis C cannot be cured. In CHC, IFN-α signaling has been found to be inhibited by an upregulation of protein phosphatase 2A (PP2A). PP2A inhibits protein arginine methyltransferase 1 (PRMT1), the enzyme that catalyzes the methylation of the important IFN-α signal transducer STAT1. Hypomethylated STAT1 is less active because it is bound by its inhibitor, PIAS1. In the present work, we investigated whether similar molecular mechanisms are also responsible for the IFN-α resistance found in many patients with chronic hepatitis B. We analyzed the expression of PP2A, the enzymatic activity of PRMT1 (methylation assays), the phosphorylation and methylation of STAT1, the association of STAT1 with PIAS1 (via coimmunoprecipitation assays), the binding of activated STAT1 to interferon-stimulated response elements (via electrophoretic mobility shift assays), and the induction of interferon target genes (via real-time RT-PCR) in human hepatoma cells expressing HBV proteins as well as in liver biopsies from patients with chronic hepatitis B and from controls. We found an increased expression of PP2A and an inhibition of IFN-α signaling in cells expressing HBV proteins and in liver biopsies of patients with CHB. The molecular mechanisms involved are similar to those found in chronic hepatitis C.


2020 ◽  
Vol 7 (1) ◽  
pp. e000543
Author(s):  
Ta-Wei Liu ◽  
Chung-Feng Huang ◽  
Ming-Lun Yeh ◽  
Pei-Chien Tsai ◽  
Tyng-Yuan Jang ◽  
...  

Background and aimsChronic hepatitis B patients in Taiwan with no or limited liver injury are not reimbursed for antiviral treatment by the Taiwan National Health Insurance (NHI). Innovative fibrosis marker, age-adjusted Fibrosis-4 Index (FIB4-AA), was implemented to evaluate the tendency of liver fibrosis in these patients.MethodsThe FIB-4 indices of 256 antiviral treatment-naïve chronic hepatitis B patients at Kaohsiung Medical University Hospital from 2003 to 2019 were reviewed. The difference in initial FIB-4 and last FIB4-AA was treated as a categorical variable, representing the tendency of liver fibrosis in each individual aside from ageing. Logistic regression was implemented to evaluate the three parameters most dependent on increment of FIB4-AA: e seroconversion, body mass index (BMI) and initial FIB-4 index.ResultsThe yearly FIB-4 growth rate of an individual without chronic hepatitis was lower than that of the study group (0.0237 vs 0.0273 for males, 0.02 vs 0.0288 for females). Patients undergoing or completing e seroconversion were less prone to increment of FIB4-AA (p=0.036, OR 0.524). Logistic regression revealed that BMI ≥25 kg/m2 significantly less increment of FIB4-AA (p=0.001, OR 0.383, 95% CI 0.212 to 0.690), while patients with initial FIB-4 <1.29 were prone to increasing liver FIB4-AA (p=0.000, OR 3.687, 95% CI 1.999 to 6.797).ConclusionChronic hepatitis B patients not meeting the reimbursement criteria of the Taiwan NHI are prone to increment of liver fibrosis marker. Overweight is associated with less increment of fibrosis marker, while initial FIB-4 <1.29 is associated with increasing fibrosis marker.


2020 ◽  
Author(s):  
Xu Cao ◽  
Xiaobin Zao ◽  
Baiquan Xue ◽  
Hening Chen ◽  
Jiaxin Zhang ◽  
...  

Abstract The Chinese herbal formula Tiao-Gan-Yi-Pi (TGYP) showed effective against Chronic Hepatitis B (CHB). In this study, we aimed to clarify the mechanisms and potential targets between TGYP and CHB through network pharmacology and molecular docking verification. The compounds of TGYP were identified in the TCMSP and CNKI databases, and their putative targets were predicted through SwissTargetPrediction and STITCH databases. The targets of CHB were obtained from the GeneCards, NCBI Gene, and DisGeNET databases. The above mentioned data were visualized using Cytoscape, and molecular docking showed the relationship between them. The expression of key targets was verified in GEO databases. Hence, we screened out 11 TGYP-related key targets for CHB included ABL1, CASP8, CCNA2, CCNB1, CDK4, CDKN1A, EP300, HIF1A, IGF1R, MAP2K1 and PGR. The key targets were predominantly enriched in the cancer, cell cycle and hepatitis B pathways and involved in the positive regulation of fibroblast proliferation, signal transduction, and negative regulation of gene expression biological processes, and expression of key target genes was related to HBV infection and liver inflammation. Through this newly constructed interaction network between TGYP and CHB, we identified active compounds and targets which could be further used for providing clinical guidance.


2019 ◽  
Author(s):  
Dafeng Liu ◽  
Lingyun Zhou ◽  
Xinyi Zhang ◽  
Yilan Zeng ◽  
Lang Bai ◽  
...  

Abstract Background Dysglycometabolism is often accompanied with decreased islet β cell function based on the homeostasis model assessment of β cell function (HOMA-β). In this study, we aimed to identify the difference in HOMA-β values between Chronic hepatitis B (CHB) and non-hepatitis B virus (non-HBV) patients.Methods The study included 110 CHB and 110 non-HBV patients matched according to gender, age, and body mass index. HOMA-β values were evaluated.Results Under the normal glucose tolerance(NGT) condition, the HOMA-β value of the CHB group was in the decompensated stage, and HOMA-β value of CHB was always lower than non-HBV patients (NGT, impaired glucose regulation, and diabetes mellitus: 47.53vs.124.19, 41.59vs.80.17, and 36.46vs.62.92mIU/mmol; t =−4.709, −2.042, and −2.091; P=0.000, 0.047, and 0.046, respectively).Conclusion Clinicians should focus on dysglycometabolism of patients with CHB.


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