Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation.

Posted by on 26 Feb 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation. Front Microbiol. 2019;10:207 Authors: Ito N, Nakashima K, Sun S, Ito M, Suzuki T Abstract Although RNA splicing of hepatitis B virus (HBV) is a commonly observed in livers of hepatitis B patients as well as in the cultured cells replicating the viral genome, its biological significance in the HBV life cycle and the detailed regulatory mechanisms are still largely unclear. In this study, we found cell-type dependency of HBV splicing of the 3.5 kb pregenomic RNA, which is efficiently spliced in human hepatoma cells but not in cells derived from human hepatic stellate, mouse hepatoma and human non-hepatic cells. It may be likely that RNA splicing is one of the determinants of host range restriction of HBV. Given the finding indicating the difference in cell-type dependency of the splicing efficiency between HBV and simian virus 40, we carried out intron-swapping experiments. The results suggest the presence of putative exonic splicing enhancer that possibly works in the cell-type dependent fashion. Together with further mutational analyses, a novel 50-nt intronic splicing silencer, whose secondary structure is well conserved among the HBV strains, was identified. It appears that this intronic silencer functions effectively independent of cell backgrounds. PMID: 30800119 [PubMed]

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Cell Type Diversity in Hepatitis B Virus RNA Splicing and Its Regulation.

Second-line Treatments of Advanced Hepatocellular Carcinoma: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Posted by on 24 Dec 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Second-line Treatments of Advanced Hepatocellular Carcinoma: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials. J Clin Gastroenterol. 2018 Dec 19;: Authors: Bakouny Z, Assi T, El Rassy E, Nasr F Abstract BACKGROUND: Advanced hepatocellular carcinoma (HCC) constitutes the second leading cause of cancer-related deaths. First-line therapy is either sorafenib or lenvatinib. Several treatment options have been recently added to the second-line treatment of advanced HCC. The aim of this network meta-analysis of randomized controlled trials was to compare the second-line treatments of advanced HCC. METHODS: Network meta-analyses were computed for overall survival (OS), progression-free survival, rates of grade 3 to 5 adverse events, and for treatment discontinuation due to adverse events. OS was considered to be the primary outcome of this study, and everolimus was chosen to be the common comparator for efficacy analyses and placebo for safety analyses. Subgroup analyses were computed for OS in patients with hepatitis B, patients with hepatitis C, Asian patients, patients with macrovascular invasion, and patients with extrahepatic metastases. RESULTS: Thirteen randomized controlled trials including 5076 patients and evaluating 11 agents were found to be eligible. Regorafenib [hazard ratio (HR)=0.60, 95% confidence interval (CI)=0.44-0.81] and cabozantinib (HR=0.72, 95% CI=0.55-0.95) were found to significantly prolong OS compared with everolimus. The effect of regorafenib on OS tended to be conserved across patient subgroups. Regorafenib was also found to significantly prolong progression-free survival (HR=0.46, 95% CI=0.35-0.62) and significantly increase the rates of grade 3 to 5 adverse events (odds ratios=3.18, 95% CI=2.22-4.54) and treatment discontinuation due to adverse events (odds ratios=2.67, 95% CI=1.21-5.87). CONCLUSIONS: This network meta-analysis concludes that, based on current evidence, regorafenib could be the agent of choice in the second-line treatment of HCC, with cabozantinib as a possible alternative for sorafenib-intolerant patients. PMID: 30575632 [PubMed – as supplied by publisher]

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Second-line Treatments of Advanced Hepatocellular Carcinoma: Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation among Asian Chronic Hepatitis B Patients: A Systematic Review.

Posted by on 19 Dec 2018 | Tagged as: Hepatitis B Alternative Medicine

The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation among Asian Chronic Hepatitis B Patients: A Systematic Review. Hepatology. 2018 Dec 18;: Authors: Liu J, Li T, Zhang L, Xu A Abstract In actual clinical practice, infinite nucleos(t)ide analogues (NAs) treatment for chronic hepatitis B virus (HBV) infection is unrealistic. The most commonly used endpoint is suppression of HBV DNA to undetectable levels with normalization of alanine aminotransferase (ALT). However, this criterion for cessation of treatment is associated with various incidences of virological and clinical relapse. Recent studies suggest that decreasing hepatitis B surface antigen (HBsAg) level at the end of treatment (EOT) to an appropriate cutoff value appears to be a practicable and attainable cessation criterion. We performed a systematic review to explore the optimal cutoff value of HBsAg at EOT for the cessation of NAs treatment. Eleven studies with 1716 patients were included in this review. When the HBsAg levels at EOT were < 100 IU/mL and > 100 IU/mL, the respective off-therapy virological relapse rates were 9.1 (range) and 31.4 (range) at ≥ 12 months off-therapy regardless of HBeAg status, the respective off-therapy clinical relapse rates were 15.4 (range) and 48.1 (range) at ≥ 12 months off-therapy regardless of HBeAg status, and the respective off-therapy HBsAg loss rates were 21.1 (range) and 3.3 (range) for HBeAg-negative patients at ≥ 39 months off-therapy. Conclusion: Cessation of long-term NAs therapy prior to HBsAg seroclearance in patients with chronic hepatitis B is a feasible alternative to indefinite treatment. A HBsAg level < 100 IU/mL at EOT seems to be a useful marker for deciding when to discontinue NAs therapy. However, regular monitoring is required after the cessation of NAs treatment, and long-term outcomes must be further evaluated. This article is protected by copyright. All rights reserved. PMID: 30561829 [PubMed – as supplied by publisher]

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The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation among Asian Chronic Hepatitis B Patients: A Systematic Review.

Emergence of oncogenic-enhancing hepatitis B virus X gene mutants in patients receiving suboptimal entecavir treatment.

Posted by on 16 Dec 2018 | Tagged as: Hepatitis B Alternative Medicine

Emergence of oncogenic-enhancing hepatitis B virus X gene mutants in patients receiving suboptimal entecavir treatment. Hepatology. 2018 Dec 15;: Authors: Lin CL, Chu YD, Yeh CT Abstract Entecavir is a widely used nucleoside analogue for antiviral therapy against chronic hepatitis B virus (HBV) infection. Despite its remarkable efficacy in suppressing HBV replication, a substantial proportion of cirrhotic patients still developed hepatocellular carcinoma (HCC) after entecavir treatment (1). Presumably, it is largely attributed to the existing precancerous hepatocytes, which sturdily progresses into cancer despite effective viral suppression. HBV X (HBx) protein is a well-known oncogenic protein. Here, we explored an alternative possibility that oncogenic-enhancing mutations developed in HBx in HCC patients having received entecavir treatment. This article is protected by copyright. All rights reserved. PMID: 30552766 [PubMed – as supplied by publisher]

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Emergence of oncogenic-enhancing hepatitis B virus X gene mutants in patients receiving suboptimal entecavir treatment.

Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis.

Posted by on 12 Dec 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis. Sci Rep. 2017 03 20;7:44788 Authors: Wang J, Liu R, Liu B, Yang Y, Xie J, Zhu N Abstract Adjuvants are common component for many vaccines but there are still few licensed for human use due to low efficiency or side effects. The present work adopted Systems Pharmacology analysis as a new strategy to screen adjuvants from traditional Chinese medicine. Ophiocordyceps sinensis has been used for many years in China and other Asian countries with many biological properties, but the pharmacological mechanism has not been fully elucidated. First in this study, 190 putative targets for 17 active compounds in Ophiocordyceps sinensis were retrieved and a systems pharmacology-based approach was applied to provide new insights into the pharmacological actions of the drug. Pathway enrichment analysis found that the targets participated in several immunological processes. Based on this, we selected cordycepin as a target compound to serve as an adjuvant of the hepatitis B vaccine because the existing vaccine often fails to induce an effective immune response in many subjects. Animal and cellular experiments finally validated that the new vaccine simultaneously improves the humoral and cellular immunity of BALB/c mice without side effects. All this results demonstrate that cordycepin could work as adjuvant to hepatitis b vaccine and systems-pharmacology analysis could be used as a new method to select adjuvants. PMID: 28317886 [PubMed – indexed for MEDLINE]

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Systems Pharmacology-based strategy to screen new adjuvant for hepatitis B vaccine from Traditional Chinese Medicine Ophiocordyceps sinensis.

Anti-hepatitis B virus effects of the traditional Chinese herb Artemisia capillaris and its active enynes.

Posted by on 14 Nov 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Anti-hepatitis B virus effects of the traditional Chinese herb Artemisia capillaris and its active enynes. J Ethnopharmacol. 2018 Oct 05;224:283-289 Authors: Geng CA, Yang TH, Huang XY, Yang J, Ma YB, Li TZ, Zhang XM, Chen JJ Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia capillaris (Yin-Chen) is a famous traditional Chinese medicine (TCM) for treating acute and chronic hepatitis in China. Enynes are one type of characteristic constituents in this herb, while their anti-hepatitis B virus (anti-HBV) properties have not been systemically investigated. AIM OF THE STUDY: This study is to reveal the active part of A. capillaris, and systemically investigate the enynes and their anti-HBV activity. MATERIALS AND METHODS: The total extract and each fraction of A. capillaris were assayed for the anti-HBV activity to reveal the active part. Bioassay-guided fractionation using various chromatographic techniques yielded the enynes, whose structures were elucidated by spectroscopic analyses and ECD calculations. The anti-HBV properties inhibiting HBsAg and HBeAg secretions and HBV DNA replication were evaluated on HepG 2.2.15 cell line in vitro. RESULTS: ACT-2 and ACT-3 was revealed to be the respective active and toxic part of A. capillaris. Twelve enynes (1-12) involving four new ones (1-4) and two unusual enyne analogs (13-14) were isolated from the active part (ACT-2). All the isolates were assayed for their anti-HBV activity, and the preliminary structure-activity relationships were summarized based on the structural features. In particular, compound 4 could significantly inhibit the secretions of HBsAg and HBeAg, and HBV DNA replication with IC50 values of 197.2 (SI > 5.1), 48.7 (SI > 20.5) and 9.8 (SI > 102) μM. CONCLUSIONS: Enynes are responsible for the anti-HBV effects of A. capillaris. Hydroxyl and glycosyl groups are preferable for maintaining activity. This is the first time to systematically investigate the anti-HBV activity of enynes in A. capillaris, which provides valuable information for understanding the ethnopharmacological application of Yin-Chen. PMID: 29890315 [PubMed – indexed for MEDLINE]

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Anti-hepatitis B virus effects of the traditional Chinese herb Artemisia capillaris and its active enynes.

Altered oral microbiota in chronic hepatitis B patients with different tongue coatings.

Posted by on 10 Nov 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Altered oral microbiota in chronic hepatitis B patients with different tongue coatings. World J Gastroenterol. 2018 Aug 14;24(30):3448-3461 Authors: Zhao Y, Mao YF, Tang YS, Ni MZ, Liu QH, Wang Y, Feng Q, Peng JH, Hu YY Abstract AIM: To elucidate tongue coating microbiota and metabolic differences in chronic hepatitis B (CHB) patients with yellow or white tongue coatings. METHODS: Tongue coating samples were collected from 53 CHB patients (28 CHB yellow tongue coating patients and 25 CHB white tongue coating patients) and 22 healthy controls. Microbial DNA was extracted from the tongue samples, and the bacterial 16S ribosomal RNA gene V3 region was amplified from all samples and sequenced with the Ion Torrent PGM™ sequencing platform according to the standard protocols. The metabolites in the tongue coatings were evaluated using a liquid chromatography-mass spectrometry (LC-MS) platform. Statistical analyses were then performed. RESULTS: The relative compositions of the tongue coating microbiotas and metabolites in the CHB patients were significantly different from those of the healthy controls, but the tongue coating microbiota abundances and diversity levels were not significantly different. Compared with the CHB white tongue coating patients, the CHB yellow tongue coating patients had higher hepatitis B viral DNA (HBV-DNA) titers (median 21210 vs 500, respectively, P = 0.03) and a significantly lower level of Bacteroidetes (20.14% vs 27.93%, respectively, P = 0.013) and higher level of Proteobacteria (25.99% vs 18.17%, respectively, P = 0.045) in the microbial compositions at the phylum level. The inferred metagenomic pathways enriched in the CHB yellow tongue coating patients were mainly those involved in amino acid metabolism, which was consistent with the metabolic disorder. The abundances of bacteria from Bacteroidales at the order level were higher in the CHB white tongue coating patients (19.2% vs 27.22%, respectively, P = 0.011), whereas Neisseriales were enriched in the yellow tongue coating patients (21.85% vs 13.83%, respectively, P = 0.029). At the family level, the abundance of Neisseriaceae in the yellow tongue patients was positively correlated with the HBV-DNA level but negatively correlated with the S-adenosyl-L-methionine level. CONCLUSION: This research illustrates specific clinical features and bacterial structures in CHB patients with different tongue coatings, which facilitates understanding of the traditional tongue diagnosis. PMID: 30122883 [PubMed – indexed for MEDLINE]

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Altered oral microbiota in chronic hepatitis B patients with different tongue coatings.

[Blood-borne occupational exposure and protection in medical staff of a traditional Chinese medicine hospital].

Posted by on 01 Nov 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Blood-borne occupational exposure and protection in medical staff of a traditional Chinese medicine hospital]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2017 Mar 20;35(3):205-208 Authors: Zhang ZG, Wei QX, Yang ZP, Wei QM, Wang XM, Wang XL Abstract Objective: To investigate blood-borne occupational exposure and related protection in the medical staff of a traditional Chinese medicine hospital, and to provide a reference for reducing the risk of blood-borne occupational exposure. Methods: Forty-eight medical workers with blood-borne occupational exposure in 2015 were selected to analyze the incidence of blood-borne occupational exposure, influencing factors, operations that caused blood-borne occupational exposure, pathogens, and occupational protection. Results: The incidence rate of blood-borne occupational exposure in the medical staff of the traditional Chinese medicine hospital in 2015 was 3.30% (48/1 455) , and the frequency was 0.04 time/person/year. The workers with blood-borne occupational exposure were mostly nurses, females, workers aged <30 years, workers with <5 working years, and workers with a junior professional title. There was a significant difference in the incidence rate of blood-borne occupational exposure between workers with different ages and working years. The main way of blood-borne occupational exposure was sharp injury (96.08%) . The main operations that caused blood-borne occupational exposure were covering or separating the syringe needle after injection and disposing used sharp instruments. The main exposure site was the hand (96.08%) , with the thumb and index finger for the left hand and the middle finger and index finger for the right hand; there was no significant difference in the exposure site distribution between the two hands (P<0.05) . The main pathogen that caused blood-borne occupational exposure was hepatitis B virus (68.96%) . The rate of correct local treatment for blood-borne occupational exposure was 88.24%. The rate of prophylactic medication was 74.51%, and hepatitis B immunoglobulin (HBIG) plus hepatitis B vaccine was the main way, followed by HBIG. In all workers with blood-borne occupational exposure, 62.74% did not wear gloves. Conclusion: The medical workers with few working years have a high risk of blood-borne occupational exposure, so the training on protection against blood-borne occupational exposure should be strengthened to reduce the risk of blood-borne occupational exposure and infection. PMID: 28511308 [PubMed – indexed for MEDLINE]

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[Blood-borne occupational exposure and protection in medical staff of a traditional Chinese medicine hospital].

Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity.

Posted by on 01 Nov 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity. J Med Toxicol. 2018 Oct 30;: Authors: Toce MS, Chai PR, Burns MM, Boyer EW Abstract Opioid use disorder continues to be a significant source of morbidity and mortality in the USA and the world. Pharmacologic treatment with methadone and buprenorphine has been shown to be effective at retaining people in treatment programs, decreasing illicit opioid use, decreasing rates of hepatitis B, and reducing all cause and overdose mortality. Unfortunately, barriers exist in accessing these lifesaving medications: users wishing to start buprenorphine therapy require a waivered provider to prescribe the medication, while some states have no methadone clinics. As such, users looking to wean themselves from opioids or treat their opioid dependence will turn to alternative agents. These agents include using prescription medications, like clonidine or gabapentin, off-label, or over the counter drugs, like loperamide, in supratherapeutic doses. This review provides information on the pharmacology and the toxic effects of pharmacologic agents that are used to treat opioid use disorder. The xenobiotics reviewed in depth include buprenorphine, clonidine, kratom, loperamide, and methadone, with additional information provided on lofexidine, akuamma seeds, kava, and gabapentin. PMID: 30377951 [PubMed – as supplied by publisher]

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Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity.

Epigenetic differences of chronic hepatitis B in different TCM syndromes: Protocol for a case-control, non-interventional, observational clinical…

Posted by on 17 Oct 2018 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Epigenetic differences of chronic hepatitis B in different TCM syndromes: Protocol for a case-control, non-interventional, observational clinical study. Medicine (Baltimore). 2018 Sep;97(39):e12452 Authors: Ma L, Zheng X, Yang Y, Wang J, Xu Y, Wang B Abstract INTRODUCTION: Chronic hepatitis B is a serious disease causing serious harm to the human health. Chinese medicine has its unique advantages in the clinical prevention and treatment, while the syndrome of Chinese medicine lacks the understanding at the micro level. There are some theoretical commonalities between the epigenetics and traditional Chinese medicine (TCM) syndromes. The biological basis of chronic hepatitis B (CHB) syndrome differentiation from the perspective of epigenetics is of great significance to diagnose and prevent the diseases. METHODS: This protocol is a case-control, noninterventional, observational clinical study. Patients with CHB for spleen-stomach damp heat and liver depression and spleen deficiency, with 12 each and 11 healthy volunteers were recruited. Peripheral venous blood was collected from the participants. DNA methylated transferase, genomic DNA methylated spectrum, methylated DNA binding protein MeCP2, chronic infection of hepatitis B virus with methylated related proteins, and miRNA target genes were analyzed. OBJECTIVES: From the perspective of DNA methylation epigenetics, “DNA methylation-miRNA-Target gene” is the main line, which further reveals the essence of TCM syndrome. To improve the level of TCM clinical syndrome differentiation and the clinical efficacy of TCM, especially in the study of TCM syndromes of CHB, discovering its underlying biological signature is necessary. TRIAL REGISTRATION: Clinical Trials Registration: ChiCTR1800017365, registered 26 July 2018. PMID: 30278525 [PubMed – indexed for MEDLINE]

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Epigenetic differences of chronic hepatitis B in different TCM syndromes: Protocol for a case-control, non-interventional, observational clinical…

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