Molecular Recalibration of PD-1+ Antigen-Specific T Cells from Blood and Liver.

Posted by on 05 Sep 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Molecular Recalibration of PD-1+ Antigen-Specific T Cells from Blood and Liver. Mol Ther. 2018 11 07;26(11):2553-2566 Authors: Otano I, Escors D, Schurich A, Singh H, Robertson F, Davidson BR, Fusai G, Vargas FA, Tan ZMD, Aw JYJ, Hansi N, Kennedy PTF, Xue SA, Stauss HJ, Bertoletti A, Pavesi A, Maini MK Abstract Checkpoint inhibitors and adoptive cell therapy provide promising options for treating solid cancers such as HBV-related HCC, but they have limitations. We tested the potential to combine advantages of each approach, genetically reprogramming T cells specific for viral tumor antigens to overcome exhaustion by down-modulating the co-inhibitory receptor PD-1. We developed a novel lentiviral transduction protocol to achieve preferential targeting of endogenous or TCR-redirected, antigen-specific CD8 T cells for shRNA knockdown of PD-1 and tested functional consequences for antitumor immunity. Antigen-specific and intrahepatic CD8 T cells transduced with lentiviral (LV)-shPD-1 consistently had a marked reduction in PD-1 compared to those transduced with a control lentiviral vector. PD-1 knockdown of human T cells rescued antitumor effector function and promoted killing of hepatoma cells in a 3D microdevice recapitulating the pro-inflammatory PD-L1hi liver microenvironment. However, upon repetitive stimulation, PD-1 knockdown drove T cell senescence and induction of other co-inhibitory pathways. We provide the proof of principle that T cells with endogenous or genetically engineered specificity for HBV-associated HCC viral antigens can be targeted for functional genetic editing. We show that PD-1 knockdown enhances immediate tumor killing but is limited by compensatory engagement of alternative co-inhibitory and senescence program upon repetitive stimulation. PMID: 30217730 [PubMed – indexed for MEDLINE]

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Molecular Recalibration of PD-1+ Antigen-Specific T Cells from Blood and Liver.

Hepatitis B Vaccination and Waning Hepatitis B Immunity in Persons Living with HIV.

Posted by on 31 Aug 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Hepatitis B Vaccination and Waning Hepatitis B Immunity in Persons Living with HIV. Curr HIV/AIDS Rep. 2019 Aug 29;: Authors: Farooq PD, Sherman KE Abstract PURPOSE OF REVIEW: Persons with HIV are at a higher risk for acquiring HBV (hepatitis B virus) than the general population due to shared modes of transmission and are significantly more likely to develop and die from sequelae of chronic HBV infection. Early vaccination is key to achieving HBV protective immunity, but response rates are still much lower than in the general population, ranging from 35 to 70%. Individuals with HIV also experience more rapidly waning immunity than those without HIV. Strategies to augment initial response and improve long-term immunity in individuals with HIV include alterations in dose, frequency, and the use of immune adjuvants. RECENT FINDINGS: Recent studies have focused on the use of different vaccine formulations, the use of vaccine adjuvants, increased number and strength of vaccine dosages, increased dose frequency, alternative routes of administration, dual vaccinations, and the use of booster vaccines. Although no consensus has been reached on the use of certain vaccination regimens, three and four double-dose vaccine schedules via the intramuscular route have demonstrated higher initial response rates. Early vaccination when CD4 cell counts are greater than 350/mm3 with low viral loads has been shown to improve initial response, along with completion of immunization series. Adjuvants such as TLR4 and TLR9 agonists appear to improve response to HBV vaccination, but further research is needed in individuals with HIV. Persons with HIV have significant lower initial and long-term seroresponse rates after HBV vaccination than immunocompetent individuals. Recent and ongoing studies continue to evaluate multiple strategies to improve these rates within a uniquely susceptible population. PMID: 31468298 [PubMed – as supplied by publisher]

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Hepatitis B Vaccination and Waning Hepatitis B Immunity in Persons Living with HIV.

Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic…

Posted by on 30 Aug 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic analysis. Biomed Pharmacother. 2019 Jun;114:108863 Authors: Cai FF, Bian YQ, Wu R, Sun Y, Chen XL, Yang MD, Zhang QR, Hu Y, Sun MY, Su SB Abstract Yinchenhao decoction (YCHD) is a classical Traditional Chinese Medicine (TCM) formula that has been widely used in the treatment of liver fibrosis caused by chronic hepatitis B and jaundice for more than 1800 years. The purpose of this study was to investigate the apoptosis regulation mechanisms of YCHD and its active components suppresses liver fibrosis. The active components and putative targets of YCHD were predicted by network pharmacology approach. Functional and pathway enrichment analysis were presented in the present study by using clusterProfiler. Further, experimental validation was done by using terminal deoxynucleotidyl transferase (TDT) dUTP nick end labelling (TUNEL) assay and western blotting in dimethylnitrosamine (DMN)-induced liver fibrosis rats, and cell proliferation assay, apoptosis assay, and western blotting in human hepatic L02 cells and LX2 cells. 45 active compounds in YCHD formula, 592 potential target proteins and 1191 liver fibrosis-related human genes were identified. Functional and pathway enrichment analysis indicated that YCHD obviously influenced TNF, PI3K-Akt signaling pathways. Further, In vivo experiment indicated that YCHD treatment not only attenuated the symptoms of liver fibrosis, but also decrease the apoptosis of hepatic parenchyma cells. Moreover, in vitro experiments showed that rhein, kaempferol and quercetin treatments remarkably decreased the protein levels of cleaved caspase-3 and increased p-ERK1/2, PI3K and Bcl-XL protein expression in TNF-α-stimulated L02 cells. On the contrary, rhein, kaempferol, aloe-emodin and quercetin inhibited the proliferation of LX2 cells and up-regulated the protein levels of Bax and cleaved caspase-8. In conclusion, 45 active components and 296 potential targets of YCHD against liver fibrosis were identified by the analysis of network pharmacology and transcriptomics combination. The mechanisms of YCHD against liver fibrosis were involved in the regulation of multiple targets, especially affecting the apoptosis-related signaling pathways. PMID: 30991286 [PubMed – indexed for MEDLINE]

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Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic…

Multi-output Perturbation-Theory Machine Learning (PTML) Model of ChEMBL Data for Antiretroviral Compounds.

Posted by on 21 Aug 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Multi-output Perturbation-Theory Machine Learning (PTML) Model of ChEMBL Data for Antiretroviral Compounds. Mol Pharm. 2019 Aug 19;: Authors: Vásquez-Domínguez E, Armijos-Jaramillo VD, Tejera E, González-Díaz H Abstract Retroviral infections, such as HIV are, until now, diseases with no cure. Determining the target proteins of new antiretroviral compounds is a huge goal for medicine and pharmaceutical chemistry. ChEMBL manages Big Data features with complex dataset, which is hard to organize. This makes information difficult to analyze due to a big number of characteristics described in order to predict new drug candidates for retroviral infections. For this reason, we propose to develop a new predictive model combining Perturbation Theory (PT) bases and Machine Learning (ML) modelling to create a new tool that can take advantage of all the available information. The PTML model proposed in this work for ChEMBL dataset preclinical experimental assays for antiretroviral compounds consists in a linear equation with four variables. The PT operators used are based on multi-condition moving averages, combining different features and simplifying the difficulty to manage all data. More than 140,000 preclinical assays for 56,105 compounds with different characteristics or experimental conditions have been carried out and can be found in ChEMBL database, covering combinations with 359 biological activity parameters (c0), 55 different protein accessions (c1), 83 cell lines (c2), 64 organisms of assay (c3), and 773 subtypes or strains. We have included 150,148 preclinical experimental assays for HIV virus, 1,188 for HTLV virus, 84 for Simian immunodeficiency virus, 370 for Murine Leukemia virus, 119 for Rous sarcoma virus, 1,581 for MMTV, etc. We also included 5,277 assays for Hepatitis B virus. The developed PTML model reached considerable values in sensibility (73.05% for training and 73.10% for validation), specificity (86.61% for training and 87.17% for validation), and accuracy (75.84% for training and 75.98% for validation). We also compared alternative PTML models with different PT operators such as covariance, moments and exponential terms. Last, we compared the PTML model with other ML models from literature, and ANN nonlinear models. We conclude that this PTML model is the first one to consider multiple characteristics of preclinical experimental antiretroviral assays combined, generating a simple, useful and adaptable instrument, which could reduce time and costs in antiretroviral drugs research. PMID: 31426639 [PubMed – as supplied by publisher]

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Multi-output Perturbation-Theory Machine Learning (PTML) Model of ChEMBL Data for Antiretroviral Compounds.

Therapeutic effects of targeted nursing interventions combined with auricular-plaster therapy on anxiety level and life quality of Hepatitis B…

Posted by on 20 Aug 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Therapeutic effects of targeted nursing interventions combined with auricular-plaster therapy on anxiety level and life quality of Hepatitis B patients. Pak J Pharm Sci. 2018 Jul;31(4):1375-1378 Authors: Yu J, Yu Y Abstract Mood disorders are common problems in patients with chronic hepatitis B virus (HBV) infection, most clinical treatment focus on anti-viral and anti-fibrosis rather than taking care of mood disorders. In the past decades, we have developed a Chinese medicine treatment method together with nursing intervention, which shows a positive treatment effect on patients. 158 cases of hepatitis B patients were randomly divided into one control group (78 cases), and one observation group (80 cases). The patients in control group received hepatology nursing, liver protecting and transaminase lowering medicine, and ear acupoint bean pressing treatment. In addition to the nursing and treatment as the control group, the patients in observation group were given targeted nursing interventions, including psychological intervention, emotional intervention, cognitive intervention, and systematic family and community support intervention. The anxiety level and sleep quality of patients in both groups were compared. The improvement of hepatic indexes was checked and life qualities in both groups were also compared. Compared to the control group, the patients in the observation group provided have statistically significant mprovement on anxiety control, sleep quality, and hepatic indexes changes (P<0.05). The observation group also showed remarkably better life quality scores (GQLI-64) than the control group (P<0.01). This research confirmed that targeted nursing intervention coupled with ear acupoint bean pressing showed effective improvement on the anxiety control and sleep quality of chronic hepatic B patients, and demonstrated better hepatic index recovery. Patients in the observation group also have higher life quality scores than the control group. PMID: 30033422 [PubMed – indexed for MEDLINE]

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Therapeutic effects of targeted nursing interventions combined with auricular-plaster therapy on anxiety level and life quality of Hepatitis B…

Evaluation of antiviral efficacy of Chinese traditional medicine Babao Dan in rabbits infected with hepatitis E virus.

Posted by on 08 Aug 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Evaluation of antiviral efficacy of Chinese traditional medicine Babao Dan in rabbits infected with hepatitis E virus. J Gen Virol. 2018 08;99(8):1036-1043 Authors: Gong W, Liu L, Li M, Wang L, Zhang M, Luo Z, Sridhar S, Woo PCY, Wang L Abstract Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Patients with chronic hepatitis B superinfected with HEV may progress to liver failure. Babao Dan (BD) is a traditional Chinese medicine widely used as an auxiliary option for the treatment of chronic hepatitis and liver cancer in China. This study aimed to evaluate the effect of BD on the management of HEV infection in a rabbit model. Sixty-two specific-pathogen-free (SPF) rabbits were divided randomly into five groups and treated with BD or placebo for 2 weeks. All rabbits were inoculated intravenously with rabbit HEV after initial administration. Then, rabbits were administered BD or ribavirin or placebo at 2 weeks post-inoculation (wpi) until faecal virus shedding showed negative. The duration of faecal virus shedding and levels of HEV RNA in faeces were reduced, and anti-HEV antibodies were detected in all rabbits in groups treated with BD before or after inoculation. Ribavirin treatment rapidly cleared HEV infection in SPF rabbits, but anti-HEV antibodies remained negative in 50 % of rabbits treated with ribavirin. These results indicate that ribavirin treatment was more effective in clearing HEV infection, while administration of BD before or after inoculation was effective in clearing HEV infection. Further clinical studies are warranted. PMID: 29923821 [PubMed – indexed for MEDLINE]

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Evaluation of antiviral efficacy of Chinese traditional medicine Babao Dan in rabbits infected with hepatitis E virus.

Therapeutic management with biological anti-TNF-α agent in severe psoriasis associated with chronic hepatitis B: A case report.

Posted by on 07 Aug 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Therapeutic management with biological anti-TNF-α agent in severe psoriasis associated with chronic hepatitis B: A case report. Exp Ther Med. 2019 Aug;18(2):895-899 Authors: Raducan A, Bucur S, Caruntu C, Constantin T, Nita IE, Manolache N, Constantin MM Abstract Systemic therapy in patients with concurrent psoriasis and chronic hepatitis B is a challenging task for both dermatologists and gastroenterologists since there is a high risk for hepatitis B virus (HBV) reactivation and hepatic toxicity under biological therapy. The therapeutic management of a patient with psoriasis and infection with the HBV is a challenge as the classical systemic treatment (methotrexate, acitretin, cyclosporine) shows a high risk of immunosuppression and/or hepatic toxicity and the biological therapy is endangered by the possibility of HBV reactivation. We present the case of a patient with moderate-severe psoriasis and chronic hepatitis B for whom we assessed the risk-benefit relation and considered useful to initiate the anti-TNF therapy concomitantly with the antiviral therapy with entecavir. The therapeutic algorithm included initiation of anti-TNF therapy with etanercept 2×50 mg/week combined with entecavir, an antiviral treatment administered continuously since the diagnosis of the HBV hepatitis, with hepatic function and viral load monitoring. After 3 months of therapy with etanercept the patient was given a dose of etanercept of 50 mg/week combined with entecavir 0.5 mg/day which he continued until week 36 when psoriatic lesions had cleared (PASI=0.6; DLQI=0). No adverse effects were registered and there was no evidence of HBV viral replication or changes in viral markers. We wish to emphasize that the use of etanercept in a patient with psoriasis and hepatitis B is a successful therapeutic alternative which may be safely used concomitantly with entecavir, with regular monitoring of viral load and hepatic function tests. PMID: 31384320 [PubMed]

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Therapeutic management with biological anti-TNF-α agent in severe psoriasis associated with chronic hepatitis B: A case report.

Case series of an alternative therapy for generalised lichen planus: Four case studies.

Posted by on 07 Aug 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles Case series of an alternative therapy for generalised lichen planus: Four case studies. Exp Ther Med. 2019 Aug;18(2):943-948 Authors: Nwabudike LC, Miulescu M, Tatu AL Abstract Lichen planus (LP) is an idiopathic, cell-mediated immune disorder, accompanied by itching. Spontaneous remission occurs. Topical and systemic therapies are utilised. Four cases of generalized LP with and without mucosal involvement treated homeopathically are presented. Case 1: A 48-year-old female presented with a 7-month history of generalized itchy rash, which had been diagnosed as LP, treated unsuccessfully with topical steroids and removal of dental fillings. Examination revealed violaceous papules on upper and lower limbs, oral mucosal lesions and an irregular, erythematous, blanching, macular rash on the chest. She received homeopathic Ignatia amara at medication dilution factor (MK) potency, weekly dose and went into remission at 3 months. Patient remains in remission. Case 2: A 65-year-old female presented with a 27-year history of generalized, LP, which had been unresponsive to topical steroids. Examination showed generalized, violaceous papules, with no mucosal involvement. She received homeopathic Aurum metallicum, MK potency, weekly, and went into remission. She relapsed at 8 months after onset of therapy, following a very stressful incident, but gained remission again with Aurum metallicum after 1 month of therapy. She remains in remission. Case 3: A 38-year-old male presented with a 21-year history of generalized LP. Medical history was significant for hepatitis B and asthma. Topical steroid therapy was only partially successful. Examination revealed generalized, violaceous papules, with oral and genital involvement. He received homeopathic Lycopodium at MK potency, weekly, and remitted by 2 months. He remains in remission. Case 4: A 41-year-old male presented with a 12-year history of generalized hypertrophic LP, which had responded partially to topical steroids and ultraviolet A therapy. Medical history was significant for reduced sense of smell. Examination revealed generalized, violaceous, hypertrophic papules and nodules. He received homeopathic Carcinosinum at MK potency and remitted at 6-months. In its long-standing, generalized form, with mucosal involvement, LP may respond to individualized homeopathy. More research may clarify homeopathy’s place in LP therapy. PMID: 31384327 [PubMed]

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Case series of an alternative therapy for generalised lichen planus: Four case studies.

[Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 15 October 2016].

Posted by on 03 Jul 2019 | Tagged as: Hepatitis B Alternative Medicine

Related Articles [Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 15 October 2016]. Orv Hetil. 2017 02;158(Suppl 1):23-35 Authors: Horváth G, Gerlei Z, Gervain J, Lengyel G, Makara M, Pár A, Rókusz L, Szalay F, Tornai I, Werling K, Hunyady B Abstract Diagnosis and treatment of HBV/HDV infection means for the patient to be able to maintain working capacity, to increase quality of life, to prevent cancer, and to prolong life expectancy, while society benefits from eliminating the chances of further transmission of the viruses, and decreasing the overall costs of serious complications. The guideline delineates the treatment algorithms for 2017 set by a consensus meeting of physicians involved in the treatment of these diseases. The prevalence of HBV infection in the Hungarian general population is 0.5-0.7%. The indications of treatment is based upon viral examinations (including viral nucleic acid determination), determinations of disease activity and stage (including biochemical, pathologic, and/or non-invasive methods), and excluding contraindications. To avoid unnecessary side effects and for cost-effective approach the guideline stresses the importance of quick and detailed virologic evaluations, the applicability of elastography as an acceptable alternative of liver biopsy in this regard, as well as the relevance of appropriate consistent follow up schedule for viral response during therapy. The first choice of therapy in chronic hepatitis B infection can be pegylated interferon for 48 weeks or continuous entecavir or tenofovir therapy. The latter two must be continued for at least 12 months after hepatitis B surface antigen seroconversion. Adefovir dipivoxil is recommended mainly in combination therapy. Lamivudine is no longer a first choice; patients currently taking lamivudine must switch if response is inadequate. Appropriate treatment of patients taking immunosuppressive medications is highly recommended. Pegylated interferon based therapy is recommended for the treatment of concomitant hepatitis D infection. Orv. Hetil., 2017, 158(Suppl. 1) 23-35. PMID: 28218868 [PubMed – indexed for MEDLINE]

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[Diagnosis and treatment of chronic hepatitis B and D. National consensus guideline in Hungary from 15 October 2016].

Environmental factors affecting self-management of chronic hepatitis B from the patients’ perspective.

Posted by on 27 Jun 2019 | Tagged as: Hepatitis B Alternative Medicine, Others

Related Articles Environmental factors affecting self-management of chronic hepatitis B from the patients’ perspective. J Clin Nurs. 2019 Jun 25;: Authors: Lin WS, Lee TT, Yang YH, Mills ME Abstract AIMS AND OBJECTIVES: To explore factors affecting self-management experiences of patients with chronic hepatitis B within their social and cultural environments. BACKGROUND: Many cases of hepatitis B are not detected until they are in end-stage liver disease. Despite an increasing trend of indicating a lack of health awareness as the reason, studies have rarely referred to the personal, social and cultural environmental constraints from patients’ perspectives. DESIGN: A descriptive qualitative study. METHODS: Forty-seven adults diagnosed with chronic hepatitis B were interviewed in a private area of a hospital clinic in Taiwan in 2018. Four open-ended questions relating to care self-management included: disease detection; disease control; preventive care; and, perceptions of screening and follow-ups. Data were examined using content analysis. This study also adhered to the consolidated COREQ guidelines. RESULTS: Five main themes emerged: personal experiences, awareness of occupational health, the availability of conventional treatment, cultural beliefs about healthcare, and family roles. Findings of note were that some participants became aware that they had never known the difference between follow-up for hepatitis B and regular adult/laborer health checks due to a lack of information within their living environment. Many participants added alternative treatments to their self-management strategies and others frequently ignored follow-up appointments because of different cultural health beliefs. CONCLUSIONS: Patients’ disease self-management perceptions are driven by dynamic influences suggesting that development of policies integrating personal, family, social, and cultural environmental factors could enhance individual screening and subsequent health behaviors of patients with chronic hepatitis B. RELEVANCE TO PRACTICE: Adding person-centered case management of hepatitis B could enhance patients’ adherence to follow-up. Attention should be given to increasing provider awareness of the influence of their own attitude and communication on patients’ participation in self-management. This article is protected by copyright. All rights reserved. PMID: 31240796 [PubMed – as supplied by publisher]

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Environmental factors affecting self-management of chronic hepatitis B from the patients’ perspective.

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