- Impact of type of calcineurin inhibitor on post-transplant tuberculosis: single- center study from India. [Journal Article]
- TITranspl Infect Dis 2016 Oct 24
- CONCLUSIONS: In conclusion, our study shows that use of Tac as compared to CsA significantly decreases incidence of PTTB. Time of infection since transplant was similar in both the groups. However, nodal and disseminated TB were more common in the Tac group. This article is protected by copyright. All rights reserved.
- Prokaryotic Expression, Purification and Immunogenicity in Rabbits of the Small Antigen of Hepatitis Delta Virus. [Journal Article]
- IJInt J Mol Sci 2016 Oct 20; 17(10)
- Hepatitis delta virus (HDV) is a viroid-like blood-borne human pathogen that accompanies hepatitis B virus infection in 5% patients. HDV has been studied for four decades; however, the knowledge on i...
Hepatitis delta virus (HDV) is a viroid-like blood-borne human pathogen that accompanies hepatitis B virus infection in 5% patients. HDV has been studied for four decades; however, the knowledge on its life-cycle and pathogenesis is still sparse. The studies are hampered by the absence of the commercially-available HDV-specific antibodies. Here, we describe a set of reproducible methods for the expression in E. coli of His-tagged small antigen of HDV (S-HDAg), its purification, and production of polyclonal anti-S-HDAg antibodies in rabbits. S-HDAg was cloned into a commercial vector guiding expression of the recombinant proteins with the C-terminal His-tag. We optimized S-HDAg protein purification procedure circumventing a low affinity of the His-tagged S-HDAg to the Ni-nitrilotriacetyl agarose (Ni-NTA-agarose) resin. Optimization allowed us to obtain S-HDAg with >90% purity. S-HDAg was used to immunize Shinchilla grey rabbits which received 80 μg of S-HDAg in two subcutaneous primes in the complete, followed by four 40 μg boosts in incomplete Freunds adjuvant. Rabbits were bled two weeks post each boost. Antibody titers determined by indirect ELISA exceeded 10⁷. Anti-S-HDAg antibodies detected the antigen on Western blots in the amounts of up-to 100 pg. They were also successfully used to characterize the expression of S-HDAg in the eukaryotic cells by immunofluorescent staining/confocal microscopy.
- Hepatitis B Virus Protein X Induces Degradation of Talin-1. [Journal Article]
- VViruses 2016 Oct 19; 8(10)
- In the infected human hepatocyte, expression of the hepatitis B virus (HBV) accessory protein X (HBx) is essential to maintain viral replication in vivo. HBx critically interacts with the host damage...
In the infected human hepatocyte, expression of the hepatitis B virus (HBV) accessory protein X (HBx) is essential to maintain viral replication in vivo. HBx critically interacts with the host damaged DNA binding protein 1 (DDB1) and the associated ubiquitin ligase machinery, suggesting that HBx functions by inducing the degradation of host proteins. To identify such host proteins, we systematically analyzed the HBx interactome. One HBx interacting protein, talin-1 (TLN1), was proteasomally degraded upon HBx expression. Further analysis showed that TLN1 levels indeed modulate HBV transcriptional activity in an HBx-dependent manner. This indicates that HBx-mediated TLN1 degradation is essential and sufficient to stimulate HBV replication. Our data show that TLN1 can act as a viral restriction factor that suppresses HBV replication, and suggest that the HBx relieves this restriction by inducing TLN1 degradation.
- Dynamics of a diffusive age-structured HBV model with saturating incidence. [Journal Article]
- MBMath Biosci Eng 2016 Oct 1; 13(5):935-968
- In this paper, we propose and investigate an age-structured hepatitis B virus (HBV) model with saturating incidence and spatial diffusion where the viral contamination process is described by the age...
In this paper, we propose and investigate an age-structured hepatitis B virus (HBV) model with saturating incidence and spatial diffusion where the viral contamination process is described by the age-since-infection. We first analyze the well-posedness of the initial-boundary values problem of the model in the bounded domain Ω ⊂ Rn and obtain an explicit formula for the basic reproductive number R0 of the model. Then we investigate the global behavior of the model in terms of R0: if R0 ≤ 1, then the uninfected steady state is globally asymptotically stable, whereas if R0 > 1, then the infected steady state is globally asymptotically stable. In addition, when R0> 1, by constructing a suitable Lyapunov-like functional decreasing along the travelling waves to show their convergence towards two steady states as t tends to ∞, we prove the existence of traveling wave solutions. Numerical simulations are provided to illustrate the theoretical results.
- Global dynamics of a vaccination model for infectious diseases with asymptomatic carriers. [Journal Article]
- MBMath Biosci Eng 2016 Aug 1; 13(4):813-840
- In this paper, an epidemic model is investigated for infectious diseases that can be transmitted through both the infectious individuals and the asymptomatic carriers (i.e., infected individuals who ...
In this paper, an epidemic model is investigated for infectious diseases that can be transmitted through both the infectious individuals and the asymptomatic carriers (i.e., infected individuals who are contagious but do not show any disease symptoms). We propose a dose-structured vaccination model with multiple transmission pathways. Based on the range of the explicitly computed basic reproduction number, we prove the global stability of the disease-free when this threshold number is less or equal to the unity. Moreover, whenever it is greater than one, the existence of the unique endemic equilibrium is shown and its global stability is established for the case where the changes of displaying the disease symptoms are independent of the vulnerable classes. Further, the model is shown to exhibit a transcritical bifurcation with the unit basic reproduction number being the bifurcation parameter. The impacts of the asymptomatic carriers and the effectiveness of vaccination on the disease transmission are discussed through through the local and the global sensitivity analyses of the basic reproduction number. Finally, a case study of hepatitis B virus disease (HBV) is considered, with the numerical simulations presented to support the analytical results. They further suggest that, in high HBV prevalence countries, the combination of effective vaccination (i.e. ≥ 3 doses of HepB vaccine), the diagnosis of asymptomatic carriers and the treatment of symptomatic carriers may have a much greater positive impact on the disease control.
- A nurse-led intervention improved blood-borne virus testing and vaccination in Victorian prisons. [Journal Article]
- ANAust N Z J Public Health 2016 Oct 23
- CONCLUSIONS: The nurse-led intervention resulted in substantially increased testing and vaccination, demonstrating the benefits of a concerted effort to improve BBV and STI management in correctional settings.The availability of new treatments for hepatitis C has precipitated expansion of treatment in prisons. Improving the testing rate of prisoners, the first step in the treatment cascade, will maximise the benefits.
- A single-center prospective study on the safety of plasma exchange procedures using a double-viral-inactivated and prion-reduced solvent/detergent fresh-frozen plasma as the replacement fluid in the treatment of thrombotic microangiopathy. [Journal Article]
- TTransfusion 2016 Oct 23
- CONCLUSIONS: Our data have demonstrated that the incidence of complications during PEX is low and using OctaplasLG is comparable to the low incidence of reactions. No cases of anaphylaxis, transfusion-related acute lung injury, or fatal plasma reactions were seen. There was no evidence of viral transmission or seroconversion after treatment.
- Study on Evaluation of Alanine Aminotransferase (ALT) as Surrogate Marker in Hepatitis Virus Test. [Journal Article]
- JMJ Med Dent Sci 2016; 63(2-3):45-52
- Nucleic acid amplification test (NAT), which was introduced by the Japanese Red Cross Society in October 1999, began to be performed for screening of blood transfusion formulations in Japan in August...
Nucleic acid amplification test (NAT), which was introduced by the Japanese Red Cross Society in October 1999, began to be performed for screening of blood transfusion formulations in Japan in August 2014. In this study, the precision of immunological screenings of hepatitis B (HBsAg, HBcAb, and HBsAb), hepatitis C (HCVAb), and human immunodeficiency (HIVAb) virus antigens in donated blood were evaluated. In addition, the sensitivity of the alanine aminotransferase (ALT) test for detection of the hepatitis B and C viruses was re-evaluated. Immunological screenings showed high precision of detecting the viral antigens. In contrast, the ALT test showed much lower precision of detecting the presence of the hepatitis B and C viruses. Results of the NAT and immunological screenings revealed that ALT levels in donors were more strongly correlated with their levels of gammaglutamyltranspeptidase (γGTP) and body mass index (BMI), than with the results of NAT and immunological screening. Our study indicates that elevated level(s) of ALT, were more likely to be associated with lifestyles factors such as high intake of alcohol or obesity than with infection. Therefore, ALT may be excluded as surrogate markers of HBV, HCV, and HIV in donated blood.
- Hepatitis B reactivation during everolimus treatment. [Journal Article]
- AOActa Oncol 2016 Oct 24; :1-2
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- Binding and Uptake into Human Hepatocellular Carcinoma Cells of Peptide-Functionalized Gold Nanoparticles. [Journal Article]
- BCBioconjug Chem 2016 Oct 22
- One of the most daunting challenges of nanomedicine is the finding of appropriate targeting agents to deliver suitable payloads precisely to cells affected by malignancies. Even more complex is to ac...
One of the most daunting challenges of nanomedicine is the finding of appropriate targeting agents to deliver suitable payloads precisely to cells affected by malignancies. Even more complex is to achieve the ability to ensure the nanosystems enter those cells. Here we use 2 nm (metal core) gold nanoparticles to target human hepatocellular carcinoma (HepG2) cells stably transfected with the SERPINB3 (SB3) protein. The nanoparticles were coated with a 85:15 mixture of thiols featuring, respectively, a phosphoryl choline, to ensure water solubility and biocompatibility, and a 28-mer peptide corresponding to the amino acid sequence 21-47 of the hepatitis B virus-PreS1 protein (PreS1(21-47)). Conjugation of the peptide was performed via the maleimide-thiol reaction in methanol allowing the use of a limited amount of the targeting molecule. This is an efficient procedure also in the perspective of selecting libraries of new targeting agents. The rationale behind the selection of the peptide is that SB3, which is undetectable in normal hepatocytes, is over-expressed in hepatocellular carcinoma and in hepatoblastoma and has been proposed as a target of the hepatitis B virus (HBV). For the latter the key recognition element is the PreS1(21-47) peptide, which is a fragment of one of the proteins composing the viral envelope. The ability of the conjugated nanoparticles to bind the target protein SB3, expressed in liver cancer cells, was investigated by surface plasmon resonance analysis and in vitro via cellular uptake analysis followed by atomic absorption analysis of digested samples. The results showed that the PreS1(21-47) peptide is a suitable targeting agent for cells overexpressing the SB3 protein. Even more important is the evidence that the gold nanoparticles are internalized by the cells. The comparison between the surface plasmon resonance analysis and the cellular uptake studies suggests the presentation of the protein on cell surface is critical for efficient recognition.