Functional B cell deficiency promotes intrahepatic HBV replication and impairs the development of anti-HBV T cell responses.

Background: The pivotal role of antibody-producing B cells in controlling hepatitis B virus (HBV) infection is well-established. However, the antiviral role of B cells extends beyond antibody production, which has been insufficiently studied for HBV infection.

Methods: Using an HBV hydrodynamic injection (HDI) mouse model with B cell depletion or functional blockade, we detected HBV infection markers and assessed T cell function through enzyme-linked immunosorbent assay, RT-PCR and flow cytometry.

Bio-Based Epoxy-Phthalonitrile Resin: Preparation, Characterization, and Properties.

Preparation of high-performance thermosetting resins via bio-based resources is important for the development of a sustainable world. In this work, we proposed the introduction of cyanide structure groups into the molecular structure of epoxy resins to give them excellent heat resistance. A eugenol-based epoxy-phthalonitrile (EEPN) resin was synthesized by a two-step process using the bio-based renewable resource of eugenol, and a series of EEPN/Epoxide resin (E51) blend resins with different EEPN contents were prepared.

Main-Chain Benzoxazines Containing an Erythritol Acetal Structure: Thermal and Degradation Properties.

In this paper, the bio-based raw material erythritol was used to introduce an acetal structure into the benzoxazine resins. The benzoxazine-based resins containing an erythritol acetal structure could be degraded in an acidic solution and were environmentally friendly thermosetting resins. Compounds and resins were characterized by H nuclear magnetic resonance (H NMR) and Fourier-transform infrared (FT-IR) analyses, and melting points were studied by a differential scanning calorimeter (DSC); the molecular weight was analyzed by gel permeation chromatography (GPC).

Toll-like receptor-mediated innate immunity orchestrates adaptive immune responses in HBV infection.

Chronic hepatitis B virus (HBV) infection remains to be a substantial global burden, especially for end-stage liver diseases. It is well accepted that HBV-specific T and B cells are essential for controlling HBV infection. Toll-like receptors (TLRs) represent one of the major first-line antiviral defenses through intracellular signaling pathways that induce antiviral inflammatory cytokines and interferons, thereby shaping adaptive immunity.

Soluble inflammatory mediators identify HCV patients who may be cured with four weeks of antiviral treatment.

Soluble inflammatory mediators (SIM) can be predictive of treatment outcome in antiviral treatment of chronic hepatitis C. Recently, it was shown that a subgroup of patients can be cured with four weeks of therapy. We here profiled patients for 70 SIM before and during treatment of hepatitis C with glecaprevir/pibrentasvir (GLE/PIB) +/- ribavirin.

Imprint of unconventional T-cell response in acute hepatitis C persists despite successful early antiviral treatment.

Unconventional T cells (UTCs) are a heterogeneous group of T cells that typically exhibit rapid responses toward specific antigens from pathogens. Chronic hepatitis C virus (HCV) infection causes dysfunction of several subsets of UTCs. This altered phenotype and function of UTCs can persist over time even after direct-acting antiviral (DAA)-mediated clearance of chronic HCV.

Mouse Models for Hepatitis B Virus Infection and Their Application.

Despite the availability of effective vaccination, hepatitis B virus (HBV) infection continues to be a major challenge worldwide. Research efforts are ongoing to find an effective cure for the estimated 250 million people chronically infected by HBV in recent years. The exceptionally limited host spectrum of HBV has limited the research progress.

Simultaneous or Prior Activation of Intrahepatic Type I Interferon Signaling Leads to Hepatitis B Virus Persistence in a Mouse Model.

It remains controversial how interferon (IFN) response contributes to hepatitis B virus (HBV) control and pathogenesis. A previous study identified that hydrodynamic injection (HI) of type I IFN (IFN-I) inducer polyinosinic-poly(C) [poly(I·C)] leads to HBV clearance in a chronic HBV mouse model. However, recent studies have suggested that premature IFN-I activation in the liver may facilitate HBV persistence.

Natural Killer Cells Regulate the Maturation of Liver Sinusoidal Endothelial Cells Thereby Promoting Intrahepatic T-Cell Responses in a Mouse Model.

Functional maturation of liver sinusoidal endothelial cells (LSECs) plays an important role in intrahepatic T-cell activation and control of viral infections. Natural killer (NK) cells have been reported to prompt the maturation of antigen-presenting cells (APCs), especially for dendritic cells (DCs), but the interaction between NK cells and LSECs is elusive. Here, we investigated whether and how NK cells are involved in regulating LSEC maturation and if this has a role in controlling hepatitis B virus (HBV) infection in a mouse model.

The impact of hepatitis B surface antigen on natural killer cells in patients with chronic hepatitis B virus infection.

Background & Aims: During chronic hepatitis B virus (HBV) infection, suppressed functionality of natural killer (NK) cells might contribute to HBV persistence but the underlying mechanisms remain elusive. A peculiar feature of HBV is the secretion of large amount of hepatitis B surface antigen (HBsAg). However, the effect of HBsAg quantities on NK cells is unclear.

Delivery of toll-like receptor 3 ligand poly(I:C) to the liver by calcium phosphate nanoparticles conjugated with an F4/80 antibody exerts an anti-hepatitis B virus effect in a mouse model.

Hepatitis B virus (HBV) is a global health issue, but currently available anti-HBV drugs have limited success. Previously, introduction of the Toll-like receptor (TLR)-3 ligand poly(I:C) to the liver via hydrodynamic injection (HI) was shown to effectively suppress HBV replication in a chronic HBV replication mouse model. However, this method cannot be applied in human beings.

Long-Lasting Imprint in the Soluble Inflammatory Milieu Despite Early Treatment of Acute Symptomatic Hepatitis C.

Background: Treatment with direct-acting antivirals (DAAs) in patients with chronic hepatitis C infection leads to partial restoration of soluble inflammatory mediators (SIMs). In contrast, we hypothesized that early DAA treatment of acute hepatitis C virus (HCV) with DAAs may normalize most SIMs.

Methods: In this study, we made use of a unique cohort of acute symptomatic hepatitis C patients who cleared HCV with a 6-week course of ledipasvir/sofosbuvir.

Plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2.

Osteoblast differentiation is a key process in bone homeostasis. Mutations in plastin 3 have been reported to be responsible for X-linked osteoporosis. Plastin 3 and plastin 2 act synergistically to regulate osteoblast differentiation.

Exosomes from activated hepatic stellate cells contain GLUT1 and PKM2: a role for exosomes in metabolic switch of liver nonparenchymal cells.

The mechanism of exosomes derived from activated hepatic stellate cells (HSCs) involved in liver fibrosis is poorly understood. We previously reported that hypoxia-inducible factor 1 (Hif-1) regulated HSC activation, and, therefore, we investigated in current work whether Hif-1 regulates exosome secretion and the metabolic switch of HSCs, thus affecting the metabolism of liver nonparenchymal cells. In this study, the characteristics of exosomes from HSCs were assessed electron microscopy, Western blot analysis, and acetylcholinesterase activity.

LSECs express functional NOD1 receptors: A role for NOD1 in LSEC maturation-induced T cell immunity in vitro.

Liver sinusoidal endothelial cells (LSECs) are organ resident APCs capable of antigen presentation and subsequent tolerization of T cells under physiological conditions. In this study, we investigated whether LSEC pretreatment with NOD-like receptor (NLR) agonists can switch the cells from a tolerogenic to an immunogenic state and promote the development of T cell immunity. LSECs constitutively express NOD1, NOD2 and RIPK2.

Local Stimulation of Liver Sinusoidal Endothelial Cells with a NOD1 Agonist Activates T Cells and Suppresses Hepatitis B Virus Replication in Mice.

Functional maturation of liver sinusoidal endothelial cells (LSECs) induced by a NOD1 ligand (diaminopimelic acid [DAP]) during viral infection has not been well defined. Thus, we investigated the role of DAP-stimulated LSEC maturation during hepatitis B virus (HBV) infection and its potential mechanism in a hydrodynamic injection (HI) mouse model. Primary LSECs were isolated from wild-type C57BL/6 mice and stimulated with DAP in vitro and in vivo and assessed for the expression of surface markers as well as for their ability to promote T cell responses via flow cytometry.

Delivery of the TLR ligand poly(I:C) to liver cells in vitro and in vivo by calcium phosphate nanoparticles leads to a pronounced immunostimulation.

Unlabelled: The selective activation of the immune system is a concurrent problem in the treatment of persistent diseases like viral infections (e.g. hepatitis).

[Fetal electrocardiogram extraction based on independent component analysis and quantum particle swarm optimizer algorithm].

Fetal electrocardiogram (FECG) is an objective index of the activities of fetal cardiac electrophysiology. The acquired FECG is interfered by maternal electrocardiogram (MECG). How to extract the fetus ECG quickly and effectively has become an important research topic.