A Novel Inhibitor IDPP Interferes with Entry and Egress of HCV by Targeting Glycoprotein E1 in a Genotype-Specific Manner.

Despite recent advances in curing chronic hepatitis C (CHC), the high economic burden to therapy, viral drug resistance, difficult to treat hepatitis C virus (HCV) genotypes and patient groups are still of concern. To address this unmet medical needs, we devised strategies to identify novel viral interventions through target-free high-throughput screening of small molecules utilizing a phenotypic-based HCV infection assay. Thereby, a very potent (EC 46 ± 26 pM) iminodipyridinopyrimidine (IDPP) drug candidate was selected, and confirmed in primary human hepatocytes (EC 0.

Regulatory T Cells in Hepatitis B and C Virus Infections.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are hepatotropic viruses that establish chronic persistent infection by effectively escaping the host immune response and can cause immune-mediated liver injury. It has recently become apparent that regulatory T (Treg) cells, specifically CD4CD25Foxp3 Treg cells, modulate viral diseases by suppressing antiviral immune responses and regulating inflammatory host injury. The roles of Treg cells in HBV and HCV infections range from suppressing antiviral T cell responses to protecting the liver from immune-mediated damage.

Ionizing Radiation Induces Innate Immune Responses in Macrophages by Generation of Mitochondrial Reactive Oxygen Species.

During radiotherapy for tumors, the innate immune system also responds to ionizing radiation and induces immune modulation. However, little is known about the molecular mechanisms by which radiation modulates innate immune responses. In this study, we observed that radiation triggered the generation of mitochondrial reactive oxygen species (mROS), leading to innate immune responses in murine bone marrow-derived macrophages (BMDM).

Immunoproteasome induction is suppressed in hepatitis C virus-infected cells in a protein kinase R-dependent manner.

By changing the relative abundance of generated antigenic peptides through alterations in the proteolytic activity, interferon (IFN)-γ-induced immunoproteasomes influence the outcome of CD8 cytotoxic T lymphocyte responses. In the present study, we investigated the effects of hepatitis C virus (HCV) infection on IFN-γ-induced immunoproteasome expression using a HCV infection cell culture system. We found that, although IFN-γ induced the transcriptional expression of mRNAs encoding the β1i/LMP2, β2i/MECL-1 and β5i/LMP7 immunoproteasome subunits, the formation of immunoproteasomes was significantly suppressed in HCV-infected cells.

Complete prevention of blood loss with self-sealing haemostatic needles.

Bleeding is largely unavoidable following syringe needle puncture of biological tissues and, while inconvenient, this typically causes little or no harm in healthy individuals. However, there are certain circumstances where syringe injections can have more significant side effects, such as uncontrolled bleeding in those with haemophilia, coagulopathy, or the transmission of infectious diseases through contaminated blood. Herein, we present a haemostatic hypodermic needle able to prevent bleeding following tissue puncture.

Immune checkpoint inhibitors for cancer treatment.

During immune responses antigen-specific T cells are regulated by several mechanisms, including through inhibitory receptors and regulatory T cells, to avoid excessive or persistent immune responses. These regulatory mechanisms, which are called 'immune checkpoints', suppress T cell responses, particularly in patients with chronic viral infections and cancer where viral antigens or tumor antigens persist for a long time and contribute to T cell exhaustion. Among these regulatory mechanisms, cytotoxic T lymphocyte associated protein-4 (CTLA-4) and programmed cell death 1 (PD-1) are the most well-known receptors and both have been targeted for drug development.

Responsive Surface Methodology Optimizes Extraction Conditions of Industrial by-products, Camellia japonica Seed Cake.

Background: The central nervous system is easily damaged by oxidative stress due to high oxygen consumption and poor defensive capacity. Hence, multiple studies have demonstrated that inhibiting oxidative stress-induced damage, through an antioxidant-rich diet, might be a reasonable approach to prevent neurodegenerative disease.

Objective: In the present study, response surface methodology was utilized to optimize the extraction for neuro-protective constituents of Camellia japonica byproducts.

Immunogenicity of MenACWY-CRM in Korean Military Recruits: Influence of Tetanus-Diphtheria Toxoid Vaccination on the Vaccine Response to MenACWY-CRM.

The quadrivalent meningococcal conjugate vaccine (MenACWY-CRM) has been introduced for military recruits in Korea since 2012. This study was performed to evaluate the immunogenicity of MenACWY-CRM in Korean military recruits. In addition, the influence of tetanus-diphtheria toxoids (Td) vaccination on the vaccine response to MenACWY-CRM was analyzed.

Cross-protective efficacies of highly-pathogenic avian influenza H5N1 vaccines against a recent H5N8 virus.

To investigate cross-protective vaccine efficacy of highly-pathogenic avian influenza H5N1 viruses against a recent HPAI H5N8 virus, we immunized C57BL/6 mice and ferrets with three alum-adjuvanted inactivated whole H5N1 vaccines developed through reverse-genetics (Rg): [Vietnam/1194/04xPR8 (clade 1), Korea/W149/06xPR8 (clade 2.2), and Korea/ES223N/03xPR8 (clade 2.5)].

Deterministic Migration-Based Separation of White Blood Cells.

Functional and phenotypic analyses of peripheral white blood cells provide useful clinical information. However, separation of white blood cells from peripheral blood requires a time-consuming, inconvenient process and thus analyses of separated white blood cells are limited in clinical settings. To overcome this limitation, a microfluidic separation platform is developed to enable deterministic migration of white blood cells, directing the cells into designated positions according to a ridge pattern.

Pyruvate dehydrogenase kinase regulates hepatitis C virus replication.

During replication, hepatitis C virus (HCV) utilizes macromolecules produced by its host cell. This process requires host cellular metabolic reprogramming to favor elevated levels of aerobic glycolysis. Therefore, we evaluated whether pyruvate dehydrogenase kinase (PDK), a mitochondrial enzyme that promotes aerobic glycolysis, can regulate HCV replication.

Immune responses and immunopathology in acute and chronic viral hepatitis.

Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that are determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not.

Hepatitis C Virus Core Protein Promotes miR-122 Destabilization by Inhibiting GLD-2.

The liver-specific microRNA miR-122, which has essential roles in liver development and metabolism, is a key proviral factor for hepatitis C virus (HCV). Despite its crucial role in the liver and HCV life cycle, little is known about the molecular mechanism of miR-122 expression regulation by HCV infection. Here, we show that the HCV core protein downregulates the abundance of miR-122 by promoting its destabilization via the inhibition of GLD-2, a non-canonical cytoplasmic poly(A) polymerase.

Post-Exercise Heart Rate Recovery Independently Predicts Clinical Outcome in Patients with Acute Decompensated Heart Failure.

Background: Post-exercise heart rate recovery (HRR) is an index of parasympathetic function associated with clinical outcome in patients with chronic heart failure. However, its relationship with the pro-inflammatory response and prognostic value in consecutive patients with acute decompensated heart failure (ADHF) has not been investigated.

Methods: We measured HRR and pro-inflammatory markers in 107 prospectively and consecutively enrolled, recovered ADHF patients (71 male, 59 ± 15 years, mean ejection fraction 28.

Root extract of water dropwort, Oenanthe javanica (Blume) DC, induces protein and gene expression of phase I carcinogen-metabolizing enzymes in HepG2 cells.

Background: Cytochrome P450 (CYP) isoenzymes are an important phase I enzyme system. In the present study, we investigated the effects of Oenanthe javanica (Blume) DC on CYP1A1 and CYP1A2.

Findings: Whole plants were completely dried and then divided into leaves, stems, and roots for extraction.

Comparative Analysis of Liver Injury-Associated Cytokines in Acute Hepatitis A and B.

Purpose: Acute hepatitis A (AHA) and acute hepatitis B (AHB) are caused by an acute infection of the hepatitis A virus and the hepatitis B virus, respectively. In both AHA and AHB, liver injury is known to be mediated by immune cells and cytokines. In this study, we measured serum levels of various cytokines and T-cell cytotoxic proteins in patients with AHA or AHB to identify liver injury-associated cytokines.

Interferon-inducible protein SCOTIN interferes with HCV replication through the autolysosomal degradation of NS5A.

Hepatitis C virus (HCV) utilizes autophagy to promote its propagation. Here we show the autophagy-mediated suppression of HCV replication via the endoplasmic reticulum (ER) protein SCOTIN. SCOTIN overexpression inhibits HCV replication and infectious virion production in cells infected with cell culture-derived HCV.

Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells.

Background: Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized.

Characterization of Nutritional Composition, Antioxidative Capacity, and Sensory Attributes of Seomae Mugwort, a Native Korean Variety of Artemisia argyi H. Lév. & Vaniot.

Few studies have investigated Seomae mugwort (a Korean native mugwort variety of Artemisia argyi H. Lév. & Vaniot), exclusively cultivated in the southern Korean peninsula, and the possibility of its use as a food resource.

Prolonged silencing of diacylglycerol acyltransferase-1 induces a dedifferentiated phenotype in human liver cells.

Diacylglycerol acyltransferase-1 (DGAT1), a key enzyme in triglyceride (TG) biogenesis, is highly associated with metabolic abnormalities, such as obesity and type 2 diabetes. However, the effects of DGAT1 silencing in the human liver have not been elucidated. To investigate the effects of DGAT1 silencing in human liver cells, we compared the cellular behaviours of DGAT1-deficient Huh-7.

Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection.

Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130-170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant.

Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression.

Amino acid (aa) polymorphisms in the hepatitis C virus (HCV) genotype 1b core protein have been reported to be a potent predictor for poor response to interferon (IFN)-based therapy and a risk factor for hepatocarcinogenesis. We investigated the effects of these polymorphisms with genotype 1b/2a chimeric viruses that contained polymorphisms of Arg/Gln at aa 70 and Leu/Met at aa 91. We found that infectious virus production was reduced in cells transfected with chimeric virus RNA that had Gln at aa 70 (aa70Q) compared with RNA with Arg at aa 70 (aa70R).

Cytomegalovirus Infection and Memory T Cell Inflation.

Cytomegalovirus (CMV) infection in healthy individuals is usually asymptomatic and results in latent infection. CMV reactivation occasionally occurs in healthy individuals according to their immune status over time. T cell responses to CMV are restricted to a limited number of immunodominant epitopes, as compared to responses to other chronic or persistent viruses.

Evaluation of hyaluronic acid-based combination adjuvant containing monophosphoryl lipid A and aluminum salt for hepatitis B vaccine.

Here, monophosphoryl lipid A (MPLA) and aluminum salt (Alum) were introduced into a hyaluronic acid (HA)-based combination vaccine adjuvant for hepatitis B vaccine (HBV). Although Alum is a well-known hepatitis B vaccine adjuvant that induces an enhanced humoral immune response, it cannot induce the cellular immune responses. On the other hand, MPLA has been generally reported to promote IFN-γ production via antigen-specific CD4(+) T cells, but it is not water soluble as a result of its long hydrophobic alkyl chains.