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.
View Article and Find Full Text PDFHepatitis 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.
View Article and Find Full Text PDFDuring 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).
View Article and Find Full Text PDFBy 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.
View Article and Find Full Text PDFBleeding 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.
View Article and Find Full Text PDFDuring 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.
View Article and Find Full Text PDFBackground: 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.
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.
View Article and Find Full Text PDFTo 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)].
View Article and Find Full Text PDFFunctional 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.
View Article and Find Full Text PDFDuring 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.
View Article and Find Full Text PDFNat Rev Immunol
August 2016
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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFBackground: 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.
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.
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.
View Article and Find Full Text PDFHepatitis 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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFFew 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.
View Article and Find Full Text PDFDiacylglycerol 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.
View Article and Find Full Text PDFHepatitis 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.
View Article and Find Full Text PDFAmino 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).
View Article and Find Full Text PDFCytomegalovirus (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.
View Article and Find Full Text PDFHere, 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.
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