Hepatitis C virus (HCV) is known to be a major cause of chronic hepatitis, liver cirrhosis and hepatocarcinoma. Therapeutic reagents are improving, but are still limited, and the protective vaccine against HCV is not available yet. However, the research of HCV life cycle and pathogenesis has been difficult due to obstacles, which are the lack of effective cell culture systems and small-animal models. Recently, breathtaking progress in terms of HCV replication system has been made using various forms of HCV clones and human hepatocarcinoma 7 cell lines (huh 7). The establishment of complete cell-culture system for HCV replication gave researchers opportunities to study the entire viral life cycle including entry, assembly, release of viral particles and the interaction with host cells. In fact, these efforts now appear to move into the identification and the development of innovative anti-HCV reagents. In this review, we go over the biological characters of HCV, a variety of in vitro cell culture, in vivo animal models of HCV infection, HCV immune-pathogenesis and the application of HCVcc system in terms of developing anti-HCV reagents.
Cell Culture Techniques ; Cell Line ; Clone Cells ; Hepacivirus* ; Hepatitis, Chronic ; Humans ; Indicators and Reagents* ; Life Cycle Stages ; Liver Cirrhosis ; Models, Animal ; Virion

The influenza viruses are divided into 3 different types, A, B and C, all of them are known as human pathogens. However, only type A influenza viruses cause both epidemic and pandemic influenza. Typically, influenza virus infects a respiratory tract, targets a lung and causes an acute infectious disease. Influenza infection can be identified by a high fever, headache, body ache and extreme fatigue. Host immune system against Influenza infection consists of innate immune response and adaptive immune response. Innate immune responses include recognition of influenza viruses by alveolar macrophages and natural killer cells. Adaptive immune responses contain influenza virus specific antibody production by B cells and killing infected cells by cytotoxic T cells. Initially, influenza viruses are recognized by pattern recognition receptors (PRRs) on respiratory epithelial cells and alveolar macrophages, which can induce efficient anti-viral immune responses. Host immune responses play crucial roles in defense against influenza virus infection but sometimes these may contribute to immuno-pathology, which results in serious tissue damage. In this review, we went over the understanding of current literature on subtypes of influenza A viruses, important viral antigens and anti-viral immune mechanisms.
Adaptive Immunity ; Antibody Formation ; Antigens, Viral ; B-Lymphocytes ; Communicable Diseases ; Epithelial Cells ; Fatigue ; Fever ; Headache ; Hemagglutinins ; Homicide ; Humans ; Immune System ; Immunity, Innate ; Influenza A virus ; Influenza, Human ; Killer Cells, Natural ; Lung ; Macrophages, Alveolar ; Neuraminidase ; Orthomyxoviridae* ; Pandemics ; Receptors, Pattern Recognition ; Respiratory System ; T-Lymphocytes

PURPOSE: Nodal infiltration has been one of the most important prognostic factors in breast cancer. In recent decades, risk stratification has greatly changed, and is applied in accordance with hormone receptor and human epidermal growth factor receptor 2 (HER2) status. We compared the prognostic power of tumor subtype to nodal involvement in early breast cancer. METHODS: We reviewed the medical records of 505 patients who had curative surgery for stage I or II breast cancer. We analyzed clinicopathologic factors according to tumor subtype and nodal involvement. Tumors were classified into 4 subtypes according to immunohistochemical status of estrogen receptor, progesterone receptor, HER2, and Ki67 labeling index. Disease-free survival (DFS) and overall survival were analyzed. RESULTS: There were 363 node-negative patients (71.9%) and 142 node-positive patients (28.1%). Luminal A, Luminal B, HER2, and triple-negative breast cancer subtypes were composed of 207 (41.0%), 147 (29.1%), 42 (8.3%), and 109 patients (21.6%), respectively. The median follow-up period was 89.5 months. Node negative-luminal A subtype showed the best prognosis with regard to 5-year DFS, and the pN1-triple negative subtype was associated with the shortest DFS (95.1% vs. 67.8%; hazard ratio, 9.554; P < 0.001). However, the node negative-triple negative subtype was associated with a worse 5-year DFS than the pN1-luminal A subtype ([86.4%; hazard ratio, 2.647; P = 0.048] vs. [93.2%; hazard ratio, 2.061; P = 0.194]). CONCLUSION: Node negative-triple negative breast cancer was associated with a poorer prognosis than pN1-luminal A subtype. Tumor subtype has greater prognostic power compared to nodal status in early breast cancer.
Breast Neoplasms* ; Breast* ; Disease-Free Survival ; Estrogens ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Medical Records ; Phenobarbital ; Prognosis ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Triple Negative Breast Neoplasms

Genipin, an aglycone derived from geniposide found in Gardenia jasminoides, is known to be an excellent natural cross-linker, strong apoptosis inducer, and antiviral agent. Although evidence suggests antiviral activity of genipin in several in vitro viral infection systems, there have been few literatures which review antitumor effects of genipin in a variety of in vitro/in vivo models of cancers yet. In this review, we present some of the latest findings in the studies of genipin focusing on antitumor effects and its mechanisms. In brief, genipin inhibits mitochondrial uncoupling protein 2 to increase accumulation of reactive oxygen species, leading to ROS/c-Jun N-terminal kinase-dependent apoptosis of cancer cells. Genipin also increase tissue inhibitors of metalloproteases (MMP), resulting to decrease activities of MMP-2 which plays a key role in metastasis of cancers. Genipin has shown a biphasic effects on cell death and survival in cancer cells as many other plant-derived phytochemicals do. Finally we discuss the potential of genipin as a promosing novel antitumor agent which could be applicable to chemotherapy and/or chemoprevention for cancers.
Apoptosis ; Cell Death ; Chemoprevention ; Drug Therapy ; Gardenia ; In Vitro Techniques ; Metalloproteases ; Neoplasm Metastasis ; Phytochemicals ; Reactive Oxygen Species

BACKGROUND/AIMS: The immunoregulatory molecules programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are associated with the dysfunction of antiviral effector T-cells, which leads to T-cell exhaustion and persistent viral infection in patients with chronic hepatitis C and chronic hepatitis B. Little is known about the role of PD-1 and CTLA-4 in patients with symptomatic acute hepatitis A (AHA). METHODS: Peripheral blood mononuclear cells were isolated from seven patients with AHA and from six patients with nonviral acute toxic hepatitis (ATH) during the symptomatic and convalescent phases of the respective diseases; five healthy subjects acted as controls. The expression of PD-1 and CTLA-4 on T-cells was measured by flow cytometry. RESULTS: PD-1 and CTLA-4 expression during the symptomatic phase was significantly higher in the T-cells of AHA patients than in those of ATH patients or healthy controls (PD-1: 18.3% vs 3.7% vs 1.6%, respectively, p<0.05; CTLA-4: 23.5% vs 6.1% vs 5.9%, respectively, p<0.05). The levels of both molecules decreased dramatically during the convalescent phase of AHA, whereas a similar pattern was not seen in ATH. CONCLUSIONS: Our findings are consistent with a viral-protective effect of PD-1 and CTLA-4 as inhibitory molecules that suppress cytotoxic T-cells and thereby prevent the destruction of virus-infected hepatocytes in AHA.
Acute Disease ; Adult ; CTLA-4 Antigen/*genetics ; Case-Control Studies ; Female ; Flow Cytometry ; Hepatitis/genetics ; Hepatitis A/*genetics/virology ; Hepatitis A Virus, Human ; Humans ; Male ; *Phenotype ; Programmed Cell Death 1 Receptor/*genetics ; T-Lymphocytes/metabolism

Herein, we report five cases of occult breast cancer treated with axillary node dissection only, without breast surgery or whole breast radio-therapy. The patients complained of a large, hard mass in the axillary area, although no breast masses were palpable. Biopsy of the axillary mass was performed in each case, and histological examination showed a metastatic carcinoma. No malignant findings were observed by mammography or ultrasonography. Magnetic resonance imaging and systemic examinations revealed no extramammary primary lesions. All patients underwent axillary lymph node dissection without breast surgery, and were administered adjuvant chemotherapy but not whole breast radiation therapy. The median follow-up period was 56 months (range, 15–241 months). The patients were all alive with no evidence of disease at the end of the follow-up period.
Axilla ; Biopsy ; Breast Neoplasms* ; Breast* ; Chemotherapy, Adjuvant ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Magnetic Resonance Imaging ; Mammography ; Neoplasms, Unknown Primary ; Ultrasonography

EBV infection has been causally associated with incidence of many carcinomas. EBV-associated gastric carcinoma (EBVaGC) has been classified as a unique gastric carcinoma subset, suggesting EBV infection is related to the development of gastric cancer. In this study, general trends of EBVaGC studies for last half-decades were reviewed in several perspectives of clinical significance, virological importance and etiological interests. Throughout this comprehensive reviewing, new study trends of EBV and EBVaGC for next half-decades were suggested.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human* ; Incidence ; Methylation ; Prognosis ; Stomach Neoplasms

Mitochondrial morphology is dynamically regulated by forming small, fragmented units or interconnected networks, and this is a pivotal process that is used to maintain mitochondrial homeostasis. Although dysregulation of mitochondrial dynamics is related to the pathogenesis of several human diseases, its molecular mechanism is not fully elucidated. In this study, we demonstrate the potential role of miR-27 in the regulation of mitochondrial dynamics. Mitochondrial fission factor (MFF) mRNA is a direct target of miR-27, whose ectopic expression decreases MFF expression through binding to its 3'-untranslated region. Expression of miR-27 results in the elongation of mitochondria as well as an increased mitochondrial membrane potential and mitochondrial ATP level. Our results suggest that miR-27 is a novel regulator affecting morphological mitochondrial changes by targeting MFF.
3' Untranslated Regions ; Cell Line ; Gene Expression Regulation ; Humans ; Membrane Potential, Mitochondrial ; Membrane Proteins/*genetics ; MicroRNAs/*metabolism ; Mitochondria/*genetics/*metabolism ; *Mitochondrial Dynamics ; Mitochondrial Proteins/*genetics ; *Protein Biosynthesis ; RNA, Messenger/genetics/metabolism

PURPOSE: Mesenchymal stem cells (MSCs) have demonstrated great promises for the treatment of ischemic stroke. Previously, we identified a new source of MSCs located in the inferior turbinate. We investigated therapeutic potentials of human turbinate- derived mesenchymal stem cells (hTMSCs) in ischemic stroke. METHODS: Ischemic stroke was induced by the intraluminal occlusion of middle cerebral artery (MCAo) for 50 minutes in rats. At one day after MCAo, hTMSCs, adipose tissue-derived MSCs (AdMSCs), or phosphate buffered saline (PBS) were transplanted into the striatum. Functional recovery was assessed by repeating behavioral tests including modified neurologic severity score and corner test. At 14 days after MCAo, brains were stained with hematoxylin and eosin (H&E) for measuring infarct volume. The survival of grafted MSCs was evaluated by immunohistochemistry to human nuclei (hNU). Immunohistochemistry with anti-doublecortin (anti-DCX) was performed to assess hippocampal neurogenesis. RESULTS: Transplantation of hTMSCs following MCAo showed improvements of neurologic function, which was comparable with that of AdMSCs. H&E staining showed no difference in infarct volume among 3 groups. Regarding the survival of grafted MSCs, the number of hNU-expressing cells was not different between hTMSCs- and AdMSCs-treated groups. Finally, hTMSCs increased the number of subgranular DCX-positive cells compared to PBS-treated controls, without affecting hilar ectopic migration of newborn neurons. CONCLUSIONS: hTMSCs could improve functional recovery following ischemic stroke, of which efficacy was similar to AdMSCs. Although hTMSCs showed comparable infarct size and survival of grafted MSCs, transplantation of hTMSCs could upregulate subgranular neurogenesis with no impact on ectopically migrating newborn neurons.
Animals ; Behavior Rating Scale ; Brain ; Eosine Yellowish-(YS) ; Hematoxylin ; Humans* ; Immunohistochemistry ; Infant, Newborn ; Mesenchymal Stromal Cells* ; Middle Cerebral Artery ; Neurogenesis ; Neurons ; Rats ; Stroke* ; Transplantation ; Transplants ; Turbinates

Purpose: To evaluate the test-retest reliability of a contour-based stereoacuity test using a head-mounted display (HMD) and compare it with other stereotests. Methods: Thirty-two healthy adults aged 23-47 years were recruited from a tertiary hospital between August 2017 and July 2018. Two separate contour-based circles (crossed disparity: 135-1,350 arcsecs) were generated on a high-resolution phone display (Galaxy S7; Samsung, Seoul, Korea) using an HMD (Galaxy Gear VR). Two images were independently projected to each eye as graded circles with a random dot background. The results of the new HMD stereotest were compared to those of the standard Randot and TNO stereotests. The test-retest reliability was assessed using the Bland-Altman plot and Cohen’s kappa statistics. Results: Among the 32 study participants, 17 (53%) were males and the mean age was 30.1 ± 4.8 years (range: 23-47). The mean stereoacuity was 160.3 ± 53.5 arcsecs in the first HMD stereotest (HMD1), 28.4 ± 12.5 arcsecs in the Randot stereotest, 96.1 ± 83.5 arcsecs in the TNO stereotest, and 143.3 ± 47.7 arcsecs in the second HMD stereotest (HMD2). The Bland-Altman plot showed a mean difference of 0.042 (-0.189 to +0.272, 95% limits of agreement) between HMD1 and HMD2. The reliability analysis showed an intraclass correlation coefficient of 0.499 (p = 0.022) and agreement of 81.25% in Cohen’s kappa statistics (Cohen’s kappa index = 0.119, p = 0.017). Conclusions The HMD stereotest without monocular cues showed fair test-retest reliability and reproducibility. Further studies using a high resolution display are needed to confirm the validity of the HMD stereotest.