Last data update: Jun 17, 2024. (Total: 47034 publications since 2009)
Records 1-9 (of 9 Records) |
Query Trace: Choi YH [original query] |
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Natural antibody IgG levels are associated with HBeAg-positivity and seroconversion in chronic hepatitis B patients treated with entecavir
Choi YH , Lee HW , Purdy MA . Sci Rep 2022 12 (1) 4382 B1 cell-derived natural antibodies are non-specific polyreactive antibodies and can activate the complement pathway leading to lysis of enveloped virus particles before activation of the adaptive immune response. We investigated the relationship between natural antibody levels and treatment outcomes of 126 treatment-naïve chronic hepatitis B (CHB) patients, who underwent entecavir (ETV) treatment. Serum IgG1-3 and complement C3 levels were significantly higher in HBeAg-positive patients. In pre-treatment, IgG1 (odd ratios [OR] 2.3, p < 0.0001), IgG2 (OR 9.8, p < 0.0001), IgG3 (OR 7.4, p < 0.0001), and C3 (OR 7.2, p < 0.0001) were associated with HBeAg-positive patients. At baseline, IgG2 (OR 10.2, p = 0.025), IgG4, (OR 3.4, p = 0.026), and complement C1q (OR 5.0, p = 0.0068) were associated with seroconverters. Post-treatment levels of IgG1-4 and C3/C1q were also associated with HBeAg-positive patients and seroconverters. High levels of IgG2-4 and C1q were observed in seroconverters but not in virological responders. Thus, high pretreatment and post-treatment levels of natural antibody IgG1-4, complement C3, and/or C1q were significantly associated with HBeAg-positivity and HBeAg seroconverters in CHB patients with ETV treatment. These results suggest that the presence of preexisting host immunity against chronic hepatitis B is closely related to outcome of ETV treatment. |
Transcriptome analysis in rhesus macaques infected with hepatitis E virus genotype 1/3 infections and genotype 1 re-infection.
Choi YH , Zhang X , Srinivasamoorthy G , Purdy MA . PLoS One 2020 15 (9) e0237618 ![]() ![]() Hepatitis E virus (HEV) genotype 1 (gt1) and gt3 infections have distinct epidemiologic characteristics and genotype-specific molecular mechanisms of pathogenesis are not well characterized. Previously, we showed differences in immune response-related gene expression profiles of HEV gt1 and gt3 infections using qPCR. We hypothesize that HEV gt1 and gt3 infections induce transcriptome modifications contributing to disease pathogenesis. RNAseq analysis was performed using liver biopsy samples of naïve (baseline), HEV gt1, or gt3-infected rhesus macaques, and nine anti-HEV positive rhesus macaques re-inoculated with HEV gt1. All 10 primary HEV gt1/gt3 infected animals exhibited the typical course of acute viral hepatitis and cleared the infection between 27 to 67 days after inoculation. Viremic stages of HEV infection were defined as early, peak, and decline based on HEV RNA titers in daily stool specimens. During early, peak, and decline phases of infection, HEV gt1 induced 415, 417, and 1769 differentially expressed genes, respectively, and 310, 678, and 388 genes were differentially expressed by HEV gt3, respectively (fold change ≥ 2.0, p-value ≤ 0.05). In the HEV gt1 infection, genes related to metabolic pathways were differentially expressed during the three phases of infection. In contrast, oxidative reduction (early phase), immune responses (peak phase), and T cell cytokine production (decline phase) were found to be regulated during HEV gt3 infection. In addition, FoxO and MAPK signaling pathways were differentially regulated in re-infected and protected animals against HEV gt1 reinfection, respectively. Significant differences of hepatic gene regulation exist between HEV gt1 and gt3 infections. These findings reveal a new link between molecular pathogenesis and epidemiological characteristics seen in HEV gt1 and gt3 infections. |
Feasibility of hepatitis B vaccination by microneedle patch: Cellular and humoral immunity studies in rhesus macaques
Choi YH , Perez-Cuevas MB , Kodani M , Zhang X , Prausnitz MR , Kamili S , O'Connor SM . J Infect Dis 2019 220 (12) 1926-1934 BACKGROUND: Dissolvable microneedle patches (dMNPs) provide ease of deployment and eliminate need for hypodermic needle disposal after conventional vaccinations. In this study, immunogenicity of dMNP delivery of adjuvant-free monovalent hepatitis B surface antigen (HBsAg) vaccine (AFV) to standard intramuscular (IM) injection of monovalent aluminum-adjuvanted monovalent hepatitis B vaccine (AAV) were compared in rhesus macaques. METHODS: Sixteen macaques were immunized twice in 4 groups: dMNP delivery of 24 +/- 8microg (n=4) or 48 +/- 14microg (n=4) AFV; IM injection of 10microg AFV (IM AFV, n=4); and IM injection of 10microg AAV (IM AAV, n=4). Levels of hepatitis B surface antibody and HBsAg-specific T-cell responses were analyzed. RESULTS: Six of 8 animals with dMNP delivery of AFV had anti-HBs levels >/=10 mIU/ml after the first vaccine dose. After dMNP delivery of AFV, IFN-gamma, IL-2, and IL-4 production by HBsAg-specific T-cells were detected. A statistically significant positive correlation was detected between anti-HBs levels and HBsAg-specific IFN-gamma and IL-2 (Th1-type cytokine) and IL-4 (Th2-type cytokine) producing cells in all anti-HBs positive animals. CONCLUSIONS: dMNP delivery of AFV can elicit seroprotective anti-HBs levels in rhesus macaques that correlate in human seroprotection, and could be particularly promising for hepatitis B vaccine birth dose delivery in resource-constrained regions. |
Expression profiles of host immune response-related genes against HEV genotype 3 and genotype 1 infections in rhesus macaques.
Choi YH , Zhang X , Tran C , Skinner B . J Viral Hepat 2018 25 (8) 986-995 ![]() Hepatitis E virus (HEV) genotype (gt) 3 infection is food-borne causing sporadic infections in older individuals and gt1 infection is water-borne, often causing epidemics affecting primarily young adults. Although HEV infection causes self-limited disease, gt3 induces chronic infection in immunocompromised individuals. Hepatic host gene expression against gt3 infection remains unknown. Host gene expression profiles for HEV gt1 (n=3) and gt3 (n=7) infections were analyzed in the livers of experimentally infected rhesus macaques. HEV RNA was detected from 2 to 24 days after inoculation (DAI) in stool and serum, elevated alanine aminotransferase (ALT) activity was detected from 7 to 31 DAI, and anti-HEV antibody became detectable between 12 and 42 DAI. All 10 animals cleared the infection between 34 to 68 DAI. We found that 24%, 48%, and 41% of hepatic immune response genes against gt3 infection were upregulated during the early, peak, and decline phases of HEV RNA replication. For gt1 infection, 25% of hepatic immune response-related genes were downregulated during early viremia, but 6%, 34%, and 37% of genes were upregulated at the early, peak and during decline of HEV RNA replication, respectively. Our study demonstrated distinct differences in the expression profiles of host immune response-related genes of HEV gt3 and gt1 infections in experimentally infected rhesus macaques. This article is protected by copyright. All rights reserved. |
Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models
Brisson M , Bénard É , Drolet M , Bogaards JA , Baussano I , Vänskä S , Jit M , Boily MC , Smith MA , Berkhof J , Canfell K , Chesson HW , Burger EA , Choi YH , De Blasio BF , De Vlas SJ , Guzzetta G , Hontelez JAC , Horn J , Jepsen MR , Kim JJ , Lazzarato F , Matthijsse SM , Mikolajczyk R , Pavelyev A , Pillsbury M , Shafer LA , Tully SP , Turner HC , Usher C , Walsh C . Lancet Public Health 2016 1 (1) e8-e17 BACKGROUND: Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination. METHODS: We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RR(prev)) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]). FINDINGS: 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RR(prev) of HPV 16 among women and men was 0·53 (80% UI 0·46-0·68) and 0·36 (0·28-0·61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RR(prev) of HPV 16 among women and men was 0·93 (0·90-1·00) and 0·83 (0·75-1·00), respectively. Vaccinating boys in addition to girls increased the RR(prev) of HPV 16 among women and men by 0·18 (0·13-0·32) and 0·35 (0·27-0·39) for 40% coverage, and 0·07 (0·00-0·10) and 0·16 (0·01-0·25) for 80% coverage, respectively. The RR(prev) were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RR(prev) of 1·00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years). INTERPRETATION: Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. FUNDING: Canadian Institutes of Health Research. |
Elevation of alanine aminotransferase activity occurs after activation of the cell-death signaling initiated by pattern-recognition receptors but before activation of cytolytic effectors in NK or CD8+ T cells in the liver during acute HCV infection
Choi YH , Jin N , Kelly F , Sakthivel SK , Yu T . PLoS One 2016 11 (10) e0165533 Pattern-recognition receptors (PRRs) promote host defenses against HCV infection by binding to their corresponding adapter molecules leading to the initiation of innate immune responses including cell death. We investigated the expression of PRR genes, biomarkers of liver cell-death, and T cell and NK cell activation/inhibition-related genes in liver and serum obtained from three experimentally infected chimpanzees with acute HCV infection, and analyzed the correlation between gene expression levels and clinical profiles. Our results showed that expression of hepatic RIG-I, TLR3, TLR7, 2OAS1, and CXCL10 mRNAs was upregulated as early as 7 days post-inoculation and peaked 12 to 83 days post-inoculation. All of the three HCV infected chimpanzees exhibited significant elevations of serum alanine aminotransferase (ALT) activity between 70 and 95 days after inoculation. Elevated levels of serum cytokeratin 18 (CK-18) and caspases 3 and 7 activity coincided closely with the rise of ALT activity, and were preceded by significant increases in levels of caspase 3 and caspase 7 mRNAs in the liver. Particularly we found that significant positive auto-correlations were observed between RIG-I, TLR3, CXCL10, 2OAS1, and PD-L1 mRNA and ALT activity at 3 to 12 days before the peak of ALT activity. However, we observed substantial negative auto-correlations between T cell and NK cell activation/inhibition-related genes and ALT activity at 5 to 32 days after the peak of ALT activity. Our results indicated cell death signaling is preceded by early induction of RIG-I, TLR3, 2OAS1, and CXCL10 mRNAs which leads to elevation of ALT activity and this signaling pathway occurs before the activation of NK and T cells during acute HCV infection. Our study suggests that PRRs and type I IFN response may play a critical role in development of liver cell injury related to viral clearance during acute HCV infection. |
Occupational noise exposure assessment using O*NET and its application to a study of hearing loss in the US general population
Choi YH , Hu H , Tak S , Mukherjee B , Park SK . Occup Environ Med 2012 69 (3) 176-83 OBJECTIVES: Although occupational noise is a well known risk factor for hearing loss, little epidemiological evidence has been reported on its association with hearing loss in the general population, in part, because of the difficulty in exposure assessment. This study introduced a quantitative occupational noise exposure assessment tool using the Occupational Information Network (O*NET) database and evaluated its applicability for epidemiological research using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. METHODS: The O*NET noise exposure data were assessed by questionnaires across numerous occupations, asking the frequency of exposure to sounds and noise levels that are distracting and uncomfortable (with five possible responses from 'never' to 'every day'). Means of the O*NET noise scores were computed to correspond to NHANES occupational categories and assigned to 3828 adults aged 20-69 years, who participated in the 1999-2004 NHANES. Pure-tone averages (PTA) of hearing thresholds at 0.5, 1, 2 and 4 kHz were computed, and hearing loss was defined as a PTA >25 dB in either ear. Linear and logistic regression models with either continuous or quintiles of the O*NET noise scores were fitted on log-transformed PTA and binary hearing loss, respectively. RESULTS: Noise scores ranged from 1.80 to 4.37 with mean+/-SE of 3.06+/-0.02. After controlling for potential confounders, the highest (vs lowest) noise score quintile had a 22.5% (95% CI 11.0% to 35.2%) increase in PTA, and there was a linear dose-dependent trend across the quintiles of noise scores (p trend<0.0001). The adjusted OR for hearing loss comparing the highest with the lowest noise score quintiles was 2.1 (95% CI 1.2 to 3.6). CONCLUSION: This study suggests that the O*NET noise score is a useful tool for examining occupational noise-induced health effects in the general population in the absence of actual occupational noise exposure assessment data. |
Leptin modulated changes in adipose tissue protein expression in ob/ob mice
Zhang W , Ambati S , Della-Fera MA , Choi YH , Baile CA , Andacht TM . Obesity (Silver Spring) 2010 19 (2) 255-61 ![]() Comparative proteomic analyses were performed in adipose tissue of leptin-deficient ob/ob mice treated with leptin or control buffer in order to identify the protein expression changes as the potential targets of leptin. Mice were treated with either phosphate-buffered saline (control) or 10 microg/day leptin for 14 days via subcutaneous osmotic minipumps. Total protein from white adipose tissue was extracted and labeled with different fluorescent cyanine dyes for analysis by two-dimensional difference gel electrophoresis (DIGE). Spots that were differentially expressed and appeared to have sufficient material for mass spectrometry analysis were picked and digested with trypsin and subjected to MALDI-TOF MS for protein identification. Twelve functional protein groups were found differentially expressed in adipose tissue of leptin-treated vs. control ob/ob mice, including molecular chaperones and redox proteins such as calreticulin (CALR), protein disulfide isomerase-associated 3 (PDIA3), prohibitin (PHB), and peroxiredoxin-6 (PRDX6); cytoskeleton proteins such as beta actin, desmin, and alpha-tubulin; and some other proteins. The mRNA levels of CALR, PDIA3, and PHB were measured by real-time reverse transcription-PCR and found to be upregulated (P < 0.05), consistent with the fold change in protein expression level. Our findings suggest that leptin's effects on lipid metabolism and apoptosis may be mediated in part by alterations in expression of molecular chaperones and redox proteins for regulating endoplasmic reticulum stress and cytoskeleton proteins for regulating mitochondrial morphology. |
Pulmonary inflammation after intraperitoneal administration of ultrafine titanium dioxide (TiO2) at rest or in lungs primed with lipopolysaccharide
Moon C , Park HJ , Choi YH , Park EM , Castranova V , Kang JL . J Toxicol Environ Health A 2010 73 396-409 Nanoparticles are widely used in nanomedicines, including for targeted delivery of pharmacological, therapeutic, and diagnostic agents. Since nanoparticles might translocate across cellular barriers from the circulation into targeted organs, it is important to obtain information concerning the pathophysiologic effects of these particles through systemic migration. In the present study, acute pulmonary responses were examined after intraperitoneal (ip) administration of ultrafine titanium dioxide (TiO2, 40 mg/kg) in mice at rest or in lungs primed with lipopolysaccharide (LPS, ip, 5 mg/kg). Ultrafine TiO2 exposure increased neutrophil influx, protein levels in bronchoalveolar lavage (BAL) fluid, and reactive oxygen species (ROS) activity of BAL cells 4 h after exposure. Concomitantly, the levels of proinflammatory mediators, such as tumor necrosis factor (TNF)-, interleukin (IL)-1β, and macrophage inflammatory protein (MIP)-2 in BAL fluid and mRNA expression of TNF- and IL-1β in lung tissue were elevated post ultrafine TiO2 exposure. Ultrafine TiO2 exposure resulted in significant activation of inflammatory signaling molecules, such as c-Src and p38 MAP kinase, in lung tissue and alveolar macrophages, and the nuclear factor (NF)-κB pathway in pulmonary tissue. Furthermore, ultrafine TiO2 additively enhanced these inflammatory parameters and this signaling pathway in lungs primed with lipopolysaccharide (LPS). Contrary to this trend, a synergistic effect was found for TNF- at the level of protein and mRNA expression. These results suggest that ultrafine TiO2 (P25) induces acute lung inflammation after ip administration, and exhibits additive or synergistic effects with LPS, at least partly, via activation of oxidant-dependent inflammatory signaling and the NF-κB pathway, leading to increased production of proinflammatory mediators. |
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