Browsing by Author "Wang, Wen-Hung"

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AIDS-related opportunistic illnesses and early initiation of HIV care remain critical in the contemporary HAART era: a retrospective cohort study in Taiwan
(2018-07-28)
Lee, Chun-Yuan
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Tseng, Yu-Ting
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Lin, Wei-Ru
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Chen, Yen-Hsu
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Tsai, Jih-Jin
Background: No study has reported the epidemiology of AIDS-related opportunistic illnesses (AOIs) in patients with newly diagnosed HIV infection in Taiwan in the past decade. Understanding the current trends in AOI-related morbidity/mortality is essential in improving patient care and optimizing current public health strategies to further reduce AOIs in Taiwan in the era of contemporary highly active antiretroviral therapy (HAART). Methods: Eligible patients were evaluated at two referral centers between 2010 and 2015. The patients were stratified by date of diagnosis into three periods: 2010-2011, 2012-2013, and 2014-2015. The demographics, HIV stage at presentation according to the United States CDC 2014 case definition, laboratory variables, and the occurrence of AOIs and associated outcomes were compared among the patients. Logistic regression and Cox regression were respectively used to identify variables associated with the occurrence of AOIs within 90 days of HIV enrollment and all-cause mortality. Results: Over a mean observation period of 469 days, 1264 patients with newly diagnosed HIV with a mean age of 29 years and mean CD4 count of 275 cells/mu L experienced 394 AOI episodes in 290 events. At presentation, 37.7% of the patients had AIDS; the frequency did not significantly differ across groups. The overall proportion of AOIs within the study period was 21.0%, and no decline across groups was observed. The majority of AOls (91.7%) developed within 90 days of enrollment. All-cause and AOI-related mortality did not significantly differ across groups. Throughout the three study periods, AOIs remained the main cause of death (47/56, 83.9%), especially within 180 days of enrollment (40/42, 95.2%). A CD4 cell count of < 200 cells/mu L at presentation was associated with increased adjusted odds of an AOI within 90 days [adjusted odds ratio, 40.84; 95% confidence intervals (CI), 12. 59-132.49] and an elevated adjusted hazard of all-cause mortality (adjusted hazard ratio, 11.03; 95% CI, 1.51-80.64). Conclusions: Despite efforts toward HIV prevention and management, early HIV care in Taiwan continues to be critically affected by AOI-related morbidity and mortality in the era of contemporary HAART. Additional targeted interventions are required for the earlier diagnosis of patients with HIV.
Capnocytophaga sputigena pneumonia and bacteremia in a patient with diabetes and gastric cancer
(2018-08-01)
Lo, Shih-Hao
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Chang, Yung-Yun
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Jao, Ya-Ting
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Wang, Wen-Hung
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Lu, Po-Liang
Characterization of the Drug Resistance Profiles of Patients Infected with CRF07_BC Using Phenotypic Assay and Ultra-Deep Pyrosequencing
(2017-01-20)
Huang, Szu-Wei
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Li, Wei-You
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Wang, Wen-Hung
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Lin, Yu-Ting
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Chou, Chih-Hung
The usefulness of ultra-deep pyrosequencing (UDPS) for the diagnosis of HIV-1 drug resistance (DR) remains to be determined. Previously, we reported an explosive outbreak of HIV-1 circulating recombinant form (CRF) 07_BC among injection drug users (IDUs) in Taiwan in 2004. The goal of this study was to characterize the DR of CRF07_BC strains using different assays including UDPS. Seven CRF07_BC isolates including 4 from early epidemic (collected in 2004 - 2005) and 3 from late epidemic (collected in 2008) were obtained from treatment-naive patient\'s peripheral blood mononuclear cells. Viral RNA was extracted directly from patient\'s plasma or from cultural supernatant and the pol sequences were determined using RT-PCR sequencing or UDPS. For comparison, phenotypic drug susceptibility assay using MAGIC-5 cells (in-house phenotypic assay) and Antivirogram were performed. In-house phenotypic assay showed that all the early epidemic and none of the late epidemic CRF07_BC isolates were resistant to most protease inhibitors (PIs) (4.4 - 47.3 fold). Neither genotypic assay nor Antivirogram detected any DR mutations. UDPS showed that early epidemic isolates contained 0.01 +/- 0.08% of PI DR major mutations. Furthermore, the combinations of major and accessory PI DR mutations significantly correlated with the phenotypic DR. The in-house phenotypic assay is superior to other conventional phenotypic assays in the detection of DR variants with a frequency as low as 0.01%.
DNA-based nanowires and nanodevices
(2017-01-01)
Pandian, Sureshbabu Ram Kumar
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Yuan, Chiun-Jye
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Lin, Chung-Ching
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Wang, Wen-Hung
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Chang, Chia-Ching
DNA (deoxyribonucleic acid) is a highly versatile biopolymer that has been a recent focus in the field of nanomachines and nanoelectronics. DNA exhibits many properties, such as high stability, adjustable conductance, vast information storage, self-organising capability and programmability, making it an ideal material in the applications of nanodevices, nanoelectronics and molecular computing. Even though native DNA has low conductance, it can easily be converted into a potential conductor by doping metal ions into the base pairs. Nickel ions have been employed to tune DNA into conducting polymers. Doping of nickel ions within DNA (Ni-DNA) increases the conductivity of DNA by at least 20 folds compared with that of native DNA. Further studies showed that Ni-DNA nanowires exhibit characteristics of memristors, making them a potential mass information storage system. In summary, DNA molecules have promising applications in a variety of fields, including nanodevices, nanomachines, nanoelectronics, organic solar cells, organic light emitting diodes and biosensors. [GRAPHICS] .
Google Trends-based non-English language query data and epidemic diseases: a cross-sectional study of the popular search behaviour in Taiwan
(2020-01-01)
Chang, Yu-Wei
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Chiang, Wei-Lun
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Wang, Wen-Hung
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Lin, Chun-Yu
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Hung, Ling-Chien
Objective This study developed a surveillance system suitable for monitoring epidemic outbreaks and assessing public opinion in non-English-speaking countries. We evaluated whether social media reflects social uneasiness and fear during epidemic outbreaks and natural catastrophes. Design Cross-sectional study. Setting Freely available epidemic data in Taiwan. Main outcome measure We used weekly epidemic incidence data obtained from the Taiwan Centers for Disease Control and online search query data obtained from Google Trends between 4 October 2015 and 2 April 2016. To validate whether non-English query keywords were useful surveillance tools, we estimated the correlation between online query data and epidemic incidence in Taiwan. Results With our approach, we noted that keywords (sic)& x5192; ('common cold'), & x767c;& x71d2; ('fever') and & x54b3;& x55fd; ('cough') exhibited good to excellent correlation between Google Trends query data and influenza incidence (r=0.898, p<0.001; r=0.773, p<0.001; r=0.796, p<0.001, respectively). They also displayed high correlation with influenza-like illness emergencies (r=0.900, p<0.001; r=0.802, p<0.001; r=0.886, p<0.001, respectively) and outpatient visits (r=0.889, p<0.001; r=0.791, p<0.001; r=0.870, p<0.001, respectively). We noted that the query & x8178;(sic)& x6bd2; ('enterovirus') exhibited excellent correlation with the number of enterovirus-infected patients in emergency departments (r=0.914, p<0.001). Conclusions These results suggested that Google Trends can be a good surveillance tool for epidemic outbreaks, even in Taiwan, the non-English-speaking country. Online search activity indicates that people are concerned about epidemic diseases, even if they do not visit hospitals. This prompted us to develop useful tools to monitor social media during an epidemic because such media usage reflects infectious disease trends more quickly than does traditional reporting.
Lipopolysaccharide-Induced Nitric Oxide, Prostaglandin E2, and Cytokine Production of Mouse and Human Macrophages Are Suppressed by Pheophytin-b
(2017-12-01)
Lin, Chun-Yu
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Wang, Wen-Hung
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Chen, Shin-Huei
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Chang, Yu-Wei
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Hung, Ling-Chien
Sepsis is an overwhelming systemic response to infection that frequently results in tissue damage, organ failure, and even death. Nitric oxide (NO), prostaglandin E2 (PGE2), and cytokine overproduction are thought to be associated with the immunostimulatory cascade in sepsis. In the present study, we analyzed the anti-inflammatory efficacy of the pheophytin-b on both RAW264.7 murine macrophage and purified human CD14(+) monocytes stimulated with lipopolysaccharide (LPS) and elucidated the mechanisms by analyzing the cell signaling pathways known to be activated in sepsis. Pheophytin-b suppressed the overexpression of NO, PGE2, and cytokines in LPS-stimulated macrophages without inducing cytotoxicity. It also reduced NOS2 and COX-2 mRNA and protein levels. The inhibitory effects on NO, PGE2, and cytokine overproduction arose from the suppression of STAT-1 and PI3K/Akt pathways; no changes in NF-kappa B, MAPK, and AP-1 signaling were detected. Thus, pheophytin-b may represent a potential candidate to beneficially modulate the inflammatory response in sepsis.
Lucidone suppresses dengue viral replication through the induction of heme oxygenase-1
(2018-01-01)
Chen, Wei-Chun
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Tseng, Chin-Kai
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Lin, Chun-Kuang
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Wang, Shen-Nien
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Wang, Wen-Hung
Dengue virus (DENV) infection causes life-threatening diseases such as dengue hemorrhagic fever and dengue shock syndrome. Currently, there is no effective therapeutic agent or vaccine against DENV infection; hence, there is an urgent need to discover anti-DENV agents. The potential therapeutic efficacy of lucidone was first evaluated in vivo using a DENV-infected Institute of Cancer Research (ICR) suckling mouse model by monitoring body weight, clinical score, survival rate, and viral titer. We found that lucidone effectively protected mice from DENV infection by sustaining survival rate and reducing viral titers in DENV-infected ICR suckling mice. Then, the anti-DENV activity of lucidone was confirmed by western blotting and quantitative-reverse-transcription-polymerase chain reaction analysis, with an EC50 value of 25 +/- 3 mu M. Lucidone significantly induced heme oxygenase-1 (HO-1) production against DENV replication by inhibiting DENV NS2B/3 protease activity to induce the DENV-suppressed antiviral interferon response. The inhibitory effect of lucidone on DENV replication was attenuated by silencing of HO-1 gene expression or blocking HO-1 activity. In addition, lucidone-stimulated nuclear factor erythroid 2-related factor 2 (Nrf2), which is involved in transactivation of HO-1 expression for its anti-DENV activity. Taken together, the mechanistic investigations revealed that lucidone exhibits significant anti-DENV activity in in vivo and in vitro by inducing Nrf2-mediated HO-1 expression, leading to blockage of viral protease activity to induce the anti-viral interferon (IFN) response. These results suggest that lucidone is a promising candidate for drug development.
Metformin is associated with a lower risk of active tuberculosis in patients with type 2 diabetes
(2018-11-01)
Lin, Shang-Yi
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Tu, Hung-Pin
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Lu, Po-Liang
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Chen, Tun-Chieh
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Wang, Wen-Hung
Background and objective Metformin is an oral anti-diabetic therapy (ADT) to manage type 2 diabetes mellitus (T2DM), and has been reported to have potential anti-tuberculosis (TB) effects. This study investigates the risk of active TB among persons with T2DM who were treated with various ADT and insulin therapies. MethodsResultsWe conducted a nationwide population-based cohort study using the Taiwan Longitudinal Health Insurance Database, including 49028 T2DM patients who were metformin users (n=44002) or non-users (n=5026). A total of 5026 propensity score-matched pairs of metformin users and non-users with T2DM were evaluated from 1998 to 2010. The data were analysed using Cox proportional hazard models. Patients with T2DM had a significantly higher rate of incident TB than did the control subjects (adjusted hazard ratio: 2.01; 95% confidence interval (95% CI): 1.80-2.25). After adjusting for comorbidities, diabetes complications, ADT type and statin use, metformin use was an independent factor for predicting a reduced risk of active TB (adjusted relative risk (aRR): 0.24; 95% CI: 0.18-0.32). The association between metformin use and active TB risk was also consistent in most subgroup analyses, except for patients with metabolic disorders (aRR: 0.46; 95% CI: 0.11-1.87). This protective effect of metformin was dose-dependent but diminished gradually in the elderly population. ConclusionAmong all types of ADT and insulin therapies, metformin is the only agent with a decreased risk of active TB in the T2DM population. However, this effect was diminished in the elderly population and was not observed in patients with metabolic disorders. See This retrospective, propensity score-matched cohort study demonstrated that the risk of active tuberculosis (TB) is higher in the type 2 diabetes mellitus population. However, the use of metformin is associated with a decreased risk of active TB in this population.
Shared IgG Infection Signatures vs. Hemorrhage-Restricted IgA Clusters in Human Dengue: A Phenotype of Differential Class-Switch via TGF beta 1
(2017-12-04)
Huang, Chung-Hao
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Chang, Ya-Hui
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Lin, Chun-Yu
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Wang, Wen-Hung
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Kuan, Hui-Chung
Phenotypic manifestations of infectious diseases are closely related to individual immune responses. Methods to extract information from patients' own immune reactions would be of great use for both diagnosis and treatment. Dengue fever is one of the diseases that clinical aggravations could occur paradoxically after humoral immunity appears. This property makes dengue fever an excellent disease model to explore. A principal component analyses (PCAs)-based framework derived from a prior vaccination study was developed. The framework was verified by successful demonstrations of known IgG signatures from a Mexico Dengue data set. Afterward the pipeline was tested upon de novo IgG and IgA libraries of Dengue patients from southern Taiwan. We discovered four infection signatures within IgG repertoires, two of which were identical to previous reports. However, it was IgA but not IgG that could differentiate hemorrhagic from non-hemorrhagic patients. IgA repertoires were found more diversified among bleeders, from whom seven signature clusters were characterized. The expressions of transforming growth factor beta 1 (TGF beta 1) and accordingly mediated class-switch activity of IgA were distinct only among the PCA-segregated bleeding group. In sum, intercontinental sharing of IgG signatures in dengue fever was demonstrated via a unified working flow. Differential regulation of IgA class-switch with associated diversity expansion plus existences of hemorrhage-restricted clusters were shown. The ability of the framework to find common IgG signatures would implicate applications to infections even from unknown pathogens. The clusters within IgA repertoires could offer perspectives to other IgA-related bleeding disorders such as Henoch-Schonlein purpura or IgA nephropathy. Substantiated grounds for IgA-specific effector function via TGF beta 1-mediated class-switch would be a new factor to consider for infectious diseases.
Tellimagrandin II, A Type of Plant Polyphenol Extracted from Trapa bispinosa Inhibits Antibiotic Resistance of Drug-Resistant Staphylococcus aureus
(2019-11-01)
Chang, Yu-Wei
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Huang, Wan-Chun
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Lin, Chun-Yu
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Wang, Wen-Hung
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Hung, Ling-Chien
The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become a critical global concern. Identifying new candidates of anti-S. aureus agents is urgently required because the therapeutic strategies for infected patients are limited currently. Therefore, the present study investigated whether Tellimagrandin II (TGII), a pure compound extracted from the shells of Trapa bispinosa, exhibits antibacterial effects against MRSA. We first showed that TGII exerted potent inhibitory activity against MRSA with a minimum inhibitory concentration of 128 mu g/mL. The obtained fractional inhibitory concentration suggested that TGII could alone exert antistaphylococcal activity, and TGII combined with low doses of antibiotics displayed synergistic effects against MRSA. Moreover, we found that TGII exerted bactericidal activity by reducing the expression of mecA followed by the negative regulation of the penicillin-binding protein 2a (PBP2a) of MRSA. Transmission electron microscopy (TEM) images further confirmed that TGII destroyed the integrity of the cell wall of MRSA and caused the loss of cytoplasm content. In conclusion, we evidenced the antibacterial effects of TGII against MRSA, which enables the effective dose of current antibiotics to be reduced and the predicament of drug-resistant S. aureus isolates to be overcome.