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Jin-Hee Kim,1,* Soon-Seok Hong,1,* Myoungsoo Lee,2 Eun-Hye Lee,1 Inmoo Rhee,1 Sun-Young Chang,2 Soo-Jeong Lim1 1Department of Integrated Bioscience and Biotechnology, Sejong University, Seoul 05006, Republic of Korea; 2Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Republic of Korea*These authors contributed equally to this workCorrespondence: Sun-Young ChangLaboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Republic of KoreaTel +82 31 219 3454Fax +82 31 219 3435Email sychang@ajou.ac.krSoo-Jeong LimDepartment of Integrated Bioscience and Biotechnology, Sejong University, 209 Neungdong-ro, Gwangjin-gu, Seoul 05006, Republic of KoreaTel +82 2 3408 3767Fax +82 2 3408 4334Email sjlim@sejong.ac.krBackground: Phosphatidylcholine (PC) and Omega-3 fatty acid (Omega-3) are promising therapeutic molecules for treating inflammatory bowel disease (IBD).Purpose: Based on the IBD therapeutic potential of nanoparticles, we herein sought to develop Omega-3-incorporated PC nanoparticles (liposomes) as an orally administrable vehicle for treating IBD.Methods: Liposomes prepared with or without Omega-3 incorporation were compared in terms of colloidal stability and anitiinflammatory effects.Results: The incorporation of free Omega-3 (alpha-linolenic acid, eicosapentaenoic acid or docosahexaenoic acid) into liposomes induced time-dependent membrane fusion, resulting in particle size increase from nm to μm during storage. In contrast, krill oil incorporation into liposomes (KO liposomes) did not induce the fusion and the particle size maintained

Yi-Chun Lin,1 Shih-Wei Li,2 Shin-Yen Ku,3 Hui-Ting Hsieh,3 Mei-Hui Lin,3 Shu-Yin Chang,3 Wei-Wei Wu,3 Na-Lee Sun,3 Shu-Hsing Cheng,1,4 Chien-Yu Cheng1,51Department of Internal Medicine, Division of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City, Taiwan; 2Division of Gastroenterology, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City, Taiwan; 3Comprehensive HIV Care Center, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan City, Taiwan; 4School of Public Health, Taipei Medical University, Taipei, Taiwan; 5School of Public Health, National Yang-Ming University, Taipei, TaiwanBackground and aims: We aimed to evaluate the efficacy and tolerability of grazoprevir/elbasvir in patients with chronic genotype 1 hepatitis C virus (HCV) and HIV co-infection who experienced peginterferon alfa plus ribavirin (PegIFN/RBV) (clinicaltrials.gov NCT03098121).Methods: This non-randomized, open-label trial study was conducted in Taoyuan General Hospital. HIV-infected patients were screened for HCV antibody since June 1, 2012, and HCV and HIV co-infected patients were tested for HCV RNA. The subjects who experienced PegIFN/RBV were enrolled in the study, and of whom with chronic genotype 1a or 1b received grazoprevir 100 mg and elbasvir 50 mg in a fixed-dose combination tablet once daily with or without ribavirin for 12 to 16 weeks.Results: Of 2,419 HIV-infected patients, 40 patients with chronic genotype 1 HCV and HIV co-infection who failed PegIFN/RBV treatment were enrolled. Sixteen patients had genotype 1a and 24 patients had genotype 1b, with or without cirrhosis. The median age was 42 (41–47) years, and 5 patients (12.5%) were diagnosed with liver cirrhosis (child Pugh score A). The median CD4 count was 504 cells/μL (321–689). All patients (100%) had HIV viral load 10 IU/mL (3.98–7.12). At the end of treatment, all patients (100%, 40/40) had undetectable HCV viral load, and 95.0% (38/40) of patients achieved sustained virologic response at 12 weeks.Conclusion: Grazoprevir/elbasvir was effective in genotype 1 patients co-infected with HIV with or without cirrhosis. This finding is consistent with that of previous trials of this regimen in monoinfected population.Keywords: hepatitis C, grazoprevir and elbasvir, PEGylated interferon plus ribavirin, direct-acting antiviral, HCV genotype 1, HCV/HIV co-infection

Chien-Yu Cheng,1,2 Mao-Song Tsai,3 Chia-Jui Yang,3,4 Shu-Hsing Cheng,1,5 Hsin-Yun Sun,6 Shu-Fang Chang,7 Li-Hsin Su,7 Yi-Ching Su,6 Chien-Ching Hung,6,8–10 Sui-Yuan Chang7,11 For the Taiwan HIV Study Group 1Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 2School of Public Health, National Yang-Ming University, Taipei, Taiwan; 3Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 4School of Medicine, National Yang-Ming University, Taipei, Taiwan; 5School of Public Health, Taipei Medical University, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; 7Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan; 8Department of Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan; 9Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 10China Medical University, Taichung, Taiwan; 11Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan Background: Increasing trends of resistance-associated mutations (RAMs) to non-nucleoside reverse-transcriptase inhibitors (nNRTIs) have raised concerns about the effectiveness of the regimens in the national HIV treatment programs in resource-limited countries. We aimed to retrospectively investigate the incidence and patterns of emergent RAMs of HIV-1 in HIV-positive adults experiencing virological failure to first-line nNRTI-containing combination antiretroviral therapy (cART) in Taiwan. Patients and methods: Between June 2012 and March 2016, 1138 antiretroviral-naïve HIV-positive adults without baseline RAMs who initiated nNRTI-containing regimens were included for analysis. Virological failure was defined as plasma viral load (PVL) ≥200 copies/mL after 6 months of cART or confirmed PVL ≥200 copies/mL after achieving PVL

Because of complex cellular microenvironments of both the liver and kidneys, accurate modeling of transport function has remained a challenge, leaving a dire need for models that can faithfully recapitulate both the architecture and cell-cell interactions observed in vivo. The study of hepatic and renal transport function is a fundamental component of understanding the metabolic fate of drugs and xenobiotics; however, there are few in vitro systems conducive for these types of studies. For both the hepatic and renal systems, we provide an overview of the location and function of the most significant phase I/II/III (transporter) of enzymes, and then review current in vitro systems for the suitability of a transporter function study and provide details on microphysiological systems that lead the field in these investigations. Microphysiological modeling of the liver and kidneys using 'organ-on-a-chip' technologies is rapidly advancing in transport function assessment and has emerged as a promising method to evaluate drug and xenobiotic metabolism. Future directions for the field are also discussed along with technical challenges encountered in complex multiple-organs-on-chips development. [ABSTRACT FROM AUTHOR]

Cytokines released by inflammatory cells around the pancreatic islets are implicated in the pathogenesis of diabetes mellitus. Specifically, interleukin-1β (IL-1β) is known to be involved in islet β-cell damage by activation of nuclear factor-κB (NF-κB)-mediated inducible nitric oxide synthase (iNOS) gene expression. Though most flavonoids are shown to have various beneficial effects, little is known about the anti-inflammatory effects of their metabolites. Therefore, we investigated the effects of quercetin and its metabolites quercetin 3'-sulfate, quercetin 3-glucuronide and isorhamnetin 3-glucuronide on IL-1β-stimulated iNOS gene expression in RINm5F β-cells. The nitrite level, iNOS protein and its mRNA expression levels and iNOS promoter activity were measured. In addition, IκBα protein phosphorylation, nuclear translocation of nuclear factor-κB (NF-κB) and NF-κB DNA binding activity were determined. Adenosine 5'-triphosphate disodium salt-induced insulin release was also measured. Quercetin significantly reduced IL-1β-induced nitrite production, iNOS protein and its mRNA expression levels, and it also inhibited IL-1β-induced IκBα phosphorylation, NF-κB activation and iNOS promoter activity. Additionally, quercetin significantly restored the inhibition of insulin secretion by IL-1β. Meanwhile, quercetin metabolites did not show any effect on IL-1β-induced iNOS gene expression and also on insulin secretion. Therefore, in terms of iNOS expression mechanism, dietary ingestion of quercetin is unlikely to show anti-inflammatory effects in rat islet β-cells exposed to IL-1β. [ABSTRACT FROM AUTHOR]

We investigated whether overexpression of catalase (CAT) in renal proximal tubular cells (RPTCs) could prevent the programming of hypertension and kidney disease in the offspring of dams with maternal diabetes. Male offspring of nondiabetic and diabetic dams from two transgenic (Tg) lines (Hoxb7-green fluorescent protein [GFP]-Tg [controls] and Hoxb7/CAT-GFP-Tg, which overexpress CAT in RPTCs) were studied from the prenatal period into adulthood. Nephrogenesis, systolic blood pressure, renal hyperfiltration, kidney injury, and reactive oxygen species (ROS) generation were assessed. Gene expression of transforming growth factor-β1 (TGF-β1), nuclear factor erythroid 2p45-related factor-2 (Nrf2), and heme oxygenase-1 (HO-1) was tested in both in vitro and in vivo studies. Renal dysmorphogenesis was observed in offspring of Hoxb7-GFP-Tg dams with severe maternal diabetes; the affected male offspring displayed higher renal ROS generation and developed hypertension and renal hyperfiltration as well as renal injury with heightened TGF-β1 expression in adulthood. These changes were ameliorated in male offspring of diabetic Hoxb7/CAT-GFP-Tg dams via the Nrf2-HO-1 defense system. CAT promoted Nrf2 nuclear translocation and HO-1 gene expression, seen in both in vitro and in vivo studies. In conclusion, CAT overexpression in the RPTCs ameliorated maternal diabetes-induced perinatal programming, mediated, at least in part, by triggering the Nrf2-HO-1 defense system. [ABSTRACT FROM AUTHOR]

We investigated the impact of heterogeneous nuclear ribonucleoprotein F (hnRNP F) overexpression on angiotensinogen (Agt) gene expression, hypertension, and renal proximal tubular cell (RPTC) injury in high-glucose milieu both in vivo and in vitro. Diabetic Akita transgenic (Tg) mice specifically overexpressing hnRNP F in their RPTCs were created, and the effects on systemic hypertension, Agt gene expression, renal hypertrophy, and interstitial fibrosis were studied. We also examined immortalized rat RPTCs stably transfected with control plasmid or plasmid containing hnRNP F cDNA in vitro. The results showed that hnRNP F overexpression attenuated systemic hypertension, suppressed Agt and transforming growth factor-β1 (TGF-β1) gene expression, and reduced urinary Agt and angiotensin II levels, renal hypertrophy, and glomerulotubular fibrosis in Akita hnRNP F-Tg mice. In vitro, hnRNP F overexpression prevented the high-glucose stimulation of Agt and TGF-β1 mRNA expression and cellular hypertrophy in RPTCs. These data suggest that hnRNP F plays a modulatory role and can ameliorate hypertension, renal hypertrophy, and interstitial fibrosis in diabetes. The underlying mechanism is mediated, at least in part, via the suppression of intrarenal Agt gene expression in vivo. hnRNP F may be a potential target in the treatment of hypertension and kidney injury in diabetes. [ABSTRACT FROM AUTHOR]

Background/purpose: Men who have sex with men (MSM) are at increased risk for hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections than the general population. Comparisons of the seroprevalence rates of these hepatitis viruses between HIV-positive and HIV-negative MSM are rarely performed in Taiwan.Methods: Between January 2009 and June 2010, data on the serologies for HAV, HBV, and HCV were collected from two groups of patients: HIV-negative MSM, aged 18-40 years, who sought voluntary counseling and testing (VCT) for HIV infection, and HIV-positive MSM of the same age group who sought HIV care at the National Taiwan University Hospital. Both groups of patients were also tested for syphilis.Results: During the 18-month study period, 690 HIV-negative MSM and 438 HIV-positive MSM were enrolled and tested for anti-HAV antibody, HBV surface antigen (HBsAg), hepatitis B core antibody (anti-HBc antibody), and anti-HCV antibody. HIV-positive MSM were older than HIV-negative MSM (30.5 ± 5.4 vs. 25.8 ± 4.7 years, p < 0.01). For HIV-positive MSM, the mean CD4 lymphocyte count was 477.6 ± 230.0 cells/μL and 46% of them had undetectable plasma HIV RNA load (< 40 copies/mL by reverse transcription-polymerase chain reaction assay). The overall seroprevalence rates of HAV, HBsAg, and HCV in HIV-positive MSM were 15.1%, 16.4%, and 5.5%, respectively, while in HIV-negative MSM, they were 7.4%, 6.2%, and 0.4%, respectively. In the multivariate analysis, age was significantly associated with seropositivity for HAV (OR [per one age group increase]: 1.96; 95% CI: 1.6-2.5), HBsAg (OR: 2.02; 95% CI: 1.6-2.6), anti-HBc (OR: 2.68; 95% CI: 2.3-3.2), anti-HCV (OR: 1.67; 95% CI: 1.0-2.7), and anti-HBs (OR: 1.25; 95% CI: 1.0-1.5). HIV infection was associated with seropositivity for HBsAg (OR: 1.73; 95% CI: 1.1-2.7), anti-HBc (OR: 2.44; 95% CI: 1.8-3.3), HCV (OR: 8.91; 95% CI: 2.5-31.4), and syphilis (OR: 11.21; 95% CI: 6.7-18.9).Conclusion: HIV-positive MSM have a higher seroprevalence rate of HBV and HCV infection than HIV-negative MSM in Taiwan. Vaccination and safe-sex counseling should be provided to prevent the transmission of hepatitis viruses among MSM who may be engaged in high-risk behaviors. [ABSTRACT FROM AUTHOR]

Rationale: Accurate, early identification of patients at risk for developing acute lung injury (ALI) provides the opportunity to test and implement secondary prevention strategies.Objectives: To determine the frequency and outcome of ALI development in patients at risk and validate a lung injury prediction score (LIPS).Methods: In this prospective multicenter observational cohort study, predisposing conditions and risk modifiers predictive of ALI development were identified from routine clinical data available during initial evaluation. The discrimination of the model was assessed with area under receiver operating curve (AUC). The risk of death from ALI was determined after adjustment for severity of illness and predisposing conditions.Measurements and Main Results: Twenty-two hospitals enrolled 5,584 patients at risk. ALI developed a median of 2 (interquartile range 1-4) days after initial evaluation in 377 (6.8%; 148 ALI-only, 229 adult respiratory distress syndrome) patients. The frequency of ALI varied according to predisposing conditions (from 3% in pancreatitis to 26% after smoke inhalation). LIPS discriminated patients who developed ALI from those who did not with an AUC of 0.80 (95% confidence interval, 0.78-0.82). When adjusted for severity of illness and predisposing conditions, development of ALI increased the risk of in-hospital death (odds ratio, 4.1; 95% confidence interval, 2.9-5.7).Conclusions: ALI occurrence varies according to predisposing conditions and carries an independently poor prognosis. Using routinely available clinical data, LIPS identifies patients at high risk for ALI early in the course of their illness. This model will alert clinicians about the risk of ALI and facilitate testing and implementation of ALI prevention strategies. Clinical trial registered with www.clinicaltrials.gov (NCT00889772). [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to identify the causes of prolonged facial edema and its associations with other clinical factors. Facial edema sometimes is observed in patients with head and neck squamous cell carcinoma (HNSCC), but its prevalence and association with other factors is unclear.Methods: Between July 2003 and July 2007, the medical records from 264 patients with HNSCC were reviewed. Prolonged facial edema is defined as persistence of edematous status (largest thickness >5 mm by CT scan) for more than 100 days. Clinical data including age, gender, tumor stage, and tumor primary sites were recorded. Statistical analyses were performed to determine the prognostic effect of prolonged facial edema, as well as its relationship to other clinical variables. The etiology of prolonged facial edema was also analyzed.Results: Prolonged facial edema occurred in 32 (12.1%) patients. The etiologies included internal jugular vein thrombosis, local infection, neck lymph nodes dissection, flap reconstruction, and direct vessel compression by tumors or metastatic lymph nodes. There was no significant difference in the incidence of prolonged facial edema in patients receiving different treatment modalities; however, patients receiving neck dissection correlated with the occurrence of late-onset facial edema. In addition to previously demonstrated prognostic factors (T status, nodal involvement and distant metastasis), prolonged facial edema was also identified as independent prognostic indicators for HNSCC patients (P = 0.001).Conclusions: Prolonged facial edema may reflect the underlying disease status, and it can be applied as a prognostic marker in patients with HNSCC. [ABSTRACT FROM AUTHOR]

T cell recognition of common and type-specific herpes simplex virus (HSV) glycoproteins was measured in 72 subjects. T cells were stimulated with whole HSV-2 antigen and glycoproteins gB2, gD2, and gG2. T cell proliferation in response to HSV-2 antigen and gG2 was significantly higher in subjects with HSV-2 infection than in those with HSV-1 infection only; responses to gB2 and gD2 were the same. T helper (Th) type 1 and Th2 cytokine production in response to whole HSV-2 antigen, gB2, and gD2 was evaluated in 33 subjects. Interleukin (IL)-2 and interferon-gamma responses to most antigens were significantly higher among HSV-2-seropositive subjects than among seronegative subjects. IL-4 synthesis was negligible; IL-10 was produced in seronegative and seropositive persons, but HSV-2 antigen responses were significantly higher in HSV-2-seropositive persons. Naturally acquired immunity to HSV involves T cell recognition of common and type-specific glycoproteins, prominent Th1 responses, and discordant Th2 responses with little IL-4 but substantial IL-10 production. [ABSTRACT FROM AUTHOR]