We investigated in vitro and in vivo glutathione (GSH)-induced intracellular thiopurine anticancer drug release on gold nanoparticle (Au NP) surfaces by means of label-free confocal Raman spectroscopy. Direct monitoring of GSH-triggered release of 6-mercaptopurine (6MP) and 6-thioguanine (6TG) was achieved in real time. Live cell imaging technique provides a nanomolar range release of 6MP and 6TG from Au NP surfaces after the injection of external GSH. In vivo SERS spectra of 6TG were obtained from the subcutaneous sites in living mice after GSH treatment. GSH-triggered releases of Cy5-dye assembled on 6TG-capped Au NPs were also compared using independent fluorescence measurements. Our work demonstrates that the time-lapse Raman spectroscopic tools are useful for monitoring of the controlled release of thiopurine drug molecules in vitro and in vivo.

Neonates with this distinctive DWI pattern had a high positive rate of rotavirus infection, without evidence of other pathogens, and were characterized as term newborns with neurologic symptoms arising approximately the fifth day after birth. Although the specificity of this pattern is unclear, rotavirus testing should be considered for neonates presenting with this DWI pattern.

Oxidant-sensitive transcription factors, nuclear factor-kappaB (NF-kappaB), and activator protein-1 (AP-1) have been considered as the regulators of inducible genes such as chemokines. Since oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis, chemokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) may be regulated by NF-kappaB and/or AP-1. Ras, the upstream activator for mitogen-activated protein kinase (MAPK) and MAPK cascade regulate AP-1 activation. The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of chemokines (IL-8, MCP-1), which is regulated by Ras, MAPK, AP-1, and NF-kappaB in gastric epithelial AGS cells, and whether these transcriptional regulations of chemokines are inhibited by transfection with mutant genes for Ras (ras N-17), c-Jun (TAM-67), and IkappaBalpha (MAD-3) or treatment with MAPK inhibitors (U0126 for extracellular signal-regulated kinase or SB203580 for p38 kinase). In addition, virulence factors of HP99 were characterized by PCR analysis for the isolated DNA. As a result, HP99 is identified as cagA+, vacA s1b, m2, iceA1 H. pylori strain. HP99 induced a time-dependent expression of mRNA and protein for IL-8 and MCP-1 via mediation of MAPK, AP-1, and NF-kappaB. Transfection with mutant genes for Ras, c-Jun, and IkappaBalpha and treatment with MAPK inhibitors suppressed H. pylori-induced activation of transcription factors (NF-kappaB, AP-1) and expression of chemokines (IL-8, MCP-1) in AGS cells. In conclusion, Ras and MAPK cascade may act as the upstream signaling for the activation of AP-1 and NF-kappaB, which induce chemokine expression in H. pylori-infected AGS cells. Specific targeting of the activation of NF-kappaB and AP-1 may be effective for the prevention or treatment of gastric inflammation associated with H. pylori infection.

Background/AimsFunctional dyspepsia (FD) is one of the most common gastrointestinal disorders, and FD imposes social and economic burden worldwide. The aim of this study is to identify the prevalence and risk factors of FD in health check-up population in tertiary centers in Korea.MethodsA nationwide multicenter prospective study was performed at 9 tertiary healthcare centers in Korea between September 2016 and June 2017. A total of 2525 subjects were investigated based on endoscopic findings and questionnaires with the Rome III criteria, and Helicobacter pylori serology (IgG).ResultsA total of 1714 subjects without organic disease were enrolled. The mean (± SD) age was 51.5 (± 12.7) years, and 917 patients (53.5%) were female. The proportion of H. pylori seropositivity was 51.0% (874/1714). The prevalence of FD was 10.3% (176/1714), and the subtypes of postprandial distress syndrome alone, epigastric pain syndrome alone, and postprandial distress syndrome-epigastric pain syndrome overlap were 4.8%, 3.0%, and 2.5%, respectively. Multivariate analysis showed that female gender (OR, 1.58; 95% CI, 1.14–2.21) and education below college level (OR, 1.45; 95% CI, 1.01–2.07) were related to FD. Multivariate analysis based on age 60 showed female gender as a significant (OR, 2.90; 95% CI, 1.06–7.94) factor in the group ≥60 years.ConclusionsThe prevalence of FD was 10.3% in the health check-up population in Korea. Female sex and education below college level were risk factors for FD. Female sex is a risk factor for FD in old age, underscoring the need for close attention in this age group.

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Summary Reactive oxygen species (ROS) including hydrogen peroxide (H 2 O 2 ) are involved in the pathogenesis of gastric inflammation. Interleukin-8 (IL-8) is a potent mediator of the inflammatory response by activating and recruiting neutrophils to the site of infection. Oxidant-sensitive transcription factor NF-B regulates the expression of IL-8 in the immune and inflammatory events. Carotenoids (carotenes and oxygenated carotenoids) show antioxidant and anti-inflammatory activities. Low intake of ␤ -carotene leads to high risk of gastric cancer. Oxygenated carotenoid lutein inhibited NF-B activation in experimental uveitis. The present study aims to investigate whether ␤ -carotene and lutein inhibit H 2 O 2 -induced activation of NF-B and expression of IL-8 in gastric epithelial AGS cells. The cells were treated with carotenoids 2 h prior to the treatment of H 2 O 2 . mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR analyses. IL-8 level in the medium was determined by enzyme-linked immunosorbent assay. NF-B activation was assessed by electrophoretic mobility shift assay. ROS levels of the cells were detected by confocal microscopic analysis for fluorescent dichlorofluorescein. As a result, H 2 O 2 induced the activation of NF-B and expression of IL-8 in AGS cells time-dependently. ␤ -Carotene and lutein showed inhibitory effects on H 2 O 2 -induced increase in intracellular ROS levels, activation of NF-B, and IL-8 expression in AGS cells. In conclusion, supplementation of carotenoids such as ␤ -carotene and lutein may be beneficial for the treatment of oxidative stress-mediated gastric inflammation.

The reported effects of a metabolically healthy obese (MHO) phenotype on diabetes and cardiovascular disease (CVD) risk are contradictory. Within the context of a population-based cohort study, we aimed to investigate the long-term risk of an MHO status for the development of diabetes and CVD, and whether consistency of this phenotype or age affected cardiometabolic outcomes.We recruited 7588 subjects without diabetes or CVD, aged 40 to 69 years at baseline examination, from the Korean Genome and Epidemiology Study, and followed-up these subjects for 10 years biennially. Participants were divided into 4 groups based on the body mass index and the presence of metabolic syndrome: metabolically healthy normal weight (MHNW), MHO, metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obese (MUO). We defined persistent phenotypes if subjects maintained the same phenotype at every visit from baseline to their last visit. Incident diabetes and CVD morbidity or mortality were identified during 10 years of follow-up.Compared to MHNW controls, MUNW and MUO groups had increased risk for development of diabetes (hazard ratio [HR] 3.0 [95% CI: 2.5–3.6], and 4.0 [3.4–4.7], respectively) and CVD (HR 1.6 [1.3–2.0], and 1.9 [1.5–2.4], respectively). However, the MHO group showed only a marginal increase in risk for diabetes and CVD (HR 1.2 [0.99–1.6], 1.4 [0.99–1.8], respectively). The impact of MHO on the development of diabetes was more prominent in younger individuals (HR 1.9 [1.2–3.1] vs 1.1 [0.8–1.4], <45 years vs ≥45 years at baseline). Only 15.8% of MHO subjects maintained the MHO phenotype at every visit from baseline to the 5th biennial examination (persistent MHO). In subjects with persistent MHO, the risk for diabetes and CVD was significantly higher than those with persistent MHNW (1.9 [1.2–3.1], 2.1 [1.2–3.7], respectively).MHO phenotype, even if maintained for a long time, was associated with a significantly higher risk for the development of diabetes and CVD in Korean subjects.

Oxidant-sensitive transcription factors, nuclear factor-jB (NF-jB), and activator protein-1 (AP-1) have been considered as the regulators of inducible genes such as chemokines. Since oxygen radicals are considered as an important regulator in the pathogenesis of Helicobacter pylori (H. pylori)-induced gastric ulceration and carcinogenesis, chemokines such as interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) may be regulated by NF-jB and/or AP-1. Ras, the upstream activator for mitogen-activated protein kinase (MAPK) and MAPK cascade regulate AP-1 activation. The present study aims to investigate whether H. pylori in a Korean isolate (HP99) induces the expression of chemokines (IL-8, MCP-1), which is regulated by Ras, MAPK, AP-1, and NF-jB in gastric epithelial AGS cells, and whether these transcriptional regulations of chemokines are inhibited by transfection with mutant genes for Ras (ras N-17), c-Jun (TAM-67), and IjBa (MAD-3) or treatment with MAPK inhibitors (U0126 for extracellular signal-regulated kinase or SB203580 for p38 kinase). In addition, virulence factors of HP99 were characterized by PCR analysis for the isolated DNA. As a result, HP99 is identified as cagA þ , vacA s1b, m2, iceA1 H. pylori strain. HP99 induced a time-dependent expression of mRNA and protein for IL-8 and MCP-1 via mediation of MAPK, AP-1, and NF-jB. Transfection with mutant genes for Ras, c-Jun, and IjBa and treatment with MAPK inhibitors suppressed H. pylori-induced activation of transcription factors (NF-jB, AP-1) and expression of chemokines (IL-8, MCP-1) in AGS cells. In conclusion, Ras and MAPK cascade may act as the upstream signaling for the activation of AP-1 and NF-jB, which induce chemokine expression in H. pylori-infected AGS cells. Specific targeting of the activation of NF-jB and AP-1 may be effective for the prevention or treatment of gastric inflammation associated with H. pylori infection.