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Kim, Hyun-Ah,Yeo, Yunshin,Jung, Hyun A,Jung, Young O,Park, Su J,Kim, Song J Oxford University Press ; Distributed by Mercury I 2012 Rheumatology Vol.51 No.6
<P>We explored the inhibitory effect of sulphoraphane (SFN), a potent inducer of Phase 2 enzymes, on cytokine-induced prostaglandin E(2) (PGE2) and nitric oxide (NO) production and cartilage degradation in articular chondrocytes. The regulatory mechanism of SFN on nuclear factor (NF)-κB was investigated.</P>
Lee Jin Wook,Gu Hyun-Oh,Jung Yunshin,Jung YunJae,Seo Seung-Yong,Hong Jeong-Hee,Hong In-Sun,Lee Dae Ho,Kim Ok-Hee,Oh Byung-Chul 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Insulin resistance is a major contributor to the pathogenesis of several human diseases, including type 2 diabetes, hypertension, and hyperlipidemia. Notably, insulin resistance and hypertension share common abnormalities, including increased oxidative stress, inflammation, and organelle dysfunction. Recently, we showed that excess intracellular Ca2+, a known pathogenic factor in hypertension, acts as a critical negative regulator of insulin signaling by forming Ca2+-phosphoinositides that prevent the membrane localization of AKT, a key serine/threonine kinase signaling molecule. Whether preventing intracellular Ca2+ overload improves insulin sensitivity, however, has not yet been investigated. Here, we show that the antihypertensive agent candesartan, compared with other angiotensin-II receptor blockers, has previously unrecognized beneficial effects on attenuating insulin resistance. We found that candesartan markedly reduced palmitic acid (PA)-induced intracellular Ca2+ overload and lipid accumulation by normalizing dysregulated store-operated channel (SOC)-mediated Ca2+ entry into cells, which alleviated PA-induced insulin resistance by promoting insulin-stimulated AKT membrane localization and increased the phosphorylation of AKT and its downstream substrates. As pharmacological approaches to attenuate intracellular Ca2+ overload in vivo, administering candesartan to obese mice successfully decreased insulin resistance, hepatic steatosis, dyslipidemia, and tissue inflammation by inhibiting dysregulated SOC-mediated Ca2+ entry and ectopic lipid accumulation. The resulting alterations in the phosphorylation of key signaling molecules consequently alleviate impaired insulin signaling by increasing the postprandial membrane localization and phosphorylation of AKT. Thus, our findings provide robust evidence for the pleiotropic contribution of intracellular Ca2+ overload in the pathogenesis of insulin resistance and suggest that there are viable approved drugs that can be repurposed for the treatment of insulin resistance and hypertension.
Segmental hair analysis and estimation of methamphetamine use pattern.
Han, Eunyoung,Yang, Heejin,Seol, Ilung,Park, Yunshin,Lee, Bongwoo,Song, Joon Myong Springer International ; Springer 2013 International journal of legal medicine Vol.127 No.2
<P>The aim of this study was to investigate whether the results of segmental hair analysis can be used to estimate patterns of methamphetamine (MA) use. Segmental hair analysis for MA and amphetamine (AP) was performed. Hair was cut into the hair root, consecutive 1?cm length segments and 1-4?cm length segments. Whole hair was also analyzed. The hair samples were incubated for 20?h in 1?mL methanol containing 1?% hydrochloric acid after washing the hair samples. Hair extracts were evaporated and derivatization was performed using trifluoroacetic anhydride in ethylacetate at 65?C for 30?min. Derivatized extract was analyzed by gas chromatography/mass spectrometry. The 15 subjects consisted of 13 males and two females and their ages ranged from 25 to 42 (mean, 32). MA and AP concentrations in the whole hair ranged from 3.00 to 105.10?ng/mg (mean, 34.53) and from 0.05 to 4.76?ng/mg (mean, 2.42), respectively. Based on the analysis of the 1?cm length segmental hair, the results were interpreted in a way to distinguish between continuous use of MA (n?=?10), no recent but previous use of MA (n?=?3), and recent but no previous use of MA (n?=?2). Furthermore, the individuals were interpreted as light, moderate, and heavy users based on concentration ranges previously published.</P>