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      • Role of acid responsive genes in the susceptibility of <i>Escherichia coli</i> to ciclopirox

        Shin, Jonghoon,Cho, Hyejin,Kim, Suran,Kim, Kwang-sun Elsevier 2018 Biochemical and biophysical research communication Vol.500 No.2

        <P><B>Abstract</B></P> <P>Antibiotic resistance poses a huge threat to the effective treatment of bacterial infections. To circumvent the limitations in developing new antibiotics, researchers are attempting to repurpose pre-developed drugs that are known to be safe. Ciclopirox, an off-patent antifungal agent, inhibits the growth of Gram-negative bacteria, and genes involved in galactose metabolism and lipopolysaccharide (LPS) biosynthesis are plausible antibacterial targets for ciclopirox, since their expression levels partially increase susceptibility at restrictive concentrations. In the present study, to identify new target genes involved in the susceptibility of <I>Escherichia coli</I> to ciclopirox, genome-wide mRNA profiling was performed following ciclopirox addition at sublethal concentrations, and glutamate-dependent acid resistance (GDAR) genes were differentially regulated. Additional susceptibility testing, growth analyses and viability assays of GDAR regulatory genes revealed that down-regulation of <I>evgS</I> or <I>hns</I> strongly enhanced susceptibility to ciclopirox. Further microscopy and phenotypic analyses revealed that down-regulation of these genes increased cell size and decreased motility. Our findings could help to maximise the efficacy of ciclopirox against hard-to-treat Gram-negative pathogens.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Ciclopirox antibacterial activity was analysed by genome-wide expression profiling. </LI> <LI> Ciclopirox affects expression of glutamate-dependent acid resistance pathway genes. </LI> <LI> Down-regulation of <I>hns</I> transcription likely increases ciclopirox activity. </LI> <LI> Susceptibility to ciclopirox accompanies increased cell size and decreased motility. </LI> <LI> The findings identify probable pathways for ciclopirox action against <I>E. coli</I>. </LI> </UL> </P>

      • SCOPUSKCI등재

        Immunogenicity and safety of a 12-valent pneumococcal conjugate vaccine in infants aged 6-10 weeks: a randomized double-blind active-controlled trial

        Shin, Jonghoon,Teeratakulpisarn, Jamaree,Puthanakit, Thanyawee,Theerawit, Tuangtip,Ryu, Ji Hwa,Shin, Jinhwan,Lee, Seulgi,Lee, Hayoung,An, Kyungjun,Kim, Hun The Korean Pediatric Society 2020 Clinical and Experimental Pediatrics (CEP) Vol.63 No.7

        Background: Pneumococcal diseases among children aged <5 years worldwide are associated with high annual mortality rates. Purpose: This study aimed to evaluate the immunogenicity and safety of GBP411, a 12-valent pneumococcal conjugant vaccine, with a dosing schedule of 2 primary doses plus 1 booster dose (2p+1) in healthy infants. Methods: This randomized active-controlled (Prevnar 13) double-blind phase 2 trial enrolled healthy subjects aged 6-10 weeks. Three serum concentrations of pneumococcal serotype-specific immunoglobulin G (IgG) were evaluated using the pneumococcal serotype-specific pneumonia polysaccharide enzyme-linked immunosorbent assay at 1 month after the primary doses and before and 1 month after the booster dose. The pneumococcal serotype-specific IgG titer was evaluated using a multiplex opsonophagocytic assay in a subset of 15 subjects per group. Results: After administration of the primary doses, the proportion of subjects who achieved pneumococcal serotype-specific IgG concentrations of >0.35 ㎍/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P<0.001). However, after administration of the booster dose, >97% of the subjects in each group achieved IgG concentrations of ≥0.35 ㎍/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003). Conclusion: The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.

      • The multi-faceted potential of plant-derived metabolites as antimicrobial agents against multidrug-resistant pathogens

        Shin, Jonghoon,Prabhakaran, Vasantha-Srinivasan,Kim, Kwang-sun Elsevier 2018 Microbial pathogenesis Vol.116 No.-

        <P><B>Abstract</B></P> <P>Multidrug-resistant (MDR) pathogens are currently causing serious problems globally in the medical setting. Improper and extensive usage of antibiotics results in a selective pressure supporting the rise of antibiotic-resistant microbes. Many key cellular bacterial components, including enzymes and small noncoding RNAs (sRNAs), and their involvement in MDR have been well studied, but exploiting such components in eradicating these pathogens requires further study. Delineation of many mechanisms that underpin the known MDR pathways necessitates urgent development of new specific strategies to control the rise of MDR pathogens. Botanical derivatives are comparatively safer than currently used antibiotics and exert multiple therapeutic benefits associated with their high efficacy. Numerous plant-derived compounds display synergistic activity with antibiotics against many MDR pathogens. Such plant derivatives include alkaloids, flavonoids, terpenoids, and tannins. A synthetic biological approach, e.g., metabolic engineering of secondary metabolites, can be utilized to exploit the natural metabolic pathways against MDR microbes. In this review, we focused on the major threats of antibiotic resistance, and the utilization of plant-derived compounds as alternative therapeutic agents to limit the rise of MDR pathogens.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Surge in microbial antibiotic resistance linked to antibiotic misuse is reviewed. </LI> <LI> Major antibiotic resistance mechanisms, and the role of sRNAs, are highlighted. </LI> <LI> Novel plant-derived phytochemicals with antimicrobial properties are summarized. </LI> <LI> Current metabolite engineering of phytochemicals against MDR microbes is discussed. </LI> <LI> Synergy of phytochemicals with multiple available antibiotics is appraised. </LI> </UL> </P>

      • KCI등재
      • Ligand-Controlled Direct Hydroformylation of Trisubstituted Olefins

        Shin, Taeil,Kim, Hyungsoo,Kim, Sungmin,Lee, Ansoo,Seo, Min-Seob,Choi, Jonghoon,Kim, Hyungjun,Kim, Hyunwoo American Chemical Society 2019 Organic letters Vol.21 No.15

        <P>The direct hydroformylation of trisubstituted olefins has been achieved with a combination of a Rh(I) catalyst and a π-acceptor phosphorus (briphos) ligand. A sterically bulky briphos ligand with a large cone angle that forms a 1:1 complex with Rh(I) is found to be reactive for the hydroformylation of trisubstituted olefins. The aldehyde products were obtained with high diastereoselectivity (>99:1) and regioselectivity (49%-81%).</P> [FIG OMISSION]</BR>

      • SCIESCOPUS

        Stable Configuration of a Li-Ion Series Battery Pack Based on a Screening Process for Improved Voltage/SOC Balancing

        Jonghoon Kim,Jongwon Shin,Changyoon Chun,Cho, B. H. IEEE 2012 IEEE transactions on power electronics Vol.27 No.1

        <P>Differences in electrochemical characteristics among Li-ion cells inevitably result in state-of-charge (SOC) imbalance when the existing voltage balancing technique is used. This paper presents a new approach based on a screening process for improved voltage/SOC balancing of a Li-ion series battery pack. Two kinds of screening processes, capacity screening and resistance screening, are implemented in an orderly manner. The capacity screening process matches open-circuit voltage (OCV)-SOC relation for achievement of voltage/SOC balancing. In the resistance screening process, pulse-type discharging/charging currents are applied to various SOC points to select the cells with similar voltage variance. Through two screening processes, the cells that have similar electrochemical characteristics are finally selected, and can be used for stable configuration of a Li-ion series battery pack. The proposed screening process has been validated by extensive experimental results and SOC estimation results based on extended Kalman filter.</P>

      • KCI등재

        Comparative analysis of energy intake and physical activity according to household type and presence of metabolic syndrome in middle-aged men based on data from the 7<sup>th</sup> Korea national health and nutrition examination survey (KNHANES) (2016-2018)

        ( Jonghoon Park ),( Yeonhee Park ),( Youngjun Lee ),( Jungwoo Lee ),( Seunghee Lee ),( Chulho Shin ),( Eun-sook Sung ) 한국운동영양학회 2021 Physical Activity and Nutrition (Phys Act Nutr) Vol.25 No.4

        [Purpose] This study analyzed data from the 7<sup>th</sup> Korean National Health and Nutrition Examination Survey (2016-2018) to compare the differences in energy intake and physical activity (PA) levels in middle-aged Korean men aged 40-59 years according to household type and the presence of metabolic syndrome (MetS). [Methods] Data from 2,266 young adults (aged >39 years and <60 years) were obtained from the KNHANES. We analyzed the differences in energy intake and PA levels according to household type and MetS. The presence or absence of MetS was determined by measuring waist circumference, blood pressure, fasting blood glucose, triglyceride, and HDL-C levels. [Results] Regarding total nutritional intake, no relationship with MetS was observed regardless of household type (interaction between MetS and household type: p = 0.875). No differences in total PA were observed between multiple- and single-person households (interaction between MetS and household type: p = 0.122). The relationship between MetS and MetS components according to nutritional intake showed that participants with a higher energy intake had a 27% lower prevalence of low high-density lipoprotein cholesterol (HDL-C) (p < 0.05) and a 36% higher prevalence of high blood pressure (p < 0.01). The relationship between MetS and MetS components according to the PA level showed significantly reduced prevalence of MetS by approximately 39%, 35%, and 43% (p < 0.01, 0.01, and 0.001) in subjects who were somewhat active, active, and very active, respectively, compared to inactivity. [Conclusion] Middle-aged men showed no difference in nutritional intake and PA between multiple- and single- person households. However, the risk of MetS was significantly higher in participants with approximately 1.5 times the energy intake compared to the group with the lowest energy intake. Moreover, higher levels of PA had a marked positive effect on the risk factors and prevalence of MetS. Therefore, we suggest that reducing the total energy intake and increasing total PA are important for preventing MetS in middle-aged men regardless of household type.

      • Gravity Applied Particle Separation in Nanoliter Volume Fluid System Toward Complexed Biosample Sorting

        Shin, Soojeong,Choi, Seri,Kim, Subin,Kim, Yuna,Park, Kyunglee,Choi, Jonghoon,Hong, Jong Wook American Scientific Publishers 2016 Journal of Nanoscience and Nanotechnology Vol.16 No.11

        <P>The separation of target molecules from complexed biosamples such as blood is essential for both biochemical understanding and pathological decision-making. As an alternative to conventional centrifugation, which has critical disadvantages, we suggest microgravitational particle separation under mild conditions to prevent distortion, lysis, and the breakage of biological particles. Polymer particles with similar sizes and different densities were used as models. We determined the optimum operating conditions, including the concentration of a sucrose solution and flow rate, based on Stokes law. A separation efficiency of more than 95% showed the potential of the designed microsystems for complexed biosample sorting.</P>

      • The polyherbal drug GGEx18 from <i>Laminaria japonica, Rheum palmatum</i>, and <i>Ephedra sinica</i> inhibits hepatic steatosis and fibroinflammtion in high-fat diet-induced obese mice

        Lim, Jonghoon,Lee, Haerim,Ahn, Jiwon,Kim, Jeongjun,Jang, Joonseong,Park, Yonghyun,Jeong, Birang,Yang, Heejung,Shin, Soon Shik,Yoon, Michung Elsevier 2018 Journal of Ethnopharmacology Vol.225 No.-

        <P><B>Abstract</B></P> <P><B>Ethnopharmacological relevance</B></P> <P>The herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of <I>Rheum palmatum</I> L. (Polygonaceae), <I>Laminaria japonica</I> Aresch (Laminariaceae), and <I>Ephedra sinica</I> Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally been reported to inhibit obesity and related metabolic diseases such as insulin resistance and dyslipidemia.</P> <P><B>Objective</B></P> <P>This study investigated the effects of GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet (HFD) and the underlying cellular and molecular mechanisms involved.</P> <P><B>Methods</B></P> <P>C57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13 weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were performed to assess NAFLD development in these mice.</P> <P><B>Results</B></P> <P>Mice fed an HFD had increases in body weight, epididymal adipose tissue mass, adipocyte size, and adipose expression of inflammation-related genes compared with those fed an LFD. These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18 without affecting food consumption profiles. GGEx18 not only decreased serum levels of triglycerides, free fatty acids, and alanine aminotransferase, but also decreased hepatic lipid accumulation, numbers of mast cells and α-smooth muscle actin-positive cells, and collagen levels induced by an HFD. Consistent with the histological data, the hepatic expression of lipogenesis-, inflammation-, and fibrosis-related genes was lower, while hepatic fatty acid β-oxidation-related gene expression was higher, in mice receiving GGEx18 compared to mice fed only the HFD.</P> <P><B>Discussion and conclusion</B></P> <P>These results indicate that GGEx18 attenuates visceral obesity and NAFLD, in part by altering the expression of genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese mice. These findings suggest that GGEx18 may be effective for preventing and treating NAFLD associated with visceral obesity.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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