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      • SCISCIESCOPUS

        The hydrogen peroxide hypersensitivity of OxyR2 in <i>Vibrio vulnificus</i> depends on conformational constraints

        Jo, Inseong,Kim, Dukyun,Bang, Ye-Ji,Ahn, Jinsook,Choi, Sang Ho,Ha, Nam-Chul American Society for Biochemistry and Molecular Bi 2017 The Journal of biological chemistry Vol.292 No.17

        <P>Most Gram-negative bacteria respond to excessive levels of H2O2 using the peroxide-sensing transcriptional regulator OxyR, which can induce the expression of antioxidant genes to restore normality. Vibrio vulnificus has two distinct OxyRs (OxyR1 and OxyR2), which are sensitive to different levels of H2O2 and induce expression of two different peroxidases, Prx1 and Prx2. Although OxyR1 has both high sequence similarity and H2O2 sensitivity comparable with that of other OxyR proteins, OxyR2 exhibits limited sequence similarity and is more sensitive to H2O2. To investigate the basis for this difference, we determined crystal structures and carried out biochemical analyses of OxyR2. The determined structure of OxyR2 revealed a flipped conformation of the peptide bond before Glu-204, a position occupied by glycine in other OxyR proteins. Activity assays showed that the sensitivity to H2O2 was reduced to the level of other OxyR proteins by the E204G mutation. We solved the structure of the OxyR2-E204G mutant with the same packing environment. The structure of the mutant revealed a dual conformation of the peptide bond before Gly-204, indicating the structural flexibility of the region. This structural duality extended to the backbone atoms of Gly-204 and the imidazole ring of His-205, which interact with H2O2 and invariant water molecules near the peroxidatic cysteine, respectively. Structural comparison suggests that Glu-204 in OxyR2 provides rigidity to the region that is important in H2O2 sensing, compared with the E204G structure or other OxyR proteins. Our findings provide a structural basis for the higher sensitivity of OxyR2 to H2O2 and also suggest a molecular mechanism for bacterial regulation of expression of antioxidant genes at divergent concentrations of cellular H2O2.</P>

      • SCISCIESCOPUS

        OxyR2 Functions as a Three-state Redox Switch to Tightly Regulate Production of Prx2, a Peroxiredoxin of <i>Vibrio vulnificus</i>

        Bang, Ye-Ji,Lee, Zee-Won,Kim, Dukyun,Jo, Inseong,Ha, Nam-Chul,Choi, Sang Ho American Society for Biochemistry and Molecular Bi 2016 The Journal of biological chemistry Vol.291 No.31

        <P>The bacterial transcriptional regulator OxyR is known to function as a two-state redox switch. OxyR senses cellular levels of H2O2 via a 'sensing cysteine' that switches from the reduced to a disulfide state upon H2O2 exposure, inducing the expression of antioxidant genes. The reduced and disulfide states of OxyR, respectively, bind to extended and compact regions of DNA, where the reduced state blocks and the oxidized state allows transcription and further induces target gene expression by interacting with RNA polymerase. Vibrio vulnificus OxyR2 senses H2O2 with high sensitivity and induces the gene encoding the antioxidant Prx2. In this study, we used mass spectrometry to identify a third redox state of OxyR2, in which the sensing cysteine was overoxidized to S-sulfonated cysteine (Cys-SO3H) by high H2O2 in vitro and in vivo, where the modification deterred the transcription of prx2. The DNA binding preferences of OxyR2(5CA)-C206D, which mimics overoxidized OxyR2, suggested that overoxidized OxyR2 binds to the extended DNA site, masking the -35 region of the prx2 promoter. These combined results demonstrate that OxyR2 functions as a three-state redox switch to tightly regulate the expression of prx2, preventing futile production of Prx2 in cells exposed to high levels of H2O2 sufficient to inactivate Prx2. We further provide evidence that another OxyR homolog, OxyR1, displays similar three-state behavior, inviting further exploration of this phenomenon as a potentially general regulatory mechanism.</P>

      • SCOPUSKCI등재

        Effects of Sediment Elutriates on the Early Reproductive Outputs in the Pacific oyster, Crassostrea gigas

        Jo, Qtae,Moon, Hyo-Bang,Cho, Yong Chul,Kim, Kwang Soo,Choy, Eun Jung,Ko, Sung-Chung,Song, Young-Chae 한국수산학회 2005 Fisheries and Aquatic Sciences Vol.8 No.1

        This is a subsequent study to our previous finding that Pacific oysters, Crassostrea gigas, gained a so-called upper plateau concentration, around 30,000 ng/g dry weight digestive gland for benzo(a)pyrene, showed reproductive behavior but produced their ensuing reproductive outputs damaged. A serial dilution of sediment elutriates from Jinhae Bay, Korea, where pollution was progressive, were exposed to gametes of the Pacific oyster for 0, 5. 10, 20, 30, and 60 min to detail the pollutant effects on very young specimens. There was an apparent critical dilution over which adverse effects are evident. This was 10% of the present sediment elutriate, corresponding to 0.3 ng/g on the basis of total polycyclic aromatic hydrocarbons (PAHs) for the oyster. Within the dilution the embryonic development was not influenced by the duration of exposure to its gamete stage. At higher dilutions over the critical dilution, occurrence of abnormality increased dependent on the pollutant dilution and the duration of exposure. Similar trends were also found in larval mortality. However, overall, the chemical toxicity was more significant to morphogenesis than to survival, suggesting a potential recruitment of the pollutants-induced abnormal larvae in the wild population to threaten the population integrity.

      • Specific Inhibition of Mammalian Oocyte Meiosis by Small Molecule Inhibitors targeting Polo-like Kinase 1

        Sung-Min Jeong,In-Won Lee,Yu-Jin Jo,Jeong-Kyu Bang,Suk Namgoong,Nam-Hyung Kim 한국동물생명공학회(구 한국동물번식학회) 2017 Reproductive & Developmental Biology(Supplement) Vol.41 No.2

        Polo-like kinase 1 (Plk1) plays crucial roles in various stages of oocyte maturation. Recently, we demonstrated that synthesized peptidomimetics AB103-8, targeting the polo- box domain (PBD) of Plk1 disrupted oocyte meiotic maturation and meiosis resumption. However, as a peptidic character of AB103-8 appeared to be defective due to poor membrane permeability and protease stability. To overcome the drawbacks, we designed and synthesized a series of pyrrole-based small-molecule inhibitors and screened against porcine oocyte maturation rates. Among the synthesized compounds, the macrocyclic inhibitor compound 4 displayed the highest inhibition potential against the oocyte meiotic maturation and embryos blastocyst formation. Furthermore, the addition of this compound to culture medium efficiently blocked the maturation of porcine and mouse oocytes, indicating that the lead compound could penetrate zona pellucida and cell membrane. We also investigated the Plk1 inhibiting ability of this compound. Treated mouse oocytes confirmed the Plk1 inhibition by showing abnormal spindle formation. Collectively, these results suggest that the novel Pyrrole-based compounds could be used for the basis of developing contraceptive agents.

      • Comparison of Hepatocellular Carcinoma Incidence between Entecavir and Tenofovir Therapy in Chronic Hepatitis B Patients in the Real-World Setting

        ( Sang Yu Oh ),( Bo Ryung Park ),( Byung Uk Lee ),( Jae Ho Park ),( Byung Gyu Kim ),( Seok Won Jung ),( In Du Jeong ),( Sung-jo Bang ),( Jung Woo Shin ),( Neung Hwa Park ),( Yun Im Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: Either entecavir (ETV) or tenofovir disoproxil fumarate (TDF) are recommended to use as the first-line nucleoside analogues (NAs) in patients with chronic hepatitis B (CHB) due to their potent viral suppression with a lower risk of drug resistance and excellent preventive effect for hepatocellular carcinoma (HCC) development. However, the effects of ETV and TDF on HCC development in CHB patients have not been fully examined. Methods: The aims of the current study were therefore to compare the effects of ETV and TDF therapy on HCC development in CHB patients in clinical practice. A total of 1,412 ETV-naïve patients and 1,318 TDF-naı¨ve patients were enrolled into the study. Results: The baseline characteristics of both groups were no significant difference. Virological and biochemical responses were similar between the two therapy groups over time. During a median 26 months of follow-up (range 1.0-60 months), 126 patients (4.6%) developed HCC. The 1-, 2-, 3- and 5-year cumulative HCC incidence rates in all cases were 2.2%, 3.8%, 5.1% and 9.9%, respectively. There was no significant difference in cumulative rates of HCC carcinoma (HCC) development (log-rank P = 0.357) between the two therapy groups. Multivariate analysis showed that male, older age, cirrhosis, lower albumin levels and HBeAg-positve status were independently associated with HCC development. Conclusions: HCC incidence and virological response were similar between ETV and TDF therapy groups in CHB patients in clinical practice. Therefore, either ETV or TDF are recommended to use as the first-line nucleoside analogues in patients with CHB due to their potent viral suppression and similar effect for HCC development.

      • KCI등재
      • KCI등재

        Clinical characteristics and nursing diagnoses of pediatric patients hospitalized with inflammatory bowel disease: a single-center retrospective study in South Korea

        Sung-Yoon Jo,Kyung-Sook Bang 한국아동간호학회 2023 Child Health Nursing Research Vol.29 No.3

        Purpose: This study aimed to identify clinical characteristics of South Korean pediatric inflammatory bowel disease (IBD) in a children's hospital over the past 5 years, with a specific focus on comparing the features observed between Crohn's disease (CD) and ulcerative colitis (UC). Additionally, it aimed to examine the nursing diagnoses given to patients. Methods: This retrospective study analyzed the medical records of Korean pediatric patients under 18 years of age who were diagnosed with IBD and hospitalized at a children's hospital in Seoul, South Korea, from January 2017 to December 2021. Results: The number of pediatric patients diagnosed with IBD steadily increased. This finding was particularly prominent for CD patients, the majority of whom were male. Pediatric patients with CD had significantly higher rates of abdominal pain and perianal lesions, while pediatric patients with UC had a higher rate of bloody stool. Laboratory findings indicated that CD patients had higher levels of inflammatory markers and lower albumin levels than UC patients. The nursing diagnoses given during hospitalization mostly related to safety and protection, physical comfort, and gastrointestinal function. Conclusion: This study provides insights into Korean pediatric IBD patients, enabling early detection and the development of nursing intervention strategies. From a comprehensive perspective, nursing care should not only address patients' physical needs but also their psychosocial needs.

      • Comparison of Tenofovir Therapy between Single and Multi-Drug Resistant Patients in Nucleos(t)ide-Resistant Chronic Hepatitis B

        ( Sang Yu Oh ),( Bo Ryung Park ),( Byung Uk Lee ),( Jae Ho Park ),( Byung Gyu Kim ),( Seok Won Jung ),( In Du Jeong ),( Sung-jo Bang ),( Jung Woo Shin ),( Neung Hwa Park ),( Yun Im Lee ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: Tenofovir (TDF) therapy has been recommended as a rescue strategy for chronic hepatitis B (CHB) patients with nucleos(t)ide (NA) resistance. Unfortunately, after sequential NA monotherapy in CHB patients with lamivudine (LAM) resistance, multidrug resistance (MDR) developed in a substantial number of patients. Very limited data are available on the comparison of TDF therapy between single drug resistant (SDR) and MDR groups in NA-resistant CHB patients. Methods: Of the 269 CHB patients with NA-resistance, 139 were SDR group and 130 were MDR group. A matched study population was constructed to compare the antiviral efficacy of TDF therapy by a propensity score analysis. Results: Two hundreds CHB patients were selected after matching propensity score with 1:1 ratio. The median follow-up period during TDF therapy was 47.3 months (range, 6-59 months). Virologic response (VR) occurred in 188 patients (95 patients in the SDR group and 93 patients in the MDR group) during the treatment period. The VR rate was lower in the MDR group than in the SDR group but statistically insignificant (74.3% vs. 85.6% at month 12, and 87.4% vs. 92.2% at month 24; log rank P=0.111). Partial virologic response (PVR) rates were not different between both groups (20.0% and 31.0% in the SDR and MDR groups, respectively; P = 0.105). The rates of ALT normalization and HBeAg seroconvesion also did not differ between both groups (P>0.05). In multivariate analysis, absolute HBV DNA level at the start of TDF rescue treatment (P<0.001; OR, 0.715; 95% CI, 0.646-0.791) was only significantly associated with VR. Conclusions: TDF rescue therapy has comparable efficacy in the SDR and MDR CHB patients, and the presence of MDR did not alter the response rates. HBV DNA level at the start of TDF rescue therapy was the only predictor of subsequent VR.

      • Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug

        Bang, Sookhee,Jang, Sung Ill,Lee, Su Yeon,Baek, Yi-Yong,Yun, Jieun,Oh, Soo Jin,Lee, Chang Woo,Jo, Eun Ae,Na, Kun,Yang, Sugeun,Lee, Don Haeng,Lee, Dong Ki Hindawi Publishing Corporation 2015 Gastroenterology Research and Practice Vol.2015 No.-

        <P>Implantation of self-expanding metal stents (SEMS) is palliation for patients suffering from inoperable malignant obstructions associated with biliary and pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed because SEMS are susceptible to occlusion by tumor in-growth. We reported recently that paclitaxel-eluting SEMS provide enhanced local drug delivery in an animal model. However, little is known about the molecular mechanisms by which paclitaxel-eluting stents attenuate tumor growth. We investigated the signal transduction pathways underlying the antiproliferative effects of a paclitaxel-eluting membrane (PEM) implanted in pancreatic/cholangiocarcinoma tumor bearing nude mice. Molecular and cellular alterations were analyzed in the PEM-implanted pancreatic/cholangiocarcinoma xenograft tumors by Western blot, immunoprecipitation, and immunofluorescence. The quantities of paclitaxel released into the tumor and plasma were determined by liquid chromatography-tandem mass spectroscopy. Paclitaxel from the PEM and its diffusion into the tumor inhibited angiogenesis, which involved suppression of mammalian target of rapamycin (mTOR) through regulation of hypoxia inducible factor (HIF-1) and increased apoptosis. Moreover, implantation of the PEM inhibited tumor-stromal interaction-related expression of proteins such as CD44, SPARC, matrix metalloproteinase-2, and vimentin. Local delivery of paclitaxel from a PEM inhibited growth of pancreatic/cholangiocarcinoma tumors in nude mice by suppressing angiogenesis via the mTOR and inducing apoptosis signal pathway.</P>

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