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Inhibition of BET selectively eliminates undifferentiated pluripotent stem cells

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Science Bulletin 2018年第8期63卷 477-487页

作者： jung Hyun im Seon In Hwang Jong-Wan Kim soon-jung Park Kyu-ree Kang Jueng Soo You Kee Pyo Kim Sung-Hwan Moon Hyuk-Jin Cha Hyung-Min Chung Hans R. Scholer jung Keun Hyun DongWook Han Department of Stem Cell Biology School of Medicine Konkuk University Seoul 05029 Republic of Korea Department of Nanobiomedical Science Dankook University Graduate School Cheonan 330714 Republic of Korea Department of Biochemistry School of Medicine Konkuk University Seoul 05029 Republic of Korea Department of Cell and Developmental Biology Max Planck Institute for Molecular Biomedicine 48149 Munster Germany Department of Life Sciences College of Natural Sciences Sogang University Seoul 04107 Republic of Korea KU Open-lnnovation Center. Institute of Biomedical Science & Technology Konkuk University Seoul 05029 Republic of Korea Department of Advanced Translational Medicine School of Medicine Konkuk University Seoul 05029 Republic of Korea

Embryonic stem cells （ESCs） maintain their cellular identity through the systematic regulation of master transcription factors and chromatin remodeling complexes. Recent work has shown that the unusually large-scale enhancers-namely super-enhancers （SEs）, on which BRD4, a member of the bromodomain and extraterminal domain （BET） family is highly enriched-could regulate pluripotency-related transcrip- tion factors. Moreover, inhibition of BRD4 binding on SEs has been shown to induce the differentiation of ESCs. However, the underlying mechanism of BRD4 inhibition-mediated stern cell differentiation remains elusive. Here we show that both mouse and human ESCs lose their capacity for self-renewal upon treat- ment with JQ1, a selective inhibitor of BET family including BRD4, with rapid suppression of pluripotency-associated genes. Notably, a high concentration of JQI could selectively eliminate ESCs via apoptosis, without affecting the functionality of differentiated somatic cells from ESCs, suggesting that inhibition of BET may have a beneficial effect on the development of pluripotent stem cell-based cell therapy.

关键词： Bromodomain and extraterminal domain (BET) JQ1 Pluripotent stem cells

Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy

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World Journal of Gastrointestinal Oncology 2021年第8期13卷 915-928页

作者： Kabsoo Shin eun-Kyo jung Se Jun Park Sangwoon Jeong In-Ho Kim Myung-ah Lee Division of Medical Oncology Department of Internal MedicineSeoul St.Mary's HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea Catholic Cancer Research Institute College of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND A decline in serum carbohydrate antigen 19-9(CA19-9)levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic ***-to-lymphocyte ratio(NLR)has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic *** To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 *** We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul ***’s *** were divided according to CA19-9 positivity(CA19-9-positive vs-negative groups)and pre-and posttreatment NLR *** determine cut-off value of NLR and CA19-9 reduction,time-dependent receiver operating characteristic curve was *** evaluated overall survival(OS)and progression-free survival(PFS)for each group using Kaplan-Meier method,and we performed multivariate analyses on the entire *** We included 271 patients in this ***-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%.Multivariate analysis showed that post-treatment NLR<2.62 and reduction of≥18%of baseline CA19-9 were significantly associated with OS and ***-treatment NLR≥2.62 showed hazard ratio(HR)of 2.47[95%confidence interval(CI):1.84-3.32,P<0.001]and CA19-9 decline(≥18%)showed HR of 0.51(95%CI:0.39-0.67,P<0.001)for *** CA19-9-positive patients were divided into groups according to CA19-9 response(responder vs non-responder)and post-treatment NLR(<2.62 vs≥2.62),CA19-9 responder and post-treatment NLR<2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR≥2.62 group(OS 11.0 mo vs 3.9 mo,P<0.001;PFS 6.3 mo vs 2.0 mo,P<0.001).The combination of CA19-9 decline and post-treatment NLR showed a significant c

关键词： Pancreatic adenocarcinoma Serum carbohydrate antigen 19-9 Neutrophil-tolymphocyte ratio Multivariate analysis Prognosis Chemotherapy

Optimally arranged TiO_(2)@MoS_(2) heterostructures with effectively induced built-in electric field for high-performance lithium-sulfur batteries

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能源化学:英文版 2023年第8期83卷 496-508,I0012页

作者： Jeongyoub Lee Changhoon Choi jung Been Park Seungho Yu Jinho Ha Hyungsoo Lee Gyumin Jang Young Sun Park Juwon Yun Hayoung im Subin Moon Soobin Lee jung-Il Choi Dong-Wan Kim Jooho Moon Department of Materials Science and Engineering Yonsei UniversitySeoul 03722Republic of Korea School of Civil Environmental and Architectural EngineeringKorea UniversitySeoul 02841Republic of Korea Energy Storage Research Center Korea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea School of Mathematics and Computing(Computational Science and Engineering) Yonsei UniversitySeoul 03722Republic of Korea

To overcome the serious technological issues affecting lithium-sulfur(Li-S) batteries,such as sluggish sulfur redox kinetics and the detrimental shuttle effect,heterostructure engineering has been investigated as a strategy to effectively capture soluble lithium polysulfide intermediates and promote their conversion reaction by integrating highly polar metal oxides with catalytically active metals ***,to fully exploit the outstanding properties of heterostructure-based composites,their detailed structure and interfacial contacts should be designed ***,optimally arranged TiO_(2)and MoS_(2)-based heterostructures(TiO_(2)@MoS_(2)) are fabricated on carbon cloth as a multifunctional interlayer to efficiently trap polysulfide intermediates and accelerate their redox *** to the synergistic effects between TiO_(2)and MoS_(2)and the uniform heterointerface distribution that induces the ideally oriented built-in electric field,Li-S batteries with TiO_(2)@MoS_(2)interlayers exhibit high rate capability(601 mA h g^(-1)at 5 C),good cycling stability(capacity-fade rate of 0.067% per cycle over 500 cycles at2 C),and satisfactory areal capacity(5.2 mA h cm^(-2)) under an increased sulfur loading of 5.2 mg cm^(-2).Moreover,by comparing with a MoS_(2)@TiO_(2)interlayer composed of reversely arranged heterostructures,the effect of the built-in electric field’s direction on the electrocatalytic reactions of polysulfide intermediates is thoroughly investigated for the first *** superior electrocatalytic activities of the rationally arranged TiO_(2)@MoS_(2)interlayer demonstrate the importance of optimizing the built-in electric field of heterostructures for producing high-performance Li-S batteries.

关键词： Lithium-sulfur batteries Shuttle effect TiO_(2)-MoS_(2)heterostructure engineering Built-in electric field Multifunctional interlayers

T/myeloid mixed-phenotype acute leukemia treated with venetoclax and decitabine:A case report

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世界临床病例杂志 2023年第26期11卷 6200-6205页

作者： Sungwoo Park eun Jeong Jeong jung Hun Kang Gyeong-Won Lee Se-Il Go Dong-Hyun Lee eun-Ha Koh Division of Hematology and Oncology Department of Internal MedicineGyeongsang National University HospitalGyeongsang National University School of MedicineGyeongsang National UniversityJinju 52727South Korea Department of Internal Medicine Institute of Health SciencesGyeongsang National University Changwon HospitalGyeongsang National University School of MedicineChangwon 52828South Korea Department of Laboratory Medicine Gyeongsang National University HospitalGyeongsang National University School of MedicineGyeongsang National UniversityJinju 52828South Korea

BACKGROUND Mixed-phenotype acute leukemia(MPAL)is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid ***,consensus regarding the ideal management strategy for MPAL is yet to be established,owing to its *** SUMMARY A 55-year-old male was diagnosed with T/myeloid ***,prednisolone,daunorubicin,and L-asparaginase were administered as induction *** shock occurred 10 days after induction,and bone marrow examination following recovery from sepsis revealed refractory *** and decitabine were administered as chemotherapy-free induction therapy to reduce the infection *** were no serious infections,including febrile neutropenia,at the end of the *** receiving two additional cycles of venetoclax/decitabine,the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response(CR)to *** CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.

关键词： Mixed-phenotype acute leukemia Venetoclax Decitabine Case report

Longitudinal evolution of cortical thickness signature reflecting Lewy body dementia in isolated REM sleep behavior disorder:a prospective cohort study

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Translational Neurodegeneration 2023年第1期12卷 514-528页

作者： jung Hwan Shin Heejung Kim Yu Kyeong Kim eun Jin Yoon Hyunwoo Nam Beomseok Jeon Jee-Young Lee Department of Neurology Seoul Metropolitan Government-Seoul National University Boramae Medical Center and Seoul National University College of MedicineSeoulSouth Korea Department of Nuclear Medicine Seoul Metropolitan Government-Seoul National University Boramae Medical Center and Seoul National University College of MedicineSeoulSouth Korea Institute of Radiation Medicine Medical Research CenterSeoul National UniversitySeoulSouth Korea Department of Neurology Seoul National University Hospital and Seoul National University College of MedicineSeoulSouth Korea

Background The isolated rapid-eye-movement sleep behavior disorder(iRBD)is a prodromal condition of Lewy body disease including Parkinson’s disease and dementia with Lewy bodies(DLB).We aim to investigate the longitudinal evolution of DLB-related cortical thickness signature in a prospective iRBD cohort and evaluate the possible predictive value of the cortical signature index in predicting dementia-first phenoconversion in individuals with *** We enrolled 22 DLB patients,44 healthy controls,and 50 video polysomnography-proven iRBD *** underwent 3-T magnetic resonance imaging(MRI)and clinical/neuropsychological *** characterized DLB-related whole-brain cortical thickness spatial covariance pattern(DLB-pattern)using scaled subprofile model of principal components analysis that best differentiated DLB patients from age-matched *** analyzed clinical and neuropsychological correlates of the DLB-pattern expression scores and the mean values of the whole-brain cortical thickness in DLB and iRBD *** repeated MRI data during the follow-up in our prospective iRBD cohort,we investigated the longitudinal evolution of the cortical thickness signature toward Lewy body ***,we analyzed the potential predictive value of cortical thickness signature as a biomarker of phenoconversion in iRBD *** The DLB-pattern was characterized by thinning of the temporal,orbitofrontal,and insular cortices and relative preservation of the precentral and inferior parietal *** DLB-pattern expression scores correlated with attentional and frontal executive dysfunction(Trail Making Test-A and B:R=−0.55,P=0.024 and R=−0.56,P=0.036,respectively)as well as visuospatial impairment(Rey-figure copy test:R=−0.54,P=0.0047).The longitudinal trajectory of DLB-pattern revealed an increasing pattern above the cut-off in the dementia-first phenoconverters(Pearson’s correlation,R=0.74,P=6.8×10−4)but no significant change in parki

关键词： Rapid eye movement sleep behavior disorder Dementia with Lewy bodies Lewy body disease Cortical thickness Spatial covariance pattern Magnetic resonance imaging

Correlations between endoscopic and clinical disease activity indices in intestinal Behcet's disease

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World Journal of Gastroenterology 2012年第40期18卷 5771-5778页

作者： Hyun jung Lee Youn Nam Kim Hui Won Jang Han Ho Jeon eun Suk jung Soo jung Park Sung Pil Hong Tae Il Kim Won Ho Kim Chung Mo Nam Jae Hee Cheon Department of Internal Medicine Institute of GastroenterologyYonsei University College of MedicineSeoul 120-752South Korea Department of Biostatistics Yonsei University College of MedicineSeoul 120-752South Korea Department of Preventive Medicine Yonsei University College of MedicineSeoul 120-752South Korea

Aim:To develop a novel endoscopic severity model of intestinal Behcet's disease(BD) and to evaluate its feasibility by comparing it with the actual disease activity index for intestinal Behcet's disease(DAIBD).METHODS:We reviewed the medical records of 167 intestinal BD patients between March 1986 and April *** also investigated the endoscopic parameters including ulcer locations,distribution,number,depth,shape,size and margin to identify independent factors associated with *** endoscopic severity model was developed using significant colonoscopic variables identified by multivariate regression analysis and its correlation with the DAIBD was *** determine factors related to the discrepancy between endoscopic severity and clinical activity,clinical characteristics and laboratory markers of the patients were ***:A multivariate regression analysis revealed that the number of intestinal ulcers(≥ 2,P = 0.031) and volcanoshaped ulcers(P = 0.001) were predictive factors for the *** endoscopic severity model(Y) was developed based on selected endoscopic variables as follows:Y = 47.44 + 9.04 × non-Ileocecal area + 11.85 ×≥ 2 of intestinal ulcers + 5.03 × shallow ulcers + 12.76 × deep ulcers + 4.47 × geographicshaped ulcers + 26.93 × volcano-shaped ulcers + 8.65 ×≥ 20 mm of intestinal ***,endoscopic parameters used in the multivariate analysis explained only 18.9% of the DAIBD *** with severe DAIBD scores but with moderately predicted disease activity by the endoscopic severity model had more symptoms of irritable bowel syndrome(21.4% vs 4.9%,P = 0.026) and a lower rate of corticosteroid use(50.0% vs 75.6%,P = 0.016) than those with severe DAIBD scores and accurately predicted disease by the ***:Our study showed that the number of intestinal ulcers and volcano-shaped ulcers were predictive factors for severe DAIBD ***,the correlation between endoscopic severity and DAIBD(r = 0.434) was weak.

关键词： Intestinal Behcet's disease Disease activityindex Colonoscopy Ulcer Endoscopic severity

Hwangryunhaedoktang exerts anti-inflammation on LPS-induced NO production by suppressing MAPK and NF-κB activation in RAW264.7 macrophages

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Journal of Integrative Medicine 2017年第4期15卷 326-336页

作者： Byung Hyuk Han Yun jung Lee jung Joo Yoon eun Sik Choi Seung Namgung Xian Jun Jin Da Hye Jeong Dae Gill Kang Ho Sub Lee College of Oriental Medicine and Professional Graduate School of Oriental Medicine Wonkwang University Hanbang Body-fluid Research Center Wonkwang University

OBJECTIVE： This study aimed to evaluate whether Hwangryunhaedoktang （HHT）, a herbal compound, has an inhibitory effect on lipopolysaccharide （LPS）-induced inflammation in RAW264.7 macrophages. METHODS： The effects of HHT were evaluated by confirming nitric oxide （NO） production and expression of inducible NO synthase （iNOS） and mitogen-activated protein kinases （MAPKs） in LPS-stimulated RAW264.7 macrophages via the Griess assay, Western blotting, and real-time reverse transcription quantitative polymerase chain reaction. Western blot analyses and luciferase assays were used to evaluate whether HHT has an effect on the phosphorylation and translocation of nuclear factor-κB （NF-κB）. The secretion and expression of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were determined via enzyme-linked immunosorbent assay and Western blot analyses. RESULTS： HHT suppressed LPS-induced NO production and expression of iNOS in a dose-dependent manner. Additionally, MAPKs activation was also attenuated via inhibition of phosphorylation of extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinase and p38 which were related to inflammatory pathway. Furthermore, HHT also effectively attenuated NF-κB activation and its translocation to the nucleus, a process that is closely linked to inflammation. LPS normally induced the expression of inflammatory cytokines such as TNF-α and IL-6, but the secretion and expression of TNF-α and IL-6 were significantly attenuated by pretreating the cells with HHT. CONCLUSION： HHT suppressed LPS-induced NO production by blocking the activation of NF-κB and MAPK signaling pathways in RAW264.7 macrophages. Furthermore, HHT may have an anti-inflammatory effect by suppressing the LPS-induced secretion of TNF-α and IL-6. Therefore, the traditional herbal formula HHT might be a useful potential therapeutic agent for inflammation.

关键词： medicine, Chinese traditional lipopolysaccharide nitric oxide nuclear factor-κB mitogen-activatedprotein kinases tumor necrosis factor-a inflammation

Involvement of heme oxygenase-1 induction in anti-vascular inflammation effects of Xanthoceras sorbifolia in human umbilical vein endothelial cells

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Journal of Traditional Chinese Medicine 2018年第6期38卷 803-814页

作者： jung Joo Yoon Byung Hyuk Han eun Sik Choi Seung Namgung Da Hye Jeong Song Nan Jin Yun jung Lee Dae Gill Kang Ho Sub Lee College of Oriental Medicine and Professional Graduate School of Oriental Medicine Wonkwang University Hanbang Cardio-Renal Syndrome Research Center Wonkwang University Institute of Materia Medica Taishan Medical University

OBJECTIVE: To define the effects of Xanthoceras sorbifolia(EXS) on vascular inflammation and the mechanisms in endothelial ***: Vascular protective effects of an ethanol extract of seeds from EXS(1-50 μg/mL) against tumor necrosis factor-α(TNF-α)-induced vascularinflammation were examined in human umbilical vein endothelial cells(HUVECs).RESULTS: EXS significantly decreased TNF-α-induced expression of cell adhesion molecules, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial cell selectin,in a dose-dependent manner. Pre-treatment with EXS significantly inhibited translocation and transcriptional activity of nuclear factor-κB(NF-κB) increased by TNF-α. EXS also significantly inhibited formation of intracellular reactive oxygen species(ROS). Moreover, the vascular protective effects of EXS were linked to up-regulation of heme oxygenase-1(HO-1) and nuclear factor E2-related factor-2(Nrf-2) expression. EXS-induced HO-1 expression was significantly decreased in SnPP(HO-1 inhibitor)-and HO-1 siRNA-treated cells, whereas an increase was found in cobalt protoporphyrin IX(CoPP)(HO-1 inducer)-treated cells. In addition, pretreatment with EXS increased HO-1 and Nrf-2 expression under TNF-α stimulation with or without N-acetyl-L-cysteine. Furthermore, the inhibitory effects of EXS on TNF-α-induced vascular inflammation were partially reversed in SnPP-and of HO-1siRNA-treated cells but increased by ***: These results suggest that EXS may have important implications for prevention of vascular complications associated with vascular inflammation by inhibition of the NF-κB/ROS pathway and activation of the Nrf-2/HO-1 pathway.

关键词： Sapindaceae Vascular disease inflammation Human umbilical vein endothelial cells Cell adhesion molecules NF-kappa B Heme oxy-genase-1

Hepatic lipid homeostasis by peroxisome proliferator-activated receptor gamma 2

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Liver Research 2018年第4期2卷 209-215页

作者： Yoon Kwang Lee jung eun Park Mikang Lee James P.Hardwick Department of Integrative Medical Sciences College of MedicineNortheast Ohio Medical UniversityRootstownOHUSA Department of Food Science and Human Nutrition Chonbuk National UniversityDeokjin-guJeonjuRepublic of Korea

Peroxisome proliferator-activated receptor gamma(PPARγor PPARG)is a ligand-activated transcription factor belonging to the nuclear hormone receptor *** plays a master role in the differentiation and proliferation of adipose *** has two major isoforms,PPARγ1 and PPARγ2,encoded from a single gene using two separate promoters and alternative *** them,PPARγ2 is most abundantly expressed in adipocytes and plays major adipogenic and lipogenic roles in the ***,it has been shown that PPARγ2 is also expressed in the liver,specifically in hepatocytes,and its expression level positively correlates with fat accumulation induced by pathological conditions such as obesity and *** of the hepatic Pparg gene ameliorates hepatic steatosis induced by diet or genetic *** activation of Pparg in the liver induces the adipogenic program to store fatty acids in lipid droplets as observed in *** how the hepatic Pparg gene expression is regulated will help develop preventative and therapeutic treatments for non-alcoholic fatty liver disease(NAFLD).Due to the potential adverse effect of hepatic Pparg gene deletion on peripheral tissue functions,therapeutic interventions that target PPAR g for fatty liver diseases require fine-tuning of this gene's expression and transcriptional activity。

关键词： Non-alcoholic fatty liver disease(NAFLD) High fat diet(HFD) Adipogenesis Gene expression Peroxisome proliferator-activated receptor gamma(PPARγ)