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Etanercept-synthesizing adipose-derived stem cell secretome:A promising therapeutic option for inflammatory bowel disease

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 882-892页

作者： Say-June Kim Ok-Hee Kim Ha-Eun Hong Ji Hyeon Ju Do Sang Lee Department of Surgery Seoul St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea catholic Central Laboratory of Surgery Institute of Biomedical IndustryCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Division of Rheumatology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its pathogenesis.Etanercept,a decoy receptor for TNF,is used to treat inflammatory conditions.The secretome derived from adipose-derived stem cells(ASCs)has anti-inflammatory effects,making it a promising therapeutic option for IBD.AIM To investigate the anti-inflammatory effects of the secretome obtained from ASCs synthesizing etanercept on colon cells and in a dextran sulfate sodium(DSS)-induced IBD mouse model.METHODS ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing cells.The secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse model.RESULTS This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing ASCs[Etanercept-Secretome(Et-Sec)group]had significantly lower expression levels of inflammatory mediators,such as interleukin-6,Monocyte Chemoattractant Protein-1,and TNF-α,when compared to the control secretome(Ct-Sec).Moreover,the Et-Sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the Ct-Sec.CONCLUSION These results suggest that the secretome derived from ASCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD,potentially enhancing treatment efficacy by merging the anti-inflam-matory qualities of the ASC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.

关键词： Adipose-derived stem cells Etanercept Inflammatory bowel disease Secretome Tumor necrosis factor-α

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Complete Solution of Diophantine Pairs Induced by Some Fibonacci Formula

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Algebra Colloquium 2023年第1期30卷 121-132页

作者： Jinseo Park Department of Mathematics Education Catholic Kwandong University Gangneung 25601Korea

A set[ai,a2,...,am)of positive integers is called a Diophantine m-tuple if aiaj+1 is a perfect square for all 1≤imax(a,b].In this paper,we find the condition for the reduction of third element c,and using this result,we prove the extendibility of Diophantine pair[F_(k)-1F_(k+1),F_(k-2)F_(k+2)],where Fn is the n-th Fibonacci number.

关键词： Diophantine m-tuple Fibonacci numbers Pell equation

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Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee Bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan Kim Donghyun Kim Wan-Uk Kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical Institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea Division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the nucleus.Nuclear receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains unclear.Here,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory conditions.Unexpectedly,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic specks.Mechanistically,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active caspase-1.Of note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in macrophages.Genetic ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in mice.Consistent with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling results.Conclusively,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

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Epidemic obesity in children and adolescents:risk factors and prevention

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Frontiers of Medicine 2018年第6期12卷 658-666页

作者： Eun Young Lee Kun-Ho Yoon Division of Endocrinology and Metabolism Department of Internal MedicineSeoul St.Mary's HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591Korea Institute of catholic Ubiquitous Health Care The Catholic University of KoreaSeoul 06591Korea

The prevalence of obesity among children and adolescents (aged 2-18 years) has increased rapidly, with more than 100 million affected in 2015. Moreover, the epidemic of obesity in this population has been an important public health problem in developed and developing countries for the following reasons. Childhood and adolescent obesity tracks adulthood obesity and has been implicated in many chronic diseases, including type 2 diabetes, hypertension, and cardiovascular disease. Furthermore, childhood and adolescent obesity is linked to adulthood mortality and premature death. Although an imbalance between caloric intake and physical activity is a principal cause of childhood and adolescent obesity, environmental factors are exclusively important for development of obesity among children and adolescents. In addition to genetic and biological factors, socioenvironmental factors, including family, school, community, and national policies, can play a crucial role. The complexity of risk factors for developing obesity among children and adolescents leads to difficulty in treatment for this population. Many interventional trials for childhood and adolescent obesity have been proven ineffective. Therefore, early identification and prevention is the key to control the global epidemic of obesity. Given that the proportion of overweight children and adolescents is far greater than that of obesity, an effective prevention strategy is to focus on overweight youth, who are at high risk for developing obesity. Multifaceted, comprehensive strategies involving behavioral, psychological, and environmental risk factors must also be developed to prevent obesity among children and adolescents.

关键词： adolescents children epidemiology obesity prevention risk factor

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Inhibition of Proliferation of Prostate Cancer Cell Line DU-145 in vitro and in vivo Using Salvia miltiorrhiza Bunge

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Chinese Journal of Integrative Medicine 2020年第7期26卷 533-538页

作者： Woong Jin Bae Jin Bong Choi Kang Sup Kim U Syn Ha Sung Hoo Hong Ji Youl Lee Tae-Kon Hwang Sung Yeoun Hwang WANG Zhi-ping Sae Woong Kim Department of Urology The Catholic University of KoreaCollege of MedicineSeoul(06591)Republic of Korea catholic Integrative Medicine Research Institute College of MedicineThe Catholic University of KoreaSeoul(06591)Republic of Korea korea Bio-Medical Science Institute Seoul(06106)Republic of Korea Department of Urology Second Hospital of Lanzhou UniversityLanzhou(730030)China

Objective:To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge.(SM)on the castration-resistant prostate cancer(CRPC)cell line DU-145 in vitro and in vivo.Methods:Prostate cancer cell line(DU-145)and normal prostate cell line(RWPE-1)were treated with SM at different concentrations(3.125,12.5,25 and 50μg/mL)to investigate the antiproliferative effects.DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells.Molecular mechanism was investigated by Western blot analysis of p53,Bcl-2,prostate specific antigen(PSA),and androgen receptor(AR).Six-week-old male BALB/c nude mice were randomly divided into normal control group(n=101)and treated group(n=101)which administered 500 mg/kg SM for 2 weeks.Tumor volumes were measured.Results:Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with RWPE-1.DNA laddering analysis indicated the apoptosis of DU-145 cells.Treatment with SM increased the expression of p53 and reduced the expression of Bcl-2 proteins.The levels of PSA were considerably reduced in SM-treated group compared to the controls,and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in PSA.In the tumour xenograft study,SM given once a day for 2 weeks significantly inhibited tumour growth.Conclusion:SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.

关键词： apoptosis prostate cancer Salvia miltiorrhiza Bunge Chinese medicine

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Unilateral versus bilateral Y-type stent-in-stent metal stent insertions in inoperable malignant hilar biliary strictures:A multicenter retrospective study

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Hepatobiliary & Pancreatic Diseases International 2021年第6期20卷 561-567页

作者： Ik Hyun Jo Chang-Nyol Paik Dae Bum Kim Jaesin Lee Jong Yul Lee Jae Hyuck Chang Kyu-Hyun Paik Won-Suk Park Department of Internal Medicine College of MedicineSt.Vincent’s HospitalThe Catholic University of KoreaSeoulKorea Department of Internal Medicine College of MedicineIncheon St.Mary’s HospitalThe Catholic University of KoreaSeoulKorea Department of Internal Medicine College of MedicineBucheon St.Mary’s HospitalThe Catholic University of KoreaSeoulKorea Department of Internal Medicine College of MedicineDaejeon St.Mary’s HospitalThe Catholic University of KoreaSeoulKorea

Background:To date,there is controversy regarding unilateral versus bilateral stent placement in patients with malignant hilar biliary strictures(MHBSs).The aim of this study was to compare the clinical outcomes and complications of unilateral and bilateral(stent-in-stent method)stent placements for these patients.Methods:We conducted a multicenter retrospective analysis of patients with inoperable MHBS who underwent endoscopic self-expandable metal stent(SEMS)placement from January 2009 to December 2019.Two groups classified according to the stent procedure method were compared for demographic,procedural,and postprocedure factors.Survival analysis for patency loss and overall survival was also conducted.Results:A total of 236 subjects were included.A superior technical success rate was found in the unilateral stent group(98.8%vs.82.5%,P<0.001),whereas the clinical success rate was higher in the bilateral group(85.7%vs.70.5%,P=0.028).There was no significant difference with respect to complications or patency loss,and the bilateral group had better overall survival(P<0.01).In the Cox proportional hazard model,MHBSs from lymph node compression were associated with a higher risk of death(HR=9.803,P=0.003).In contrast,bilateral SEMS insertion showed reduced postprocedural mortality(HR=0.316,P=0.001).Conclusions:Y-type stent-in-stent bilateral SEMSs are technically difficult but demonstrated more favorable overall survival for palliative bile drainage of inoperable MHBS patients compared to unilateral insertions.

关键词： Cholestasis Extrahepatic neoplasm Cholangiopancreatography Endoscopy Self-expandable metal stents

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Bilateral primary breast lymphoma

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Chinese Medical Journal 2010年第11期123卷 1482-1484页

作者： Jung Im Yi Byung Joo Chae Ja Seong Bae Bong Joo Kang Ahwon Lee Byung Joo Song Sang Seol Jung Departments of Surgery Catholic University of Korea Seoul Korea Department of Radiology Catholic University of Korea Seoul Korea Department of Pathology Catholic University of Korea Seoul Korea

Pprimary breast lymphoma （PBL） is rare, accounting for 0.04%-0.50% of breast malignancies and 1.7% of extranodal lymphoma The originally descnibect diagnostic criteria for PBL2 remains the standard definition for this disease. These criteria are breast location as the clinical site of presentation, absence of history of previous lymphoma or evidence of widespread disease at diagnosis, close association of lymphoma with breast tissue in pathologic specimens, and involvement of ipsilateral lymph nodes if they develop simultaneously with PBL.

关键词： breast lymphoma treatment

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Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation

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World Journal of Gastrointestinal Surgery 2023年第12期15卷 2727-2738页

作者： Ji Won Han Jong Young Choi Eun Sun Jung Ji Hoon Kim Hee Sun Cho Jae-Sung Yoo Pil Soo Sung Jeong Won Jang Seung Kew Yoon Ho Joong Choi Young Kyoung You Department of Internal Medicine The Catholic University of KoreaSeoul 06591South Korea The catholic university Liver Research Center College of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Hospital Pathology The Catholic University of KoreaSeoul 06591South Korea Department of Surgery The Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Clinical factors predicting graft survival(GS)after ABO-incompatible(ABOi)liver transplantation(LT),and differences between recipients with and without hepatocellular carcinoma(HCC)are unclear.AIM To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without(HCC)in ABOi living-donor liver transplantation(LDLT).METHODS We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT,including 47 patients with HCC.RESULTS The 1-,3-,5-,and 10-year GS rates were 85.9%,73.3%,71.4%,and 71.4%,respectively,and there were no significant differences between HCC and non-HCC recipients.In multivariate Coxregression analyses,tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT,in addition to the antibody-mediated rejection(AMR)were associated with poor-graft outcomes.In HCC patients,AMR[hazard ratio(HR)=63.20,P7.3 ng/mL were significant predictive factors for HCC recurrence.After propensity score matching,patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival.CONCLUSION Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence.Therefore,careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

关键词： ABO-incompatible Liver transplantation Tacrolimus Hepatocellular carcinoma

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Anti-inflammatory and Antimicrobial Effects of Anthocyanin Extracted from Black Soybean on Chronic Bacterial Prostatitis Rat Model

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Chinese Journal of Integrative Medicine 2018年第8期24卷 621-626页

作者： Byung Il Yoon Woong Jin Bae Yong Sun Choi Su Jin Kim U Syn Ha Sung-Hoo Hong Dong Wan Sohn Sae Woong Kim Department of Urology International St Mary's HospitalThe Catholic Kwandong University of Korea Department of Urology College of MedicineThe Catholic University of Korea

Objective： To investigated the anti-inflammatory and antimicrobial effects of anthocyanins extracted from black soybean on the chronic bacterial prostatitis（CBP） rat model.Methods： The SpragueDawley rats were divided into 4 groups,including control,ciprofloxacin,anthocyanins and anthocyanins with ciprofloxacin groups（n=8 in each group）.Then,drip infusion of bacterial suspension（Escherichia coli Z17O2：K1：H^-） into Sprague-Dawley rats was conducted to induce CBP.In 4 weeks,results of prostate tissue,urine culture,and histological analysis on the prostate were analyzed for each group.Results： The use of ciprofloxacin,anthocyanins,and anthocyanins with ciprofloxacin showed statistically significant decreases in bacterial growth and improvements in the reduction of prostatic inflammation compared with the control group（P〈0.05）.The anthocyanins with ciprofloxacin group showed a statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the ciprofloxacin group（P〈0.05）.Conclusions： These results suggest that anthocyanins may have anti-inflammatory and antimicrobial effects,as well as a synergistic effect with ciprofloxacin.Therefore,we suggest that the combination of anthocyanins and ciprofloxacin may be effective in treating CBP to obtain a higher rate of treatment success.

关键词： prostatitis anti-bacterial agents anthocyanins

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Suppression of Oxidative Stress of Modified Gongjin-Dan (WSY^1075) in Detrusor Underactivity Rat Model Bladder Outlet Induced by Obstruction

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Chinese Journal of Integrative Medicine 2018年第9期24卷 670-675页

作者： Jin-Woo Jung Seung Hwan Jeon Woong Jin Bae Su Jin Kim Mun Su Chung Byung II Yoon Sae Woong Choi U Syn Ha Sung Yeoun Hwang Sae Woong Kim Department of Urology International St. Mary's Hospital Catholic Kwandong University College of Medicine Incheon Republic of Korea Institute for Bio-Medical Convergence College of Medicine Catholic Kwandong University Gangneungsi Gangwon-do Republic of Korea Department of Urology College of Medicine The Catholic University of Korea Seoul Republic of Korea catholic Integrative Medicine Research Institute College of Medicine The Catholic University of Korea Seoul Republic of Korea korea Bio Medical Science Institute Seoul Republic of Korea

Objective： To investigate the anti-oxidative stress and preventive effect of modified Gongjin-dan （WSY-1075） in a detrusor underactivity rat model. Methods： Rats were randomly allocated to three groups： sham- operated （control）, bladder outlet obstruction-induced detrusor underactivity （BOO-DU）, and BOO-DU with WSY-1075 （WSY） groups. WSY-1075 was orally administrated to rats 200 mg daily for 2 weeks pdor to the operation and 4 weeks after the operation. Bladder outlet obstruction was surgically induced in rats by ligation around the urethra avoiding total obstruction. Cystometrography was conducted on rats in each group for examination of bladders. Results： Compared with the control group, bladder outlet obstruction led to a significant increase in oxidative stress with consequent changes to molecular composition, and decrease in maximal detrusor pressure （P〈0.05）. WSY-1075 treatment significantly suppressed oxidative stress and prevented degenerative and dysfunctional changes in bladder, as compared with BOO-DU group （P〈0.05）. Conclusion： WSY-1075 had beneficial effect on prevention of BOO-DU.

关键词： detrusor underactivity anti-oxidant herbal

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