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Transplantation of mesenchymal stem cells from human umbilical cord versus human umbilical cord blood for peripheral nerve regeneration

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Neural Regeneration Research 2010年第11期5卷 838-845页

作者： Kang-Mi Pang Mi-Ae sung Mohammad S.Alrashdan Sang Bae Yoo Samir Jabaiti Soung-Min kim sung-june kim Myung-Jin kim Jeong Won Jahng Jong-Ho Lee Department of Oral Maxillofacial Surgery Seoul National University Seoul 110-768 Korea Department of Craniofacial Structure & Functional Biology Seoul National University Seoul 110-768 Korea Dental Research Institute School of Dentistry Seoul National University Seoul 110-768 Korea Department of Plastic and Reconstructive Surgery Faculty of Medicine Jordan University Hospital Amman 11942 Jordan Department of Electrical Engineering School of Electrical and Computer Science Seoul National University Seoul 110-768 Korea

BACKGROUND： Mesenchymal stem cells （MSCs） appear to be a good alternative to Schwann cells in the treatment of peripheral nerve injury. Fetal stem cells, like umbilical cord blood （UCB） and umbilical cord （UC） stem cells, have several advantages over adult stem cells. OBJECTIVE： To assess the effects of UC-derived MSCs （UCMSCs） and UCB-derived MSCs （UCBMSCs） in repair of sciatic nerve defects. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at the laboratory of Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, from July to December 2009. MATERIALS： UCMSCs were provided by the Research Institute of Biotechnology, Dongguk University. UCBMSCs were provided by the Laboratory of Stem Cells and Tumor Biology, College of Veterinary Medicine, Seoul National University. Dulbecco＇s modified Eagle＇s medium （DMEM） was purchased from Gibco-BRL, USA. METHODS： Seven-week-old Sprague-Dawley rats were randomly and evenly divided into three groups： DMEM, UCBMSCs, and UCMSCs. A 10-mm defect in the left sciatic nerve was constructed in all rats. DMEM （15 μL） containing 1×10^6 UCBMSCs or UCMSCs was injected into the gap between nerve stumps, with the surrounding epineurium as a natural conduit. For the DMEM group, simple DMEM was injected. MAIN OUTCOME MEASURES： At 7 weeks after sciatic nerve dissection, dorsal root ganglia neurons were labeled by fluorogold retrograde labeling. At 8 weeks, electrophysiology and histomorphometry were performed. At 2, 4, 6, and 8 weeks after surgery, sciatic nerve function was evaluated using gait analysis. RESULTS： The UCBMSCs group and the UCMSCs group exhibited similar sciatic nerve function and electrophysiological indices, which were better than the DMEM group, as measured by gait analysis （P 〈 0.05）. Fluorogold retrograde labeling of sciatic nerve revealed that the UCBMSCs group demonstrated a higher number of labeled neurons; however, the differences were not significant. His

关键词： peripheral nerve regeneration umbilical cord mesenchymal stem cell umbilical cord blood mesenchymal stem cell axotomy defect stem cells

Construction of recombinant human nerve growth factor beta adenovirus and evaluation of its function An in vitro and in vivo study

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Neural Regeneration Research 2010年第16期5卷 1261-1269页

作者： En-Feng Gao Si-Ho Choi Mi-Ae sung Bo-Han Li Samir Jabaiti Sang Bae Yoo sung-june kim Soung-Min kim Jeong Won Jahng Jong-Ho Lee Department of Stomatology China-Japan Friendship Hospital Beijing 100029 China Center for Stem Cell and Regenerative Medicine Keck School of Medicine University of Sourthern Californina USA Department of Oral and Maxillofacial Surgery & Dental Research Institute Seoul National University Seoul Korea Department of Plastic and Reconstructive Surgery Jordan University Hospital Amman Jordan Department of Electrical Engineering School of Electrical and Computer Science Seoul National University Seoul Korea

Exogenous delivery of nerve growth factor （NGF） promotes neural regeneration. However, the short half-life limits delivery efficacy. Therefore, a long-term, efficient, local delivery tool or scheme is needed. The purpose of this study was to construct a functioning, recombinant, adenoviral vector carrying human NGF-β （hNGF-β） DNA, and to measure expression of the constructed vector in vitro and in vivo. rhNGF-β adenoviral vector containing full-length hNGF-β cDNA was generated by homologous recombination in Escherichia CoIL The rhNGF-β adenovirus was packaged and amplified in human embryonic kidney HEK293 cells. Transformation efficiency, expression and function of rhNGF-β adenovirus for primary Schwann cells, Schwann cell lines, human embryonic kidney HEK 293 cells, CRH myoblasts, and NIH3T3 fibroblasts were evaluated. Subsequently, expression of rhNGF-β adenovirus at the peripheral nerve of rat was also assessed. Recombinant adenoviral vector carrying hNGF-β was successfully constructed and confirmed by restriction endonuclease analysis and DNA sequence analysis. Green fluorescent protein expression was observed in 90% of rhNGF-β adenovirus-infected cells （primary Schwann cells, Schwann cell line, human embryonic kidney HEK 293 cells, CRH myoblasts, and NIH3T3 fibroblasts） compared with non-infected cells. Total mRNA isolated from rhNGF-β adenovirus-infected cells exhibited strong expression. Maximum NGF release was induced by primary cultured Schwann cells at 4 days after infection, which steadily continued for 14 days. PC-12 cells exposed to media conditioned with rhNGF-β adenovirus-infected Schwann cells exhibited increased neurite extension. In vivo experiment revealed that the injected rhNGF-β adenovirus was transfected into the cells at the injected site and promoted expression of NGF, p75NTR and brain derived neurotrophic factor at the sciatic nerve and dorsal root ganglia.

关键词： nerve growth factor Schwann cell peripheral nerve regeneration adenoviral vector HEK293 cells myoblasts fibroblasts

A pipeline to characterize p53 effectors by integrative cistrome and transcriptome analysis in a genetically-defined organoid model

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Genes & Diseases 2024年第2期11卷 512-515页

作者： june-Ha Shin Hwa-Ryeon kim Jae-Seok Roe Department of Biochemistry College of Life Science and BiotechnologyYonsei UniversitySeoul 120-749Republic of Korea

Tumor-protein 53(p53)is a transcription factor(TF)encoded by TP53(Trp53 in mice)and is a master regulator of tumor-suppressive programs'.Importantly,TP53 is the most frequently mutated gene in human cancer,and its loss of function contributes to tumor development,exemplified by variable p53 mutations detected in 50%-75%of pancreatic cancers.2 From these perceptions,a number of targets transcribed by p53 that confer tumor suppression have been ***,our understanding of how p53 prevents normal cells from initiating tumorigenesis is still *** complement this limitation,herein,we established a new approach to identify underlying effectors transcribed by p53 in normal physiology.

关键词： incomplete initiating herein

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 ***,a decoy receptor for TNF,is used to treat inflammatory *** secretome derived from adipose-derived stem cells(ASCs)has anti-inflammatory effects,making it a promising therapeutic option for *** 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 *** ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing *** secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse *** 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 *** 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

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3521-3528页

作者： Shin Woo Kang sung Hee Lim Min-Ji kim Jeeyun Lee Young Suk Park Ho Yeong Lim Won Ki Kang Seung Tae kim Division of Hematology Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Samsung Biomedical Research Institute Samsung Medical CenterSeoul 06351South Korea

BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor *** VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab *** cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and *** To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of *** This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between june 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with *** A total of 124 patients was included in this *** all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line *** 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line *** numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),*** results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

关键词： Bevacizumab Colorectal cancer Programmed cell death ligand 1 expression First-line chemotherapy Metastatic colorectal cancer

Is a Mini-Screen for Fetal Alcohol Spectrum Disorder Feasible?

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Open Journal of Pediatrics 2024年第4期14卷 767-781页

作者： Tyler Mueller Devin Evavold june-Yung kim Marilyn G. Klug Larry Burd School of Medicine and Health Sciences University of North Dakota Grand Forks USA Department of Social Work University of North Dakota Grand Forks USA

Background: Fetal Alcohol Spectrum Disorders (FASDs) are a global public health concern with lifelong consequences for affected individuals. Recent prevalence studies suggest FASD prevalence rates range from 1-5% among school age children. Most people with FASD are not correctly diagnosed and inadequate screening to identify patients with increased risk may contribute to under-diagnosis. This study developed a 10-item screening tool for FASD and examined its feasibility. Methods: The sample consisted of 355 children who had been evaluated at an FASD clinic. Data from the 33-item Alcohol Related Neurodevelopmental Disorder Behavioral Checklist was used to develop a brief FASD screen by comparing the changes in Cronbach’s alpha for different combinations of items. The validity of the brief scale was then further examined using receiving operating characteristic analyses. Results: The 10-item screen demonstrated acceptable sensitivity, specificity, and accuracy to identify children at high risk for FASD. The percentage correctly classified was 91.3 and the area under the receiving operating characteristic curve was 0.971. Conclusions: This feasibility study demonstrated that a screen for FASD consisting of 10 items with yes or no responses can be completed in 3 - 4 minutes. The tool is brief, with a low administration burden and has acceptable epidemiologic performance characteristics including accuracy. Future research should examine the performance of this tool when used in larger, community-based populations where screening for FASD would be appropriate.

关键词： Fetal Alcohol Spectrum Disorders (FASDs) Children Screening Prevalence

Surgical Repair of Ventricular Septal Defect in Neonates: Indications and Outcomes

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Congenital Heart Disease 2024年第1期19卷 69-83页

作者： Jae Hong Lee sungkyu Cho Jae Gun Kwak Hye Won Kwon Woong-Han kim Mi Kyoung Song Sang-Yun Lee Gi Beom kim Eun Jung Bae Department of Thoracic and Cardiovascular Surgery Research Institute for Convergence of Biomedical Science and TechnologyPusan National University Yangsan HospitalYangsanKorea Department of Thoracic and Cardiovascular Surgery Seoul National University Children’s HospitalSeoulKorea Department of Pediatrics Seoul National University Children’s HospitalSeoulKorea

Background:The optimal surgical timing and clinical outcomes of ventricular septal defect(VSD)closure in neo-nates remain *** aimed to evaluate the clinical outcomes of VSD closure in neonates(age≤30 days).Methods:We retrospectively reviewed 50 consecutive neonates who underwent VSD closure for isolated VSDs between August 2003 and june *** for the procedure included congestive heart failure/failure to thrive and pulmonary *** adverse events(MAEs)were deﬁned as the composite of all-cause mortality,reoperation,persistent atrioventricular block,and signiﬁcant(≥grade 2)valvular ***:The median age and body weight at operation were 26.0 days(interquartile range[IQR],18.8–28.3)and 3.7 kg(IQR,3.3–4.2),*** median follow-up duration was 110.4 months(IQR,56.8–165.0).Seven patients required preoperative respiratory support,andﬁve had signiﬁcant(≥grade 2)preoperative valvular *** early mortality occurred due to irreversible cardiogenic shock;no late mortality was *** reopera-tion was due to hemodynamically signiﬁcant residual VSD at 103.8 months *** overall survival,freedom from reoperation,and freedom from MAE at 15-years were 98.0%,96.3%,and 94.4%,***-operative mechanical ventilation was associated with a longer duration of postoperative mechanical ventilation(p<0.001)and a longer length of intensive care unit stay(p<0.001).Conclusions:VSD closure with favorable outcomes without morbidities is feasible even in ***,neonates requiring preoperative respiratory support may require careful postoperative management considering the long-term postoperative ***,surgical VSD closure might be indicated earlier in neonates with respiratory compromise.

关键词： Ventricular septal defect neonate early surgery neonatal surgery

HoLEP does not affect the overall sexual function of BPH patients： a prospective study

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Asian Journal of Andrology 2014年第6期16卷 873-877页

作者： sung Hart kim Hyung-Kook Yang Hahn-Ey Lee Jae-Seung Paick Seung-june Oh Department of Urology Prostate Cancer Center National Cancer Center Goyang Korea Department of Epidemiology and Statistics and Cancer Policy Branch of National Cancer Control Research Institute National Cancer Center Goyang Korea Department of Urology Seoul National University Hospital Seoul Korea.

We aimed to prospectively evaluate the influence of holmium laser enucleation of the prostate （HoLEP） on the overall postoperative sexual function of benign prostatic hyperplasia （BPH） patients with lower urinary tract symptoms （LUTS） and to explore the relationship between sexual function and LUTS. From January 2010 to December 2011, sixty sexually active consecutive patients with BPH who underwent HoLEP were prospectively enrolled in the study. All patients filled out the Male Sexual Health Questionnaire （MSHQ） for evaluation of their overall sexual function and the International Prostatic Symptom Score （IPSS） for pre- and post-operative 6 months evaluation of their voiding symptoms. The LUTS and sexual function changes were statistically analyzed. The preoperative and 6 months postoperative status of the patients was compared using uroflowmetry and IPSS questionnaires. The analysis revealed significant improvements following HoLEP. Among the sub-domains of the MSHQ, postoperative sexual function, including erection, ejaculation, sexual satisfaction, anxiety or sexual desire, did not significantly change after HoLEP （P 〉 0.05）, whereas satisfaction scores decreased slightly due to retrograde ejaculation in 38 patients （63.3%）. Sexual satisfaction improved significantly and was correlated with the improvements of all LUTS and the quality-of-life （QoL） domains in IPSS after surgery （QoL; relative risk [RR]： -0.293; total symptoms, RR： -0.411; P 〈 0.05）. The nocturia score was associated with the erectile function score （odds ratio 0.318, P = 0.029）. The change in ejaculatory scores did not show significant association with IPSS scores. HoLEP did not influence overall sexual function, including erectile function. In addition, sexual satisfaction improved in proportion with the improvement of LUTS.

关键词： benign prostatic hyperplasia ejaculation erectile dysfunction lasers prostatectomy sex disorders

Sodium butyrate prevents radiation-induced cognitive impairment by restoring pCREB/BDNF expression

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Neural Regeneration Research 2019年第9期14卷 1530-1535页

作者： Hae june Lee Yeonghoon Son Minyoung Lee Changjong Moon sung Ho kim In Sik Shin Miyoung Yang Sangwoo Bae Joong Sun kim Division of Basic Radiation Bioscience Korea Institute of Radiological&Medical Sciences(KIRMAS)SeoulRepublic of Korea National Primate Research Center Korea Research Institute of Bioscience and Biotechnology(KRIBB)CheongjuRepublic of Korea College of Pharmacy Kyungpook National UniversityDaeguRepublic of Korea College of Veterinary Medicine Veterinary Medical Research InstituteChonnam National UniversityGwangjuRepublic of Korea School of Medicine Wonkwang UniversityJeonbukRepublic of Korea Research Center Dongnam Institute of Radiological&Medical Sciences(DIRAMS)BusanRepublic of Korea

Sodium butyrate is a histone deacetylase inhibitor that affects various types of brain *** investigate the effects of sodium butyrate on hippocampal dysfunction that occurs after whole-brain irradiation in animal models and the effect of sodium butyrate on radiation exposure-induced cognitive impairments,adult C57BL/6 mice were intraperitoneally treated with 0.6 g/kg sodium butyrate before exposure to 10 Gy cranial *** impairment in adult C57BL/6 mice was evaluated via an object recognition test 30 days after *** also detected the expression levels of neurogenic cell markers(doublecortin)and phosphorylated cAMP response element binding protein/brain-derived neurotrophic ***-exposed mice had decreased cognitive function and hippocampal doublecortin and phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor *** butyrate pretreatment reversed these *** findings suggest that sodium butyrate can improve radiation-induced cognitive dysfunction through inhibiting the decrease in hippocampal phosphorylated cAMP response element binding protein/brain-derived neurotrophic factor *** study procedures were approved by the Institutional Animal Care and Use Committee of Korea Institute of Radiological Medical Sciences(approval ***16-0002)on December 30,2016.

关键词： sodium butyrate radioprotector ionizing radiation hippocampal damage cAMP response element binding brain-derived neurotrophic factor histone deacetylase inhibitor neurogenesis