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Delayed hippocampal neuronal death in young gerbil following transient global cerebral ischemia is related to higher and longer-term expression of p63 in the ischemic hippocampus

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Neural Regeneration Research 2015年第6期10卷 944-950页

作者： eun Joo Bae Bai Hui Chen Bing Chun Yan Bich Na Shin Jeong Hwi cho In Hye Kim Ji Hyeon Ahn Jae Chul Lee Hyun-Jin Tae Seongkweon Hong Dong Won Kim Jun Hwi cho Yun Lyul Lee Moo-Ho Won Joon Ha Park Department of Pediatrics Chuncheon Sacred Heart HospitalCollege of MedicineHallym University Department of Physiology College of MedicineInstitute of Neurodegeneration and NeuroregenerationHallym University Institute of Integrative Traditional & Western Medicine Medical CollegeYangzhou University Department of Neurobiology School of MedicineKangwon National University Department of Biomedical Science and Research Institute for Bioscience and Biotechnology Hallym University Department of Surgery School of MedicineKangwon National University Department of Emergency Medicine Chuncheon Sacred Heart HospitalCollege of MedicineHallym University Department of Emergency Medicine School of MedicineKangwon National University

The tumor suppressor p63 is one of p53 family members and plays a vital role as a regulator of neuronal apoptosis in the development of the nervous system. However, the role of p63 in mature neuronal death has not been addressed yet. In this study, we first compared ischemia-induced effects on p63 expression in the hippocampal regions （CA1-3） between the young and adult gerbils subjected to 5 minutes of transient global cerebral ischemia. Neuronal death in the hippocampal CA1 region of young gerbils was significantly slow compared with that in the adult gerbils after transient global cerebral ischemia, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons in the sham-operated young group was significantly low compared with that in the sham-operated adult group, p63 immunoreactivity was apparently changed in ischemic hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. In the ischemia-operated adult groups, p63 immunoreactivity in the hippocampal CA1 pyramidal neurons was significantly decreased at 4 days post-ischemia; however, p63 immunoreactivity in the ischemia-operated young group was significantly higher than that in the ischemia-operated adult group. At 7 days post-ischemia, p63 immunoreactivity was decreased in the hippocampal CA1 pyramidal neurons in both ischemia-operated young and adult groups. Change patterns of p63 level in the hippocampal CA1 region of adult and young gerbils after ischemic damage were similar to those observed in the immunohistochemical results. These findings indicate that higher and longer-term expression of p63 in the hippocampal CA1 region of the young gerbils after ischemia/reperfusion may be related to more delayed neuronal death compared to that in the adults.

关键词： p53 tumor suppressor gene family cerebral ischemia/reperfusion pyramidal neurons CA1 region delayed neuronal death immunohistochemistry western blotting neural regeneration

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Anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium-induced colitis model

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World Journal of Gastroenterology 2017年第25期23卷 4559-4568页

作者： Seung Kak Shin Jae Hee cho Eui Joo Kim eun-Kyung Kim Dong Kyun Park Kwang An Kwon Jun-Won Chung Kyoung Oh Kim Yoon Jae Kim Division of Gastroenterology and Hepatology Department of Internal Medicine Gachon University Gil Medical Center

AIM To evaluate the anti-inflammatory and anti-apoptotic effects of rosuvastatin by regulation of oxidative stress in a dextran sulfate sodium(DSS)-induced colitis *** An acute colitis mouse model was induced by oral administration of 5% DSS in the drinking water for 7 d. In the treated group, rosuvastatin(0.3 mg/kg per day) was administered orally before and after DSS administration for 21 d. On day 21, mice were sacrificed and the colons were removed for macroscopic examination, histology, and Western blot analysis. In the in vitro study, IEC-6 cells were stimulated with50 ng/m L tumor necrosis factor(TNF)-α and then treated with or without rosuvastatin(2 μmol/L). The levels of reactive oxygen species(ROS), inflammatory mediators, and apoptotic markers were measured. RESULTS In DSS-induced colitis mice, rosuvastatin treatment significantly reduced the disease activity index and histological damage score compared to untreated mice(P < 0.05). Rosuvastatin also attenuated the DSSinduced increase of 8-hydroxy-2'-deoxyguanosine and NADPH oxidase-1 expression in colon tissue. Multiplex ELISA analysis revealed that rosuvastatin treatment reduced the DSS-induced increase of serum IL-2, IL-4, IL-5, IL-6, IL-12 and IL-17, and G-CSF levels. The increased levels of cleaved caspase-3, caspase-7, and poly(ADP-ribose) polymerase in the DSS group were attenuated by rosuvastatin treatment. In vitro, rosuvastatin significantly reduced the production of ROS, inflammatory mediators and apoptotic markers in TNF-α-treated IEC-6 cells(P < 0.05).CONCLUSION Rosuvastatin had the antioxidant, anti-inflammatory and anti-apoptotic effects in DSS-induced colitis model. Therefore, it might be a candidate anti-inflammatory drug in patients with inflammatory bowel disease.

关键词：氧化应力煽动性的肠疾病 Rosuvastatin Apoptosis

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Γ-Aminobutyric acid promotes methionine-choline deficient diet-induced nonalcoholic steatohepatitis

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The Journal of Biomedical Research 2017年第1期31卷 65-73页

作者： Yoon Seok Roh Ara cho Zixiong Zhou Hyuneui Jeong Jeong-eun Park Youn-Soo Cha Suk-Heung Oh Chae-Woong Lim Bumseok Kim Biosafety Research Institute and Laboratory of Pathology College of Veterinary Medicine Chonbuk National University lksan-si Jeollabuk-do 54596 Republic of Korea Department of Food Science and Human Nutrition Fermented Food Research Center Chonbuk National University Jeonju-si Jeollabuk-do 54896 Republic of Korea Department of Food & Biotechnology Woosuk University Jeonju 565701 Republic of Kore Animal Disease & Biosecurity Team National Institute of Animal Science Rural Development Administration Wanjugun 55365 Republic of Korea

Nonalcoholic steatohepatitis（NASH） is one of the most common liver diseases and a major cause of liver fibrosis worldwide.r-Aminobutyric acid（GABA） is one of the most abundant inhibitory neurotransmitters in the central nervous ***,it has been reported that GABAergic signaling pathways are found in various non-neuronal tissues including the immune system and play a functional *** the present study,we investigated whether administration of GABA has effects on NASH through its immunomodulatory *** test this hypothesis,C57BL/6 mice were fed a methionine-choline-deficient（MCD） diet for 8 *** four weeks into MCD feeding,mice were provided with plain water（control） or water containing 2 mg/mL of GABA for the subsequent 4 *** this MCD diet-induced NASH model,we found that mice receiving GABA showed more severe steatohepatitis and liver fibrosis than control *** increased liver damage was confirmed by higher levels of serum alanine transaminase（ALT） and aspartate aminotransferase（AST） compared to the control *** accordance with increased liver steatohepatitis,NASH-related and inflammatory gene expression（collagen al,tissue inhibitor of metalloproteinase-1,TNF-α） in the liver was markedly increased in GABA-treated ***,GABA directly enhanced production of inflammatory cytokines including IL-6 and TNF-α in LPS activated RAW macrophage cells and increased TIB-73 hepatocyte *** effects were abolished when GABA was treated with bicuculline,a competitive antagonist of GABA *** results suggest that oral administration of GABA may be involved in changes of the liver immune milieu and conferred detrimental effects on NASH progression.

关键词： Γ-Aminobutyric acid nonalcoholic steatohepatitis methionine-choline-deficient diet mice GABA

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The Application of the Korean Dietary Pattern Score;KNHANES (Korean National Health and Nutrition Examination Survey) 2007

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Food and Nutrition Sciences 2012年第12期3卷 1688-1696页

作者： Kyung Won Lee Ji eun Oh Mi Sook cho Department of Nutrition Science and Food Management Ewha Womans University Seoul Korea.

The aim of this study was to apply the Korean Dietary Pattern Score (KDPS) to Korean subjects based on traditional Korean-style meals. The KDPS is based on the 3-Chup Bansang (the traditional Korean daily table setting) and considers the intake of 6 major food groups according to the Korean Dietary Reference Intakes (KDRIs). The KDPS consists of 2 parts: the Korean-Style Meal Score (KSMS) and the Food Group Score (FGS). The KDPS was applied dietary data collected during the Korean National Health and Nutrition Examination Survey (KNHANES) in 2007. Socio-demographic status, gender, age, and body mass index are all factors that have been shown to be meaningful predictors for the KDPS. When the effect of the KDPS on risk of disease was evaluated, a higher total KDPS was associated with a decreased risk of elevated systolic blood pressure (p cholesterolemia (p < 0.05). In addition, as the KSMS increased, the risk of central obesity (p < 0.05) and hypertension (p < 0.01) significantly decreased. A higher total KDPS suggests a greater diversity of food intake, and therefore greater dietary diversity appears to lower the risk of disease. The KDPS is relevant because it integrates scores for Korean-style meal patterns and meal evaluation from a nutritional perspective. In conclusion, the KDPS is appropriate for evaluating the quality of diet, adherence to Korean-style meal patterns, and risk of related diseases. These results will be useful for evaluating the nation’s dietary patterns, nutrition, and health status when planning nutrition policies and programs.

关键词： Korean Dietary Pattern Korean Dietary Index Korean Dietary Pattern Score (KDPS) Korean-Style MealScore (KSMS) Food Group Score (FGS)

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Neuroprotective effects of tamsulosin on intracerebral hemorrhage

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Neural Regeneration Research 2011年第32期6卷 2505-2510页

作者： Hong-Jin Suh Sung-Min So Young-Gil Na Il-Gyu Ko Sung-eun Kim Yun-Hee Sung Mal-Soon Shin Chang-Ju Kim Young-Sam cho Khae-Hawn Kim Department of Urology Incheon St. Mary's Hospital the Catholic University of Korea School of Medicine Department of Urology Chungnam National University School of Medicine Department of Physiology Kyung Hee University School of Medicine Department of Urology Kangbuk Samsung Hospital Sungkyunkwan University School of Medicine Department of Urology Gachon University Gil Hospital Gachon University of Medicine and Science

The alpha1 adrenoreceptor antagonist tamsulosin is primarily used to treat benign prostatic hypertrophy. In this study, we intragastrically administered rats with 0.01,0.1 and 1 mg/kg tamsulosin to investigate the effects of tamsulosin on memory function, and hippocampal cell apoptosis and proliferation following intracerebral hemorrhage. Step-down avoidance task results showed that tamsulosin treatment markedly alleviated intracerebral hemorrhage- induced short-term memory impairment. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results showed that tamsulosin treatment markedly suppressed intracerebral hemorrhage-induced caspase-3 expression in the hippocampal CA1 region and cell proliferation in the hippocampal dentate gyrus. Tamsulosin treatment at a dose of 0.01 mg/kg exhibited the most potent inhibitory effects on cell apoptosis and proliferation. These findings suggest that tamsulosin treatment facilitates the recovery of rat memory function by inhibiting hippocampal cell apoptosis and proliferation followincl intracerebral hemorrhaQe.

关键词： tamsulosin, intracerebral hemorrhage short-term memory apoptosis cellproliferation hippocampus neural regeneration

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Tacrolimus for children with refractory nephrotic syndrome:a one-year prospective,multicenter,and open-label study of Tacrobell®,a generic formula

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世界儿科杂志:英文版 2016年第1期12卷 60-65页

作者： eun Mi Yang Sang Taek Lee Hyun Jin choi Hee Yeon cho Joo Hoon Lee Hee Gyung Kang Young Seo Park Hae Il Cheong Il-Soo Ha Department of Pediatrics Chonnam National University HospitalGawngjuKorea Department of Pediatrics Seoul National University Children's HospitalSeoulKorea Department of Pediatrics Samsung Medical CenterSungkynkwan University School of MedicineSeoulKorea Department of Pediatrics Asan Medical Center Children's HospitalUniversity of Ulsan College of MedicineSeoulKorea Research Coordination Center for Rare Diseases Seoul National University HospitalSeoulKorea Kidney Research Institute Medical Research CenterSeoul National University College of MedicineSeoulKorea

Background:Cyclosporine A and tacrolimus(TAC)are often used as a second-line treatment for children with refractory nephrotic syndrome(NS).This study was undertaken to investigate the efficacy and safety of Tacrobell®,a locally produced generic form of ***:This study was a one-year prospective,open-label,single-arm,multicenter ***-four children with steroid-dependent NS(SDNS)and 33 children with steroid-resistant NS(SRNS)were *** primary endpoints were defined as the remission rates,whereas the secondary endpoints were recognized as the duration of remission and adverse effects of ***:After one-year treatment,34(77.3%)of the 44 patients with SDNS were in complete remission,and 6(13.6%)were in partial ***(43.2%)patients did not relapse during the study;for those who did relapse,the mean duration of remission was 4.6±2.9 *** number of relapse episodes during the study period(0.90 per patient-year)was significantly lower than that in the preceding year(2.8 per patientyear).After treatment for 3 and 6 months,12(36.4%)of the 33 patients with SRNS were in remission,and after treatment for 12 months,the number of patients had increased to 13(39.4%).The mean time to achieve remission was 4.0±3.2 *** remission(duration,3.7±2.7 months),12(54.5%)of 22 patients *** fasting blood glucose and blood pressure levels during the therapy were similar to those at the time of study ***:Treatment with Tacrobell®was effective and safe for children with refractory *** efficacy of this generic form of TAC was better than that of the original TAC formula.

关键词： generic drugs nephrotic syndrome tacrolimus

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Effects of feeding a diet containing Gymnema sylvestre extract: attenuating progression of obesity in C57BL/6J mice

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Asian Pacific Journal of Tropical Medicine 2016年第5期9卷 425-431页

作者： Hyeon-Jeong Kim Seong-Ho Hong Seung-Hee Chang Sanghwa Kim Ah Young Lee Yoonjeong Jang Orkhonselenge Davaadamdin Kyeong-Nam Yu Ji-eun Kim Myung-Haing cho Laboratory of Toxicology College of Veterinary Medicine Seoul National University Graduate Group of Tumor Biology Seoul National University Graduate School of Convergence Science and Technology Seoul National University Advanced Institutes of Convergence Technology Seoul National University Institute of Green Bio Science Technology Seoul National University

Objective: To investigate the effect of Gymnema sylvestre extract(GS) on initial anti-obesity, liver injury, and glucose homeostasis induced by a high-fat diet(HFD). Methods: The dry powder of GS was extracted with methanol, and gymnemic acid was identified by high performance liquid chromatography as deacyl gymnemic acid. Male C57BL/6J mice that fed on either a normal diet, normal diet containing 1 g/kg GS(CON+GS) HFD, or HFD containing 1.0 g/kg GS(HFD+GS) for 4 weeks were used to test the initial anti-obesity effect of GS. Body weight gain and food intake, and serum levels about lipid and liver injury markers were measured. Histopathology of adipose tissue and liver stained with hematoxylin and eosin(H&E) and oil-red O were analyzed. After 4 weeks of GS extract feeding, intraperitoneal glucose tolerance test(IPGTT) was performed. Results: The methanol extracts of GS exerted significant anti-obesity effects in HFD+GS group. They decreased body weight gain, a lower food and energy efficiency ratio, and showed lower serum levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein(LDL)-cholesterol, very-low density lipoprotein(VLDL)-cholesterol and leptin compared with the HFD group. The decreases of abdominal as well as epididymal fat weight and adipocyte hypertrophy, lipid droplets in liver, and serum levels of aspartate aminotransferase(AST) and alanine transaminase(ALT) were also observed. The CON+GS group showed an effect of glucose homeostasis compared to the CON group. Conclusions: This study shows that GS provide the possibility as a key role in an initial anti-obesity effects feeding with a HFD.

关键词： Gymnema sylvestre extract Obesity Adipocyte Body weight gain High-fat diet Liver injury

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Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection

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World Journal of Gastroenterology 2016年第42期22卷 9427-9436页

作者： Junhyeon cho Sang Soo Lee Yun Suk choi Yejoo Jeon Jung Wha Chung Joo Yeong Baeg Won Keun Si eun Sun Jang Jin-Wook Kim Sook-Hyang Jeong Department of Internal Medicine Seoul National University College of Medicine Seoul National University Bundang Hospital Department of Internal Medicine Gyeongsang National University Changwon Hospital Gyeongsang National University College of Medicine

AIM To clarify the prevalence of occult hepatitis B virus(HBV) infection(OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma(HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus(HCV) infection. METHODS This prospective cohort study enrolled 174 patients with chronic HCV infection(chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or moredifferent viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. RESULTS The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively(P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response(SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.

关键词：肝炎 B 病毒丙肝病毒疾病控制 Oncogenesis

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Time-course pattern of neuronal loss and gliosis in gerbil hippocampi following mild, severe, or lethal transient global cerebral ischemia

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Neural Regeneration Research 2019年第8期14卷 1394-1403页

作者： Tae-Kyeong Lee Hyunjung Kim Minah Song Jae-Chul Lee Joon Ha Park Ji Hyeon Ahn Go eun Yang Hyeyoung Kim Taek Geun Ohk Myoung Cheol Shin Jun Hwi cho Moo-Ho Won Depart merit of Neurobiology School of Medici ne Kangw on National University Chuncheon Gangwon Republic of Korea Department of Biomedical Science and Research Institute for Bioscience and Biotechnology Hallym University Chuncheon Gangwon Republic of Korea Department of Radiology Kangwon National University Hospital Chuncheon Gangxvon Republic of Korea Department of Anesthesiology and Pain Medicine Chungju Hospital Konkuk University School of Medicine Chungju Chungcheongbuk Republic of Korea Department of Emergency Medicine School of Medicine Kangwon National University Chuncheon Gangwon Republic of Korea

Transient ischemia in the whole brain leads to neuronal loss/death in vulnerable brain regions. The striatum, neocortex and hippocampus selectively loose specific neurons after transient ischemia. Just 5 minutes of transient ischemia can cause pyramidal neuronal death in the hippocampal cornu ammonis (CA) 1 field at 4 days after transient ischemia. In this study, we investigated the effects of 5-minute (mild), 15-minute (severe), and 20-minute (lethal) transient ischemia by bilateral common carotid artery occlusion (BCCAO) on behavioral change and neuronal death and gliosis (astrocytosis and microgliosis) in gerbil hippocampal subregions (CA1-3 region and dentate gyrus). We performed spontaneous motor activity test to evaluate gerbil locomotor activity, cresyl violet staining to detect cellular distribution, neuronal nuclei immunohistochemistry to detect neuronal distribution, and Fluoro-Jade B histofluorescence to evaluate neuronal death. We also conducted immunohistochemical staining for glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 (Ibal) to evaluate astrocytosis and microgliosis, respectively. Animals subjected to 20-minute BCCAO died in at least 2 days. BCCAO for 15 minutes led to pyramidal cell death in hippocampal CA1-3 region 2 days later and granule cell death in hippocampal de匚tate gyrus 5 days later. Similar results were not found in animals subjected to 5-minute BCCAO. Gliosis was much more rapidly and severely progressed in animals subjected to 15-minute BCCAO than in those subjected to 5- minute BCCAO. Our results indicate that neuronal loss in the hippocampal formation following transient ischemia is significantly different according to regions and severity of transient ischemia. The experimental protocol was approved by Institutional Animal Care and Use Committee (AICUC) of Kangwon National University (approval No. KW-180124-1) on May 22, 2018.

关键词： transient global brain ischemia delayed neuronal death glial activation ischemic duration hippocampus spontaneous motor activity Mongolian gerbil histology neural regeneration

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非运动员患者前交叉韧带重建术后的心理学因素以及功能恢复的临床研究

非运动员患者前交叉韧带重建术后的心理学因素以及功能恢复的临床...

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作者： cho eun Shi Nae（赵恩始娜）上海交通大学

学位级别：硕士

目的:探究ACL重建手术后非运动员患者的功能恢复与心理因素的关系以及其特征,以进一步优化治疗、改善预后。方法:临床回顾性研究;选取2017年3月至2018年4月至在上海市民第六人民医院运动医学科接受关节镜下ACL重建术的90例ACL损伤的非... 详细信息

目的:探究ACL重建手术后非运动员患者的功能恢复与心理因素的关系以及其特征,以进一步优化治疗、改善预后。方法:临床回顾性研究;选取2017年3月至2018年4月至在上海市民第六人民医院运动医学科接受关节镜下ACL重建术的90例ACL损伤的非运动员患者。通过门诊或电话随访。膝关节功能恢复进行了以下三个不同方面:“重返运动”、“下肢功能现况”和“恢复运动水平”。常规评分表:IKDC、Lysholm和Marx;心理因素评估,使用4DSQ、ACL-RSI、KOOS和TSK-11总结归纳的评分表。对三种功能恢复和心理因素进行了分析。结果:62.22%患者重返运动或重返活动,36.66%患者报告“下肢功能现况”评分（≥80）,24.44%患者报告“恢复运动水平”评分（≥80）。心理因素（对手术方式了解,手术满意度,再损伤恐惧,生活改变）与“下肢功能现况”有关,但与重返运动无关。IKDC、Lysholm和Marx平均评分分别为81.77、89.62和34.16,与“下肢功能现况”和“恢复运动水平”有关,重返运动只与IKDC有关。此外,经济压力影响功能恢复、再损伤的恐惧和生活改变。结论:在非运动员患者中,重返运动与患者心理因素无关;然而,其他功能恢复指标（“下肢功能现况”和“恢复运动水平”）与心理因素有关,由此,对非运动员患者术后功能恢复与心理因素需要更深层次的理解。

关键词：前交叉韧带康复功能恢复心理因素生活质量

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