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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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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

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Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virusinduced oxidative stress

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Acta Pharmaceutica Sinica B 2023年第1期13卷 174-191页

作者： eun-Bin Kwon Wei Li Young Soo Kim Buyun Kim Hwan-Suck Chung Younghoon go Hyun-Jeong Ko Jae-Hyoung Song Young Ho Kim Chun Whan Choi Jang-Gi Choi Korean Medicine(KM)Application Center Korea Institute of Oriental MedicineDaegu 41062Republic of Korea College of Pharmacy Chungnam National UniversityDaejeon 34134Republic of Korea Natural Product Research Team BiocenterGyeonggido Business and Science AcceleratorGyeonggi-Do 16229Republic of Korea Laboratory of Microbiology and Immunology College of PharmacyKangwon National UniversityChuncheon 24341Republic of Korea

The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral ***,neuraminidase(NA)inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration(FDA)for the prevention and treatment of ***,we show that vitisin B(VB)inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 *** oxygen species(ROS),which frequently occur during viral infection,increase virus replication by activating the NF-κB signaling pathway,downmodulating glucose-6-phosphate dehydrogenase(G6PD)expression,and decreasing the expression of nuclear factor erythroid2-related factor 2(Nrf2)antioxidant response *** decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity,and inhibiting NF-κB translocation to the nucleus through IKK *** addition,VB reduced body weight loss,increased survival,decreased viral replication and the inflammatory response in the lungs of influenza A virus(IAV)-infected *** together,our results indicate that VB is a promising therapeutic candidate against IAV infection,complements existing drug limitations targeting viral *** modulated the intracellular ROS by G6PD,Nrf2 antioxidant response pathway,and NF-κB signaling *** results demonstrate the feasibility of a multi-targeting drug strategy,providing new approaches for drug discovery against IAV infection.

关键词： Influenza Vitisin B Vitis vinifera L. Neuraminidase Reactive oxygen species NF-κB Multi-targeting Nrf2 G6PD

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Is the AIM65 score useful in predicting outcomes in peptic ulcer bleeding?

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World Journal of Gastroenterology 2014年第7期20卷 1846-1851页

作者： Sung Hoon Jung Jung Hwan Oh Hye Yeon Lee Joon Won Jeong Se eun go Chan Ran You eun Jung Jeon Sang Wook Choi Division of Gastroenterology Department of Internal MedicineCollege of MedicineThe Catholic University of KoreaSeoul 130-709South Korea

AIM:To evaluate the applicability of AIMS65 scores in predicting outcomes of peptic ulcer ***:This was a retrospective study in a single center between January 2006 and December *** enrolled 522 patients with upper gastrointestinal haemorrhage who visited the emergency *** patients were regarded as those who had rebleeding within 30 d from the first endoscopy as well as those who died within 30 d of visiting the Emergency room.A total of 149 patients with peptic ulcer bleeding were analysed,and the AIMS65 score was used to retrospectively predict the high-risk ***:A total of 149 patients with peptic ulcer bleeding were *** poor outcome group comprised 28 patients[male:23(82.1%)vs female:5(10.7%)]while the good outcome group included 121patients[male:93(76.9%)vs female:28(23.1%)].The mean age in each group was not significantly *** mean serum albumin levels in the poor outcome group were slightly lower than those in the good outcome group(P=0.072).For the prediction of poor outcome,the AIMS65 score had a sensitivity of35.5%(95%CI:27.0-44.8)and a specificity of 82.1%(95%CI:63.1-93.9)at a score of *** AIMS65 score was insufficient for predicting outcomes in peptic ulcer bleeding(area under curve=0.571;95%CI:0.49-0.65).CONCLUSION:The AIMS65 score may therefore not be suitable for predicting clinical outcomes in peptic ulcer *** albumin levels may be a risk factor associated with high mortality in peptic ulcer bleeding.

关键词： Gastrointestinal haemorrhage Peptic ulcer Mortalit

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Effects of aqueous extract from red Liriope platyphylla on phthalic-anhydride-induced atopic dermatitis in Interleukin-4/Luciferase/Consensus non-coding sequence-1 transgenic mice evaluated in terms of luciferase signal and general phenotype biomarkers

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Journal of Traditional Chinese Medicine 2017年第4期37卷 475-485页

作者： Moon Hwa Kwak Ji eun Kim Jun go Hong Joo Son Hee Seob Lee Jin Tae Hong Dae Youn Hwang College of Natural Resources and Life Science/Life and Industry Convergence Research Institute Pusan National UniversityMiryang 627-706South of Korea College of Human Ecology Pusan National UniversityBusan 609-735south of Korea College of Pharmacy and Medical Research Center Chungbuk National UniversityChungju 361-763south of Korea College of Pharmacology Chungbuk National UniversityChungju 361-763south of Korea

OBJECTIVE: To quantitatively evaluate the therapeutic effects of Red Liriope platyphylla(RLP) on atopic dermatitis(AD), alterations in the luciferase(Luc) signal and general phenotype biomarkers were compared in phthalic anhydride(PA) treated Interleukin-4(IL-4)/Luc/Consensus non-coding sequence-1(CNS-1) transgenic(Tg) mice following treatment with aqueous extract of RLP(AEt RLP) for4 ***: Alterations in AD phenotypes were measured in IL-4/Luc/CNS-1 Tg mice following treatment with AEt RLP using inflammation parameter analysis, bioluminescence imaging analysis, histological analysis, reverse transcription-polymerase chain reaction, enzyme linked immunosorbent assay and Western blot ***: RLP contained high concentrations of total phenolic compounds, total flavonoid compounds and 5-HNE related to AD therapy. The Luc signal was only detected in the abdominal region and the submandibular lymph node(SL), mesenteric lymph node(ML), thymus and pancreas of the PA treated group. This signal was significantly decreased by 28%-73% throughout the body and in the four organs in PA + AEt RLP treated group. Furthermore, the lymph node weight, immunoglobulin E concentration and dermal thickness were decreased by 37%-67% in the PA + AEt RLP treated ***: Our findings suggest that the therapeutic effect of AEt RLP on PA induced AD could be successfully quantified by comparison of Luc signals and AD phenotype markers in IL-4/Luc/CNS-1Tg mice, and that the Luc signal was as sensitive as the general AD phenotypes, enabling detection of effects without euthanasia.

关键词：皮炎,遗传性过敏症 Liriope 植物 Interleukin-4 酶老鼠,转基因酞酸酐免疫球蛋白 E

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Krill oil ameliorates benign prostatic hyperplasia by regulating G-phase cell cycle arrest and altering signaling pathways and benign prostatic hyperplasia-associated markers

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Food Science and Human Wellness 2023年

作者： Hoon Kim Jongyeob Kim Byungdoo Hwang Sang Yong Park Ji-Yeon Shin eun Byeol go Jae Sil Kim Youngjin Roh Soon Chul Myung Seok-Joong Yun Yung Hyun Choi Wun-Jae Kim Sung-Kwon Moon Department of Biochemistry College of Oriental Medicine Dongeui University Institute of Urotech Cheongju Department of Urology Chungbuk National University Cheongju SD Biotechnologies 66 Magojungang 8-ro 1-gil Gangseo-gu Department of Food and Nutrition Chung-Ang University Department of Urology College of Medicine Chung-Ang University

Krill oil (KO) exhibits various biological activities， such as anti-inflammatory and antitumor effects. However， the inhibitory effects of benign prostatic hyperplasia (BPH) in vitro and in vivo have not yet been studied. This study investigated the anti-BPH effects of KO extracted by an enzymatic hydrolysis method. KO treatment inhibited the proliferation of WMPY-1 and BPH-1 cells by induction of G0/G1phase arrest through the modulation of positive and negative regulators in both prostate cell types. KO treatment stimulated phosphorylation of JNK and p38 signaling. In addition， KO changed the expression of BPH-related markers (5α-reductase， androgen receptor， FGF， Bcl-2， and Bax) and the activity of the proliferation-mediated NF-κB binding motif. KO-induced levels of proliferation-mediated molecules of prostate cells were attenuated in the presence of siRNA-specific p-38 (si-p38) and JNK (si-JNK). Furthermore， the administration of KO alleviated prostate size and weight and the cell layer thickness of prostate glands in a testosterone enanthate-induced BPH rat model. KO treatment altered the level of dihydrotestosterone in serum and the expression levels of BPH-related markers in prostate tissues. Finally， KO-mediated inhibition of prostatic growth was validated by histological analysis. These results suggest that KO has an inhibitory effect on BPH in prostate cells in vitro and in vivo. Thus， KO might be a potential prophylactic or therapeutic agent for patients with BPH.

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Ssu72 is a T-cell receptor-responsive modifier that is indispensable for regulatory T cells

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Cellular & Molecular Immunology 2021年第6期18卷 1395-1411页

作者： Jin-Kwan Lee Seo-Young Koo Hye-Mi Nam Jee-Boong Lee Jiwon Ko Kyung-Mo Kim eun-Ji Park Tae Jin Kim Ho Lee Heounjeong go Chang-Woo Lee Research Institute Curogen TechnologySuwonSouth Korea Department of Molecular Cell Biology Samsung Medical CenterSungkyunkwan University School of MedicineSuwonSouth Korea MOGAM Institute for Biomedical Research GyeonggiSouth Korea Department of Pathology Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea Asan Institute for Life Sciences Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea Department of Immunology Sungkyunkwan University School of MedicineSeoulSouth Korea Department of Cancer Biomedical Science Graduate School of Cancer Science and PolicyResearch InstituteNational Cancer CenterGyeonggiSouth Korea

The homeostatic balance between effector T cells and regulatory T cells(Tregs)is crucial for adaptive immunity;however,epigenetic programs that inhibit phosphorylation to regulate Treg development,peripheral expression,and suppressive activity are ***,we found that the Ssu72 phosphatase is activated by various T-cell receptor signaling pathways,including the T-cell receptor and IL-2R pathways,and localizes at the cell *** of Ssu72 in T cells disrupts CD4+T-cell differentiation into Tregs in the periphery via the production of high levels of the effector cytokines IL-2 and IFNγ,which induce CD4+T-cell activation and differentiation into effector cell *** also found a close correlation between downregulation of Ssu72 and severe defects in mucosal tolerance in ***,Ssu72 forms a complex with PLCγ1,which is an essential effector molecule for T-cell receptor signaling as well as Treg development and ***72 deficiency impairs PLCγ1 downstream signaling and results in failure of Foxp3 ***,our studies show that the Ssu72-mediated cytokine response coordinates the differentiation and function of Treg cells in the periphery.

关键词： Ssu72 Regulatory T cells FoxP3 T cell receptor Autoimmunity

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Effects of microalgal polyunsaturated fatty acid oil on body weight and lipid accumulation in the liver of C57BL/6 mice fed a high fat diet

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The Journal of Biomedical Research 2016年第3期30卷 234-242页

作者： Ryeo-eun go Kyung-A Hwang Geon-Tae Park Hae-Miru Lee Geum-A Lee Cho-Won Kim So-Ye Jeon Jeong-Woo Seo Won-Kyung Hong Kyung-Chul Choi Laboratory of Biochemistry and Immunology College of Veterinary Medicine Chungbuk National University Cheongju Chungbuk ASI/KR/KS001 Republic of Korea Korea Research Institute of Bioscience & Biotechnology Jeongup Jeonbuk ASI/KR/KS004 Republic of Korea LED Agri-bio Fusion Technology Research Center College of Environmental & Bioresource Science Chonbuk National University Iksan Campus Jeonbuk ASI/KR/KS004 Republic of Korea

Dietary polyunsaturated fatty acids （PUFAs）, which are abundant in marine fish oils, have recently received global attention for their prominent anti-obesogenic effects. Among PUFAs, eicosapentaenoic acid （EPA; 20：5n-3） and docosahexaenoic acid （DHA; 22：6n-3）, which are n-3 long-chain PUFAs widely referred to as omega-3 oils, were reported to prevent the development of obesity in rodents and humans. In the present study, we evaluated the anti-obesity effects of microalgal oil on high-fat induced obese C57BL/6 mice, compared with commercial omega-3 fish oil and vegetable corn oil. Microalgal oil is an inherent mixture of several PUFAs, including EPA, DHA and other fatty acids produced from a marine microalgal strain of Thraustochytriidae sp. derived mutant. It was found to contain more PUFAs （〉80%） and more omega-3 oils than commercial omega-3 fish oil （PUFAs 〉31%） and corn oil （PUFAs 59%）. All three types of oils induced weight loss in high-fat-induced obese mice, with the loss induced by microalgal oil being most significant at 9 weeks （10% reduction）. However, the oils tested did not improve blood lipid levels, although microalgal oil showed an apparent inhibitory effect on lipid accumulation in the liver. These findings may be attributed to the higher PUFA content, including omega-3 oils of microalgal oil than other oils. Collectively, these findings suggest that microalgal oil, derived from Thraustochytriidae sp. derived mutant, is a prominent candidate for replacement of omega-3 fish oils based on its apparent anti-obesity effect in vivo.

关键词： anti-obesity polyunsaturated fatty acid saturated fatty acid omega-3 oil microalgae

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Circulating immune cell landscape in patients who had mild ischaemic stroke

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Stroke & Vascular Neurology 2022年第4期7卷 319-327,I0020-I0022页

作者： Young-eun Cho Hyangkyu Lee Heekyong R.Bae Hyungsuk Kim Sijung Yun Rany Vorn Ann Cashion Mary Jo Rucker Mariam Afzal Lawrence Latour Jessica Gill College of Nursing The University of IowaIowa CityIowaUSA National Institute of Nursing Research National Institutes of HealthBethesdaMarylandUSA Mo-Im Kim Nursing Research Institute College of NursingYonsei UniversitySeoulSouth Korea National Eye Institute National Institutes of HealthBethesdaMarylandUSA Predictiv Care IncSunnyvaleCaliforniaUSA School of Nursing Johns Hopkins UniversityBaltimoreMarylandUSA College of Nursing University of Tennessee Health Science CenterMemphisTennesseeUSA Suburban Hospital BethesdaMarylandUSA National Institute of Neurological Disorders and Stroke National Institutes of HealthBethesdaMarylandUSA

Introduction Patients who had a mild ischaemic stroke who present with subtle or resolving symptoms sometimes go undiagnosed,are excluded from treatment and in some cases clinically *** immune cells are potential biomarkers that can assist with diagnosis in ischaemic *** the transcriptomic changes of each cell population caused by ischaemic stroke is critical because they work closely in a complicated *** this study,we investigated peripheral blood mononuclear cells(PBMCs)transcriptomics of patients who had a stroke using a single-cell RNA sequencing to understand peripheral immune response after mild stroke based on the gene expression in an unbiased *** Transcriptomes of PBMCsfrom 10 patients who had an acute ischaemic stroke within 24 hours after stroke onset were compared with 9 race-matched/age-matched/gender-matched *** PBMCs were prepared with ddSeqTM(Illumina-BioRad)and sequenced on the Illumina NovaSeq 6000 *** Notable population changes were observed in patients who had a stroke,especially in NK cells and CD14+*** number of NK cells was increased,which was further confirmed by flow *** analysis implied that the activity of NK cells also is enhanced in patients who had a ***14+monocytes were clustered into two groups;dendritic cell-related CD14+monocytes and NK cell-related CD14+*** found CD14+monocyte subclusters were dramatically reduced in patients who had a *** This is the first study demonstrating the increased number of NK cells and new monocyte subclusters of mild ischaemic stroke based on the transcriptomic *** findings provide the dynamics of circulating immune response that could assist diagnosis and potential therapeutic development of mild ischaemic stroke.

关键词： patients diagnosis Circulating

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Macrophage PD-L1 strikes back: PD-1/PD-L1 interaction drives macrophages toward regulatory subsets

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Advances in Bioscience and Biotechnology 2013年第8期4卷 19-29页

作者： Yun-Jung Lee Young-Hye Moon Kyeong eun Hyung Jong-Sun Yoo Mi Ji Lee Ik Hee Lee Byung Sung go Kwang Woo Hwang Laboratory of Host Defense Modulation College of Pharmacy Chung-Ang University Seoul Korea

Activated macrophages have been simply de?ned as cells that secrete in?ammatory mediators and kill intracellular pathogens until few years ago. Recent studies have proposed a new classification system to separate activated macrophages based on their functional phenotypes: host defense, wound healing, and immune regulation. Regulatory macrophages can arise following innate or adaptive immune responses and hinder macrophage-mediated host defense and inflammatory functions by inhibiting the production of pro-inflammatory mediators. In this study, we investigated whether PD-1 and PD-L1 interaction between macrophages and T cells alters macrophage activities. Our data provide evidence for PD-1/PD-L1 engagement inducing a regulatory profile in macrophages. Regulatory macrophages derived from PD-L1 signaling lost their host defense activity, which consists of the production of pro-inflammatory cytokine IL-6 and the exhibition of increased IL-10, SPHK1 and LIGHT gene levels in early phases of LPS stimulation. This differentiation seems to occur through excessive activation of TLR4 downstream MAPK signaling pathways. Regulatory macrophages induced from PD-1/PD-L1 interaction decrease inflammatory mediators and produce anti-inflammatory cytokines, so this macrophage subset has been under considerable attention as a possible immune regulation mechanism. Understanding and modulating regulatory macrophages may lead to new approches to treat or prevent auto-immune diseases such as type I diabetes, rheumatic syndrome and hypersensitivity-related diseases, which are concerned with the overproduction of inflammatory cytokines in macroages.

关键词： Regulatory Macrophage PD-1 PD-L1

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