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Enhanced delivery of a low dose of aducanumab via FUS in 5×FAD mice,an AD model

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Translational Neurodegeneration 2022年第1期11卷 31-45页

作者： chanho Kong Eun-Jeong yang Jaewoo Shin Junwon Park Si-Hyun Kim Seong-wook Park Won Seok chang chang-Han Lee Hyunju Kim Hye-Sun Kim Jin woo chang Department of Neurosurgery Yonsei University College of Medicine50 Yonsei-RoSeodaemun-GuSeoulRepublic of Korea Department of Pharmacology College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Neuroscience Research center College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Department of Biomedical Sciences College of MedicineSeoul National University103 DaehakroJongro-GuSeoulRepublic of Korea Bundang Hospital Seoul National University College of MedicineBundang-GuSungnamRepublic of Korea.

Background:Aducanumab(Adu),which is a human IgG1 monoclonal antibody that targets oligomer and fibril forms of beta-amyloid,has been reported to reduce amyloid pathology and improve impaired cognition after administration of a high dose(10 mg/kg)of the drug in Alzheimer’s disease(AD)clinical *** purpose of this study was to investigate the effects of a lower dose of Adu(3 mg/kg)with enhanced delivery via focused ultrasound(FUS)in an AD mouse ***:The FUS with microbubbles opened the blood-brain barrier(BBB)of the hippocampus for the delivery of *** combined therapy of FUS and Adu was performed three times in total and each treatment was performed biweekly.y-maze test,Brdu labeling,and immunohistochemical experimental methods were employed in this *** addition,RNA sequencing and ingenuity pathway analysis were employed to investigate gene expression profiles in the hippocampi of experimental ***:The FUS-mediated BBB opening markedly increased the delivery of Adu into the brain by approximately 8.1 times in the *** combined treatment induced significantly less cognitive decline and decreased the level of amyloid plaques in the hippocampi of the 5×FAD mice compared with Adu or FUS *** treatment with FUS and Adu activated phagocytic microglia and increased the number of astrocytes associated with amyloid plaques in the hippocampi of 5×FAD ***,RNA sequencing identified that 4 enriched canonical pathways including phagosome formation,neuroinflammation signaling,cREB signaling and reelin signaling were altered in the hippocami of 5×FAD mice receiving the combined ***:In conclusion,the enhanced delivery of a low dose of Adu(3 mg/kg)via FUS decreases amyloid deposits and attenuates cognitive function ***-mediated BBB opening increases adult hippocampal neurogenesis as well as drug *** present an AD treatment strategy through the synergistic effect of the combined therapy of

关键词： Aducanumab Alzheimer’s disease Focused ultrasound Transcriptome profiling

Long-term culture-induced phenotypic difference and efficient cryopreservation of small intestinal organoids by treatment timing of Rho kinase inhibitor

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World Journal of Gastroenterology 2017年第6期23卷 964-975页

作者： Sung-Hoon Han Sehwan Shim Min-Jung Kim Hye-yun Shin Won-Suk Jang Sun-Joo Lee young-woo Jin Seung-Sook Lee Seung Bum Lee Sunhoo Park Laboratory of Radiation Exposure and Therapeutics National Radiation Emergency Medical CenterKorea Institute of Radiological and Medical ScienceSeoul 01812South Korea

To investigate a suitable long-term culture system and optimal cryopreservation of intestinal organoid to improve organoid-based therapy by acquiring large numbers of *** were isolated from jejunum of c57BL/6 mouse. Two hundred crypts were cultured in organoid medium with either epidermal growth factor/Noggin/R-spondin1 (ENR) or ENR/cHIR99021/VPA (ENR-cV). For subculture, organoids cultured on day 7 were passaged using enzyme-free cell dissociation buffer (STEMcELL Technologies). The passage was performed once per week until indicated passage. For cryopreservation, undissociated and dissociated organoids were resuspended in freezing medium with or without Rho kinase inhibitor subjected to different treatment times. The characteristics of intestinal organoids upon extended passage and freeze-thaw were analyzed using EdU staining, methyl thiazolyl tetrazolium assay, qPcR and time-lapse live cell *** established a three-dimensional culture system for murine small intestinal organoids using ENR and ENR-cV media. Both conditions yielded organoids with a crypt-villus architecture exhibiting Lgr5+ cells and differentiated intestinal epithelial cells as shown by morphological and biochemical analysis. However, during extended passage (more than 3 mo), a comparative analysis revealed that continuous passaging under ENR-cV conditions, but not ENR conditions induced phenotypic changes as observed by morphological transition, reduced numbers of Lgr5+ cells and inconsistent expression of markers for differentiated intestinal epithelial cell types. We also found that recovery of long-term cryopreserved organoids was significantly affected by the organoid state, i.e., whether dissociation was applied, and the timing of treatment with the Rho-kinase inhibitor y-27632. Furthermore, the retention of typical morphological characteristics of intestinal organoids such as the crypt-villus structure from freeze-thawed cells was observed

关键词： intestinal organoid Rho kinase inhibitor three-dimensional culture cryopreservation long-term culture

Novel endogenous endoplasmic reticulum transmembrane protein SURF4 suppresses cell death by negatively regulating the STING-STAT6 axis inmyeloid leukemia

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cancer communications 2023年第3期43卷 395-399页

作者： Jayoung Kim Hansong Lee chae Mi Hong Ji Ho Nam Hye Ju yeo woo Hyun cho Hyung-Sik Kim changwan Hong yun Hak Kim Dongjun Lee Department of convergence Medicine School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Biomedical Informatics School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Radiation Oncology School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Division of Allergy Pulmonaryand Critical Care MedicineDepartment of Internal MedicinePusan National University Yangsan HospitalYangsanGyeongsangnam-do 50612Republic of Korea Department of Oral Pathology Dental and Life Science InstituteSchool of DentistryPusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea Department of Anatomy School of MedicinePusan National UniversityYangsanGyeongsangnam-do 50612Republic of Korea

Dear Editor,Myeloid differentiation was shown to be associated with reduced leukemic cell burden and leukemia-initiating cells and improved survival[1].Reactive oxygen species(ROS)are associated with leukemia and can induce endoplasmic reticulum(ER)*** stress induces several mechanisms,including cell death[2].The stimulator of interferon genes(STING)is also an ER transmembrane protein and promotes anti-tumor immunity by linking innate and adaptive immunity[3].Signal transducer and activator of transcription 6(STAT6)plays a prominent role in adaptive immunity by transducing signals fromextracellular cytokines and inducing apoptosis in cancer cells[4].

关键词： STAT6 immunity reticulum

Regulation of dipeptidyl peptidase 8 and 9 expression in activated lymphocytes and injured liver

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World Journal of Gastroenterology 2013年第19期19卷 2883-2893页

作者： Sumaiya chowdhury yiqian chen Tsun-Wen yao Katerina Ajami Xin M Wang yury Popov Detlef Schuppan patrick Bertolino Geoffrey W Mccaughan Denise MT yu Mark D Gorrell centenary Institute and Sydney Medical School University of SydneySydneyNSW 2006Australia Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215United States Molecular Hepatology Centenary InstituteNewtownSydneyNSW 2042Australia

AIM:To investigate the expression of dipeptidyl peptidase(DPP) 8 and DPP9 in lymphocytes and various models of liver ***:DPP8 and DPP9 expression were measured in mouse splenic cD4 + T-cells,cD8 + T-cells and B-cells(B220 +),human lymphoma cell lines and mouse splenocytes stimulated with pokeweed mitogen(PWM) or lipopolysaccharide(LPS),and in dithiothreitol(DTT) and mitomycin-c treated Raji ***8 and DPP9 expression were measured in epidermal growth factor(EGF) treated Huh7 hepatoma cells,in fibrotic liver samples from mice treated with carbon tetrachloride(ccl 4) and from multidrug resistance gene 2(Mdr2 /Abcb4) gene knockout(gko) mice with biliary fibrosis,and in human end stage primary biliary cirrhosis(PBc).RESULTS:All three lymphocyte subsets expressed DPP8 and DPP9 ***8 and DPP9 expression were upregulated in both PWM and LPS stimulated mouse splenocytes and in both Jurkat T-and Raji B-cell ***8 and DPP9 were downregulated in DTT treated and upregulated in mitomycin-c treated Raji ***9transfected Raji cells exhibited more annexin V + cells and associated ***8 and DPP9 mRNA were upregulated in ccl 4 induced fibrotic livers but not in the lymphocytes isolated from such livers,while DPP9 was upregulated in EGF stimulated Huh7 *** contrast,intrahepatic DPP8 and DPP9 mRNA expression levels were low in the Mdr2 gko mouse and in human PBc compared to non-diseased ***:These expression patterns point to biological roles for DPP8 and DPP9 in lymphocyte activation and apoptosis and in hepatocytes during liver disease pathogenesis.

关键词： Dipeptidyl peptidase cD26 Lymphocytes Liver fibrosis Biliary fibrosis

Analysis of the Interface between Primary and Secondary Metabolism in catharanthus roseus cell cultures Using ^13c-Stable Isotope Feeding and coupled Mass Spectrometry

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Molecular Plant 2013年第2期6卷 581-584页

作者： carla Antonio Natali R. Mustafa Sonia Osorio Takayuki Tohge patrick Giavalbco Lothar Willmitzer Heiko Rischer Kirsi-Marj Oksman-caldentey Robert Verpoorte Alisdair R. Fernie central Metabolism Group Max Planck Institute of Molecular Plant Physiology Am Muehlenberg 1 D-14476 Potsdam-Golm Germany Natural Products Laboratory Institute of Biology Leiden University Einsteinweg 55 2300 RA Leiden The Netherlands Present address: Departamento de Biologia Molecular y Bioquimica Universidad de M.~laga 29071 M=~laga Spain Genes and Small Molecules Group Max Planck Institute of MolecularPlant Physiology Am Muehlenberg 1 D-14476 Potsdam-Golm Germany VTT Technical Research centre of Finland PO Box 1000 F1-02044 VTT (Espoo) Finland

Dear Editor, The tropical plant Madagascar periwinkle catharanthus roseus （L.） *** is a rich source of plant-derived medicinal ter-penoid indole alkaloids （TIAs）, including the anti-hypertensive ajmalicine, the sedative compound serpentine, and the anti-cancer drugs vinblastine and vincristine. However, the latter two compounds are produced in c. roseus plants only in very low amounts. Elicitors such as hormones （e.g. jasmonates or salicylic acid） activate plant natural defense responses, includ-ing increased secondary metabolite production （EI-Sayed and Verpoorte, 2007; Lackman et al.. 2011）.

关键词： Secondary Metabolism Terpenes jasmonate biosynthesis Pathway Salicylic Acid cultured cells Interfaces cisplatin/Etoposide/Methotrexate catharanthus roseus Interface

联合高能聚焦超声(HIFU)消融术和经皮乙醇注射术治疗良性甲状腺结节

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国际医学放射学杂志 2021年第3期44卷 371-371页

作者： B.H.H.Lang y.c.woo K.W.H.chiu 谷鹏

摘要目的评估联合高能聚焦超声(HIFU)消融术和经皮乙醇注射术(PEI)治疗良性甲状腺结节的6个月疗效并与只接受HIFU消融术进行比较。方法收集实性或实性为主

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P21-activated kinase 1 (PAK1)-mediated cytoskeleton rearrangement promotes SARS-coV-2 entry and AcE2 autophagic degradation

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5353-5367页

作者： Ming Liu Bingtai Lu yue Li Shuofeng yuan Zhen Zhuang Guangyu Li Dong Wang Liuheyi Ma Jianheng Zhu Jinglu Zhao chris chung-Sing chan Vincent Kwok-Man Poon Kenn Ka-Heng chik Zhiyao Zhao Huifang Xian Jingxian Zhao Jincun Zhao Jasper Fuk-woo chan yuxia Zhang Guangzhou Institute of Pediatrics Guangzhou Women and Children's Medical CentreState Key Laboratory of Respiratory DiseasesGuangzhou Medical University510623 GuangzhouGuangdongChina Medical Research Institute Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangdongChina State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of MedineThe University of Hong KongPokfulamHong KongChina Department of clinical Microbiology and Infection control The University of Hong Kong Shenzhen HospitalShenzhenGuangdongChina centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong KongChina State Key Laboratory of Respiratory Disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affliated Hospital of Guangzhou Medical UniversityGuangzhouChina The Third Afliated Hospital of Zhengzhou University 450052 ZhengzhouChina Guangzhou Laboratory GuangzhouGuangdong ProvinceChina chongqing International Institute for Immunology ChongqingChina

Severe acute respiratory syndrome coronavirus 2(SARS-coV-2),the causative agent of coronavirus disease 2019(cOVID-19),has had a significant impact on healthcare systems and economies *** continuous emergence of new viral strains presents a major challenge in the development of effective antiviral *** that possess broad-spectrum antiviral activities are desirable to control SARS-coV-2 ***2,an angiotensin-containing enzyme that prevents the overactivation of the renin angiotensin system,is the receptor for ***2 interacts with the spike protein and facilitates viral attachment and entry into host ***,SARS-coV-2 infection also promotes AcE2 *** restoring AcE2 surface expression has an impact on SARS-coV-2 infection is yet to be ***,we show that the AcE2-spike complex is endocytosed and degraded via autophagy in a manner that depends on clathrin-mediated endocytosis and PAK1-mediated cytoskeleton *** contrast,free cellular spike protein is selectively cleaved into S1 and s2 subunits in a lysosomal-dependent ***,we show that the pan-PAK inhibitor FRAX-486 restores AcE2 surface expression and suppresses infection by different SARS-coV-2 ***-486-treated Syrian hamsters exhibit significantly decreased lung viral load and alleviated pulmonary inflammation compared with untreated *** summary,our findings have identified novel pathways regulating viral entry,as well as therapeutic targets and candidate compounds for controlling the emerging strains of SARS-coV-2 infection.

关键词： AcE2 inflammation rearrangement

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EDITORIAL cOMMITTEE

Science in china,Ser.A 1963年第3期 455-455页

作者： chairman Wu you-xun(y.H.woo) Vice.chairmen yun Zi-qiang(T.c.yun)Bei Shi-zhang(S.Pai)Zhang Wen-yu(W.y.chang)

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EDITORIAL cOMMITTEE

Science in china,Ser.A 1963年第4期 623-623页

作者： chairman Wu you-xun(y.H.woo) Vice.chairmen yun Zi-qiang(T.c.yun)Bei Shi-zhang(S.Pai)Zhang Wen-yu(W.y.chang)