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First progeria monkey model generated using base editor

Protein & Cell 2020年第12期11卷 862-865页

作者： Pradeep Reddy Yanjiao Shao Reyna Hernandez-Benitez estrella nunez delicado Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA Universidad Catolica San Antonio de Murcia(UCAM) Campus de los JerdnimosN°13512Guadalupe 30107Spain

In this issue,Wang et *** on the generation of a nonhuman primate model of Hutchinson-Gilford progeria syndrome(HGPS)using a base *** editing is an emerging novel genome editing technique for modifying a single base pair at specific sites in the *** editors(BEs)have two prin cipal comp orients,a catalytically in active or single strand cleaving Cas-variant,which binds to the guide RNA and a nucleobase deaminase domain to convert specific base pairs at the target loci(Komor et al.,2016;Nishida et al.,2016;Gaudelli et al.,2017).Cytosine base editor(CBE)and adenine base editor(ABE)are two baseeditors,which con vert Cytosi ne-Gua nine(C-G)to Thymine-Adenine(T-A)and A-T to G-C,respectively.

关键词： base convert editor

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Mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-Martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy Min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia estrella nunez delicado Antoni Castells Josep M. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain Molecular and Cell Biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Howard Hughes Medical Institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative Genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and Research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCR2 stratified epithelia

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αKLOTHO and sTGFβR2 treatment counteract the osteoarthritic phenotype developed in a rat model

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Protein & Cell 2020年第3期11卷 219-226页

作者： Paloma Martinez-Redondo Isabel Guillen-Guillen Noah Davidsohn Chao Wang Javier Prieto Masakazu Kurita Fumiyuki Hatanaka Cuiqing Zhong Reyna Hernandez-Benitez Tomoaki Hishida Takashi Lezaki Akihisa Sakamoto Amy NNemeth Yuriko Hishida Concepcion Rodriguez Esteban Kensaku Shojima Ling Huang Maxim Shokhirev estrella nunez-delicado Josep MCampistol Isabel Guillen-Vicente Elena Rodriguez-Inigo Juan Manuel Lopez-Alcorocho Marta Guillen-Vicente George Church Pradeep Reddy Pedro Guillen-Garcia Guang-Hui Liu Juan Carlos Izpisua Belmonte Gene Expression Laboratory Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA Wyss Institute for Biologically Inspired Engineering Harvard UniversityCambridgeMA 02115USA Department of Genetics Harvard Medical SchoolBostonMA 02115USA Integrative Genomics and Bioinformatics Core Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA Universidad Catolica San Antonio de Murcia(UCAM) Campus de los JeronimosNo 1351230107 GuadalupeSpain Hospital Clinic of Barcelona Career Villarroel17008036 BarcelonaSpain Department of Traumatology and Research Unit Clinica CEMTRO28035 MadridSpain National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Translational Medical Center for Stem Cell Therapy Shanghai East HospitalTongji University School of MedicineShanghai 200120China

Dear Editor,Homeostasis and repair are critical biological processes that allow for tissue and organ preservation and function in multicellular *** regulation and extension vary drastically across the animal kingdom,and mammals show limited tissue-specific regenerative capacity that declines with *** aging,articular cartilage is one of the tissues that undergo substantial changes in the matrix structure,molecular composition,metabolic activity,and mechanical properties(Loeser et al.2016).

关键词： aging treatment critical

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Complexation of Eugenol(EG),as Main Component of Clove Oil and as Pure Compound,withβ-and HP-β-CDs

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Food and Nutrition Sciences 2012年第6期3卷 716-723页

作者： Pilar Hernández-Sánchez Santiago López-Miranda Carmen Lucas-Abellán estrella Núnez-delicado Departament of Food Technology and Nutrition Catholic University of San AntonioMurciaSpain.

Eugenol, both in its pure form (EG) and included in essential clove oil (CO) was successfully solubilized in aqueous solution by forming inclusion complexes with β-cyclodextrins (β-CDs) and its modified hydroxy-propyl-β-CDs (HP-β-CDs). To investigate the molecular association between β-CDs/HP-β-CDs with pure EG and essential CO, phase solubility studies were undertaken. Essential CO formed insoluble complexes with β-CDs, but not with HP-β-CDs. The work clearly demonstrates complexes formation follow an order higher than 1:1 when high essential CO and β-CDs concentrations were used, however it was 1:1 in the case of essential CO-HP-β-CDs complexes. When pure EG was studied the results indicated that EG could form 1:1 inclusion complexes with β-CDs and HP-β-CDs. Based on the studies, the Kc values for pure EG were 4555 ± 225 M-1 and 10,633 ± 614 M-1 for β-CDs and HP-β-CDs, respectively, and 2005 ± 199 M-1 for essential CO-HP-β-CDs. These finding indicate that CDs are suitable for encapsulating EG.

关键词： Eugenol Essential Clove Oil β-CDs HP-β-CDs

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Complexation of Eugenol (EG), as Main Component of Clove Oil and as Pure Compound,with β- and HP-β-CDs

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Food and Nutrition Sciences（食品与营养科学） 2012年第6期

作者： Pilar Hernández-Sánchez Santiago López-Miranda Carmen Lucas-Abellán estrella Núñez-delicado

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