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Overexpression of Sirt6 ameliorates sleep deprivation induced-cognitive impairment by modulating glutamatergic neuron function

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Neural Regeneration Research 2023年第11期18卷 2449-2458页

作者： Jinpiao Zhu Chang Chen Zhen Li Xiaodong Liu Jingang He Ziyue Zhao Mengying He Binbin Nie Zili Liu Yingying Chen Kuanpin Su Xiang Li Juxiang Chen Hongbing Xiang Fuqiang Xu Kangguang Lin Zongze Zhang Jie Wang Department of Anesthesiology Brain Research CenterDepartment of NeurosurgeryZhongnan HospitalWuhan UniversityWuhanHubei ProvinceChina Department of Anesthesiology and Pain Medicine Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Anesthesia and Intensive Care Peter Hung Pain Research InstituteThe Chinese University of Hong KongHong Kong Special Administration RegionChina Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of Sciences-Wuhan National Laboratory for OptoelectronicsWuhanHubei ProvinceChina Key Laboratory of Nuclear Radiation and Nuclear Energy Technology Institute of High Energy PhysicsChinese Academy of SciencesBeijingChina The Brain Cognition and Brain Disease Institute(BCBDI) NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsShenzhen Key Laboratory of Viral Vectors for BiomedicineShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhenGuangdong ProvinceChina Mind-Body Interface Research Center(MBI-Lab) China Medical University HospitalTaichungTaiwanChina An-Nan Hospital China Medical UniversityTainanTaiwanChina Department of Neurosurgery Changhai HospitalNaval Medical UniversityShanghaiChina Department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Institute of Neuroscience and Brain Diseases Xiangyang Central HospitalAffiliated Hospital of Hubei University of Arts and ScienceXiangyangHubei ProvinceChina University of Chinese Academy of Sciences BeijingChina

Sleep benefits the restoration of energy metabolism and thereby suppo rts neuronal plasticity and cognitive ***6 is a NAD+-dependent protein deacetylase that has been recognized as an essential regulator of energy metabolism because it modulates various transcriptional regulators and metabolic *** aim of this study was to investigate the influence of Sirt6 on cerebral function after chronic sleep deprivation(CSD).We assigned C57BL/6J mice to control or two CSD groups and subjected them to AAV2/9-CMV-EGFP or AAV2/9-CMV-Sirt6-EGFP infection in the prelimbic cortex(PrL).We then assessed cerebral functional connectivity(FC) using resting-state functional MRI,neuron/astrocyte metabolism using a metabolic kinetics analysis;dendritic spine densities using sparse-labeling;and miniature excitato ry postsynaptic currents(mEPSCs) and action potential(AP) firing rates using whole-cell patchclamp *** addition,we evaluated cognition via a comprehensive set of behavioral *** with controls,Sirt6 was significantly decreased(Pnucleus,piriform cortex,motor co rtex,somatosensory co rtex,olfactory tubercle,insular cortex,and ***6 ove rexpression reve rsed CSD-induced cognitive impairment and reduced *** analysis of metabolic kinetics using [1-13C] glucose and [2-13C] acetate showed that CSD reduced neuronal Glu4and GABA2synthesis,which could be fully restored via forced Sirt6 ***,Sirt6 ove rexpression reversed CSD-induced decreases in AP firing rates as well as the frequency and amplitude of mEPSCs in PrL pyramidal *** data indicate that Sirt6 can improve cognitive impairment after CSD by regulating the PrL-associated FC network,neuronal glucose metabolism,and glutamatergic ***,Sirt6 activation may have potential as a novel strategy for treating sleep disorder-related diseases.

关键词： chronic sleep deprivation cognitive impairment functional connectivity glutamatergic neurons metabolic kinetics neuronal-astrocytic glucose metabolism prelimbic cortex REM sleep Sirt6 synaptic function

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*** binding properties of the C-terminal segment of retinol dehydrogenase 8

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Annals of Eye Science 2018年第1期 428-428页

作者： AndréHädicke Ana I.A.Coutinho François Otis Mustapha Lhor Line Cantin Manuel Prieto Normand Voyer Christian Salesse PROTEO and CUO-Recherche Centre de recherche du CHU de Québec-UniversitéLavalHôpital St-SacrementQuébecCanada Centro Química-Física molecular Instituto Superior TécnicoUniversidade de LisboaLisboaPortugal PROTEO and Dépt.Chimie FacultéSciences et génieUniversitéLavalQuébecCanada

Background:Retinol dehydrogenase 8(RDH8)is a 312-amino acid(aa)protein involved in the visual *** to the outer segment disk membranes of photoreceptors,it reduces all-trans-retinal to all-trans-retinol1 as one of the rate-limiting steps of the visual ***8 is a member of the short-chain dehydrogenase/reductase *** C-terminal segment allows its membrane-anchoring through the postulated presence of an amphipathicα-helix and of 1 to 3 acyl groups at positions 299,302 and *** secondary structure and membrane binding characteristics of RDH8 and its C-terminal segment have not yet been ***:To evaluate the membrane binding of RDH8,the full-length protein(aa 1-312),a truncated form(aa 1-296),its C-terminal segment(aa 281-312 and 297-312)as well as different additional variants of this segment were *** truncated protein binds membranes less efficiently than the full-length ***,the C-terminal segment of RDH8 is essential for the binding and has thus been further *** intrinsic fluorescence of tryptophan residues at positions 289 and 310 of the wild-type C-terminal segment of RDH8 and the mutants W289F,W310F and W310R have thus been used to determine their extent of binding to lipid vesicles and to monitor their local *** lipid vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC)or a mixture of POPC and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine(POPS)were used to mimic the phospholipid content of the outer segment disk membranes of ***:An increase in fluorescence intensity and in fluorescence lifetime is observed upon increasing the concentration of lipid *** data allowed calculating values of partition coefficient of the C-terminal segment of RDH8 varying between Kp=1.1 E6 to 1.7 *** is noteworthy that the observation of a more intense shift to lower wavelengths upon membrane binding of the mutant W310R and W310F indicates a deeper inco

关键词： Peptide-membrane binding electrostatic interactions hydrophobic interactions fluorescence spectroscopy

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Kinectin 1 promotes the growth of triple-negative breast cancer via directly co-activating NF-kappaB/p65 and enhancing its transcriptional activity

Kinectin 1 promotes the growth of triple-negative breast can...

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2022CCTB中国肿瘤标志物学术大会暨中国整合肿瘤学大会暨第十六届肿瘤标志物青年科学家论坛暨中国肿瘤标志物产业创新大会

作者： Lin Gao Shanze Chen Malin Hong Wenbin Zhou Bilan Wang Junying Qiu Jinquan Xia Pan Zhao Li Fu Jigang Wang Yong Dai Ni Xie He Yang Hsien-Da Huang Xiang Gao Chang Zou The Second Clinical Medical College Jinan University (Shenzhen People's Hospital) Department of Respiratory and Critical Care Medicine First Affiliated Hospital of Southern University of Science and TechnologyThe Second Clinical Medical CollegeJinan University (Shenzhen People's Hospital)Shenzhen Institute of Respiratory Diseases Shenzhen Public Service Platform on Tumor Precision Medicine and molecular Diagnosis the Second Clinical Medical CollegeJinan University (Shenzhen People's Hospital) Department of Pharmacy West China Second University Hospital of Sichuan University Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Pharmacology and International Cancer CenterShenzhen University Health Science Center Department of Integrated Chinese and Western Medicine Jinan University Warshel Institute for Computational Biology The Chinese University of HongKong Department of Neurosurgery State Key Laboratory of BiotherapyWest China HospitalSichuan University School of Life and Health Sciences The Chinese University of Kong Hong

Triple-negative breast cancer(TNBC) is the most challenging subtype of breast *** endeavor has been made to explore the molecular biology basis of ***,we reported a novel function of factor Kinectin 1(KTN1) as a carcinogenic promoter in ***1 expression in TNBC was increased compared with adjacent tissues or luminal or Her2subtypes of breast cancer,and TNBC patients with high KTN1 expression have poor *** functional studies,knockdown of KTN1 inhibited the proliferation and invasiveness of TNBC both in vitro and in vivo,while overexpression of KTN1 promoted cancer cell proliferation and ***-seq analysis revealed that the interaction of cytokine-cytokine receptor,particularly CXCL8 gene,was upregulated by KTN1,which was supported by the further ***8 depletion inhibited the tumorigenesis and progression of ***,rescue experiments validated that KTN1-mediated cell growth acceleration in TNBC was dependent on CXCL8 both in vitro and in ***,it was found that KTN1 enhanced the phosphorylation of NF-κB/p65 protein at Ser536 site,and specifically bound to NF-κB/p65 protein in the nucleus and cytoplasm of ***,the transcription of CXCL8 gene was directly upregulated by the complex of KTN1 and NF-κB/p65 *** together,our results elucidated a novel mechanism of KTN1 gene in TNBC tumorigenesis and ***1 may be a potential molecular target for the development of TNBC treatment.

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