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Pharmacokinetics of radioimmunotherapeutic agent of direct labeling mAb ^(188)Re-HAb18

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World Journal of Gastroenterology 2002年第1期8卷 69-73页

作者： Chao Lou Zhi-Nan Chen Hui-Jie Bian Department of cell Engineering Research Centre,Jie Li,Department of Oral cell Biology,Qingdu Hospital,Fourth Military Medical University,Xi’an 710033,Shaanxi Province,China Shou-Bo Zhou School of Biological Sciences,University of Manchester,Oxford Road,United Kingdom Department of cell Engineering Research Centre Fourth Military Medical University Xi'an 710033 Shaanxi Province China. wall1970@***

AIM: To labed Anti-hepatoma monoclonal antibody (mAb)fragment HAb18 F (ab')2 was labeled with 188 Re for thepharmacokinetic model of 188 Re-HAb18 F (ab')2 and toevaluate its pharmacokinetic parameters in hepatoma-bearing nude ***: HAb18 F(ab')2 was directly labeled with 188Reusing 2-mercaptoethanol (2-ME) as reducing *** efficiency and immunoreactivity of 188 Re-HAb18 F( ab')2 were evaluated by Whatman 3MM paperchromatography and live cell assay, *** analysis was also conducted in nude micebearing human hepatoma in which animals were sacrificed atdifferent time points(1, 4, 18, 24 and 24h) after 188Re-HAb18F(ab' )2 was injected through tail-vein into hepatoma-bearingnude mice. The blood and radioactivity of organs and masswere measured. The concentrations of 188 Re-HAb18 F(ab')2were evaluated with a pharmacokinetic 3P97 ***: The optimum labeling efficiency andimmunoreactive fraction were 91.7% and 0.78%,respectively. The parameters of 188Re-HAb18 F(ab')2 were:T1/2, 2.29h; Vd, 1.49 × 10-9L@ Bq- 1; AUC, 20.49 × 109Bq@ h@L-1 ;CL, 0.45 × 10-3L@ h- 1. 188Re- HAb18 F(ab')2 could locatespecially in hepatoma with high selective reactivity of HAb18F(ab')2. 188 Re-HAb18 F(ab')2 was mainly eliminated bykidney. The maximal tumor to blood ratio was at 48h, andmaximal tumor to liver ratio was at ***: The pharmacokinetics of 188Re-HAb18 F(ab')2fit a I-compartment model. 188 Re-HAb18 F(ab')2 can beuptaken selectively at the hepatoma site.

关键词：肝癌放射免疫疗法药物动力学 188Re 实验研究

The SWI/SNF chromatin-remodeling factors BAF60a, b, and c in nutrient signaling and metabolic control

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Protein & cell 2018年第2期9卷 207-215页

作者： Ruo-Ran Wang Ran Pan Wenjing Zhang Junfen Fu Jiandie D. Lin Zhuo-Xian Meng Department of Pathology and Pathophysiology Key Laboratory of Disease Proteomics of Zhejiang Province School of Medicine Chronic Disease Research Institute of School of Public Health Zhejiang University Hangzhou 310058 China Children's Hospital Zhejiang University School of Medicine Hangzhou 310003 China Life Sciences Institute and Department of cell & Developmental Biology University of Michigan Medical Center Ann Arbor MI 48109 USA

Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWlISNF *** complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological sigrials. The ATP-dependent SWl/SNF ing complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different m^abolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.

关键词： BAF60a BAF60b BAF60c chromatin- remodeling SWI/SNF energy metabolism nutrient sensing glucose lipid skeletal muscle liver

Akt signaling is involved in neonatal stress-induced autisticlike behaviors

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Akt signaling is involved in neonatal stress-induced autisti...

Interferon-gamma and tumor necrosis factor-alpha synergistically enhance the immunosuppressive capacity of human umbilical-cordderived mesenchymal stem cells by increasing PD-L1 expression

中国神经科学学会第十二届全国学术会议

作者： Xiao-Yun ZHANG Zi-Kai ZHOU The Key laboratory of Developmental Genes and human Disease Ministry of Education Institute of Life Sciences Southeast University

The serine/threonine kinase Akt, also known as protein kinase B, plays an essential role in diverse signaling transduction pathways, such as cell survival, proliferation, apoptosis, cell migration, glucose metabolism and cell-cycle progression. A critical period of brain development refers to a specific time window during early postnatal life, when the brain is extremely flexible to acquire certain information or environment stimuli. It is known that brain circuits can be shaped by experience during critical period, which modulates adult emotion, cognition and behaviors. Although accumulating studies have indicated that aberrant Akt signaling underlies pathogenesis of complex human disorders including diabetes, cancer and neurological diseases, little is known about the function of Akt signaling in brain development during the critical period. We employed maternal separation, a commonly used early life stress model, to investigate the functions of Akt signaling cascade in neonatal brain development. With a combination of behavioral, electrophysiological and biochemical assays, our results suggest an important role of Akt signaling in synaptic modulation during the critical period, and that neonatal stress may cause autistic-like behaviors in adult mice through the Akt signaling pathway.

关键词： Akt neonatal brain development critical period autistic-like behaviors

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世界干细胞杂志:英文版(电子版) 2023年第8期15卷 787-806页

作者： Zhuo Chen Meng-Wei Yao Zhi-Lin Shen Shi-Dan Li Wei Xing Wei Guo Zhan Li Xiao-Feng Wu Luo-Quan Ao Wen-Yong Lu Qi-Zhou Lian Xiang Xu Xiang Ao Department of Stem cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042China College of Basic Medical Sciences Army Medical UniversityChongqing 400038China Department of Orthopedics Daping HospitalArmy Medical UniversityChongqing 400042China Department of Hepatobiliary Surgery The First Affiliated Hospital of Wenzhou Medical UniversityThe South of Shangcai VillageWenzhou 325005Zhejiang ProvinceChina Department of Medicine Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China Department of Orthopedics 953 Hospital of PLA ArmyShigatse Branch of Xinqiao HospitalArmy Medical UniversityShigatse 857000Tibet Autonomous RegionChina

BACKGROUND The immunosuppressive capacity of mesenchymal stem cells(MSCs)is dependent on the“license”of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1(PD-L1),which determines the clinical therapeutic efficacy of MSCs for inflammatory or immune *** MSCs,interferon-gamma(IFN-γ)is a key inducer of PD-L1 expression,which is synergistically enhanced by tumor necrosis factor-alpha(TNF-α);however,the underlying mechanism is *** To reveal the mechanism of pretreated MSCs express high PD-L1 and explore the application of pretreated MSCs in ulcerative *** We assessed PD-L1 expression in human umbilical-cord-derived MSCs(hUC-MSCs)induced by IFN-γand TNF-α,alone or in ***,we performed signal pathway inhibitor experiments as well as RNA interference experiments to elucidate the molecular mechanism by which IFN-γalone or in combination with TNF-αinduces PD-L1 ***,we used luciferase reporter gene experiments to verify the binding sites of the transcription factors of each signal transduction pathway to the targeted gene ***,we evaluated the immunosuppressive capacity of hUC-MSCs treated with IFN-γand TNF-αin both an in vitro mixed lymphocyte culture assay,and in vivo in mice with dextran sulfate sodium-induced acute *** Our results suggest that IFN-γinduction alone upregulates PD-L1 expression in hUC-MSCs while TNF-αalone does not,and that the co-induction of IFN-γand TNF-αpromotes higher expression of ***-γinduces hUCMSCs to express PD-L1,in which IFN-γactivates the JAK/STAT1 signaling pathway,up-regulates the expression of the interferon regulatory factor 1(IRF1)transcription factor,promotes the binding of IRF1 and the PD-L1 gene promoter,and finally promotes PD-L1 *** TNF-αalone did not induce PD-L1 expression in hUCMSCs,the addition of TNF-αsignificantly enhanced IFN-γ-induced JAK/STAT1/IRF1 ***-αup

关键词： human umbilical-cord-derived mesenchymal stem cells Programmed cell death 1 ligand 1 Immunomodulation Interferon-gamma Tumor necrosis factor-alpha Ulcerative colitis

Molecular characterization and functional expression of opioid receptor-libe1 receptor

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cell Research 1997年第1期7卷 69-77页

作者： WU YA LAN LU PU KUN LING JIAN ZHAO ZHI JIE CHENG LAN MA GANG PEI(Shanghai Institute of cell Biology, Chinese Academy of Sciences, Shanghai 200031, China)(Shanghai Medical University, Shanghai 200032, China) Shanghai Institute of cell Biology Chinese Academy of Sciences Shanghai China Shanghai Medical University Shanghai China

The opioid receptor-libel receptor (ORL), an orphan receptor whose human and murine complementary DNAs,has been characterized recently. ORL transcripts are particularly abundant in the central nervous system. We demonstrated that ORL expressed in human neuroblastoma SK-N-SH and SH-SY5Y cell lines by radioligand binding assay, reverse transcription polymerase chain reaction (RT-PCR) and Northern analysis in the present study. Stimulation with ORL1 specific agonist, nociceptin/orphanin Fo, increased [34S]GTPrγS binding to SK-N-SH cell membranes (EC50 = 14 ±0.45 nM), and attenuated forskolin-stimulated accumulation of cellular cAMP (EC50= 0.80 ±0.45 nM, indicative that activation of ORL1 activates G proteins and inhibits adenylyl cyclase. Activation of ORL1 receptor was also accessed using CHO:hORL1 cell line by microphysiometer. Treatment of nociceptin/orphanin FQ increased extracellular acidification rate significantly.

关键词： Opioid receptor-libe1 receptor (ORL1) nociceptin/orphanin FQ (N/OFQ) SK-N-SH cells extracellular acidification functional expression

Comparison of Reference Genes for Transcriptional Studies in Postmortem human Brain Tissue Under Different Conditions

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Neuroscience Bulletin 2019年第2期35卷 225-228页

作者： Qing Zhang Hanlin Zhang Fan Liu Qian Yang Kang Chen Pan Liu Tianyi Sun Chao Ma Wenying Qiu Xiaojing Qian Department of human Anatomy Histology and EmbryologySchool of Basic Medicine Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences Joint laboratory of Anesthesia and Pain Peking Union Medical College Chinese Academy of Medical Sciences Eight-Year MD Program Peking Union Medical College

Dear Editor Research on neurodegenerative diseases is a hot topic worldwide[1],and MRI,genetics and epigenetics,and animal models have been commonly *** species differences,research on human brain samples is irreplaceable(2)Many countries and regions have built brain banks to collect and store brain tissue from *** provided by a brain bank can be used to study synaptic structure,protein,DNA,RNA[3,4],and lipids to illuminate the pathological mechanisms underlying neurodegenerative *** brain tissue is used for gene expression research,the quantitative real-time polymerase chain reaction(RT-qPCR)is an accurate method,which simultaneously amplifies and quantifies the expression of target genes by measuring the intensity of fluorescence in each PCR cycle.

关键词： TBP Comparison of Reference Genes for Transcriptional Studies in Postmortem human Brain Tissue Under Different Conditions

Multifaceted roles of complementary sequences on circRNA formation

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Frontiers of Electrical and Electronic Engineering in China 2017年第3期5卷 205-209页

作者： Qin Yang Ying Wang Li Yang CAS Key laboratory of Computational Biology Collaborative Innovation Center of Genetics and Development CAS-MPG Partner Institute for Computational Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai 200031 China School of Life Science and Technology ShanghaiTech University Shanghai 201210 China

Background： Circular RNAs （circRNAs） from back-spliced exon（s） are characterized by the covalently closed loop feature with neither 5＇ to 3＇ polarity nor polyadenylated tail. By using specific computational approaches that identify reads mapped to back-splice junctions with a reversed genomic orientation, ten thousands of cireRNAs have been recently re-identified in various cell lines/tissues and across different species. Increasing lines of evidence suggest that back-splicing is catalyzed by the canonical spliceosomal machinery and modulated by cis-elements and trans-factors. Results： In this mini-review, we discuss our current understanding of circRNA biogenesis regulation, mainly focusing on the complex regulation of complementary sequences, especially Alus in human, on circRNA formation. Conclusions： Back-splicing can be significantly facilitated by RNA pair formed by orientation-opposite complementary sequences that juxtapose flanking introns of circularized exon（s）. RNA pair formed within individual introns competes with RNA pair formed across flanking introns in the same gene locus, leading to distinct choices for either canonical splicing or back-splicing. Multiple RNA pairs that bracket different circle-forming exons compete for alternative back-splicing selection, resulting in multiple circRNAs generated in a single gene locus.

关键词： circRNA circRNA biogenesis back-splicing cis-elements complementary sequences Alu

Neurodevelopmental impairment induced by prenatal valproic acid exposure shown with the human cortical organoid-on-a-chip model

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Microsystems & Nanoengineering 2020年第1期6卷 754-767页

作者： Kangli Cui Yaqing Wang Yujuan Zhu Tingting Tao Fangchao Yin Yaqiong Guo Haitao Liu Fei Li Peng Wang Yuejun Chen Jianhua Qin Division of Biotechnology CAS Key Laboratory of SSACDalian Institute of Chemical PhysicsChinese Academy of Sciences457 Zhongshan RoadDalian 116023China University of Chinese Academy of Sciences Beijing 100049China CAS Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijingChina

Prenatal exposure to environmental insults can increase the risk of developing neurodevelopmental *** of the antiepileptic drug valproic acid(VPA)during pregnancy is tightly associated with a high risk of neurological disorders in ***,the lack of an ideal human model hinders our comprehensive understanding of the impact of VPA exposure on fetal brain development,especially in early ***,we present the first report indicating the effects of VPA on brain development at early stages using engineered cortical organoids from human induced pluripotent stem cells(hiPSCs).Cortical organoids were generated on micropillar arrays in a controlled manner,recapitulating the critical features of human brain development during early *** VPA exposure,cortical organoids exhibited neurodevelopmental dysfunction characterized by increased neuron progenitors,inhibited neuronal differentiation and altered forebrain *** analysis showed new markedly altered genes(e.g.,KLHL1,LHX9,and MGARP)and a large number of differential expression genes(DEGs),some of which are related to *** particular,comparison of transcriptome data via GSEA and correlation analysis revealed the high similarity between VPA-exposed organoids with the postmortem ASD brain and autism patient-derived organoids,implying the high risk of autism with prenatal VPA exposure,even in early *** new findings facilitate a better understanding of the cellular and molecular mechanisms underlying postnatal brain disorders(such as autism)with prenatal VPA *** established cortical organoid-on-a-chip platform is valuable for probing neurodevelopmental disorders under environmental exposure and can be extended to applications in the study of diseases and drug testing.

关键词： markedly inhibited exposure

DISC1,mTOR and adult neurogenesis

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DISC1,mTOR and adult neurogenesis