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Quantification and pharmacokinetic study of tumor-targeting agent MHI148-clorgyline amide in mouse plasma using liquid chromatography-electrospray ionization tandem mass spectrometry

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Journal of Pharmaceutical Analysis 2018年第3期8卷 153-159页

作者： Zhijun wang Bogdan Z.Olenyuk Jean Chen Shih jeffrey wang Center for Advancement of Drug Research and Evaluation College of Pharmacy Western University of Health Sciences Department of Pharmaceutical Sciences College of Pharmacy Marshall B.Ketchum University Department of Pharmacology and Pharmaceutical Sciences School of Pharmacy Department of Cell and Neurobiology Keck School of Medicine USC-Taiwan Center for Translational Research University of Southern California Department of Pharmaceutical Sciences College of Pharmacy Western University of Health Sciences

A high-performance liquid chromatography-electrospray ionization tandem mass spectrometric （HPLC- ESI-MS/MS） method was developed for the quantification of MHl148-clorgyline amide （NMl-amide）, a novel tumor-targeting monoamine oxidase A inhibitor, in mouse plasma. The method was validated in terms of sensitivity, precision, accuracy, recovery and stability and then applied to a pharmacokinetic study of NMl-amide in mice following intravenous administration. NMl-amide together with the internal standard （IS）, MHI-148, was extracted by protein precipitation using acetonitrile. Multiple reaction monitoring was used for quantification of NMl-amide by detecting m/z transition of 491.2-361.9, and 685.3-258.2 for NMl-amide and the IS, respectively. The lower limit of quantification （LLOQ） of the HPLC- MS/MS method for NMl-amide was 0.005 μg/mL and the linear calibration curve was acquired with R2〉 0.99 in the concentration range of 0.005-2μg/mL. The intra- and inter-day precisions of the assay were assessed by percentage of the coefficient of variations, which was within 9.8% at LLOQ and 14.0% for other quality control samples, whereas the mean accuracy ranged from 86.8% to 113.2%. The samples were stable under storage and experimental conditions. This method was successfully applied to a pharmacokinetic study in mice following intravenous administration of 5 mg/kg NMl-amide.

关键词： MH1148-clorgyline HPLC Mass spectrometry Pharmacokinetics

Phytochemical Analysis of Medicinal Plants with Kidney Protective Activities

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Chinese Journal of Integrative Medicine 2012年第10期18卷 790-800页

作者： Eric Jung-chi Lien Linda Lin-min Lien Rubin wang jeffrey wang Department of Pharmacology and Pharmaceutical Sciences School of PharmacyUniversity of Southern California Department of Chemistry & Biochemistry University of California Department of Pharmaceutical Sciences College of PharmacyWestern University of Health Sciences

In view of the increasing number of patients undergoing kidney dialysis or transplant every year, a survey of the literature on renal protective medicinal plants was undertaken. Most of them are from traditional Chinese medicine （TCM）. Although many of the medicinal herbs reported have not been investigated in terms of active chemical ingredients, some do have compounds well characterized. They fall into a wide range of structures. Several groups of compounds with well established activities are discussed. These include： antioxidant phenolic compounds like tannins, flavonoids, isoflavonoids, unsaturated organic acids and lignans; circulation enhancing compounds like saponins, and basic alkaloids with multiple targets （G-protein coupled receptors）. Also presented are proinflammatory and antiinflammatory fatty acids like linoleic （n-6） and α-Iinolenic （n-3） acids, respectively. Attention is also drawn to the plants containing nephrotoxic aristolochic acid. Different directions of future research are also presented. We hope that this review may provide some leads for new drug discovery and development, and more rational application of TCM.

关键词： kidney protective herbs kidney protection natural products antioxidants free radical scavengers immunomodulating agents antiinflammatory agents structure-activity relationship physicochemical parameters

Chemotherapy-induced small extracellular vesicles prime the pre-metastatic niche to accelerate neuroblastoma metastasis

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Genes & Diseases 2024年第4期11卷 65-68页

作者： Carson A.Wills Xiaoming Liu Longgui Chen Yuanjun Zhao Zhenqiu Liu Vladimir S.Spiegelman jeffrey Sundstrom Hong-Gang wang Department of Pediatrics Division of Pediatric Hematology and OncologyThe Pennsylvania State University Collegeof MedicinePA 17033USA Department of Ophthalmology The Pennsylvania State University College of MedicinePA 17033USA Department of Public Health Sciences The Pennsylvania StateUniversityCollegeofMedicinePA 17033USA

Neuroblastoma is the most common extracranial solid tumor in children,accounting for more than 10%of cancerrelated deaths in this *** standard of care for patients diagnosed with medium-to high-risk neuroblastoma,incl... 详细信息

关键词： neuroblastoma metastatic metastasis

Differentiation of human bone marrow precursor cells into neuronal-like cells after transplantation into canine spinal cord organotypic slice cultures

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Chinese Medical Journal 2012年第22期125卷 4049-4054页

作者： FEI Zhi-qiang, XIONG Jian-yi CHEN Lei SHEN Hui-yong Ngo Stephanie wang jeffrey wang Da-ping Shenzhen Second Peoples Hosp Dept Orthopaed Shenzhen Key Lab Tissue Engn Res Ctr Shenzhen 518035 Guangdong Peoples R China Sun Yat Sen Univ Mem Hosp Dept Orthopaed Guangzhou 510120 Guangdong Peoples R China Univ Calif Los Angeles UCLA Spine Ctr Santa Monica CA 90404 USA

Background Treatments to regenerate different tissue involving the transplantation of bone marrow derived mesenchymal precursor cells are anticipated. Using an alternative methods, in vitro organotypic slice culture method, would be useful to transplant cells and assessing the effects. This study was to determine the possibility of differentiating human bone marrow precursor cells into cells of the neuronal lineage by transplanting into canine spinal cord organotypic slice cultures. Methods Bone marrow aspirates were obtained from posterior superior iliac spine （PSIS） of patients that had undergone spinal fusion due to a degenerative spinal disorder. For cell imaging, mesenchymal precursor cells （MPCs） were pre-stained with PKH-26 just before transplantation to canine spinal cord slices. Canine spinal cord tissues were obtained from three adult beagle dogs. Spinal cords were cut into transverse slices of 1 mm using tissue chopper. Two slices were transferred into 6-well plate containing 3 ml DMEM with antibiotics. Prepared MPCs （lx104） were transplanted into spinal cord slices. On days 0, 3, 7, 14, MPCs were observed for morphological changes and expression of neuronal markers through immunofluorescence and reverse transcription-polymerase chain reaction （RT-PCR）. Results The morphological study showed： spherical cells in the control and experiment groups on day 0; and on day 3, cells in the control group had one or two thick, short processes and ones in the experiment group had three or four thin, long processes. On day 7, these variously-sized processes contacted each other in the experiment group, but showed typical spindle-shaped cells in the control group. Immunofluorescence showed that PKH-26（＋） MPCs stained positive for NeuN （＋） and GFAP（＋） in experimental group only. Also RT-PCR showed weak expression of β-tubulin III and GFAP. Conclusions Human bone marrow mesenchymal precursor cells （hMPCs） have the potential to differentiate into the neuronal like cells i

关键词： differentiation mesenchymal precursor cell organotypic slice culture spinal cord

High-quality assembled and annotated genomes of Nicotiana tabacum and Nicotiana benthamiana reveal chromosome evolution and changes in defense arsenals

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Molecular Plant 2024年第3期17卷 423-437页

作者： Jubin wang Qingling Zhang jeffrey Tung Xi Zhang Dan Liu Yingtian Deng Zhendong Tian Huilan Chen Taotao wang Weixiao Yin Bo Lij Zhibing Lai Savithramma P.Dinesh-Kumar Barbara Baker Feng Li National Key Laboratory for Germplasm Innovation and Utilization for Fruit and Vegetable Horticultural Crops College of Horticulture and Forestry SciencesHuazhong Agricultural UniversityWuhanHubei 430070China Plant Gene Expression Center Department of Plant and Microbial BiologyUniversity of CaliforniaBerkeleyBerkeleyCA 94706USA College of Plant Science and Technology Huazhong Agricultural UniversityWuhanHubei 430070China College of Life Science and Technology Huazhong Agricultural UniversityWuhanHubei 430070China Department of Plant Biology and The Genome Center College of Biological SciencesUniversity of CalforniaDavisDavisCA 95616USA The Key Laboratory of Horticultural Plant Genetic and Improvement of Jiangxi Province Institute of Biological ResourcesJiangxi Academy of SciencesNanchang 330299China institute of Vegetables and Flowers Jiangxi Academy of Agricultural SciencesNanchang 330200Chin Hubei Hongshan Laboratory WuhanHubei 430070China

Nicotiana tabacum and Nicotiana benthamiana are widely used models in plant biology ***,genomic studies of these species have *** we report the chromosome-level reference genome assemblies for *** and *** with an estimated 99.5%and 99.8%completeness,*** transcription start and termination site sequencing methods were developed and used for accurate gene annotation in *** analyses revealed evidence for the parental origins and chromosome structural changes,leading to hybrid genome formation of each ***,theantiviral silencinggenesRDR1,RDR6,DCL2,DCL3,andAGO2were lost from one or both subgenomes in ***,while both homeologs were kept in ***,the *** genome encodes fewer immune receptors and signaling components than that of *** find-ings uncover possible reasons underlying the hypersusceptible nature of *** developed the user-friendly Nicomics(http:/***/Nicomics/)web server to facilitate better use of Nicotiana genomic resources as well as gene structure and expression analyses.

关键词： Nicotiana tabacum Nicotiana benthamiana genomics evolution disease resistance NLR

Coupled Inversion of Pressure and Tiltmeter Data for Mapping Hydraulic Fracture Geometry

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Acta Mechanica Solida Sinica 2024年第3期37卷 396-405页

作者： Zuorong Chen Xiaofang Jiang Zhejun Pan Robert G.jeffrey National Key Laboratory of Continental Shale Oil Northeast Petroleum UniversityDaqing163318China SCT Operation Pty.Ltd. PO Box 824WollongongNSW2520Australia

Pressure and tilt data are jointly inverted to simultaneously map the orientation and dimensions of a hydraulic *** deformation induced by a fracture under internal pressure is modeled using the distributed dislocation *** planar fracture is represented by four quarter ellipses,joined at the center and sharing *** configuration provides a straightforward model for characterizing asymmetric fracture *** inverse problem of mapping the fracture geometry is formulated using the Bayesian probabilistic method,combining the a priori information on the fracture model with updated information from pressure and tilt *** the nonlinear inverse problem is achieved by pseudo-randomly sampling the posterior probability distribution through the Markov chain Monte Carlo *** resulting posterior probability distribution is then explored to assess uncertainty,resolution,and correlation between model *** experiments are conducted to verify the accuracy and validity of the proposed analysis method in mapping the fracture geometry using synthetic pressure and tilt data.

关键词： Hydraulic fracture mapping Coupled inversion Tilt Treating pressure

Reflections on COPD comorbidities

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Chinese Medical Journal 2024年第12期137卷 1504-1506页

作者： Zhenming He Yue wang Lin Shan Yan Mou Yunhuan Liu Guanhua Ma Yanxu Wu Huili Zhu jeffrey L.Curtis Shilei Cui Haiyan Ge Department of Pulmonary and Critical Care Medicine Huadong HospitalFudan UniversityShanghai 200040China Medical Service VA Ann Arbor Healthcare SystemAnn ArborMI 48105USA Pulmonary&Critical Care Medicine Division Department of Internal MedicineUniversity of MichiganAnn ArborMI 48109USA Graduate Program in Immunology University of MichiganAnn ArborMI 48109USA

To the Editor:Chronic obstructive pulmonary disease(COPD)is a common disease among the elderly,affecting over one-third of the elderly population *** progressive decline in lung function characteristic of COPD significantly impacts the quality of life and employability of affected individuals,resulting in a substantial direct and indirect socioeconomic *** frequently has comorbidities involving other organ *** all elderly COPD patients present with one or more comorbid conditions,collectively exacerbating health and economic *** viral and bacterial infections remain the most common triggers for COPD exacerbations(ECOPD).

关键词： morbid lung collective

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui wang Annie wang Zander Schwartz jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

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World Journal of Gastroenterology 2024年第25期30卷 3182-3184页

作者： jeffrey A Lowell Michael J Farber Keith Sultan Department of Medicine Zucker School of Medicine at HofstraNorth Shore University Hospital-Long Island Jewish Medical CenterManhassetNY 11030United States Preclinical Studies New York Institute of Technology College of Osteopathic MedicineGlen HeadNY 11545United States Division of Gastroenterology Northwell HealthNorth Shore University Hospital and Long Island Jewish Medical CenterGreat NeckNY 10021United States

Inflammatory bowel disease(IBD)is entering a potentially new era of combined *** et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this *** importance of controlled trials should be stressed in establishing new treatment *** prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

关键词： Inflammatory bowel disease Biologics Immunomodulators Dual-therapy Combination therapy