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第十一届全国免疫学学术大会

作者：桑威王莹张聪潘彬陈伟闫冬梅 thomas p.loughran Jr 徐开林徐州医科大学附属医院血液科

目的 :研究miR-150作为异体造血干细胞移植后出现急性植物抗宿主病的预防与诊断指标的作用机制方法 :通过三质粒包装构建过表达miR-150的慢病毒载体。利用磁珠分选的方法从人外周血分离纯化出CD4+T细胞,流式细胞术分选出GFp阳性细胞,活... 详细信息

目的 :研究miR-150作为异体造血干细胞移植后出现急性植物抗宿主病的预防与诊断指标的作用机制方法 :通过三质粒包装构建过表达miR-150的慢病毒载体。利用磁珠分选的方法从人外周血分离纯化出CD4+T细胞,流式细胞术分选出GFp阳性细胞,活化后进行慢病毒转染。采用q RT-pCR方法,检测miR-150的水平。利用q RT-pCR及Western Blot法检测转染LV-miR-150后ARRB2 m RNA水平及蛋白表达,并利用荧光素酶报告基因实验进行把基因验证。进行胞内细胞因子染色后上流式检测Th细胞亚群情况;Annexin V/7-AAD法检测细胞凋亡;CCK-8法检测细胞增殖情况;Western Blot法检测蛋白表达。c AMp检测试剂盒检测c AMp水平;Csk、Lck及pI3K活性检测试剂盒分别检测其活性。ELISA法检测细胞因子水平。结果 :miR-150可通过靶向ARRB2抑制CD28/B7共刺激信号通路的传导,并削弱IL-2等细胞因子的产生;miR-150可以增加c AMp水平,活化c AMp-pKA-Csk抑制性信号通路。并进一步证实miR-150不仅影响ARRB2/pDE4入筏量,还可以通过正反馈调控使pKB/ARRB2/pDE4三聚体入筏受阻,影响T细胞完全活化。综上,miR-150通过靶向ARRB2,影响pDE4/ARRB2二聚体的功能,在CD28/B7共刺激信号通路中削弱炎症细胞因子的产生,可能发挥免疫耐受的作用。结论 :miR-150可能成为移植免疫中的新的潜在治疗靶点。

关键词： MiR-150 炎性细胞因子 ARRB-2 共刺激

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STAT3 mediates C6-ceramide-induced cell death in chronic lymphocytic leukemia

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Signal Transduction and Targeted Therapy 2017年第1期2卷 61-72页

作者： Ushma A Doshi Jeremy Shaw Todd E Fox David F Claxton thomas p.loughran Mark Kester Department of pharmacology Penn State College of MedicineHersheyPAUSA Department of Experimental pathology University of Virginia School of MedicineCharlottesvilleVAUSA Department of pharmacology University of Virginia School of MedicineCharlottesvilleVAUSA Division of Hematology and Oncology Penn State Milton S Hershey Medical Center and College of MedicineHersheyPAUSA Department of Medicine University of Virginia School of MedicineCharlottesvilleVAUSA NanoSTAR Institute University of VirginiaCharlottesvilleVAUSA

The pathogenesis of chronic lymphocytic leukemia(CLL)is poorly understood and it remains incurable with current *** have previously shown that nanoliposomal C6-ceramide(CNL)is an effective therapy in an in vivo murine model of ***,the key signaling pathways mediating CNL-induced cell death in CLL remains *** hypothesized that CNL targets STAT3,a critical regulator of hematopoietic *** observed that CNL treatment reduced phosphorylated STAT3 at both Y705 and S727 residues in CLL cell lines and patient ***,in turn,reduced STAT3 transcriptional activity and expression of critical STAT3-dependent survival factors like Mcl-1 and *** effect of CNL on STAT3 was further confirmed ex vivo as shown by reduced STAT3 phosphorylation in xenograft tumors obtained from mice treated with *** suppressed STAT3 phosphorylation at Y705 and S727 through reduction in BTK activity and MEK1/2 kinase/pKC activities,***,a synergistic reduction in CLL cell viability was observed on co-treatment with CNL and the BTK inhibitor,*** of an oncogenic form of STAT3 conferred partial resistance to CNL,providing confirmation that STAT3 mediates CNL-induced cell *** together,these findings provide the first body of evidence demonstrating ceramide regulation of STAT3 *** results are also the first to demonstrate an effect of ceramide on BTK,a critical kinase mediating the B-cell receptor signaling in CLL cells and suggest a novel and synergistic combination of CNL and BTK inhibitors for CLL treatment.

关键词： STAT3 lymphocytic media

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MicroRNA-181a, a potential predictor, Alleviates Acute Graft Versus Host Disease by Regulating IFN-γ production

MicroRNA-181a, a Potential Predictor, Alleviates Acute Graft...

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第十一届全国免疫学学术大会

作者： sang wei zhang cong wang ying niu mingshan pan bin chen wei yan dongmei thomas p.loughran Jr xu kailin Department of Hematology the Affiliated Hospital of Xuzhou Medical University

Object:To study the role of micro RNA as the biomarkers for prediction and diagnosis of the onset of acute graft versus host disease after allo-geneic hematopoietic stem cell ***:Healthy volunteers and patients withou... 详细信息

关键词： MicroRNA-181a IFN-γ aGVHD

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Automated control and optimization of laser-driven ion acceleration

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High power Laser Science and Engineering 2023年第3期11卷 32-40页

作者： B.loughran M.J.V.Streeter H.Ahmed S.Astbury M.Balcazar M.Borghesi N.Bourgeois C.B.Curry S.J.D.Dann S.DiIorio N.p.Dover T.Dzelzainis O.C.Ettlinger M.Gauthier L.Giuffrida G.D.Glenn S.H.Glenzer J.S.Green R.J.Gray G.S.Hicks C.Hyland V.Istokskaia M.King D.Margarone O.McCusker p.McKenna Z.Najmudin C.parisuaña p.parsons C.Spindloe D.R.Symes A.G.R.thomas F.Treffert N.Xu C.A.J.palmer School of Mathematics and physics Queen’s University BelfastBelfastUK Central Laser Facility STFC Rutherford Appleton LaboratoryDidcotUK Gérard Mourou Center for Ultrafast Optical Science University of MichiganAnn ArborMIUSA SLAC National Accelerator Laboratory Menlo ParkCAUSA Department of Electrical and Computer Engineering University of AlbertaEdmontonABCanada The John Adams Institute for Accelerator Science Imperial College LondonLondonUK ELI Beamlines Centre Institute of PhysicsCzech Academy of SciencesDolníBˇrežanyCzech Republic Department of Applied physics Stanford UniversityStanfordCAUSA Department of physics SUPAUniversity of StrathclydeGlasgowUK Faculty of Nuclear Sciences and physical Engineering Czech Technical University in PraguePragueCzech Republic Department of Mechanical Engineering Stanford UniversityStanfordCAUSA Institut für Kernphysik Technische Universität DarmstadtDarmstadtGermany

The interaction of relativistically intense lasers with opaque targets represents a highly non-linear,multi-dimensional parameter *** limits the utility of sequential 1D scanning of experimental parameters for the optimization of secondary radiation,although to-date this has been the accepted methodology due to low data acquisition *** repetition-rate(HRR)lasers augmented by machine learning present a valuable opportunity for efficient source ***,an automated,HRR-compatible system produced high-fidelity parameter scans,revealing the influence of laser intensity on target pre-heating and proton generation.A closed-loop Bayesian optimization of maximum proton energy,through control of the laser wavefront and target position,produced proton beams with equivalent maximum energy to manually optimized laser pulses but using only 60%of the laser *** demonstration of automated optimization of laser-driven proton beams is a crucial step towards deeper physical insight and the construction of future radiation sources.

关键词： Bayesian optimization high repetition-rate laser-target interaction laser-driven particle acceleration proton generation

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