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improving Oxygen Binding of Desiccated Human Red Blood Cells

Advances in Bioscience and Biotechnology 2016年第2期7卷 47-54页

作者： Steingrimur Stefansson david S. Chung Jamie Yoon Won Seok Yoo Young Wook Park George Kim david Hahn Huyen Le Sung-Jae Chung Stephen P. Bruttig david H. Ho HeMemics Biotechnologies inc. Rockville MD USA Division of Biology & Medicine Brown University Providence RI USA Earl Warren College UC San Diego CA USA Department of Chemistry Michigan University Ann Arbor MI USA Seoul international School Seongnam South Korea Fuzbien Technology institute Rockville MD USA Nauah Solutions Mclean VA USA Marymount University School of Arts & Science Arlington VA USA

Desiccating human red blood cells (RBCs) to increase their storage life has been the subject of intense research for a number of years. However, drying RBCs invariably compromises their integrity and has detrimental effects on hemoglobin function due to autoxidation. We have previously demonstrated an RBC desiccation and rehydration process that preserves RBC antigenic epitopes better than frozen RBCs. This study expands on those observations by examining what effects this desiccation process has on RBC hemoglobin function with respect to oxygen binding properties. in this paper, we examined RBCs from normal donors which were desiccated to 25% moisture content and stored dry for 2 weeks at room temperature prior to rehydration with plasma followed by structural and functional studies. Our data showed that approximately 98% of the RBCs were intact upon rehydration based on hemolysis assays. Oxygen dissociation curves for the desiccated/rehydrated RBCs showed a left shift compared to fresh RBCs (pO2 = 17 mmHg vs. 26 mmHg, respectively). The desiccated/rehydrated RBCs also showed an increase in methemoglobin compared to fresh RBCs (4.5% vs 0.9%, respectively). 2,3-Diphosphoglycerate concentration of the desiccated/rehydrated RBCs was reduced by 20%. in conclusion, although this RBC dehydration process preserves RBC integrity and hemoglobin oxygen binding properties better than most other dehydration techniques described so far, further optimization and long-term studies are needed to make this procedure acceptable for human transfusion.

关键词： Desiccation Red Blood Cells Oxygen Binding Hemolysis Methemoglobin 2 3-Diphosphoglycerate

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G蛋白偶联雌激素受体在雌激素相关肿瘤发生中的作用

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中国药理学通报 2014年第8期30卷 1037-1041页

作者：赵丕文 david Yue-Wei Lee 陶仕英陈梦牛建昭北京中医药大学基础医学院北京100029 mclean Hospital (Harvard Medical School) belmontma02478

在经典的雌激素核受体α和β之外,雌激素或雌激素样物质也可以经过膜受体,即G蛋白偶联雌激素受体(GPER)发挥功能。G蛋白偶联雌激素受体是雌激素非基因通路信号转导过程的重要介导因子,在雌激素相关肿瘤细胞的发生和治疗中具有重要的意... 详细信息

在经典的雌激素核受体α和β之外,雌激素或雌激素样物质也可以经过膜受体,即G蛋白偶联雌激素受体(GPER)发挥功能。G蛋白偶联雌激素受体是雌激素非基因通路信号转导过程的重要介导因子,在雌激素相关肿瘤细胞的发生和治疗中具有重要的意义。现针对G蛋白偶联雌激素受体在雌激素相关肿瘤细胞中介导的效应及有关机制的研究进展进行综述。

关键词： G蛋白偶联雌激素受体 G蛋白偶联受体30 雌激素受体肿瘤雌激素植物雌激素乳腺癌

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刺梨不同提取部位对人类肝癌细胞株(HepG2)胆固醇代谢的影响

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中国中药杂志 2007年第2期32卷 170-171页

作者：吴水生郭改革王宏 david Lee 福建中医学院药学系 Bio-organic and Natural Product Lab Mclean Hospital Harvard Medical School MA USA02478 Bio-organic

刺梨Rosa roxburghii Tratt．为蔷薇科属野生植物，用于治疗积食腹胀、肠炎痢疾、维生素C缺乏症等。刺梨含维生素C、维生素E、超氧化物歧化酶（SOD）、多糖，以及伊谷缁醇、原儿茶酸、委陵菜酸、euscaphic acid、硬脂酸和廿一烷酸等成... 详细信息

刺梨Rosa roxburghii Tratt．为蔷薇科属野生植物，用于治疗积食腹胀、肠炎痢疾、维生素C缺乏症等。刺梨含维生素C、维生素E、超氧化物歧化酶（SOD）、多糖，以及伊谷缁醇、原儿茶酸、委陵菜酸、euscaphic acid、硬脂酸和廿一烷酸等成分。具有清除自由基、增强机体免疫力、防动脉粥样硬化、抗细胞突变和抗癌等药理作用，此外还有明显的降血脂作用。本实验以人类肝癌细胞系HepG2为模型，测定刺梨各部位对细胞胆固醇合成与代谢的影响，以筛选刺梨降血脂作用有效成分或有效部位，为进一步开发刺梨降血脂药用部位奠定基础。

关键词：胆固醇代谢肝癌细胞株刺梨提取部位人类维生素C缺乏症细胞系HepG2 降血脂作用

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Transporting Mammalian Cells at Ambient Temperature:A Viable Alternative to Dry ice

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Advances in Bioscience and Biotechnology 2017年第4期8卷 127-133页

作者： Steingrimur Stefansson Seunghyun Han Ye in Jeon david S.Chung Peter Hwang Huyen Le John L.Warden david Ho HeMemics Biotechnologies inc RockvilleUSA Johns Hopkins University BaltimoreUSA George Washington University WashingtonDCUSA Division of Biology and Medicine Brown UniversityProvidenceUSA Thomas Jefferson High School for Science and Technology AlexandriaUSA Nauah Solutions McleanUSA

The most common method of shipping cells between institutes and companies is sending them frozen, usually treated with anti-freeze solution (most commonly DMSO because it is less toxic than many alternatives), and then packaging them in dry ice for shipment. However many countries place restrictions on dry ice shipments. An alternative to shipping frozen cell vials is to send flasks of growing cells in media. This also has problems because cells in media have limited viability and the flasks can leak. Here we report on an alternative method for shipping viable cells at ambient temperature without dry ice or in media filled flasks. in this study we report on the development and properties of HemSol?. This is an inexpensive, eco-friendly and protects cell integrity at ambient temperature while maintaining viability. We have previously shown that HemSol? protects platelet and RBC function in cold storage and circulating tumor cells up to 6 days. Therefore we wanted to know if HemSol? could also be used to transport live cells. Since HemSol? is a liquid, we experimented with encasing the cells with HemSol? and gelatin so as to prevent dry ice shipment of cells and circumvent the shipping of cells in media. We performed mock shipping experiments where cells were stored in HemSol? gel kept at room temperature on a lab benchtop and cells stored in dry ice was also kept on lab benchtop for up to 2 days. After the mock shipping period, we analyzed cells for their functions. Our results show that cells in HemSol? gel have greater than 95% viability and restored biological functions in 2 hours, whereas, cells shipped in dry ice required more than 24 hours to recover and needed media change to remove the DMSO.

关键词： HemSol^(TM) HemSol^(TM) Gel Transportation Short Term Storage Cells Shipment Dry ice Ambient Temperature Shipment

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Applications of Pueraria lobata in treating diabetics and reducing alcohol drinking

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Chinese Herbal Medicines 2019年第2期11卷 141-149页

作者： Jing Liu Yeu-Ching Shi david Yue-Wei Lee Bio-Organic and Natural Products Research Laboratory Mailman Research Center McLean Hospital/Harvard Medical School Belmont MA 02478 USA Taiwan lndigena Botanica Taipei 10684 China

Pueraria lobata is one of the most important medicinal herbs used traditionally in China. According to Shanghan Lun(Treatise on Exogenous Febrile Disease), it has been used traditionally to relieve body heat,eye soring, dry mouth, headache associated with high blood pressure, and stiff neck problems. Modern studies in the 1970 s revealed that isoflavonoids extracted from P. lobata were the bioactive components of an herbal remedy namely Yufeng Ningxin Tablets for the treatment of patients after stroke. This article reviews recent application of P. lobota in the treatment of diabetics and in reducing alcohol drinking. in view of its low toxicity profile, P. lobota stands an excellent chance to be developed as a phytomedicine for treating human diseases.

关键词： diabetics Pueraria lobata(Willd) Ohwi reducing alcohol drinking

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Water Contamination Modeling—A Review of the State of the Science

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Journal of Water Resource and Protection 2013年第2期5卷 142-155页

作者： Rakesh Bahadur david E. Amstutz William B. Samuels Center for Water Science and Engineering Science Applications International Corporation McLean USA

This paper reports on the current state of surface water and ocean contamination models—based on the needs of US Government agencies, their information Technology (iT) systems, and business processes. in addition, down-selection and evaluation criteria were applied in a two-step process. in Step 1, sixty five surface water and ocean models were identified and researched. in Step 2, the following criteria were explored for each model: 1) model environment (river, lake estuary, coastal ocean and watershed);2) degree of analysis (screening model intermediate model, advanced model);3) availability (public domain, proprietary);4) temporal variability (steady state or time variable/dynamic);5) spatial resolution (one, two or three dimensional);6) processes (flow, transport, both flow and transport in an integrated system);7) water quality (chemical, biological, radionuclides, sediment);and 8) support (user support/training available, user manuals/documents available).

关键词： Watershed Coastal Ocean Rivers Modeling Simulation

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中药及其活性成分对绝经后骨质疏松症的治疗及其作用机制

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中国中药杂志 2012年第12期37卷 1693-1699页

作者：赵丕文牛建昭 david Yue-Wei Lee 王继峰孙艳玲李亚东北京中医药大学基础医学院北京100029 mclean Hospital BelmontMA 02478

绝经后骨质疏松症是更年期妇女的常见全身性骨代谢疾病,体内雌激素水平下降是其重要病因。激素替代疗法(HRT)虽然在多年的临床实践中有着良好和肯定的疗效,但其在提高妇科肿瘤发生率等方面具有明显的副作用。临床实践已经证明,多种妇科... 详细信息

绝经后骨质疏松症是更年期妇女的常见全身性骨代谢疾病,体内雌激素水平下降是其重要病因。激素替代疗法(HRT)虽然在多年的临床实践中有着良好和肯定的疗效,但其在提高妇科肿瘤发生率等方面具有明显的副作用。临床实践已经证明,多种妇科中药方剂、单味中药及中药植物雌激素样活性成分对骨质疏松症有确凿疗效且副作用小。其主要通过作用于靶组织、靶细胞的雌激素受体并进而影响其下游信号传导通路中骨代谢相关调节蛋白和因子的表达情况,达到对骨质疏松症的防治效果。同时,近年来雌激素相关受体的研究也为全面揭示中药及其活性成分抗骨质疏松症的作用机制提供了新的可能角度和途径。

关键词：妇科中药活性成分绝经后骨质疏松症植物雌激素雌激素受体雌激素相关受体

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泽泻提取物Alisol Monoacetate A和B对HepG2细胞株胆固醇代谢的影响

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中华中医药杂志 2007年第7期22卷 475-477页

作者：吴水生郭改革施红王宏 david Lee 福建中医学院药学系 Bio-organic and Natural Product Lab Mclean HospitalHarvard Medical SchoolMAUSA 02478

目的:考察泽泻有效成分Alisol Monoacetate A和B对人类肝癌细胞株(HepG2)胆固醇合成与代谢的影响。方法:以HepG2细胞为模型,Lipitor为阳性对照,加入不同浓度的Alisol Monoacetate A和B,培养24h后分别收集与测定培养液及细胞内的胆固醇... 详细信息

目的:考察泽泻有效成分Alisol Monoacetate A和B对人类肝癌细胞株(HepG2)胆固醇合成与代谢的影响。方法:以HepG2细胞为模型,Lipitor为阳性对照,加入不同浓度的Alisol Monoacetate A和B,培养24h后分别收集与测定培养液及细胞内的胆固醇含量。结果:Alisol Monoacetate A和B在10μM、20μM浓度时开始出现10%左右的细胞毒性,但线粒体代谢活性却增强约50%。而当浓度超过50μM时细胞毒性显著增强达70%以上。随着Alisol Monoacetate A和B浓度的增加(0、3、10、20μM),细胞内胆固醇含量也显著升高,分别为24.4、26.7、32.3、38.3μg/mg蛋白质,存在正量效关系;但培养液内的胆固醇含量无明显不同。结论:Alisol Monoac-etate A和B可能具有增强细胞的线粒体代谢活性而促进HepG2合成胆固醇的作用,其机制有待进一步研究。

关键词：泽泻 Misol Monoacetate A Misol Monoacetate B 人类肝癌细胞株胆固醇

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Global River Basin Modeling and Contaminant Transport

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American Journal of Climate Change 2013年第2期2卷 138-146页

作者： Rakesh Bahadur Christopher Ziemniak david E. Amstutz William B. Samuels Center for Water Science and Engineering Science Applications International Corporation McLean USA

Using geographic information system techniques, elevation derived datasets such as flow accumulation, flow direction, hillsope and flow length were used to delineate river basin boundaries and networks. These datasets included both HYDRO1K (based on 1 kmresolution DEM) and HydroSHEDs (based on100 meterShuttle Radar Topography Mission). Additional spatial data processing of global landuse and soil type data were used to derive grids representing soil depth, texture, hydraulic conductivity, water holding capacity, and curve number. These grids were input to the Geospatial Stream Flow model to calculate overland flow (both travel time and velocity). The model was applied to river basins across several continents to calculate river discharge and velocity based on the use of satellite derived rainfall estimates, numerical weather forecast fields, and geographic data sets describing the land surface. Model output was compared to historical stream gauge observations as a validation step. The stream networks with associated discharge and velocity are used as input to a riverine water contamination model.

关键词： Hydrology Geographic information Systems Surface Water

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鼠尾草酚抗乳腺癌细胞增殖活性及其雌激素受体亚型介导和调节机制的研究

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中国中药杂志 2014年第17期39卷 3344-3348页

作者：赵丕文 david Yue-Wei LEE Zhongze Ma 孙艳玲陶仕英臧金凤牛建昭北京中医药大学基础医学院北京100029 mclean Hospital Harvard Medical Schoolbelmontma02478

既往研究已经表明,鼠尾草酚(carnoso1)具有一定的抗乳腺癌效应,但其ER亚型特异性调节和介导机制与该物质抑制细胞增殖效应的相关性尚不清楚。该研究利用雌激素受体(ER)阳性乳腺癌T47D细胞观察鼠尾草酚对细胞增殖活性的影响及其雌激素受... 详细信息

既往研究已经表明,鼠尾草酚(carnoso1)具有一定的抗乳腺癌效应,但其ER亚型特异性调节和介导机制与该物质抑制细胞增殖效应的相关性尚不清楚。该研究利用雌激素受体(ER)阳性乳腺癌T47D细胞观察鼠尾草酚对细胞增殖活性的影响及其雌激素受体α,卢亚型特异性介导和调节机制。以ERα和ERβ特异性拮抗剂MPP,PHTPP为工具药,采用MTT细胞增殖实验观察鼠尾草酚对T47D细胞增殖的影响;检测T47D细胞增殖周期的变化。利用Western blot方法检测鼠尾草酚对T47D细胞ERα和ERβ表达情况的影响。研究发现,1×10^(-5)~1×10^(-7)mol·L^(-1)鼠尾草酚能够显著抑制T47D细胞增殖,该抑制作用可被ERα拮抗剂MPP增强、被ERβ拮抗剂PHTPP减弱;1×10^(-1),1×10^(-6)mol·L^(-1)鼠尾草酚可使T47D细胞增殖指数显著下降。Western blot检测结果显示1×10^(-5),1×10^(-6)mol·L^(-1)鼠尾草酚可使T47D细胞ERα和ERβ蛋白表达显著增加,并可明显提高ERα/ERβ。结果表明鼠尾草酚具有抑制ER阳性乳腺癌细胞增殖的作用,其效应是通过靶细胞雌激素受体,特别是ERβ途径实现的;同时,鼠尾草酚对靶细胞雌激素受体ERα和ERβ亚型的表达及其比例具有调节功能。

关键词：鼠尾草酚乳腺癌 T47D细胞细胞增殖细胞周期雌激素受体

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