971 research outputs found

    Iodine Radiolabeled Mesenchymal Stem Cell (MSC)-Exosomes and Their CD73 Enzymatic Activities

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    IODINE RADIOLABELLED MESENCHYMAL STEM CELL (MSC)-EXOSOMES AND THEIR CD73 ENZYMATIC ACTIVITIES Chang-Tong Yang a,b*,Ruenn Chai Laic, Sai Kiang Limc, David Chee Eng Ng a,b a Department of Nuclear Medicine and Molecular Imaging, Radiological Sciences Division, Singapore General Hospital, Outram Road, 169608 Singapore; b Duke-NUS Medical School, 8 College Road, 169857 Singapore; cInstitute of Molecular & Cell Biology, 8A Biomedical Grove #05-16 Immunos, 138648, Singapore; *[email protected] Introduction MSC-derived exosomes have shown therapeutic potential in the areas of cardiovascular, orthopaedic, ophthalmologic, immune, dermatologic diseases and radiation sickness. Efficient radioisotope-labelling of exosomes remains as a challenging process. We demonstrate iodine-131 radiolabeled exosomes using both chloramine-T and Pierce Iodination methods, and characterized I-labelled exosomes via their CD73 enzymatic activities. Experimental methodology and results Two classic radio-iodination methods have been used to label exosomes due to several advantages: relatively long half-life of I-131 (half-life 8 days) and I-124 (half-life 4.2 days, 25.6% positron emission) could enable a desired tracking kinetics of exosomes in vitro and in vivo; radiolabeling of iodine to peptides and antibodies is a well-established chemistry; the unlabeled free iodine after radio-labelling can be easily removed to reach high radiochemical purity. By using chloramine-T, the radiolabeling yield of 131I-labeled-exosomes achieved ~30-40% with a radiochemical purity > 90% after running through PD10 column purification. Using Pierce Iodination, the radiolabeling yield drops to ~15-20%, radiochemical purity achieved >90% after the same purification process. The integrity of I-labeled-exosomes is important in the reproducibility and development of exosome clinical therapeutics. No radioactive iodine was labelled to exosome for characterization of their integrity. The results showed that chloramine T radiolabeling affected the structures of I-labeled-exosomes as the CD73 enzymatic activity of I-labeled exosomes was destroyed, the particle size became much larger and caused broader exosome size distribution. While with Pierce iodination the CD73 activity drops by 50 % when compared to that of the unlabeled exosomes, and the particles kept the same size. Conclusions Using chloramine T method showed that the CD73 enzymatic activity of I-labelled exosomes was destroyed, suggesting the labeling process damaged the structure of exosomes. By comparison, using Pierce Iodination method preserved the CD73 enzymatic activity, indicating that exosomes can be radiolabeled using Pierce Iodination for in vitro and in vivo tracking and pharmacokinetic studies

    Iodine Radiolabeled Mesenchymal Stem Cell (MSC)-Exosomes and Their CD73 Enzymatic Activities

    No full text
    IODINE RADIOLABELLED MESENCHYMAL STEM CELL (MSC)-EXOSOMES AND THEIR CD73 ENZYMATIC ACTIVITIES Chang-Tong Yang a,b*,Ruenn Chai Laic, Sai Kiang Limc, David Chee Eng Ng a,b a Department of Nuclear Medicine and Molecular Imaging, Radiological Sciences Division, Singapore General Hospital, Outram Road, 169608 Singapore; b Duke-NUS Medical School, 8 College Road, 169857 Singapore; cInstitute of Molecular & Cell Biology, 8A Biomedical Grove #05-16 Immunos, 138648, Singapore; *[email protected] Introduction MSC-derived exosomes have shown therapeutic potential in the areas of cardiovascular, orthopaedic, ophthalmologic, immune, dermatologic diseases and radiation sickness. Efficient radioisotope-labelling of exosomes remains as a challenging process. We demonstrate iodine-131 radiolabeled exosomes using both chloramine-T and Pierce Iodination methods, and characterized I-labelled exosomes via their CD73 enzymatic activities. Experimental methodology and results Two classic radio-iodination methods have been used to label exosomes due to several advantages: relatively long half-life of I-131 (half-life 8 days) and I-124 (half-life 4.2 days, 25.6% positron emission) could enable a desired tracking kinetics of exosomes in vitro and in vivo; radiolabeling of iodine to peptides and antibodies is a well-established chemistry; the unlabeled free iodine after radio-labelling can be easily removed to reach high radiochemical purity. By using chloramine-T, the radiolabeling yield of 131I-labeled-exosomes achieved ~30-40% with a radiochemical purity > 90% after running through PD10 column purification. Using Pierce Iodination, the radiolabeling yield drops to ~15-20%, radiochemical purity achieved >90% after the same purification process. The integrity of I-labeled-exosomes is important in the reproducibility and development of exosome clinical therapeutics. No radioactive iodine was labelled to exosome for characterization of their integrity. The results showed that chloramine T radiolabeling affected the structures of I-labeled-exosomes as the CD73 enzymatic activity of I-labeled exosomes was destroyed, the particle size became much larger and caused broader exosome size distribution. While with Pierce iodination the CD73 activity drops by 50 % when compared to that of the unlabeled exosomes, and the particles kept the same size. Conclusions Using chloramine T method showed that the CD73 enzymatic activity of I-labelled exosomes was destroyed, suggesting the labeling process damaged the structure of exosomes. By comparison, using Pierce Iodination method preserved the CD73 enzymatic activity, indicating that exosomes can be radiolabeled using Pierce Iodination for in vitro and in vivo tracking and pharmacokinetic studies

    Implementation of environmental life cycle assessment model in organic municipal solid waste management in Malaysia / Ng Chee Guan

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    Organic Municipal Solid Waste (OMSW) generation in Malaysia is overwhelming and most of the waste generated ended up in the waste stream to be disposed in landfills. However, there has been minimal research on the comprehensive evaluation of the Malaysian OMSW management system from environmental perspective despite priority being given to increase recycling rate and composting of OMSW by the Malaysian government. The main aim of the thesis is to study the environmental benefits of OMSW management. The objectives include: (1) to determine the characteristics and elemental composition of OMSW generated in Malaysia; (2) to provide a comprehensive Life Cycle Inventory (LCI) of medium scale co-composting of OMSW; (3) to evaluate environmental impacts and benefits associated with alternative OMSW management system; and (4) to quantify the total CO2 equivalent reduction potential from OMSW recycling via composting as compared to landfilling (Business-as-Usual) in Peninsular Malaysia. A comprehensive Life Cycle Inventory (LCI) of medium scale co-composting of OMSW was carried out based on comprehensive field studies. Substance Flow Analysis of C, N, P, K, Cd, Cr, Cu, Ni and Pb were carried out by using STAN 2.5 software. The inputs and outputs of OMSW composting process were also recorded. The life cycle environmental impacts from alternative OMSW management system were evaluated based on ISO 14000 series. The total CO2 equivalent reduction potential from OMSW recycling via composting as compared to landfilling was assessed through scenarios comparison in accordance to Malaysian municipal solid waste management strategic plan. The LCI of medium-scale co-composting of OMSW in tropical environment was presented. The C/N reduction during the process was in the range of 10-23%. In general, the compost composition was considered to be within the ranges previously reported in literature. Heavy metals were found to remain in the finished compost where the release of heavy metal to atmosphere is insignificant. No iv major environmental problems were identified from the OMSE composting process, except for the emissions of GHGs. LCA studies revealed that anaerobic digestion is the most environmentally sound management for OMSW with net environmental gain whereas disposal of OMSW at landfill are generally less environmental favourable. This study also highlights the importance of decomposition emissions control during OMSW composting, particularly CH4, N2O and NH3. OMSW diversion from disposal created significant climate change benefits in term of net GHG emissions reduction. The current study reveals that an additional of 21% GHG emissions reduction including the recycling of OMSW via composting in all sectors, on top of 25.5% GHG emission reduction from Malaysia waste by increasing the recycling rate to 22% as reported by previous study. A knowledge-based goal-oriented OMSW management study is necessary to analyse the state-of-art of OMSW management in Malaysia and direct it towards fulfilling the main goals of waste management. The results provide information of all significant inputs and outputs in the form of elementary flow to and from the environment from OMSW management involved. Based on the experience of SFA in the present study, the emissions quantified are likely to be in agreement with that from previous studies. Hence, author agrees and advocates that SFA is able to be integrated with LCI and eventually LCIA studies upon OMSW management sector in Malaysia

    Effective acupunture treatment for heart diseases

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    In the recent years, the population have been aging and people are more concerned about health. It has become increasingly important for clinical researches to look for remedy and cures for various disease with least side effects and maintain one’s health. Traditional Chinese Medicine (TCM) has become one of the most researched areas of alternate cure for disease. In this report, topics on how TCM and western medical science inter-connects and if acupuncture of TCM has its effects in curing heart disease are discussed and studied. As the project is focused on heart diseases, it is important to know how the heart functions and the circulation of blood in the human body. Thus the understanding of anatomy and physiology of the cardiovascular system is discussed in the beginning of the report. In addition, the analysis of electrocardiogram and some theories of TCM and Acupuncture are also discussed as literature review. In addition, an experiment is carried out to test the resistance between main acupuncture meridian points of 10 male volunteers. the description of procedure and an analysis of the results are also included in this report. This project is still in its primitive stage and therefore, information inside this report should only be taken as a reference and further development of the experiment is encouraged.Bachelor of Engineerin

    Lumped-parameter model of renal hemodynamics

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    The blood flow through a porous and distensible vessel such as a glomerular capillary is studied using a lumped-parameter model, and based on simplified Navier-Stokes’ equations to derive the governing equations in the form of second-order hyperbolic partial differential equations in pressure. Further modelling of the autoregulation of flow is performed based on a extravascular tissue-pressure model. Lumped-parameter model of a compliant, porous vescular compartment was studied through simplification of Navier-Stokes equation where hyperbolic second-order partial differential equations governing flow and pressure were derived.Master of Science (Biomedical Engineering

    InGaAs/AlGaAsSb avalanche photodiode with high gain - bandwidth product

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    Increasing reliance on the Internet places greater and greater demands for high -speed optical communication systems. Increasing their data transfer rate allows more data to be transferred over existing links. With optical receivers being essential to all optical links, bandwidth performance of key components in receivers, such as avalanche photodiodes (APDs), must be improved. The APDs rely on In0.53Ga0.47As (grown lattice-matched to InP substrates) to efficiently absorb and detect the optical signals with 1310 or 1550 nm wavelength, the optimal wavelengths of operation for these optical links. Thus developing InP -compatible APDs with high gain-bandwidth product (GBP) is important to the overall effort of increasing optical links’ data transfer rate. Here we demonstrate a novel InGaAs/AlGaAsSb APD, grown on an InP substrate, with a GBP of 424 GHz, the highest value reported for InP -compatible APDs, which is clearly applicable to future optical communication systems at or above 10 Gb/s

    Effective acupuncture back pain treatment

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    This final year report aims to identify the effective acupuncture points for the back pain treatment and develop an intelligent software consultant package. First of all, a brief introduction of the report is introduced. It followed by the literature review in Chapter 2. In the following chapter, literature survey for effective acupuncture for back pain treatment was conducted and a result of 15 common acupuncture points has been identified. In order to provide acupuncture treatment recommendations to TCM practitioners, a system consists of syndromes, diagnosis and acupuncture treatment recommendation is developed. In Chapter 4, based on the information found in previous chapter, the basic design of the intelligent system is discussed. However, due to time constraint, the development of web-based intelligent software consultation package has not been completed yet. An investigation on the body impedance between effective acupuncture points for back pain treatment is carried on in Chapter 5. A conclusion which consists of project summary, knowledge gained by the author and further improvements is made in the last chapter.Bachelor of Engineerin

    sj-docx-1-tam-10.1177_17588359221087555 – Supplemental material for A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies

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    Supplemental material, sj-docx-1-tam-10.1177_17588359221087555 for A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies by Jingshan Ho, Valerie Heong, Wei Peng Yong, Ross Soo, Cheng Ean Chee, Andrea Wong, Raghav Sundar, Yee Liang Thian, Anil Gopinathan, Mei Yan Pang, Priscillia Koe, Santhiay Nathan Jeraj, Phyu Pyar Soe, Mu Yar Soe, Tiffany Tang, Matthew C.H. Ng, David W.M. Tai, Tira J.Y. Tan, Hongmei Xu, Hua Chang, Yosef Landesman, Jatin Shah, Sharon Shacham, Soo Chin Lee, Daniel S.W. Tan, Boon Cher Goh and David S.P. Tan in Therapeutic Advances in Medical Oncology</p

    sj-docx-2-tam-10.1177_17588359221087555 – Supplemental material for A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies

    No full text
    Supplemental material, sj-docx-2-tam-10.1177_17588359221087555 for A phase 1 study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of the selective inhibitor of nuclear export (SINE) selinexor in Asian patients with advanced or metastatic malignancies by Jingshan Ho, Valerie Heong, Wei Peng Yong, Ross Soo, Cheng Ean Chee, Andrea Wong, Raghav Sundar, Yee Liang Thian, Anil Gopinathan, Mei Yan Pang, Priscillia Koe, Santhiay Nathan Jeraj, Phyu Pyar Soe, Mu Yar Soe, Tiffany Tang, Matthew C.H. Ng, David W.M. Tai, Tira J.Y. Tan, Hongmei Xu, Hua Chang, Yosef Landesman, Jatin Shah, Sharon Shacham, Soo Chin Lee, Daniel S.W. Tan, Boon Cher Goh and David S.P. Tan in Therapeutic Advances in Medical Oncology</p
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