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Polymorphisms of the oxidant enzymes glutathione S-transferase and glutathione reductase and their association with resistance of Plasmodium falciparum isolates to antimalarial drugs

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Asian Pacific Journal of Tropical Medicine 2010年第9期3卷 673-677页

作者： Raewadee Wisedpanichkij Wanna Chaicharoenkul Poonuch Mahamad Prapichaya Prompradit Kesara Na-Bangchang Pharmacology and Toxicology Unit Graduate Program in Biomedical SciencesThammasat UniversityThailand

Objective:To investigate the association between amplification of the two regulatory genes controlling glutathione(GSH) levels,glutathione reductase(PfGR) and glutathione S-transferase (PfGST) genes and sensitivity of Plasmodium falciparum(***) isolates collected from different malaria endemic areas of Thailand to standard antimalarial ***:A total of 70 *** isolates were collected from endemic areas of multi-drug resistance (Tak,Chantaburi and Ranong Provinces) during the year *** in vitro assessment of antimalarial activity of *** clones(K1- and Dd2 chloroquine resistant and 3D7- chloroquine sensitive) and isolates to chloroquine,quinine,mefloquine and arteusnate was performed based on SYBR Green modified ***:68(97.14%),11(15.71%) and 28(40%) isolates respectively were classified as chloroquine-,quinine- and mefloquine-resistant isolates. With this limited number of *** isolates included in the analysis,no significant association between amplification of PfGST gene and sensitivity of the parasite to chloroquine, quinine,mefloquine and quinine was *** on PCR analysis,Dd2,Kl and 3D7 clones all contained only one copy of the PfGST *** isolates(70) also carried only one copy number of PfGST *** appears to be an association between amplification of PfGR gene and chloroquine *** 3D7 and Dd2 clones were found to carry only one PfGR gene copy, whereas the K1 clone carried two gene ***:Chloroquine resistance is likely to be a consequence of multi-factors and enzymes in the GSH system may be partly involved. Larger number of parasite isolates are required to increase power of the hypothesis testing in order to confirm the involvement of both genes as well as other genes implicated in glutathione metabolism in conferring chloroquine resistance.

关键词： Plasmodium falciparum Drug resistance Glutathione reductase(PfGR) Glutathione S-transferase(P/GST)

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Antioxidant activities and phytochemical constituents of Antidesma thwaitesianum Müll. Arg. leaf extracts

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Journal of Integrative Medicine 2017年第4期15卷 310-319页

作者： Bhanuz Dechayont Arunporn Itharat Pathompong Phuaklee Jitpisute Chunthorng-Orn Thana Juckmeta Nuntika Prommee Nitra Nuengchamnong Pintusorn Hansakul Department of Applied Thai Traditional Medicine Faculty of Medicine Thammasat University Center of Excellence in Applied Thai Traditional Medicine Research Thammasat University Division of Applied Thai Traditional Medicine Faculty of Public Health Naresuan University Science Laboratory Centre Faculty of Science Naresuan University Department of Preclinical Science Faculty of Medicine Thammasat University

OBJECTIVE： To investigate the antioxidant activities as well as phytochemical constituents of Antidesma thwaitesianum Mull. Arg. leaf extracts. METHODS： The leaves of A. thwaitesianum were extracted using three different methods： blending with distilled water, maceration with ethanol and decoction. The chemical antioxidant activity of the plant leaf extracts was evaluated using 2,2-diphenyl-1-picryhydrazyl （DPPH） radical and 2,2＇-azinobis（3- ethylbenzo-thiazoline-6-sulfonic acid） diammonium salt （ABTS＊） radical scavenging assays, as well as the ferric reducing antioxidant power assay. Cellular antioxidant activity was determined by superoxide and nitric oxide scavenging assays. The cytotoxicity of the leaf extracts in RAW 264.7 and differentiated HL-60 cells was tested in parallel using 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2H-tetrazolium bromide and 3-（4,5-dimethylthiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H-tetrazolium assays, respectively. The total phenolic and flavonoid contents were also assessed by spectrophotometric analysis Phytochemical constituents of the most potent extract were investigated by liquid chromatography with an electrospray ionization quadrupole time-of-flight mass spectrometer （LC-ESI-QTOF-MS/MS）. RESULTS： The ethanolic （ME） and decoction （LW） extracts of dried leaves had the highest chemical scavenging activity against DPPH and ABTS＋ free radicals with half maximal effective concentration （EC50） values ranging from 3.54 to 6.44 μg/mL. ME and LW exerted moderate ferric reducing activity, with ferric reducing antioxidant power values of 847.41 and 941.26 mg Fe2＋/g extract, respectively. Similarly, ME showed potent cellular scavenging activity against superoxide and nitric oxide radicals with EC50 values of 58.12 and 71.90 μg/mL, respectively. However, LW exhibited only strong nitric oxide scavenging activity with an EC50 value of 91.20 μg/mL. The cell viability of RAW 264.7 and HL-60 cells was greater than 70% in all tes

关键词： Antidesma thwaitesianum Mull. Arg. antioxidants phytochemicals spectrometry, mass,electrospray ionization chromatography, liquid

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Simulations of H-Mode Plasmas in Tokamak Using a Complete Core-Edge Modeling in the BALDUR Code

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Plasma Science and Technology 2012年第9期14卷 778-788页

作者： Y.PIANROJ T.ONJUN School of Manufacturing Systems and Mechanical Engineering Sirindhorn International Institute of TechnologyThammasat UniversityPathum Thani 12121Thailand

A theory-based model for predicting the pedestal formation in both ion and electron temperatures, and hydrogenic and impurity density is developed and implemented in the 1.5D BALDUR codes for self-consistently simulating H-mode plasma in tokamak. In the simulation, the transports around pedestal, including the electron and ion thermal, hydrogenie and impurity particle transports are calculated using an （Mixed B/gB） model, which is modified to anomalous semi-empirical mixed Bohm/gyro-Bohm include the effects of ωE×B flow shear and magnetic shear. Because of the reduction of transport, the pedestal can be formed. For a preliminary test, this core-edge model is used to simulate the temporal evolution of plasma current, temperature, and density profiles for DIII-D discharges. It is found that the simulations successfully reproduce the experimental results. A statistical analysis, including RMSE and offset, is used to quantify the agreement between the prediction and the corresponding experimental results. The simulation results show an agreement with average RMSE of 11.87%, 14.53%, 7.59% and 12.21% for electron temperature, ion temperature, electron density, and deuterium density profiles, respectively. In addition, it is found that the suppression function developed is effective only in the edge region.

关键词： ITER pedestal H-mode BALDUR fusion performance transport

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Successful recanalization with multimodality endovascular interventional therapy in acute ischemic stroke

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World Journal of Clinical Cases 2014年第3期2卷 78-85页

作者： Amorn Jongsathapongpan Anuchit Raumthanthong Sombat Muengtaweepongsa Department of Cardiology Phyathai 2 Hospital (Bangkok Hospital Group) Department of Radiology Pramong-kutklao Hospital Department of Medicine Thammasat University

Stroke is an important cause of death and disability in adults. However, effective treatments for patients with acute ischemic stroke are limited. Intravenous recombinant tissue plasminogen activator(iv rtPA) within 4.5 h after onset has been approved as a standard treatment for patients with acute ischemic stroke. However, due to time constraints, less than one percent of acute ischemic stroke patients in Thailand are able to obtain iv rtPA. Although endovascular interventional therapy has not yet been approved as standard treatment in acute ischemic stroke, it is the one of the potentially effective treatment options. There are several reliable methods of endovascular therapy for acute ischemic stroke patients. Endovascular interventional therapy has rarely been done in Thailand. We report seven patients with successful recanalization after endovascular treatment in acute large vessel stroke from a single stroke center in Thailand. Patient screening and selection with multimodal imaging protocol and multimodality methods of endovascular interventional therapy are described.

关键词： Acute ischemic stroke Intra-arterial thrombolysis Endovascular therapy Mechanical thrombectomy

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Glycoproteomics analysis of plasma proteins associated with Opisthorchis viverrini infection-induced cholangiocarcinoma in hamster model

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Asian Pacific Journal of Tropical Medicine 2016年第12期9卷 1142-1147页

作者： Pramote Sriwanitchrak Atchara Paemanee Sittiruk Roytrakul Vithoon Viyanant Kesara Na-Bangchang Graduate Program in Biomedical Sciences Faculty of Allied Health SciencesThammasat University Proteomics Research Laboratory National Center for Genetic Engineering and Biotechnology Graduate Program in Bioclinical Sciences Center of Excellence in Pharmacology and Molecular Biology of Malaria and CholangiocarcinomaChulabhorn International College of Medicine Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Chulabhorn International College of Medicine Excellence Center in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Thammasat University

Objective: To apply lectin affinity chromatography and glycoproteomics-based LC-MS/MS to preliminarily investigate the possible potential plasma biomarkers of Opisthorchis viverrini(OV)-associated CCA in OV/dimethylnitrosamine(DMN)-induced CCA hamster model. Methods: Nine Syrian hamsters were divided into 3 groups as follows(n=3 each): normal(healthy control group); OV group; and OV/DMN group(CCA group). Pooled plasma samples collected from animals in each group at the 6th month post-infection with OV metacercarae were subjected to glycoproteomics analysis. Glycoproteins in the pooled sample from each group were initially isolated by concanavilin A(Con A)-based affinity chromatography. The expression of glycoproteins isolated by both enrichment methods were determined using LCMS/MS. Results: Among the 24 Con A-binding glycoproteins isolated, two proteins, N-myc downstream regulated gene 1(NDRG1) and fetuin-B(FETUB) were found up-regulated only in the samples from the OV and control groups, but not in the OV/DMN(CCA) groups. On the other hand, one protein, i.e., NSFL1 cofactor p47 isoform x3(NSFL1C) was found only in the samples from OV/DMN(CCA) and control groups, but not in the OV group. The remaining 21 proteins were upregulated in the samples from all groups. Conclusions: NDRG1, FETUB and NSFL1 C glycoproteins isolated by Con A-based affinity chromatography could be potential biomarkers for CCA. Plasma samples with negative for NDRG1 and FETUB proteins but positive for NSFL1 C are likely to be OV-associated CCA. Nevertheless, this conclusion remains to be confirmed whether this battery test can discriminate OV-associated CCA from other risk factors.

关键词： Cholangiocarcinoma Opisthorchis viverrini Glycoprotein Hamster model ConA binding protein LC-MS/MS

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Inhibitory activities of plumbagin on cell migration and invasion and inducing activity on cholangiocarcinoma cell apoptosis

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Asian Pacific Journal of Tropical Medicine 2018年第7期11卷 430-435页

作者： Luxsana Panrit Tullayakorn Plengsuriyakarn Pongsakorn Martviset Kesara Na-Bangchang Drug Discovery and Development Center Thammasat University Center of Excellence in Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma Chulabhorn International College of MedicineThammasat University Graduate Program in Bioclinical Sciences Chulabhorn International College of Medicine Thammasat University Faculty of Medical Technology Rangsit University

Objective: To investigate the cytotoxic, apoptotic and inhibitory activities on cell migration and invasion of plumbagin in the human cholangiocarcinoma(CCA) cell line(CL-6) in comparison with human embryonic fibroblast cell line(OUMS). Methods: Cytotoxicity activity was evaluated using MTT assay. Inhibitory effect on cell migration and invasion were investigated using label-free real-time cell analysis and QCM ECMatrix cell invasion chamber, respectively. Apoptotic activity was evaluated using flow cytometry and Cell Event? Caspase 3/7 assay. Results: Based on results of the cytotoxicity test in CL-6 cells, 50% inhibitory concentration(IC_(50), Mean±SD) values of plumbagin and the standard drug 5-fluorouracil were(24.00±3.33) and(1 036.00±137.77) μmol/L, respectively. The corresponding values for OUMS cells were(57.00±5.23) and(2 147.00±209.98) μmol/L, respectively. The selectivity index was 2.28. The inhibitory activities of plumbagin on cell migration and invasion were potent and concentration-dependent with IC_(50) of 25.0 μmol/L and complete inhibition at 25.0 μmol/L. Flow cytometry analysis showed that plumbagin at 12.5 μmol/L(half IC_(50)) induced CL-6 cell apoptosis(43.24% of control) through stimulation of caspase 3/7 activities. Complete cell apoptosis was observed at 12.5 μmol/L. Conclusions: The cytotoxic activity and inhibition of migration and invasion including apoptosis induction in the human CCA cell line(CL-6) suggest that plumbagin could be a promising candidate for CCA chemotherapeutics. However, its relatively low selective cytotoxic effect on CCA cells is a major concern.

关键词： Cholangiocarcinoma Plumbagin Cancer migration Cancer invasion Apoptosis

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In vitro inhibitory effects of plumbagin,the promising antimalarial candidate,on human cytochrome P450 enzymes

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Asian Pacific Journal of Tropical Medicine 2015年第11期8卷 894-898页

作者： Wiriyaporn Sumsakul Wanna Chaijaroenkul Kesara Na-Bangchang Graduate Program in Biomedical Sciences.Faculty of Allied Health Sciences Thammasat University Center of Excellence in Pharmacology and Molecular Biology Graduate Program in Bioclinical SciencesChulabhorn International College of MedicineThammasat University

Objective:To investigate the propensity of plumbagin to inhibit the three isoforms of human cytochrome P450(CYP),ie.,CYP1A2,CYP2C19,and CYP3A4 using human liver microsomes in ***:Inhibitory effects of plumbagin on the three human CYP isoformswere investigated using pooled human liver *** O-deethylation,omeprazole hydroxylation and nifedipine oxidation were used as selective substrates for CYP1A2,CYP2C19 and CYP3A4 activities,*** of paracetamol,5-hydroxyomeprazole,and oxidized nifedipine were determined in microsomal incubation mixture using high performance liquid ***:Plumbagin showed significantinhibitory effects on all CYP *** with the most potent activity on CYP2C19-mediated omeprazole *** IC50(concentration that inhibits enzyme activity by 50%) values of plumbagin and nootkatone(selective inhibitor) for CYP2C19 were(0.78±0.01) and(27.31±0.66) μM,*** inhibitory activities on CYP1 A2-mediated phenacetin O-deethylation and CYP3A4-mediated nifedipine oxidation were *** IC_(50) values of plumbagin and-naphthoflavone(selective inhibitor) for CYP1A2 were(1.39±0.01) and(0.02±.0.36) μM,*** corresponding IC_(50) values of plumbagin and ketoconazole(selective inhibitor) for CYP3A4 were(2.37+0.10) and(0.18±0.06) μM,***:Clinical relevance of the interference of human drug metabolizing enzymes should be aware of for further development scheme of plumbagin as antimalarial drug when used in combination with other antimalarial drugs which are metabolized by these CYP isoforms.

关键词： Metabolism Human liver microsomes Plumbagin Cytoch

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Synthesis of ZrSiN composite films using a plasma focus device

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Chinese Physics B 2014年第6期23卷 381-386页

作者： R.Ahmad T.Hussain I.A.Khan R.S.Rawat Center for Advanced Studies in Physics GC University Physics Department GC Universit National Institute of education Nanyang Technological University

ZrSiN thin films are synthesized by using plasma focus through various numbers of focus shots （10, 20, and 30）, with samples placed at 9 cm away from the tip of the anode. Crystal structures, surface morphologies, and elemental compositions of ZrSiN films are characterized by an X-ray diffractometer （XRD） and scanning electron microscope （SEM） attached with energy dispersive X-ray spectroscopy （EDS）. XRD patterns confirm the formations of polycrystalline ZrSiN films. Crystallinity of nitride increases with the increase of focus shot number. The average crystallite size of zirconium nitride increases from 27 ± 3 nm to 73±8 nm and microstrain decreases from 2.28 to 1.0 with the increase of the focus shot number. SEM results exhibit the formations of granular and oval-shaped microstructures, depending on the number of focus shots. EDS results confirm the presences of silicon, zirconium, nitrogen, and oxygen in the composite films. The content values of Zr and N in the composite films increase with the increase of the focus shot number.

关键词： DPF ZrSiN thin films XRD SEM

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Characterization of Modified Tapioca Starch in Atmospheric Argon Plasma under Diverse Humidity by FTIR Spectroscopy

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Chinese Physics Letters 2013年第1期30卷 215-218页

作者： P.Deeyai M.Suphantharika R.Wongsagonsup S.Dangtip Materials Science and Engineering Programme Faculty of ScienceMahidol UniversityBangkok10400Thailand Department of Biotechnology Faculty of ScienceMahidol UniversityBangkok10400Thailand Food Technology program Kanchanaburi CampusMahidol UniversityKanchanaburi71150Thailand Department of Physics Faculty of ScienceMahidol UniversityBangkok10400Thailand

Tapioca is economical crop grown in Thailand and continues to be one of the major sources of ***,tapioca starch has been widely used in industrial applications,however the native form of starch has limited the *** scientists try to modify the properties of starch for increasing the stability of the granules,pastes to low pH,heat,and shear during the food *** modify the tapioca starch by plasma treatment under an argon *** degree of modification is determined by following water content in the starch *** tablet samples of native starch are also prepared and compared with the plasma treated *** plasma treatment,the starch tablets are stored under three different relative humilities(RH)including 11%,68%,and 78%RH,*** samples are characterized using FTIR spectroscopy associated with the degree of *** results show that the water molecules are engulfed into the starch structure in two ways,a tight bond and a weak absorption of water molecules which is represented at two wave number of 1630 cm^(-1) and 3272 cm^(-1),*** degree of cross-linking can be identified from the relative intensity of these two peaks with the C–O–H peak at 993 cm^(-1).The results show that the degree of cross-linking increase in the plasma treated *** degree of cross-linking of the treated starch with high relative humidity is less than that of the treated starch with low relative humidity.

关键词： linking humidity Starch

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The role of heme-oxygenase-1 in pathogenesis of cerebral malaria in the co-culture model of human brain microvascular endothelial cell and ITG Plasmodium falciparum-infected red blood cells

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Asian Pacific Journal of Tropical Medicine 2017年第1期10卷 20-24页

作者： Pimwan Thongdee Kesara Na-Bangchang Graduate Program in Bioclinical Sciences Chulabhorn International College of MedicineThammasatUniversityPathumthaniThailand Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Thammasat UniversityPathumthaniThailand

Objective: To investigate the role of human host heme-oxygenase-1(HO-1) in pathogenesis of cerebral malaria in the in vitro model,Methods: The effect of human host HO-1 [human brain microvascular endothelial cell(HBMEC)] on hemoglobin degradation in the co-culture model of HBMEC and ITG Plasmodium falciparum-infected red cells(i RBC) through measurement of the enzymatic products iron and bilirubin,Results: Following exposure to the HO-1 inducer Co PPIX at all concentrations,the HBMEC cells apoptosis occurred,which could be prominently observed at 15 μM of 3 h exposure,In contrast,there was no significant change in the morphology in the non-exposed i RBC at all concentrations and exposure time,This observation was in agreement with the levels of the enzymatic degradation products iron and bilirubin,of which the highest levels(106.03 and 1 753.54% of baseline level,respectively) were observed at 15 μM vs,20 μM at 3 h vs,24 h exposure,For the effect of the HO-1 inhibitor Zn PPIX,HBMEC cell morphology was mostly unchanged,but significant inhibitory effect on cell apoptosis was seen at 10 μM for the exposure period of 3 h(37.17% of baseline level),The degree of the inhibitory effect as reflected by the level of iron produced was not clearly observed(highest effect at 10 μM and 3 h exposure),Conclusions: Results provide at least in part,insight into the contribution of HO-1 on CM pathogenesis and need to be confirmed in animal model.

关键词： Plasmodium falciparum Heme-oxygenase-1 Zn(Ⅱ)-protoporphyrin Ⅸ inhibitor Co-protoporphyrin Ⅸ inducer Human brain microvascular endothelial cell

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