Browsing by Author "Thidarat Suksangpleng"

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    Feasibility of and barriers to thalassemia screening in migrant populations: a cross-sectional study of Myanmar and Cambodian migrants in Thailand
    (2021-12-01) Julia Z. Xu; Wilaslak Tanongsaksakul; Thidarat Suksangpleng; Supachai Ekwattanakit; Suchada Riolueang; Marilyn J. Telen; Vip Viprakasit; Siriraj Hospital; National Heart, Lung, and Blood Institute (NHLBI); Duke University School of Medicine; Laem Chabang Hospital
    Background: Thalassemia, an inherited hemoglobin disorder, has become a global public health problem due to population migration. Evidence-based strategies for thalassemia prevention in migrants are lacking. We characterized barriers to thalassemia screening and the burden of thalassemia in migrant workers in Thailand. Methods: Multilingual demographic and KAP surveys were completed by 197 Thai, 119 Myanmar, and 176 Cambodian adults residing in Thailand. Thalassemia awareness, socio-demographic predictors, and knowledge and attitude scores were compared between migrant and Thai subjects. Comprehensive thalassemia testing was performed for migrants. Results: Migrants had extremely poor thalassemia awareness (4.1%) compared to Thai subjects (79.6%) and had lower thalassemia knowledge scores but similar attitude scores. Surveys identified differing sociodemographic factors predicting awareness in Thai and migrant subjects, as well as key misconceptions likely to hinder thalassemia screening uptake. Nearly all migrants consented to thalassemia testing. We identified abnormal hemoglobin profiles in 52.7% of migrants and a higher projected rate of severe thalassemia births in migrants. Conclusions: The high burden of thalassemia and tremendous knowledge gap in migrants needs urgent attention. Thalassemia screening was feasible and acceptable in our migrant population. Sociocultural and structural barriers merit further attention when designing thalassemia screening and prevention policies for migrants in Thailand and globally.
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    Identification of optimal thalassemia screening strategies for migrant populations in Thailand using a qualitative approach
    (2021-12-01) Julia Z. Xu; Meghan Foe; Wilaslak Tanongsaksakul; Thidarat Suksangpleng; Supachai Ekwattanakit; Suchada Riolueang; Marilyn J. Telen; Bonnie N. Kaiser; Vip Viprakasit; Siriraj Hospital; University of California, San Diego; Mahidol University; Duke University; UCSF Benioff Children's Hospital Oakland; National Heart, Lung, and Blood Institute (NHLBI); Duke University School of Medicine; Laem Chabang Hospital
    Background: Thalassemia is a common inherited hemoglobin disorder in Southeast Asia. Severe thalassemia can lead to significant morbidity for patients and economic strain for under-resourced health systems. Thailand’s thalassemia prevention and control program has successfully utilized prenatal screening and diagnosis to reduce the incidence of severe thalassemia in Thai populations, but migrant populations are excluded despite having high thalassemia prevalence. We sought to identify key barriers to and facilitators of thalassemia screening and to develop tailored recommendations for providing migrants with access to thalassemia prevention and control. Methods: We conducted 28 in-depth interviews and 4 focus group discussions (FGDs) in Chonburi, Thailand with Myanmar and Cambodian migrants, Thai healthcare providers, Thai parents of children affected by thalassemia, and migrant agents. Results: Participant narratives revealed that migrants’ lack of knowledge about the prevalence, manifestations, severity, and inherited nature of thalassemia led to misconceptions, fear, or indifference toward thalassemia and screening. Negative perceptions of pregnancy termination were based in religious beliefs but compounded by other sociocultural factors, presenting a key obstacle to migrant uptake of prenatal screening. Additionally, structural barriers included legal status, competing work demands, lack of health insurance, and language barriers. Participants recommended delivering public thalassemia education in migrants’ native languages, implementing carrier screening, and offering thalassemia screening in convenient settings. Conclusions: An effective thalassemia prevention and control program should offer migrants targeted thalassemia education and outreach, universal coverage for thalassemia screening and prenatal care, and options for carrier screening, providing a comprehensive strategy for reducing the incidence of severe thalassemia in Thailand and establishing an inclusive model for regional thalassemia prevention and control.
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    Molecular characterization of Plasmodium falciparum uracil-DNA glycosylase and its potential as a new anti-malarial drug target
    (2014) Thidarat Suksangpleng; Ubolsree Leartsakulpanich; Saengduen Moonsom; Saranya Siribal; Usa Boonyuen; Wright, George E; Porntip Chavalitshewinkoon-Petmitr; Mahidol University. Faculty of Tropical Medicine. Department of Protozoology,
    Background: Based on resistance of currently used anti-malarials, a new anti-malarial drug target against Plasmodium falciparum is urgently needed. Damaged DNA cannot be transcribed without prior DNA repair; therefore, uracil-DNA glycosylase, playing an important role in base excision repair, may act as a candidate for a new anti-malarial drug target. Methods: Initially, the native PfUDG from parasite crude extract was partially purified using two columns, and the glycosylase activity was monitored. The existence of malarial UDG activity prompted the recombinant expression of PfUDG for further characterization. The PfUDG from chloroquine and pyrimethamine resistant P. falciparum strain K1 was amplified, cloned into the expression vector, and expressed in Escherichia coli. The recombinant PfUDG was analysed by SDS-PAGE and identified by LC-MS/MS. The three dimensional structure was modelled. Biochemical properties were characterized. Inhibitory effects of 12 uracil-derivatives on PfUDG activity were investigated. Inhibition of parasite growth was determined in vitro using SYBR Green I and compared with results from human cytotoxicity tests. Results: The native PfUDG was partially purified with a specific activity of 1,811.7 units/mg (113.2 fold purification). After cloning of 966-bp PCR product, the 40-kDa hexa-histidine tagged PfUDG was expressed and identified. The amino acid sequence of PfUDG showed only 24.8% similarity compared with the human enzyme. The biochemical characteristics of PfUDGs were quite similar. They were inhibited by uracil glycosylase inhibitor protein as found in other organisms. Interestingly, recombinant PfUDG was inhibited by two uracil-derived compounds; 1-methoxyethyl-6-(p-n-octylanilino) uracil (IC50 of 16.75 μM) and 6-(phenylhydrazino)uracil (IC50 of 77.5 μM). Both compounds also inhibited parasite growth with IC50s of 15.6 and 12.8 μM, respectively. Moreover, 1-methoxyethyl-6-(p-n-octylanilino)uracil was not toxic to HepG2 cells, with IC50 of > 160 μM while 6-(phenylhydrazino)uracil exhibited cytoxicity, with IC50 of 27.5 μM. Conclusions: The recombinant PfUDG was expressed, characterized and compared to partially purified native PfUDG. Their characteristics were not significantly different. PfUDG differs from human enzyme in its size and predicted amino acid sequence. Two uracil derivatives inhibited PfUDG and parasite growth; however, only one non-cytotoxic compound was found. Therefore, this selective compound can act as a lead compound for anti-malarial development in the future.
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    Molecular characterization of Plasmodium falciparum uracil-DNA glycosylase and its potential as a new anti-malarial drug target
    (2014-04-17) Thidarat Suksangpleng; Ubolsree Leartsakulpanich; Saengduen Moonsom; Saranya Siribal; Usa Boonyuen; George E. Wright; Porntip Chavalitshewinkoon-Petmitr; Mahidol University; Thailand National Center for Genetic Engineering and Biotechnology; Western University; GLSynthesis Inc.
    Background: Based on resistance of currently used anti-malarials, a new anti-malarial drug target against Plasmodium falciparum is urgently needed. Damaged DNA cannot be transcribed without prior DNA repair; therefore, uracil-DNA glycosylase, playing an important role in base excision repair, may act as a candidate for a new anti-malarial drug target. Methods. Initially, the native PfUDG from parasite crude extract was partially purified using two columns, and the glycosylase activity was monitored. The existence of malarial UDG activity prompted the recombinant expression of PfUDG for further characterization. The PfUDG from chloroquine and pyrimethamine resistant P. falciparum strain K1 was amplified, cloned into the expression vector, and expressed in Escherichia coli. The recombinant PfUDG was analysed by SDS-PAGE and identified by LC-MS/MS. The three dimensional structure was modelled. Biochemical properties were characterized. Inhibitory effects of 12 uracil-derivatives on PfUDG activity were investigated. Inhibition of parasite growth was determined in vitro using SYBR Green I and compared with results from human cytotoxicity tests. Results: The native PfUDG was partially purified with a specific activity of 1,811.7 units/mg (113.2 fold purification). After cloning of 966-bp PCR product, the 40-kDa hexa-histidine tagged PfUDG was expressed and identified. The amino acid sequence of PfUDG showed only 24.8% similarity compared with the human enzyme. The biochemical characteristics of PfUDGs were quite similar. They were inhibited by uracil glycosylase inhibitor protein as found in other organisms. Interestingly, recombinant PfUDG was inhibited by two uracil-derived compounds; 1-methoxyethyl-6-(p-n-octylanilino) uracil (IC50of 16.75 μM) and 6-(phenylhydrazino)uracil (IC50of 77.5 μM). Both compounds also inhibited parasite growth with IC50s of 15.6 and 12.8 μM, respectively. Moreover, 1-methoxyethyl-6-(p-n-octylanilino)uracil was not toxic to HepG2 cells, with IC50of > 160 μM while 6-(phenylhydrazino)uracil exhibited cytoxicity, with IC50of 27.5 μM. Conclusions: The recombinant PfUDG was expressed, characterized and compared to partially purified native PfUDG. Their characteristics were not significantly different. PfUDG differs from human enzyme in its size and predicted amino acid sequence. Two uracil derivatives inhibited PfUDG and parasite growth; however, only one non-cytotoxic compound was found. Therefore, this selective compound can act as a lead compound for anti-malarial development in the future. © 2014 Suksangpleng et al.; licensee BioMed Central Ltd.
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    The origin of sickle cell disease in Thailand
    (2019-02-01) Julia Z. Xu; Suchada Riolueang; Waraporn Glomglao; Kalaya Tachavanich; Thidarat Suksangpleng; Supachai Ekwattanakit; Vip Viprakasit; Faculty of Medicine, Siriraj Hospital, Mahidol University; Duke University
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    Paper-based microchip electrophoresis for point-of-care hemoglobin testing
    (2020-04-07) Muhammad Noman Hasan; Arwa Fraiwan; Ran An; Yunus Alapan; Ryan Ung; Asya Akkus; Julia Z. Xu; Amy J. Rezac; Nicholas J. Kocmich; Melissa S. Creary; Tolulope Oginni; Grace Mfon Olanipekun; Fatimah Hassan-Hanga; Binta W. Jibir; Safiya Gambo; Anil K. Verma; Praveen K. Bharti; Suchada Riolueang; Takdanai Ngimhung; Thidarat Suksangpleng; Priyaleela Thota; Greg Werner; Rajasubramaniam Shanmugam; Aparup Das; Vip Viprakasit; Connie M. Piccone; Jane A. Little; Stephen K. Obaro; Umut A. Gurkan; Duke University Medical Center; University Hospitals Rainbow Babies & Children's Hospital; Max Planck Institute for Intelligent Systems; Indian Council of Medical Research; University Hospitals Case Medical Center; UNC School of Medicine; University of Michigan School of Public Health; University of Nebraska Medical Center; Faculty of Medicine, Siriraj Hospital, Mahidol University; Bayero University; Case Western Reserve University; Thogus Products; HEMEX HEALTH, INC.; Hasiya Bayero Pediatric Hospital; International Foundation Against Infectious Diseases in Nigeria; eHealth Africa; Murtala Muhammad Specialist Hospital
    © The Royal Society of Chemistry 2020. Nearly 7% of the world's population live with a hemoglobin variant. Hemoglobins S, C, and E are the most common and significant hemoglobin variants worldwide. Sickle cell disease, caused by hemoglobin S, is highly prevalent in sub-Saharan Africa and in tribal populations of Central India. Hemoglobin C is common in West Africa, and hemoglobin E is common in Southeast Asia. Screening for significant hemoglobin disorders is not currently feasible in many low-income countries with the high disease burden. Lack of early diagnosis leads to preventable high morbidity and mortality in children born with hemoglobin variants in low-resource settings. Here, we describe HemeChip, the first miniaturized, paper-based, microchip electrophoresis platform for identifying the most common hemoglobin variants easily and affordably at the point-of-care in low-resource settings. HemeChip test works with a drop of blood. HemeChip system guides the user step-by-step through the test procedure with animated on-screen instructions. Hemoglobin identification and quantification is automatically performed, and hemoglobin types and percentages are displayed in an easily understandable, objective way. We show the feasibility and high accuracy of HemeChip via testing 768 subjects by clinical sites in the United States, Central India, sub-Saharan Africa, and Southeast Asia. Validation studies include hemoglobin E testing in Bangkok, Thailand, and hemoglobin S testing in Chhattisgarh, India, and in Kano, Nigeria, where the sickle cell disease burden is the highest in the world. Tests were performed by local users, including healthcare workers and clinical laboratory personnel. Study design, methods, and results are presented according to the Standards for Reporting Diagnostic Accuracy (STARD). HemeChip correctly identified all subjects with hemoglobin S, C, and E variants with 100% sensitivity, and displayed an overall diagnostic accuracy of 98.4% in comparison to reference standard methods. HemeChip is a versatile, mass-producible microchip electrophoresis platform that addresses a major unmet need of decentralized hemoglobin analysis in resource-limited settings.
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    Thienopyrimidine sulphonamide hybrids: Design, synthesis, antiprotozoal activity and molecular docking studies
    (2016-01-01) Saadia Leeza Zaidi; Subhash M. Agarwal; Porntip Chavalitshewinkoon-Petmitr; Thidarat Suksangpleng; Kamal Ahmad; Fernando Avecilla; Amir Azam; Jamia Millia Islamia; Institute of Cytology and Preventive Oncology Noida; Mahidol University; Centre for Interdisciplinary Research in Basic Science; Universidade da Coruña
    © 2016 The Royal Society of Chemistry. A series of hybrid compounds containing the thienopyrimidine scaffold as a DHFR inhibitor fused with a bioactive sulphonamide piperazine skeleton were synthesized and evaluated against the chloroquine and pyrimethamine resistant K1 strain of Plasmodium falciparum and the HM1:1MSS strain of Entamoeba histolytica, respectively. A few of the compounds showed better results than the standard drugs. The toxicity of the hybrids was measured on the Chinese hamster cell line. The majority of the compounds had low toxicity. The binding modes of the most potent antimalarial compounds (5, 6 and 8) were also investigated against PfDHFR using molecular docking and enzyme binding studies, whereby 5 and 6 were found to the most promising against PfDHFR. The present studies suggest that these hybrids might be possible antiprotozoal lead compounds worth further investigation.