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กระบวนการเสริมสร้างจิตสำนึกของบุคลากรและนักศึกษาคณะเทคนิคการแพทย์ ด้านการอนุรักษ์พลังงานและสิ่งแวดล้อม
(2557) ชาตรี ลุนดำ; กุลธิดา โพธิ์แดง; พรรษชล สมิติวัณฑิกุล; ธนพัฒน์ นพโสภณ; ศิริอร มโนมัธยา; Chatree Lundammrs; Kuntida Podangms; Patshachon Samitiwantikul; Thanapat Nopsopon; Siro-On Manomuttaya; มหาวิทยาลัยมหิดล. คณะเทคนิคการแพทย์
การศึกษาครั้งนี้เป็นการศึกษาแบบมีส่วนร่วม (Participation Action Research) เพื่อสะท้อนกระบวนการ ดำเนินนโยบายด้านการอนุรักษ์พลังงานและสิ่งแวดล้อม รวมถึงกระบวนการถอดบทเรียนให้เห็นสภาวะปัจจุบัน ของทัศนคติจิตสำนึกที่เปลี่ยนไปในการมีส่วนร่วมของผู้เกี่ยวข้อง ได้แก่ นักศึกษาและบุคลากรของคณะเทคนิค การแพทย์ เพื่อนำไปสู่การเสริมสร้างแนวทางการเป็นต้นแบบแห่งการอนุรักษ์พลังงานและธรรมชาติ ให้เกิดจากการอยู่ร่วมกันอย่างสมดุล นอกจากนี้ ยังเป็นการสนับสนุนพันธกิจของคณะฯ ตามเป้าประสงค์เชิงยุทธศาสตร์ด้านที่ 5 : มุ่งสู่การเป็นสถาบันการเรียนรู้ที่มีชีวิตชีวา และยุทธศาสตร์ของมหาวิทยาลัยมหิดล ด้านที่ 7 Harmony ความกลมกลืนในความหลากหลาย ในการศึกษาครั้งนี้ มีวัตถุประสงค์ คือ 1) เพื่อศึกษากระบวนการเสริมสร้างการอนุรักษ์พลังงานและสิ่งแวดล้อมของคณะเทคนิคการแพทย์ 2) เพื่อศึกษาทัศนคติเกี่ยวกับกระบวนเสริมสร้างการอนุรักษ์พลังงานและสิ่งแวดล้อมของบุคลากรและนักศึกษาคณะเทคนิคการแพทย์ โดยแบ่งวิธีการศึกษาออกเป็น 2 ส่วน คือ 1) ศึกษาวิเคราะห์กระบวนการดำเนินงานเพื่อเสริมสร้างจิตสำนึกด้านการอนุรักษ์พลังงานและสิ่งแวดล้อมของคณะเทคนิคการแพทย์ โดยเก็บรวบรวมข้อมูลหน่วยการใช้พลังงาน ได้แก่ ไฟฟ้ า น้ำประปา น้ำมัน และกระดาษ รวมถึงการจัดการขยะ และนำข้อมูลการจัดการไปใช้ในการเปรียบเทียบให้เห็นปริมาณการใช้พลังงานในแต่ละปีงบประมาณ (พ.ศ. 2554-2555) 2) ศึกษาในเชิงคุณภาพ โดยสุ่มสัมภาษณ์กลุ่มตัวอย่างเพื่อการสะท้อนกลับข้อมูลโดยมีเกณฑ์การคัดเลือกคือ 1) คัดเลือกจากตัวแทนอ้างอิงของนักศึกษาและบุคลากรที่ครอบคลุมและเชื่อถือได้ 2) คัดเลือกจากตัวแทนทีที่ไม่มีส่วนเกี่ยวข้องกับการดำเนินการด้านนโยบายและผลักดันการปฏิบัติการ ผลการศึกษาพบว่า การดำเนินนโยบายด้านการอนุรักษ์พลังงานและสิ่งแวดล้อมของคณะเทคนิคการแพทย์ ได้ถูกนำไปปฏิบัติอย่างจริงจัง โดยมีกลไกหลักที่สำคัญอยู่ 2 ประการ คือ 1) มีผู้บริหารมุ่งมั่นในการสื่อสารและสนับสนุนตระหนักต่อการอนุรักษ์พลังงานและมุ่งสู่การเป็นต้นแบบของสถาบันการเรียนรู้ที่มีชีวิตชีวา 2) การเกิดเครือข่ายทีมทำงานชุมชนนักปฏิบัติ (CoPs) และสามารถรองรับภาระงาน กล่าวคือ เป็นผู้ดำ เนินกิจกรรม โครงการเพื่อสร้างความตระหนักให้เกิดบรรยากาศและทัศนคติและจิตสำนึกที่มีต่อการอนุรักษ์พลังงานและสิ่งแวดล้อม ซึ่งได้ดำเนินการในรูปแบบของการจัดการความรู้ภายในทีมทำงาน อีกทั้งขยายผลความสำเร็จของการดำเนินงานสู่สังคม ชุมชนใกล้เคียง เช่น เครือข่ายโรงเรียนในชุมชนตำบลคลองโยง และชุมชนตำบลบางแก้วฟ้า จังหวัดนครปฐม นอกจากนี้ การจัดการเรียนการสอนให้กับนักศึกษาของคณะเทคนิคการแพทย์ ชั้นปีที่ 1 ในรายวิชา Transformative Learning เช่น กิจกรรมสมุดทำมือ เป็นต้น รวมถึงในกลุ่มบุคลากรอีกด้วย ในด้านผลลัพธ์ของอัตราการลดลงของปริมาณพลังงาน ไฟฟ้า น้ำประปา ของคณะฯ มีอัตราที่ลดลงอย่างต่อเนื่อง อย่างน้อยร้อยละ 3 ต่อปี ติดต่อกัน 3 ปี ซึ่งมีแนวโน้มดีขึ้น และสามารถนำข้อมูลดังกล่าวไปสื่อสารให้เกิดการรับรู้และปรับเปลี่ยนพฤติกรรมให้เกิดความร่วมมือของนักศึกษาและบุคลากรเพิ่มมากขึ้น
Open Access
Molecular basis of human cerebral malaria development
(2016) Saw Thu Wah; Hathairad Hananantachai; Usanee Kerdpin; Chotiros Plabplueng; Virapong Prachayasittikul; Pornlada Nuchnoi; Mahidol University. Faculty of Medical Technology. Department of Clinical Microscopy; Mahidol University. Faculty of Medical Technology. Center for Research and Innovation
Cerebral malaria is still a deleterious health problem in tropical countries. The wide spread of malarial drug resistance and the lack of an effective vaccine are obstacles for disease management and prevention. Parasite and human genetic factors play important roles in malaria susceptibility and disease severity. The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. Currently, much genomic data and a novel body of knowledge, including the identification of microRNAs, are being increasingly accumulated for the development of laboratory testing cassettes for cerebral malaria prevention. Therefore, understanding of the underlying complex molecular basis of cerebral malaria is important for the design of strategy for cerebral malaria treatment and control.
Open Access
Cucurbitacin B inhibits human breast cancer cell proliferation through disruption of microtubule polymerization and nucleophosmin/B23 translocation
(2012) Suwit Duangmano; Phorntip Sae-lim; Apichart Suksamrarn; Frederick E Domann; Pimpicha Patmasiriwat; Mahidol University. Faculty of Medical Technology
Background: Cucurbitacin B, an oxygenated tetracyclic triterpenoid compound extracted from the Thai medicinal plant Trichosanthes cucumerina L., has been reported to have several biological activities including anti-inflammatory, antimicrobial and anticancer. Cucurbitacin B is great of interest because of its biological activity. This agent inhibits growth of various types of human cancer cells lines. Methods: In this study, we explored the novel molecular response of cucurbitacin B in human breast cancer cells, MCF-7 and MDA-MB-231. The growth inhibitory effect of cucurbitacin B on breast cancer cells was assessed by MTT assay. The effects of cucurbitacin B on microtubules morphological structure and tubulin polymerization were analyzed using immunofluorescence technique and tubulin polymerization assay kit, respectively. Proteomic analysis was used to identify the target-specific proteins that involved in cucurbitacin B treatment. Some of the differentially expressed genes and protein products were validated by real-time RT-PCR and western blot analysis. Cell cycle distributions and apoptosis were investigated using flow cytometry. Results: Cucurbitacin B exhibited strong antiproliferative effects against breast cancer cells in a dose-dependent manner. We show that cucurbitacin B prominently alters the cytoskeletal network of breast cancer cells, inducing rapid morphologic changes and improper polymerization of the microtubule network. Moreover, the results of 2D-PAGE, real-time RT-PCR, and western blot analysis revealed that the expression of nucleophosmin/B23 and c-Myc decreased markedly after cucurbitacin B treatment. Immunofluorescence microscopy showed that cucurbitacin B induced translocation of nucleophosmin/B23 from the nucleolus to nucleoplasm. Treatment with cucurbitacin B resulted in cell cycle arrest at G2/M phase and the enhancement of apoptosis. Conclusions: Our findings suggest that cucurbitacin B may inhibit the proliferation of human breast cancer cells through disruption of the microtubule network and down-regulation of c-Myc and nucleophosmin/B23 as well as the perturbation in nucleophosmin/B23 trafficking from the nucleolus to nucleoplasm, resulting in G2/M arrest.
Open Access
Erratum: Cucurbitacin B causes increased radiation sensitivity of human breast cancer cells via G2/M cell cycle arrest
(Mahidol University, 2015) Suwit Duangmano; Phorntip Sae-lim; Apichart Suksamrarn; Pimpichaya Patmasiriwat; Frederick E. Domann
Open Access
Influenza Neuraminidase Subtype N1: Immunobiological Properties and Functional Assays for Specific Antibody Response
(2016-04) Don Changsom; Hatairat Lerdsamran; Witthawat Wiriyarat; Warunya Chakritbudsabong; Bunpote Siridechadilok; Jarunee Prasertsopon; Pirom Noisumdaeng; Wanibtisam Masamae; Pilaipan Puthavathana; Mahidol University. Faculty of Medical Technology. Center for Research and Innovation
Influenza neuraminidase (NA) proteins expressed in TK- cells infected with recombinant vaccinia virus carrying NA gene of highly pathogenic avian influenza H5N1 virus or 2009 pandemic H1N1 (H1N1pdm) virus were characterized for their biological properties, i.e., cell localization, molecular weight (MW), glycosylation and sialidase activity. Immune sera collected from BALB/c mice immunized with these recombinant viruses were assayed for binding and functional activities of anti-NA antibodies. Recombinant NA proteins were found localized in cytoplasm and cytoplasmic membrane of the infected cells. H1N1pdm NA protein had MW at about 75 kDa while it was 55 kDa for H5N1 NA protein. Hyperglycosylation was more pronounced in H1N1pdm NA compared to H5N1 NA according to N-glycosidase F treatment. Three dimensional structures also predicted that H1N1 NA globular head contained 4 and that of H5N1 contained 2 potential glycosylation sites. H5N1 NA protein had higher sialidase activity than H1N1pdm NA protein as measured by both MUNANA-based assay and fetuin-based enzyme-linked lectin assay (ELLA). Plaque reduction assay demonstrated that anti-NA antibody could reduce number of plaques and plaque size through inhibiting virus release, not virus entry. Assay for neuraminidase-inhibition (NI) antibody by ELLA showed specific and cross reactivity between H5N1 NA and H1N1pdm NA protein derived from reverse genetic viruses or wild type viruses. In contrast, replication-inhibition assay in MDCK cells showed that anti-H1N1 NA antibody moderately inhibited viruses with homologous NA gene only, while anti-H5N1 NA antibody modestly inhibited the replication of viruses containing homologous NA gene and NA gene derived from H1N1pdm virus. Anti-H1N1 NA antibody showed higher titers of inhibiting virus replication than anti-H5N1 NA antibody, which are consistent with the results on reduction in plaque numbers and sizes as well as in inhibiting NA enzymatic activity. No assay showed cross reactivity with reassorted PR8 (H1N1) virus and H3N2 wild type viruses.
Open Access
Derivatives (halogen, nitro and amino) of 8-hydroxyquinoline with highly potent antimicrobial and antioxidant activities
(2016-07) Rungrot Cherdtrakulkiat; Somchai Boonpangrak; Nujarin Sinthupoom; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology; Mahidol University. Faculty of Medical Technology. Center for Innovation Development and Technology Transfer; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics
8-Hydroxyquinoline (8HQ) compounds have been reported to possess diverse bioactivities. In recent years, drug repositioning has gained considerable attention in drug discovery and development. Herein, 8HQ (1) and its derivatives (2-9) bearing various substituents (amino, nitro, cyano and halogen) were investigated for their antimicrobial against 27 microorganisms (agar dilution method) and antioxidant (DPPH method) activities. The parent 8HQ (1) exerted a highly potent antimicrobial activity against Gram-positive bacteria including diploid fungi and yeast with MIC values in the range of 3.44-13.78 μM. Moreover, the halogenated 8HQ, especially 7-bromo-8HQ (4) and clioquinol (6), displayed a high antigrowth activity against Gram-negative bacteria compared with the parent compound (1). Apparently, the derivatives with a relatively high safely index, e.g., nitroxoline (2), exhibited strong antibacterial activity against Aeromonas hydrophila (MIC=5.26 μM) and selectively inhibited the growth of P. aeruginosa with the MIC value of 84.14 μM; cloxyquin (3) showed a strong activity against L. monocytogenes and P. shigelloides with MIC values of 5.57 and 11.14 μM, respectively. Most compounds displayed an antioxidant activity. Specifically, 5-amino-8HQ (8) was shown to be the most potent antioxidant (IC50=8.70 μM) compared with the positive control (α-tocopherol) with IC50 of 13.47 μM. The findings reveal that 8HQ derivatives are potential candidates to be further developed as antimicrobial and antioxidant agents.
Open Access
Antimalarial and Antimicrobial Activities of 8-Aminoquinoline-Uracils Metal Complexes
(2015-12) Kamonrat Phopin; Nujarin Sinthupoom; Lertyot Treeratanapiboon; Sarun Kunwittaya; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology
8-Aminoquinoline (8AQ) derivatives have been reported to have antimalarial, anticancer, and antioxidant activities. This study investigated the potency of 8AQ-5-substituted (iodo and nitro) uracils metal (Mn, Cu, Ni) complexes (1-6) as antimalarial and antimicrobial agents. Interestingly, all of these metal complexes (1-6) showed fair antimalarial activities. Moreover, Cu complexes 2 (8AQ-Cu-5Iu) and 5 (8AQ-Cu-5Nu) exerted antimicrobial activities against Gram-negative bacteria including P. shigelloides and S. dysenteriae. The results reveal application of 8AQ and its metal complexes as potential compounds to be further developed as novel antimalarial and antibacterial agents.
Unknown
Nitric Oxide Protects against Infection-Induced Neuroinflammation by Preserving the Stability of the Blood-Brain Barrier
(2016-02) Gabriela C. Olivera; Xiaoyuan Ren; Suman K. Vodnala; Jun Lu; Lucia Coppo; Chaniya Leepiyasakulchai; Arne Holmgren; Krister Kristensson; Martin E. Rottenberg; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology
Nitric oxide (NO) generated by inducible NO synthase (iNOS) is critical for defense against intracellular pathogens but may mediate inflammatory tissue damage. To elucidate the role of iNOS in neuroinflammation, infections with encephalitogenic Trypanosoma brucei parasites were compared in inos-/- and wild-type mice. Inos-/- mice showed enhanced brain invasion by parasites and T cells, and elevated protein permeability of cerebral vessels, but similar parasitemia levels. Trypanosome infection stimulated T cell- and TNF-mediated iNOS expression in perivascular macrophages. NO nitrosylated and inactivated pro-inflammatory molecules such as NF-κΒp65, and reduced TNF expression and signalling. iNOS-derived NO hampered both TNF- and T cell-mediated parasite brain invasion. In inos-/- mice, TNF stimulated MMP, including MMP9 activity that increased cerebral vessel permeability. Thus, iNOS-generated NO by perivascular macrophages, strategically located at sites of leukocyte brain penetration, can serve as a negative feed-back regulator that prevents unlimited influx of inflammatory cells by restoring the integrity of the blood-brain barrier.
Unknown
Origin of aromatase inhibitory activity via proteochemometric modeling
(2016-04) Saw Simeon; Ola Spjuth; Maris Lapins; Chanin Nantasenamat; Jarl ES Wikberg; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics
Aromatase, the rate-limiting enzyme that catalyzes the conversion of androgen to estrogen, plays an essential role in the development of estrogen-dependent breast cancer. Side effects due to aromatase inhibitors (AIs) necessitate the pursuit of novel inhibitor candidates with high selectivity, lower toxicity and increased potency. Designing a novel therapeutic agent against aromatase could be achieved computationally by means of ligand-based and structure-based methods. For over a decade, we have utilized both approaches to design potential AIs for which quantitative structure-activity relationships and molecular docking were used to explore inhibitory mechanisms of AIs towards aromatase. However, such approaches do not consider the effects that aromatase variants have on different AIs. In this study, proteochemometrics modeling was applied to analyze the interaction space between AIs and aromatase variants as a function of their substructural and amino acid features. Good predictive performance was achieved, as rigorously verified by 10-fold cross-validation, external validation, leave-one-compound-out cross-validation, leave-one-protein-out cross-validation and Y-scrambling tests. The investigations presented herein provide important insights into the mechanisms of aromatase inhibitory activity that could aid in the design of novel potent AIs as breast cancer therapeutic agents.
Unknown
Computational identification of miRNAs that modulate the differentiation of mesenchymal stem cells to osteoblasts
(2016-04) Kanokwan Seenprachawong; Pornlada Nuchnoi; Chanin Nantasenamat; Aungkura Supokawej; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics; Mahidol University. Faculty of Medical Technology. Department of Clinical Microscopy
MicroRNAs (miRNAs) are small endogenous noncoding RNAs that play an instrumental role in post-transcriptional modulation of gene expression. Genes related to osteogenesis (i.e. RUNX2, COL1A1 and OSX) is important in controlling the differentiation of mesenchymal stem cells (MSCs) to bone tissues. The regulated expression level of miRNAs is critically important for the differentiation of MSCs to preosteoblasts. The understanding of miRNA regulation in osteogenesis could be applied for future applications in bone defects. Therefore, this study aims to shed light on the mechanistic pathway underlying osteogenesis by predicting miRNAs that may modulate this pathway. This study investigates RUNX2, which is a major transcription factor for osteogenesis that drives MSCs into preosteoblasts. Three different prediction tools were employed for identifying miRNAs related to osteogenesis using the 3’UTR of RUNX2 as the target gene. Of the 1,023 miRNAs, 70 miRNAs were found by at least two of the tools. Candidate miRNAs were then selected based on their free energy values, followed by assessing the probability of target accessibility. The results showed that miRNAs 23b, 23a, 30b, 143, 203, 217, and 221 could regulate the RUNX2 gene during the differentiation of MSCs to preosteoblasts.
Unknown
Roles of D-amino acids on the bioactivity of host defense peptides
(2016-04) Hao Li; Nuttapat Anuwongcharoen; Aijaz Ahmad Malik; Chanin Nantasenamat; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics
Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of D-amino acids (D-AA) is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of D-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists, given the impact that D-AA incorporation has on HDPs. In this review, we aim to fill that void with a systematic discussion of the impact of D-AA on HDPs.
Unknown
Endothelial Progenitor Cell Migration-Enhancing Factors in the Secretome of Placental-Derived Mesenchymal Stem Cells
(2016) Witchayaporn Kamprom; Pakpoom Kheolamai; Yaowalak U-Pratya; Aungkura Supokawej; Methichit Wattanapanitch; Chuti Laowtammathron; Sittiruk Roytrakul; Surapol Issaragrisil; Mahidol University. Faculty of Medical Technology. Department of Clinical Microscopy
Therapeutic potentials of mesenchymal stem cells (MSCs) depend largely on their ability to secrete cytokines or factors that modulate immune response, enhance cell survival, and induce neovascularization in the target tissues. We studied the secretome profile of gestational tissue-derived MSCs and their effects on functions of endothelial progenitor cells (EPCs), another angiogenic cell type that plays an important role during the neovascularization. MSCs derived from placental tissues (PL-MSCs) significantly enhanced EPC migration while BM-MSCs, which are the standard source of MSCs for various clinical applications, did not. By using protein fractionation and mass spectrometry analysis, we identified several novel candidates for EPC migration enhancing factor in PL-MSCs secretome that could be used to enhance neovascularization in the injured/ischemic tissues. We recommend that the strategy developed in our study could be used to systematically identify therapeutically useful molecules in the secretomes of other MSC sources for the clinical applications.
Unknown
P-Glycoprotein transporter in drug development
(2016-02-12) Veda Prachayasittikul; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology
Open Access
Retinol-binding protein 4 and its potential roles in hypercholesterolemia revealed by proteomics
(2015-08-28) Watcharapong Jugnam-Ang; Supitcha Pannengpetch; Patcharee sarankura-Na-Ayudhya; Chadinee Thippakorn; Chartchalerm Isarankura-Na-Ayudhya; Ratana Lawung; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology; Mahidol University. Faculty of Medical Technology. Center for Research and Innovation
Effects of hypercholesterolemia on alterations of serum proteins have not been fully elucidated. Herein, using two-dimensional gel electrophoresis (2-DE) in conjunction with LC-MS searching has successfully been carried out to investigate the change of protein expression profiles as consequences of raised blood cholesterol at different levels (normal group: total cholesterol <= 200 mg/dL; borderline high group: total cholesterol 200-239 mg/dL; and high group: total cholesterol ≥ 240 mg/dL) (n = 45). Results revealed that down-regulation of retinol-binding protein 4 (RBP4) (-2.26 fold), transthyretin (-1.25 fold) and gelsolin (-1.47 fold) was observed in the high group. Meanwhile, the other proteins such as haptoglobin, complement factor B and CD5 antigen-like protein were upregulated upto +3.24, +1.96 and +2.04 fold, respectively. Confirmation by Western blotting revealed a significant reduction of RBP4 (approximately 50%) in individual samples derived from the high group. Presumptive conclusion can be drawn that down-regulation of RBP4 might be attributable to the inflammation of adipocytes caused by the release of proinflammatory cytokines (e.g. tumor necrosis factor α and interleukin-1β) from adipose tissues. Moreover, the decrease of transthyretin might also be taken into accounts since it is known that the transthyretin usually forms complex with RBP4 to prevent glomerular filtration and excretion through the kidney. The suppressing effect on RBP4 should be potentiated by the increase of complement factor B and CD5 antigen-like protein, which rendered the adipose tissues to overwhelm the liberation of RBP4 to blood circulation by metabolic and inflammatory processes. Such inflammation could further modulate the induction of cytokine release (e.g. IL-6 and IL-1β), resulting in the synthesis of acute phase protein, in particular, haptoglobin and Creactive proteins from hepatocytes. However, the mechanism of gelsolin reduction remains unclear. Among these differentially expressed proteins, the RBP4 has been proposed as a major linkage between hypercholesterolemia, adipose tissues, liver and kidney, which is believed to be a potential biomarker for metabolic and cardiovascular disorders associated with dyslipidemia in the future. © 2015, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
Open Access
A comparative study of natural immune responses against Plasmodium vivax C-terminal merozoite surface protein-1 (PvMSP-1) and apical membrane antigen-1 (PvAMA-1) in two endemic settings
(2015-08-06) Hui Xia; Qiang Fang; Kulachart Jangpatarapongsa; Tao Zhiyong; Liwang Cui; Baiqing Li; Rachanee Udomsangpetch; Mahidol University. Faculty of Medical Technology. Center for Research and Innovation; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology
The mechanisms of cellular and humoral immune responses against P. vivax parasite remain poorly understood. Several malaria immunological studies have been conducted in endemic regions where both P. falciparum and P. vivax parasites co-exist. In this study, a comparative analysis of immunity to Plasmodium vivax antigens in different geography and incidence of Plasmodium spp. infection was performed. We characterised antibodies against two P. vivax antigens, PvMSP-1 and PvAMA-1, and the cross-reactivity between these antigens using plasma from acute malaria infected patients living in the central region of China and in the western border of Thailand. P. vivax endemicity is found in central China whereas both P. vivax and P. falciparum are endemic in Thailand. There was an increased level of anti-PvMSP-1/anti-PvAMA-1 in both populations. An elevated level of antibodies to total P. vivax proteins and low level of antibodies to total P. falciparum proteins was found in acute P. vivax infected Chinese, suggesting antibody cross-reactivity between the two species. P. vivax infected Thai patients had both anti-P. vivax and anti-P. falciparum antibodies as expected since both species are present in Thailand. More information on humoral and cell mediated immunity during acute P. vivax-infection in the area where only single P. vivax species existed is of great interest in the relation of building up anti-disease severity caused by P. falciparum. This knowledge will support vaccine development in the future. © 2015, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.
Open Access
Discovery of novel 1,2,3-triazole derivatives as anticancer agents using QSAR and in silico structural modification
(2015-10-05) Veda Prachayasittikul; Ratchanok Pingaew; Nuttapat Anuwongcharoen; Apilak Worachartcheewan; Chanin Nantasenamat; Supaluk Prachayasittikul; Somsak Ruchirawat; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics
Considerable attention has been given on the search for novel anticancer drugs with respect to the disease sequelae on human health and well-being. Triazole is considered to be an attractive scaffold possessing diverse biological activities. Structural modification on the privileged structures is noted as an effective strategy towards successful design and development of novel drugs. The quantitative structure–activity relationships (QSAR) is well-known as a powerful computational tool to facilitate the discovery of potential compounds. In this study, a series of thirty-two 1,2,3-triazole derivatives (1–32) together with their experimentally measured cytotoxic activities against four cancer cell lines i.e., HuCCA-1, HepG2, A549 and MOLT-3 were used for QSAR analysis. Four QSAR models were successfully constructed with acceptable predictive performance affording RCV ranging from 0.5958 to 0.8957 and RMSE CV ranging from 0.2070 to 0.4526. An additional set of 64 structurally modified triazole compounds (1A–1R, 2A–2R, 7A–7R and 8A–8R) were constructed in silico and their predicted cytotoxic activities were obtained using the constructed QSAR models. The study suggested crucial moieties and certain properties essential for potent anticancer activity and highlighted a series of promising compounds (21, 28, 32, 1P, 8G, 8N and 8Q) for further development as novel triazole-based anticancer agents.
Open Access
Epidemiological and Molecular Characterization of Dengue Virus Circulating in Bhutan, 2013-2014
(2015-08-21) Sangay Zangmo; Chonticha Klungthong; Piyawan Chinnawirotpisan; Srisurang Tantimavanich; Nathamon Kosoltanapiwat; Butsaya Thaisomboonsuk; Kelzang Phuntsho; Sonam Wangchuk; In-Kyu Yoon; Stefan Fernandez; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology
Dengue is one of the most significant public health problems in tropical and subtropical countries, and is increasingly being detected in traditionally non-endemic areas. In Bhutan, dengue virus (DENV) has only recently been detected and limited information is available. In this study, we analyzed the epidemiological and molecular characteristics of DENV in two southern districts in Bhutan from 2013–2014. During this period, 379 patients were clinically diagnosed with suspected dengue, of whom 119 (31.4%) were positive for DENV infection by NS1 ELISA and/or nested RT-PCR. DENV serotypes 1, 2 and 3 were detected with DENV-1 being predominant. Phylogenetic analysis of DENV-1 using envelope gene demonstrated genotype V, closely related to strains from northern India.
Open Access
Predicting the Oligomeric States of Fluorescent Proteins
(2015) Saw Simeon; Watshara Shoombuatong; Likit Preeyanon; Virapong Prachayasittikul; Chanin Nantasenamat; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology
Currently, monomeric fluorescent proteins (FP) are ideal markers for protein tagging. The prediction of oligomeric states is helpful for enhancing live biomedical imaging. Computational prediction of FP oligomeric states can accelerate the effort of protein engineering to create monomeric FPs by saving time and money. To the best of our knowledge, this study represents the first computational model for predicting and analyzing FP oligomerization directly from their amino acid sequences. An exhaustive dataset consisting of 397 unique FP oligomeric states was compiled from the literature. FP were described by 3 classes of protein descriptors including amino acid composition, dipeptide composition and physicochemical properties. The oligomeric states of FP was predicted using decision tree (DT) algorithm and results demonstrated that DT provided robust performance with accuracies in ranges of 79.97-81.72% and 80.76-82.63% for the internal (e.g. 10-fold cross-validation) and external sets, respectively. This approach was also benchmarked with other common machine learning algorithms such as artificial neural network, support vector machine and random forest. A thorough analysis of amino acid sequence features was conducted to provide informative insights into FP oligomerization, which may aid in engineering novel monomeric fluorescent proteins. The following differentiating characteristics of monomeric and oligomeric fluorescent proteins were derived from DT: (i) substitution of any amino acid to Glu led to the reduction of aggregated proteins and (ii) oligomerization of FP appears to be stabilized by several hydrophobic contacts.
Open Access
Navigating the chemical space of dipeptidyl peptidase-4 inhibitors
(2015-08-10) Watshara Shoombuatong; Veda Prachayasittikul; Nuttapat Anuwongcharoen; Napat Songtawee; Teerawat Monnor; Supaluk Prachayasittikul; Virapong Prachayasittikul; Chanin Nantasenamat; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics; Mahidol University. Faculty of Medical Technology. Department of Clinical Microbiology and Applied Technology
This study represents the first large-scale study on the chemical space of inhibitors of dipeptidyl peptidase-4 (DPP4), which is a potential therapeutic protein target for the treatment of diabetes mellitus. Herein, a large set of 2,937 compounds evaluated for their ability to inhibit DPP4 was compiled from the literature. Molecular descriptors were generated from the geometrically optimized low-energy conformers of these compounds at the semiempirical AM1 level. The origins of DPP4 inhibitory activity were elucidated from computed molecular descriptors that accounted for the unique physicochemical properties inherently present in the active and inactive sets of compounds as defined by their respective half maximal inhibitory concentration values of less than 1 µM and greater than 10 µM, respectively. Decision tree analysis revealed the importance of molecular weight, total energy of a molecule, topological polar surface area, lowest unoccupied molecular orbital, and number of hydrogen-bond donors, which correspond to molecular size, energy, surface polarity, electron acceptors, and hydrogen bond donors, respectively. The prediction model was subjected to rigorous independent testing via three external sets. Scaffold and chemical fragment analysis was also performed on these active and inactive sets of compounds to shed light on the distinguishing features of the functional moieties. Docking of representative active DPP4 inhibitors was also performed to unravel key interacting residues. The results of this study are anticipated to be useful in guiding the rational design of novel and robust DPP4 inhibitors for the treatment of diabetes.
Open Access
Classification of P-glycoprotein-interacting compounds using machine-learning methods
(2015-07) Watshara Shoombuatong; Apilak Worachartcheewan; Veda Prachayasittikul; Chanin Nantasenamat; Virapong Prachayasittikul; Mahidol University. Faculty of Medical Technology. Center of Data Mining and Biomedical Informatics
P-glycoprotein (Pgp) is a drug transporter that plays important roles in multidrug resistance and drug pharmacokinetics. The inhibition of Pgp has become a notable strategy for combating multidrug-resistant cancers and improving therapeutic outcomes. However, the polyspecific nature of Pgp, together with inconsistent results in experimental assays, renders the determination of endpoints for Pgp-interacting compounds a great challenge. In this study, the classification of a large set of 2,477 Pgp-interacting compounds (i.e., 1341 inhibitors, 913 non-inhibitors, 197 substrates and 26 non-substrates) was performed using several machine learning methods (i.e., decision tree induction, artificial neural network modelling and support vector machine) as a function of their physicochemical properties. The models provided good predictive performance, producing MCC values in the range of 0.739-1 for internal cross-validation and 0.665-1 for external validation. The study provided simple and interpretable models for important properties that influence the activity of Pgp-interacting compounds, which are potentially beneficial for screening and rational design of Pgp inhibitors that are of clinical importance.