Mahidol University's Institutional Repository

คลังสารสนเทศสถาบันของมหาวิทยาลัยมหิดล

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Recent Submissions

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Repurpose antimalarials to target Toxoplasma gondii dihydrofolate reductase thymidylate synthase
(2026-09-05) Decharuangsilp S.; Koompapong K.; Arwon U.; Tuyapala N.; Hoarau M.; Tanasugarn L.; Pengon J.; Talawanich Y.; Saeyang T.; Vanichtanankul J.; Yuthavong Y.; Kamchonwongpaisan S.; Mahittikorn A.; Kongkasuriyachai D.; Decharuangsilp S.; Mahidol University
Toxoplasma gondii is an obligate intracellular blood and tissue protozoan parasite that infects up to a third of the population worldwide. Several antimalarial drugs, in particular pyrimethamine (PYR), have been used for decades to treat toxoplasmosis. Here, the clinical candidate P218, a potent inhibitor of Plasmodium falciparum dihydrofolate reductase (PfDHFR), and a series of flexible diaminopyrimidine butyrolactone analogues were identified as potent T. gondii dihydrofolate reductase (TgDHFR) inhibitors. The most promising butyrolactone analogue, LA4, displayed an improved TgDHFR inhibition (Ki 1.71 nM), increased antiparasitic properties in vitro (IC50 0.44 nM), and a higher cell selectivity compared to PYR (Ki 13.0 nM, IC50 410 nM) while P218 (Ki 2.19 nM, IC50 370 nM) presented an improved activity with comparable cell selectivity to PYR. The in vivo results against T. gondii RH strain-infected mice showed that P218 reduced parasitic burden in blood whereas LA4 decreased parasite load in peritoneal fluid and blood with an extended mice survival. These findings position butyrolactone LA4 as a new potential for the treatment of acute toxoplasmosis.
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Valorization of Desalted Duck Egg White through Enzymatic Hydrolysis: Gastric Digestion Behavior and Antioxidant Responses
(2026-04-01) Jiamyangyuen S.; Tosuk N.; Numthuam S.; Sringarm C.; Winuprasith T.; Rungchang S.; Jiamyangyuen S.; Mahidol University
This study investigated the gastric-phase digestion behavior and antioxidant responses of enzymatic protein hydrolysates produced from desalted duck egg white (DS-DEW) and evaluated their potential for value-added food ingredient development. Duck egg white proteins were subjected to enzymatic hydrolysis, and a modified INFOGEST static in vitro digestion model focusing exclusively on the gastric phase was applied to native duck egg white (DEW), desalted duck egg white (DS-DEW), duck egg white hydrolysate (DEWH), desalted duck egg white hydrolysate (DS-DEWH), and commercial egg white powder (EWP). Proteolysis during digestion was assessed by acid consumption kinetics, while free amino acid (FAA) release and antioxidant responses were evaluated using HPLC, DPPH radical-scavenging, and ferric-reducing antioxidant power (FRAP) assays. Native and non-hydrolyzed samples (DEW, DS-DEW, and EWP) exhibited high acid uptake during gastric digestion (90%-95%), whereas pre-hydrolyzed samples (DEWH and DS-DEWH) showed markedly lower acid consumption (< 20%), reflecting extensive peptide bond cleavage prior to gastric digestion rather than reduced digestibility. DS-DEWH exhibited the highest absolute FAA content after digestion (303.25 ± 4.38 mg/g), approximately 22-fold higher than EWP, indicating greater availability of hydrolysis products under acidic, pepsin-driven conditions. Antioxidant evaluation using chemical assays showed that DS-DEWH displayed significantly higher DPPH radical-scavenging activity (42.67%) and FRAP values (3.71 ± 0.69 µmol TE/g) than DEW and DS-DEW (p < 0.05). Due to analytical constraints, EWP was excluded from antioxidant assays. Overall, enzymatic hydrolysis altered gastric-phase digestion behavior and enhanced free amino acid availability and antioxidant responses of desalted duck egg white at the chemical-assay level, supporting its valorization as a sustainable food protein ingredient.
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Trends and Patterns of Animal Poisoning in Thailand: A 10-Year Retrospective Study from Ramathibodi Poison Center
(2026-04-01) Tansuwannarat P.; Trakulsrichai S.; Sanprasert K.; Ploypetch S.; Ariyaviraplorn N.; Tongpoo A.; Tansuwannarat P.; Mahidol University
Animal poisoning remains an underreported public health and veterinary concern in many low- and middle-income countries where comprehensive surveillance systems are limited. This study was initiated to describe the epidemiology, clinical characteristics, and outcomes of animal poisoning cases reported to a national poison center in Thailand over a 10-year period. We performed a retrospective review of cases recorded in the Ramathibodi Poison Center Toxic Exposure Surveillance System between 2015 and 2024. Descriptive statistics were used to summarize species distribution, exposure categories, clinical signs, treatment, and outcomes, and comparisons were conducted to identify factors associated with mortality. A total of 118 poisoning cases were identified, with annual numbers increasing over time. Companion animals accounted for most exposures (93.2%), particularly dogs. Pesticides were the most common toxic agents, followed by household products, pharmaceuticals, and plant toxins. Neurological signs were the predominant clinical presentation. Respiratory compromise and neurological involvement at presentation were significantly associated with mortality. Overall survival was 88.1%. Fatalities were mainly linked to exposure to highly toxic pesticides or plants, including confirmed cassava-associated cyanide poisoning in elephants. This study highlights preventable environmental toxic risks affecting animals in Thailand and demonstrates the value of centralized poison surveillance. Strengthening pesticide safety practices and integrating veterinary toxicology into broader public health monitoring may reduce avoidable poisonings within shared human–animal environments.
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Domain-guided engineering of a thermoresistant Vip3A toxin for enhanced functional robustness
(2026-12-01) Kunlawatwimon T.; Bourdeaux F.; Boonserm P.; Soonsanga S.; Luka J.; Promdonkoy B.; Schwaneberg U.; Kunlawatwimon T.; Mahidol University
Vip3A toxins from Bacillus thuringiensis are effective insecticidal agents for lepidopteran pest control, but their application is limited by poor thermal stability and loss of activity during storage. In this study, we engineered a thermoresistant Vip3Aa64 variant using a combined rational design and directed-evolution approach. Structural analysis and thermal profiling identified domains IV and V as the primary determinants of instability. Rational design targeting domain V yielded stabilizing substitutions that enhanced interdomain interactions, while error-prone mutagenesis of domain IV coupled with high-throughput nanoscale differential scanning fluorimetry screening identified additional mutations conferring increased thermal resistance. Combining the most effective substitutions and removing a mutation that reduced toxicity produced the variant Vip3A-TR6 (I408E/M755K/N633V/G580E), which exhibited a 5.1 °C increase in melting temperature without compromising insecticidal activity against Spodoptera exigua. Vip3A-TR6 displayed enhanced resistance to heat-induced aggregation and retained bioactivity after prolonged storage at 25 °C and 37 °C. Importantly, the variant was efficiently produced and secreted by B. thuringiensis. These results demonstrate a robust strategy for improving the robustness of Vip3A toxins and support the development of more durable Vip3A-based biopesticides.