Mahidol University's Institutional Repository
คลังสารสนเทศสถาบันของมหาวิทยาลัยมหิดล
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Recent Submissions
Transferability of polygenic risk scores for metabolic and cardiovascular traits in an underrepresented population
(2025-12-01) Pasookhush P.; Surawit A.; Suta S.; Pumeiam S.; Mongkolsucharitkul P.; Pinsawas B.; Ophakas S.; Udomphorn Y.; Tongsima S.; Wangkumhang P.; Poonsin T.; Mayurasakorn K.; Pasookhush P.; Mahidol University
Polygenic risk scores (PRSs) are promising tools for genetic risk stratification, but their performance across ancestries remains uncertain. We evaluated 64 published PRSs for eight cardiometabolic traits in 4879 Thai individuals using imputed SNP-array data. Cross-sectional and six-year longitudinal analyses were performed to assess predictive performances. PRSs for type 2 diabetes (T2D) and lipid traits showed the strongest utility, with the best-performing LDL-C and TC scores explaining up to 9.8% and 7.8% of trait variance, respectively. The T2D PRS achieved an area under the curve (AUC) of 0.70 and consistently stratified disease risk over time. In contrast, PRSs for glycemic traits and cardiovascular disease (CVD) had weaker predictive value; notably, the best-performing CVD PRS showed an inverse association with disease risk. Reduced SNP retention and ancestry-related linkage disequilibrium differences contributed to variability. These findings highlight both the potential and current limitations of PRSs in underrepresented Southeast Asian populations.
General Characteristics of Eastern Indonesian Household Dietary Diversity Score
(2024-08-01) Maretalinia; Suryani D.; Angriani Y.; Maretalinia; Mahidol University
Household dietary diversity score (HDDS) is a crucial indicator of food security and nutritional outcomes. The data collection was done from 2017 to 2018 in Eastern Indonesia. This study aimed to capture the characteristics of HDDS based on district, province, religion, and head of household age. This study used secondary data from the Coastal Community Development Project (CCDP), IFAD Impact Assessment Survey 2018. The total sample of this study was 2,884 households. The HDDS was calculated based on the score of 12 food groups and presented in a bar graph using STATA version 17. The result revealed that the lowest HDDS was found in the Kupang district, East Nusa Tenggara Province, Confucianism or Konghucu Religion, and 15 to 25 years of head of household age. Household dietary diversity score is a critical measure of food security and nutritional status, reflecting a household's access to a variety of foods. Understanding and addressing these determinants are essential for improving household dietary diversity and ultimately enhancing nutrition outcomes.
Optimized delivery of RNA silencing prolyl hydroxylase domain 2 for enhanced angiogenesis and osteogenesis using bioactive glass scaffolds
(2025-12-01) Kunwong N.; Wongrakpanich A.; Amornphimoltham P.; Dechkunakorn S.; Srikhirin T.; Saranpuetti C.; Sritanaudomchai H.; Kunwong N.; Mahidol University
This study investigated the delivery of small interfering RNA (siRNA) silencing prolyl hydroxylase domain 2 (PHD2) via poly(lactic-co-glycolic acid) (PLGA)-bioactive glass scaffold to improve angiogenesis and osteogenesis for biomineralized tissue engineering. Polyethylenimine (PEI) was complexed with PHD2siRNA at 3:1, 6:1, and 8:1 ratios, and the resulting complexes were characterized by transmission electron microscopy, NanoSight analysis, and gel retardation assays. Their biological effects on human umbilical vein endothelial cells (HUVECs) were evaluated to determine the optimal ratio. PLGA-bioactive glass scaffolds were prepared and loaded with the most effective PEI/PHD2siRNA complex. HUVECs were used to confirm controlled RNA release from the scaffolds. The angiogenic effects of HUVECs and osteogenic differentiation of stem cells derived from human exfoliated deciduous teeth (SHED) were evaluated. The 8:1 ratio of PEI/PHD2siRNA demonstrated the highest efficiency, improving HUVEC tube formation. Incorporating these complexes into PLGA-bioactive glass scaffolds confirmed RNA release, as indicated by improved tube formation. The scaffolds promoted the proliferation and angiogenic differentiation of HUVECs. SHED cells cultured on the scaffolds demonstrated improved proliferation and osteogenic differentiation, evidenced by elevated alkaline phosphatase activity and mineral deposition. Coculturing SHED cells with HUVECs on the scaffolds exerted synergistic effects, producing more robust osteogenic differentiation than culturing SHED cells alone. Immunofluorescence staining revealed increased expression of both angiogenic and osteogenic markers. PHD2 siRNA delivery via PLGA-bioactive glass scaffolds enhanced angiogenesis and osteogenesis, supporting its potential in tissue engineering. This dual-function scaffold offers a promising strategy for dental and craniofacial regeneration.
Practical and Site-Selective Photoinitiated C(sp3)–H Bond Chlorination of Ketones, (E)-1,3-Enones, and Alkylbenzenes by Chloramine-T and N-Chlorosuccinimide
(2025-01-01) Zhang Y.; Diaz J.; Senapati S.; La-ongthong K.; Ung Y.C.; Kuhakarn C.; Jin J.; Koenigs R.M.; Chan P.W.H.; Zhang Y.; Mahidol University
A practical photoinitiated synthetic method for the site-selective γ - and α-chlorination of C(sp3)–H bonds of ketones, (E)-1,3-enones, and alkylbenzenes by chloramine-T (CAT) and N-chlorosuccinimide (NCS) under blue LED (λmax = 456 nm) light irradiation is reported. Mechanistic studies suggest the reaction to proceed via a radical pathway where the chlorination reagent dichloramine-T (DCT) is generated in situ from the reaction of CAT with NCS. Its premised controlled formation along with that of the carbon-centered radical species derived from the substrate is thought to contribute to product site-selectivity. The developed protocol operates under mild reaction conditions at room temperature and demonstrates excellent functional group tolerance as exemplified by the site-selective γ-C(sp3)–H bond chlorination of carboxylic esters and amides, and late-stage functionalization of several bioactive natural products and drug molecules. The study also highlights the potential of CAT for the first time as a versatile and controllable chlorine radical atom source for site-selective halogenation reactions, expanding its synthetic utility beyond traditional applications.
Molecular and structural characterization of a novel β-hemoglobinopathy caused by in Cis β-globin mutations in a Thai individual
(2025-12-01) Singha K.; Pansuwan A.; Sanachai K.; Nutho B.; Fucharoen G.; Fucharoen S.; Singha K.; Mahidol University
Hemoglobin (Hb) E is the most common Hb variant in Southeast Asia. We described a novel form of Hb E caused by an in cis combination of Hb E and another β-hemoglobinopathy affecting Hb stability. Study was done on a Thai woman at a routine prenatal screening of thalassemia. Hb analysis was carried out by HPLC and capillary electrophoresis. Mutation and β-globin gene haplotype analyses were done using PCR-based assays. Structure of the abnormal Hb molecule was predicted using molecular dynamics simulations. The subject had mild normocytic anemia with Hb 10.3 g/dL. Hb-HPLC analysis revealed Hb A2A with 6.9% Hb A2, whereas capillary electrophoresis showed Hb A2EA with 3.6% Hb A2 and 3.4% Hb E. No α- and β-thalassemia mutations were detected. Further β-globin gene analysis identified a novel variant caused by two in cis mutations, i.e., Hb E (codon 26 GAG > AAG) and Hb Palmerston North (codon 23 GTT > TTT), namely Hb E-Hb Palmerston North. Splicing site prediction of the Hb E-Palmerston North gene showed similar splicing scores at both normal and cryptic splice sites with those of the Hb E gene. System stability prediction of the Hb E-Palmerston North expression indicated a weakening αβ contact, resulting in instability and a dramatic reduction of Hb variant (3.4%). The novel Hb E variant, designated Hb E-Palmerston North, was characterized by unusually low levels, which was attributed to its high instability. The diagnosis of this novel Hb variant is best by multiplex PCR assay developed.