Mahidol University's Institutional Repository
คลังสารสนเทศสถาบันของมหาวิทยาลัยมหิดล
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Recent Submissions
Intracellular delivery of anti-dengue envelope monoclonal antibodies via PEG-PLGA nanoparticles suppresses viral replication and attenuates hepatocyte apoptosis
(2026-04-01) Intrarakasem N.; Kaewkarn S.; Proykhunthod P.; Songjaeng A.; Avirutnun P.; Prommool T.; Puttikhunt C.; Makeudom A.; Morchang A.; Tian X.; Battaglia G.; Patikarnmonthon N.; Kraivong R.; Intrarakasem N.; Mahidol University
Dengue virus (DENV) infection remains a major global health threat, with no specific antiviral treatment currently approved. Monoclonal antibody (mAb) therapy represents a promising strategy for viral inhibition; however, conventional antibodies are largely restricted to extracellular compartments and lack access to intracellular viral replication sites. In this study, we encapsulated a cross-reactive mAb targeting the DENV envelope protein (m513) into poly(ethylene glycol)- block -poly(lactide- co -glycolide) (PEG-PLGA) nanoparticles to facilitate intracellular delivery. When applied to immortalized hepatocyte-like cells (imHCs), the formulation demonstrated efficient cellular uptake, low cytotoxicity, and significantly reduced intracellular viral RNA and protein levels. The resulting formulation consisted of mAb-loaded PEG-PLGA nanoparticles (∼100 nm in diameter) with spherical morphology and an encapsulation efficiency of approximately 50%. Furthermore, nanoparticle treatment significantly reduced hepatocyte apoptosis in infected cells. Collectively, these findings demonstrate that nanoparticle-mediated intracellular antibody delivery can overcome a key limitation of conventional antibody therapy and represents a mechanistically distinct antiviral strategy for DENV and other intracellular viral infections.
Analysis of Plasma Epstein–Barr Virus DNA and Clinical Outcomes to Pembrolizumab or Chemotherapy in Recurrent/Metastatic Nasopharyngeal Cancer in KEYNOTE-122
(2026-02-01) Chan A.T.C.; Lee V.H.F.; Hong R.L.; Ahn M.J.; Chong W.Q.; Spreafico A.; Kim S.B.; Ho G.F.; Caguioa P.B.; Ngamphaiboon N.; Swaby R.F.; Wei B.; Webber A.L.; Kang J.; Gumuscu B.; Yuan J.; Siu L.L.; Chan A.T.C.; Mahidol University
Background: Plasma Epstein–Barr virus (EBV) DNA has clinical utility for prognosis, recurrence, surveillance, and treatment response in nasopharyngeal carcinoma (NPC). This exploratory analysis evaluated associations between plasma EBV DNA load and clinical outcomes in participants treated with pembrolizumab or chemotherapy in the phase 3 KEYNOTE-122 trial (NCT02611960). Methods: Participants with platinum-pretreated, histologically confirmed, EBV-positive, recurrent/metastatic NPC were randomly assigned (1:1) to pembrolizumab 200 mg intravenously every 3 weeks (≤ 35 cycles) or standard of care (SOC; investigator's choice of capecitabine, gemcitabine, or docetaxel). Associations between baseline plasma EBV DNA load as a continuous variable and plasma EBV DNA fold change at cycle 2 day 1 (C2D1), with clinical outcomes (progression-free survival [PFS], overall survival [OS], and objective response rate [ORR]) were evaluated within each treatment arm. Nominal significance was prespecified at 0.05 for 1-sided p values. Results: Of 228 treated participants, 215 (94.3%) had evaluable baseline plasma EBV DNA load data (pembrolizumab, 111; SOC, 104). Baseline plasma EBV DNA load was negatively associated with PFS and OS for pembrolizumab and SOC (both p < 0.005) but not ORR (p = 0.105, pembrolizumab; p = 0.473, SOC). Larger decreases in plasma EBV DNA load at C2D1 relative to baseline were associated with improved PFS, OS, and ORR for pembrolizumab and SOC (p ≤ 0.005). Conclusions: Higher baseline plasma EBV DNA load was negatively associated with outcomes in participants with NPC treated with pembrolizumab or SOC. These findings provide additional support for plasma EBV DNA as a prognostic biomarker for NPC. Trial Registration: ClinicalTrials.gov, NCT02611960.
Structure–property relationships in saccharide-derived carbon dots: Tuning oxygen functionalities and sp2 domains for antioxidant performance
(2026-05-15) Wibowo A.; Khan M.J.; Sawatdee S.; Pornputthapitak W.; Tuntithavornwat S.; Srifa A.; Posoknistakul P.; Pornsuwan S.; Laosiripojana N.; Jiang Y.; Sansanaphongpricha K.; Sakdaronnarong C.; Wibowo A.; Mahidol University
Excessive reactive oxygen species (ROS) drive oxidative stress and disease progression, yet the structural determinants of antioxidant activity in carbon dots (CDs) remain unclear. In this study, the influence of oxygenated surface functional groups and carbon hybridization states on the performance of saccharide-derived CDs was elucidated. CDs were synthesized from five saccharide precursors via hydrothermal carbonization, and synthesis parameters were systematically optimized using response surface methodology combined with central composite design (200–240 °C, 6–12 h). Among the tested precursors, xylose yielded CDs (X-CDs) with the smallest size (2.17–4.38 nm), the strongest blue emission (427–450 nm), the highest negative surface charge (−38.5 to −84.6 mV), and the highest quantum yield (0.80–2.81%). Spectroscopic analyses revealed enriched oxygen functionalities (O/C ratio up to 0.32) and graphitic sp2 domains with reduced sp3 content, correlating with enhanced electronic delocalization. Optimized X-CDs exhibited potent radical scavenging activity (EC₅₀ = 0.047 mg/mL for DPPH; 0.008 mg/mL for ABTS) while showing low cytotoxicity toward normal and cancer cells. These findings establish a mechanistic framework linking oxygenated groups and sp2 hybridization to enhanced antioxidant properties and provide a green, tunable strategy for designing high-performance CDs from renewable precursors for biomedical, nutraceutical, and environmental applications.
Microalgae-assisted biomineralization of Lysinibacillus sp. WH for sustainable low-carbon biocement Production
(2026-03-07) Ditta Z.M.; Thaweesub P.; Pudsakaew P.; Laohana P.; Tanapongpisit N.; Saenrang W.; Pongtharangkul T.; Sata V.; Chindaprasirt P.; Ekprasert J.; Ditta Z.M.; Mahidol University
Microbially induced calcium carbonate (CaCO3) precipitation (MICP) is a promising biochemical process for improving cement strength and durability of cementitious materials through biomineralization of CaCO3. This study investigates the use of bacteria Lysinibacillus sp. WH bacteria and microalgae Chlorella vulgaris (C. vulgaris), both in monoculture and co-culture, for biocement production and micro-crack remediation. Synergistic effects of these microbes on the mechanical properties and microstructural development were examined for the first time. Incorporating Lysinibacillus sp. WH with C. vulgaris resulted in maximum cement strength of ∼58 MPa, accounting for ∼14 % increment compared to the control, and promoted microcrack healing starting from 9 days of treatment. Conversely, incorporation of C. vulgaris solely inhibited the main hydration phase of tricalcium silicate (C3S), as confirmed by TGA-DTG and XRD-Rietveld refinement analysis, which reduced cement quality. However, the co-culture system with Lysinibacillus sp. WH minimized this detrimental effect and improved overall cement quality. SEM-EDS analysis confirmed that the morphology of the precipitated bio-CaCO3 was influenced by the microbial species present. The formation of this crystal effectively seals the crack, particularly with the presence of Lysinibacillus sp. WH. Overall, this work provides an effective method to develop durable and eco-friendly cement paste by leveraging a renewable biological source to achieve enhanced performance and sustainability.
Micro-CT Analysis of MTA Apical Plug Placement: Manual Condensation, Indirect Ultrasonic Activation, and Sonic-Activated Rotary Compaction Techniques
(2026-01-01) Harndamrong N.; Wichai W.; Jindachot S.; Jantarat J.; Harndamrong N.; Mahidol University
Introduction Mineral trioxide aggregate is widely used for apexification in immature permanent teeth owing to sealing ability and biocompatibility; however, placement in teeth with open apices may result in void, potentially compromising the apical seal. This study compared mineral trioxide aggregate (MTA) apical plug quality and procedural time among 3 placement techniques. Methods Thirty extracted human mandibular premolars with simulated open apices (apical diameter, 0.8 mm) were randomly assigned to 3 groups ( n = 10). Four-millimeter MTA apical plugs were placed using manual condensation, indirect ultrasonic activation, or sonic-activated rotary compaction. Micro–computed tomography quantified closed porosity (internal voids) and open porosity (interfacial gaps) as percentages of total apical plug volume. Procedural time was recorded, and data were analyzed statistically. Results Sonic-activated rotary compaction produced the lowest open porosity (0.001% ± 0.001%) and shortest procedural time (160.00 ± 6.50 s) but resulted in the highest closed porosity (0.412% ± 0.076%). Manual condensation demonstrated the highest open porosity (0.122% ± 0.063%) and moderate closed porosity (0.108% ± 0.076%), whereas indirect ultrasonic activation showed intermediate open porosity (0.006% ± 0.002%) and lowest closed porosity (0.079% ± 0.030%). Importantly, closed porosity did not differ significantly between the manual and ultrasonic groups ( P = .523). Indirect ultrasonic activation required the longest procedural time (270.30 ± 7.27 s), followed by manual condensation (229.20 ± 6.34 s), whereas sonic-activated rotary compaction was the most time-efficient. All other intergroup differences were statistically significant ( P < .001). Conclusions Sonic-activated rotary compaction demonstrated the lowest open porosity and greatest time efficiency among 3 techniques, although it produced the highest closed porosity.