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Fulltext Stem Cell Therapy in Dengue Virus-Infected BALB/C Mice Improves Hepatic Injury

Sakinah S, Priya SP, Mok PL, Munisvaradass R, Teh SW, Sun Z, et al.

Front Cell Dev Biol, 2021;9:637270.
PMID: 34291043 DOI: 10.3389/fcell.2021.637270

Extensive clinical efforts have been made to control the severity of dengue diseases; however, the dengue morbidity and mortality have not declined. Dengue virus (DENV) can infect and cause systemic damage in many organs, resulting in organ failure. Here, we present a novel report showing a tailored stem-cell-based therapy that can aid in viral clearance and rescue liver cells from further damage during dengue infection. We administered a combination of hematopoietic stem cells and endothelial progenitor cells in a DENV-infected BALB/c mouse model and found that delivery of this cell cocktail had improved their liver functions, confirmed by hematology, histopathology, and next-generation sequencing. These stem and progenitor cells can differentiate into target cells and repair the damaged tissues. In addition, the regime can regulate endothelial proliferation and permeability, modulate inflammatory reactions, enhance extracellular matrix production and angiogenesis, and secrete an array of growth factors to create an enhanced milieu for cell reparation. No previous study has been published on the treatment of dengue infection using stem cells combination. In conclusion, dengue-induced liver damage was rescued by administration of stem cell therapy, with less apoptosis and improved repair and regeneration in the dengue mouse model.
Fulltext Synthesis, characterization and evaluation of antidengue activity of enantiomeric Schiff bases derived from S-substituted dithiocarbazate

Maryam M, Tan SL, Crouse KA, Mohamed Tahir MI, Chee HY

Turk J Chem, 2020;44(5):1395-1409.
PMID: 33488239 DOI: 10.3906/kim-2006-22

A series of Schiff bases have been successfully synthesized through the acid-catalyzed condensation of S-substituted dithiocarbazates and three enantiomerically pure monoterpenes, (1 R )-(+)-camphor, (1 S )-(-)-camphor, (1 R )-(-)-camphorquinone, (1 S )-(+)-camphorquinone, ( R )-(-)-carvone and ( S )-(+)-carvone. Spectroscopic results revealed that the Schiff bases containing camphor or carvone likely adopted an E -configuration along the characteristic imine bond while those containing camphorquinone assumed a Z -configuration. The antidengue potential of these compounds was evaluated based on DENV 2 caused cytopathic effect (CPE) reduction-based in vitro evaluation. The compounds were validated through secondary foci forming unit reduction assay (FFURA). Compounds were also tested for their cytotoxicity against Vero cells. The compounds showed variable degrees of antiviral activity with the camphor compounds displaying the highest antidengue potential. The enantiomers of the compounds behaved almost similarly during the antiviral evaluation.
Fulltext Systematic review and meta-analysis of the efficacy and safety of oseltamivir (Tamiflu) in the treatment of Coronavirus Disease 2019 (COVID-19)

Aliyu B, Raji YE, Chee HY, Wong MY, Sekawi ZB

PLoS One, 2022;17(12):e0277206.
PMID: 36454880 DOI: 10.1371/journal.pone.0277206

Efforts are ongoing by researchers globally to develop new drugs or repurpose existing ones for treating COVID-19. Thus, this led to the use of oseltamivir, an antiviral drug used for treating influenza A and B viruses, as a trial drug for COVID-19. However, available evidence from clinical studies has shown conflicting results on the effectiveness of oseltamivir in COVID-19 treatment. Therefore, this systematic review and meta-analysis was performed to assess the clinical safety and efficacy of oseltamivir for treating COVID-19. The study was conducted according to the PRISMA guidelines, and the priori protocol was registered in PROSPERO (CRD42021270821). Five databases were searched, the identified records were screened, and followed by the extraction of relevant data. Eight observational studies from four Asian countries were included. A random-effects model was used to pool odds ratios (ORs), mean differences (MD), and their 95% confidence intervals (CI) for the study analysis. Survival was not significantly different between all categories of oseltamivir and the comparison groups analysed. The duration of hospitalisation was significantly shorter in the oseltamivir group following sensitivity analysis (MD -5.95, 95% CI -9.91--1.99 p = 0.003, heterogeneity I2 0%, p = 0.37). The virological, laboratory and radiological response rates were all not in favour of oseltamivir. However, the electrocardiographic safety parameters were found to be better in the oseltamivir group. However, more studies are needed to establish robust evidence on the effectiveness or otherwise of oseltamivir usage for treating COVID-19.
Fulltext The predictive and diagnostic accuracy of vascular endothelial growth factor and pentraxin-3 in severe dengue

Low GKK, Gan SC, Zainal N, Naidu KD, Amin-Nordin S, Khoo CS, et al.

Pathog Glob Health, 2018 09;112(6):334-341.
PMID: 30246621 DOI: 10.1080/20477724.2018.1516417

This study aimed to evaluate vascular endothelial growth factor (VEGF) and pentraxin 3 (PTX-3) as predictive and diagnostic markers in differentiating severe dengue from non-severe dengue. The study was conducted in Ampang Health Clinic, Ampang Hospital and Serdang Hospital. The plasma levels of VEGF and PTX-3 were compared between severe dengue and non-severe dengue by ELISA from the day of presentation until discharged. Multiple logistic regression was used to develop predictive and diagnostic models by incorporating other clinical parameters. The receiver operating characteristics (ROC) analysis was used to assess the accuracy of the biomarkers and the developed models. Eighty-two patients were recruited, 29 with severe dengue and four died. The Area Under the Curve (AUC) was statistically significant in VEGF as diagnostic marker at Day 2 and 3 of illness with sensitivity of 80.00%-100.00% and specificity of 76.47%-80.00%. The predictive model with AUC of 0.84 (p
Ultrastructural aspects of sylvatic dengue virus infection in Vero cell

Fish-Low CY, Abubakar S, Othman F, Chee HY

Malays J Pathol, 2019 Apr;41(1):41-46.
PMID: 31025636

INTRODUCTION: Dengue virus (DENV), the causative agent of dengue disease exists in sylvatic and endemic ecotypes. The cell morphological changes and viral morphogenesis of two dengue ecotypes were examined at the ultrastructural level to identify potential similarities and differences in the surrogate model of enzootic host.
MATERIALS AND METHODS: Vero cells were inoculated with virus at a multiplicity of infection (MOI) of 0.1. Cell cultures were harvested over a time course and processed for transmission electron microscopic imaging.
RESULTS: The filopodia protrusions on cell periphery preceded virus entry. Additionally, sylvatic DENV infection was found spreading slower than the endemic DENV. Morphogenesis of both dengue ecotypes was alike but at different level of efficiency in the permissive cells.
CONCLUSIONS: This is the first ultrastructural study on sylvatic DENV and this comparative study revealed the similarities and differences of cellular responses and morphogenesis of two dengue ecotypes in vitro. The study revealed the weaker infectivity of sylvatic DENV in the surrogate model of enzootic host, which supposed to support better replication of enzootic DENV than endemic DENV.
Ultrastructural changes of cell morphology and viral morphogenesis of two ecotypes of dengue virus infection in human monocytic U-937 cell

Fish-Low CY, Abu Bakar S, Othman F, Chee HY

Trop Biomed, 2018 Dec 01;35(4):1154-1159.
PMID: 33601863

Dengue virus (DENV) is maintained and circulated in both sylvatic/enzootic and endemic/human cycles and spill over infection of sylvatic DENV into human populations has been reported. Extensive deforestation and increase human activities in forest may increase the risk of human exposure to sylvatic dengue infection and this may become a threat to human. Present study investigated the changes in cell morphology and viral morphogenesis upon infection with sylvatic and endemic ecotypes in human monocytic U-937 cells using transmission electron microscopy. Autophagy, a process that is either pro-viral or anti-viral, was observed in U-937 cells of both infections, however only the replication of endemic DENV was evidenced. An insight into the infection responses of sylvatic progenitors of DENV in susceptible host cells may provide better understanding on dengue emergence in human populations.
Viability of dengue virus in culture stocks is efficiently preserved by storage in diluted forms

Suppiah J, Nadaraju S, Hamzah S, Chee HY

Trop Biomed, 2020 Jun 01;37(2):282-287.
PMID: 33612798

Storage of dengue virus (DENV) culture stocks in -80°C is a common laboratory practice to maintain the viability of the virus for long-term usage. However, the efficiency of this method could still be hindered by multiple factors. In our laboratory, we observed a constant and substantial deterioration in the titer of DENV in Vero culture supernatant stored in -80°C. Such incident had badly hampered the laboratory work and prompted an investigation to determine the cause. DENV isolates representing all four serotypes were propagated and the culture supernatants were harvested and stored in aliquots of original stock and 10 fold dilutions (10-1 -10-4). DENV titer in these stocks was determined prior to storage and reassessed on the third and sixth month of storage by focus forming unit assay (FFUA). The result demonstrated a constant preservation of titer ranging from 104 ffu/ml to 105 ffu/ml in the diluted DENV virus culture stocks of 10-1, and 10-2 of DENV1-4, a minor reduction of titer from 103 ffu/ml to 102 ffu/ml at dilution 10-3 for DENV4 only and complete deterioration in undiluted culture stock and lower dilution (10-4) within 6 months of storage in -80°C for all serotypes. It is recommended that propagated DENV in Vero cells are stored in 10 fold dilutions as compared to the original form to preserve the titer for long-term usage.