The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during ...infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue. We then postulated that disease severity in infants with primary infections would be associated with a robust immune response, possibly as a consequence of higher viral burdens in vivo. Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3133–142-specific CD8+ T cells were not measurable until early convalescence. Plasma levels of cytokines/chemokines were generally higher in infants with dengue shock syndrome. Collectively, these data support a model of dengue pathogenesis in infants whereby antibody-dependent enhancement of infection explains the age-related case epidemiology and could account for antigen-driven immune activation and its association with disease severity. These results also highlight potential risks in the use of live attenuated dengue vaccines in infants in countries where dengue is endemic.
•Vitamin B6 and Mg were simultaneously determined by CE-C4D.•Vitamin B6 and Mg peaks were well separated within < 10 min.•A simple and reliable method was developed for pharmaceutical/nutraceutical ...samples.•Single-run CE-C4D analysis can replace HPLC and ICP-OES conventional methods.•Acceptable agreement between measured/label claim contents was achieved.
Vitamins and minerals are usually incorporated in pharmaceutical and nutraceutical products, but a simple, rapid, and inexpensive analytical method for their simultaneous determination is still lacking. In this study, we developed a quantification method for pyridoxine (vitamin B6) and magnesium (Mg) by using purpose-made capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) instrument. Main analytical conditions include: fused silica capillary (total length 55 cm, effective length 40 cm, inner diameter 50 μm); background electrolyte consisted of 10 mM L-arginine/acetic acid (pH 5) with 20% acetonitrile; separation voltage + 20 kV; hydrodynamic injection (siphoning at 20 cm in 25 s). Detection limits of vitamin B6 and Mg were 1 and 0.1 mg/L, respectively. Good linearity (R2 > 0.999) was observed for vitamin B6 and Mg calibration curves over concentration ranges of 3–100 and 0.3–200 mg/L, respectively. The method was applied to analyze vitamin B6 and Mg in several pharmaceutical and nutraceutical samples. The analytical results obtained by our method were in good agreement with reference methods (i.e., HPLC for vitamin B6 and ICP-OES for Mg). High-efficient and low-cost CE-C4D method can accordingly serve as a promising tool for concurrent analysis of inorganic and organic species in pharmaceutical and nutraceutical analysis.
Dengue hemorrhagic fever can occur in primary dengue virus (DENV) infection of infants. The decay of maternally derived DENV immunoglobulin (Ig) G and the incidence of DENV infection were determined ...in a prospectively studied cohort of 1244 Vietnamese infants. Higher concentrations of total IgG and DENV-reactive IgG were found in cord plasma relative to maternal plasma. Maternally derived DENV-neutralizing and E protein–reactive IgG titers declined to below measurable levels in >90% of infants by 6 months of age. In contrast, IgG reactive with whole DENV virions persisted until 12 months of age in 20% of infants. Serological surveillance identified 10 infants with asymptomatic DENV infection for an incidence of 1.7 cases per 100 person-years. DENV-neutralizing antibodies remained measurable for ⩾1 year after infection. These results suggest that whereas DENV infection in infants is frequently subclinical, there is a window between 4 and 12 months of age where virion-binding but nonneutralizing IgG could facilitate antibody-dependent enhancement
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In this work, we report 14 novel quinazoline derivatives as immune checkpoint inhibitors, IDO1 and PD-L1. The antitumor screening of synthesized compounds on ovarian cancer cells ...indicated that compound V-d and V-l showed the most activity with IC50 values of about 5 μM. Intriguingly, compound V-d emerges as a stand out, triggering cell death through caspase-dependent and caspase-independent manners. More importantly, V-d presents its ability to hinder tumor sphere formation and re-sensitized cisplatin-resistant A2780 cells to cisplatin treatment. These findings suggest that compound V-d emerges as a promising lead candidate for the future development of immuno anticancer agents.
Summary
Bats and rodents are being increasingly recognized as reservoirs of emerging zoonotic viruses. Various studies have investigated bat viruses in tropical regions, but to date there are no data ...regarding viruses with zoonotic potential that circulate in bat and rat populations in Viet Nam. To address this paucity of data, we sampled three bat farms and three wet markets trading in rat meat in the Mekong Delta region of southern Viet Nam. Faecal and urine samples were screened for the presence of RNA from paramyxoviruses, coronaviruses and filoviruses. Paramyxovirus RNA was detected in 4 of 248 (1%) and 11 of 222 (4.9%) bat faecal and urine samples, respectively. Coronavirus RNA was detected in 55 of 248 (22%) of bat faecal samples; filovirus RNA was not detected in any of the bat samples. Further, coronavirus RNA was detected in 12 of 270 (4.4%) of rat faecal samples; all samples tested negative for paramyxovirus. Phylogenetic analysis revealed that the bat paramyxoviruses and bat and rat coronaviruses were related to viruses circulating in bat and rodent populations globally, but showed no cross‐species mixing of viruses between bat and rat populations within Viet Nam. Our study shows that potentially novel variants of paramyxoviruses and coronaviruses commonly circulate in bat and rat populations in Viet Nam. Further characterization of the viruses and additional human and animal surveillance is required to evaluate the likelihood of viral spillover and to assess whether these viruses pose a risk to human health.
Summary
Viral pathogens account for a significant proportion of the burden of emerging infectious diseases in humans. The Wellcome Trust‐Vietnamese Initiative on Zoonotic Infections (WT‐VIZIONS) is ...aiming to understand the circulation of viral zoonotic pathogens in animals that pose a potential risk to human health. Evidence suggests that human exposure and infections with hepatitis E virus (HEV) genotypes (GT) 3 and 4 results from zoonotic transmission. Hypothesising that HEV GT3 and GT4 are circulating in the Vietnamese pig population and can be transmitted to humans, we aimed to estimate the seroprevalence of HEV exposure in a population of farmers and the general population. We additionally performed sequence analysis of HEV in pig populations in the same region to address knowledge gaps regarding HEV circulation and to evaluate if pigs were a potential source of HEV exposure. We found a high prevalence of HEV GT3 viral RNA in pigs (19.1% in faecal samples and 8.2% in rectal swabs) and a high HEV seroprevalence in pig farmers (16.0%) and a hospital‐attending population (31.7%) in southern Vietnam. The hospital population was recruited as a general‐population proxy even though this particular population subgroup may introduce bias. The detection of HEV RNA in pigs indicates that HEV may be a zoonotic disease risk in this location, although a larger sample size is required to infer an association between HEV positivity in pigs and seroprevalence in humans.
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