Neuroprotective effects of total alkaloids fraction of Huperzia serrata on scopolamine-induced neurodegenerative animals.

Huperzia serrata contains Huperzine A (HupA)-an alkaloid used to treat cognitive dysfunction. In this study, we used the total alkaloids (HsAE) to investigate their potential in managing cognitive impairment in comparison with HupA. The antioxidant activity was measured by DPPH assay. In the cellular study, the cell viability and level of ACh of SH-SY5Y cells were evaluated after pretreated with HsAE and scopolamine. For in vivo assay, mice were pre-treated with HsAE, and HupA and undergone scopolamine injection for cognitive impairment. The behavioral tests including the Y-maze and Morris water maze test and the AChE activity, the SOD, CAT, MDA level in the hippocampus and cortex were evaluated. HsAE showed significant scavenging properties on DPPH radicals. HsAE was not toxic to SH-SY5Y cells, and can rescue these cells upon scopolamine treatment. Intriguingly, HsAE showed the neuroprotection against scopolamine-induced amnesia in mice. Moreover, HsAE decreased AChE activity, MDA level, increased antioxidative enzyme activity in the hippocampus as well as cortex of mice, which was relatively better than that of HupA. These findings suggested that HsAE may significantly protect the neurons of mice with scopolamine-induced memory impairment connected to AChE depletion and oxidative stress.

Spatial and temporal analysis and quantification of pollution sources of the surface water quality in a coastal province in Vietnam.

The surface water quality in coastal areas may be highly vulnerable to degradation due to various pollution sources such as seawater intrusion and anthropogenic activities. The current study sought to spatially and temporally analyze and quantify pollution sources of the surface water system in the coastal province of Tra Vinh, Vietnam. A total of 600 surface water samples were taken from 30 monitoring sites distributed over 4 spatial zones. Water samples were collected in four campaigns each year during the dry and rainy seasons from 2016 to 2020 and analyzed for 10 physiochemical and biological parameters. The analyzed data were calculated for the water quality index (WQI). Two-way analysis of variance, principal component analysis/factor analysis (PCA/FA), and multivariable regression analysis (MRA) were conducted over the whole dataset. The results showed that the WQI decreased from the inland zone to the coastal area, was greater in the river zone than in the canal zone, and was higher in the dry season than in the rainy season. The PCA/FA revealed that surface water quality was affected by at least 4 main pollution sources, including agricultural production, seawater intrusion, residential activities, and mixed sources. MRA revealed that these pollution sources explained 68.3%, 12.8%, 7.0%, and 2.7% of the total variance of the WQI, respectively. In summary, the surface water quality in the study area significantly changed spatially and temporally, depending on four pollution sources, which need to be managed properly for a better environment and sustainable development.

CYP2C19 genetic polymorphism in the Vietnamese population.

Background: Genetic polymorphism of CYP2C19 has been shown to affect enzyme activity and thereby contribute to inter-individual variability in drug metabolism and response. The complete genetic variation of CYP2C19 in Vietnam still remains obscure even though data of common alleles in Vietnamese Kinh have been reported.Aim: To establish the extent of CYP2C19 polymorphism in Vietnamese.Subjects and methods: The promoter and all nine exons of CYP2C19 in 100 healthy unrelated Vietnamese Kinh subjects were sequenced. Additionally, the CYP2C19 variants, *2, *3 and *17 were analysed by RFLP-PCR in 275 subjects of four minor ethnic groups in Vietnam (Tay, Muong, H'Mong and Nung).Results: In 100 Kinh subjects, the percentages of CYP2C19*1, CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles were 76%, 20.5%, 2.5% and 1%, respectively. Three novel variants in introns 2, 5 and 8 had no impact on mRNA splicing according to the Human Splicing Finder. The prevalence of CYP2C19*17 in Vietnamese Kinh was significantly lower compared with figures found in Western Asia and Europe, while CYP2C19*2 frequency was statistically higher than that in Western Asia and several countries in Europe. The frequency of CYP2C19*2 in Kinh was significantly lower than in the other four ethnic minorities.Conclusion: These results provide information on CYP2C19 polymorphism in the Vietnamese population, which could be useful for optimising drug therapies and precision medicine studies.

Polymorphic analysis of CYP2C9 gene in Vietnamese population.

Genetic variations in CYP2C9 are associated to inter-individual variability of drugs metabolism and response. The only report has been done previously mainly focusing on the common variant alleles of CYP2C9 in Vietnamese Kinh subjects. However, little is known about the complete spectrum of this gene polymorphism in different ethnic groups of Vietnam. We sequenced the promoter region and all exons of CYP2C9 in 100 healthy unrelated Vietnamese Kinh subjects. Additionally, common CYP2C9 variants, *2 and *3, were also analyzed by RFLP-PCR in extra 194 Kinh subjects and 279 of other four ethnic groups in Vietnam. The results of these common variants observed from five ethnic groups were compared with other populations in the world. Seven previously reported alleles and two genotypes were determined in Kinh subjects. The percentage of CYP2C9*1 and CYP2C9*3 alleles are 96.5 and 3.5%, respectively. We found one novel non-synonymous variant in exon 7 leading to amino acid change at 363 position from proline to histidine. Functional analysis by SIFT and Polyphen-2 indicated that this mutation is intolerant and probably damaging. Prevalence of CYP2C9*2 observed in Vietnamese population was significantly lower compared with that of other populations in the South and West of Asia as well as in Europe. This study provides information of genetic distribution pattern of CYP2C9 in Vietnamese, which would be useful for optimizing drug therapies in Vietnam.

The therapeutic landscape for COVID-19 and post-COVID-19 medications from genetic profiling of the Vietnamese population and a predictive model of drug-drug interaction for comorbid COVID-19 patients.

Despite the raised awareness of the role of pharmacogenomic (PGx) in personalized medicines for COVID-19, data for COVID-19 drugs is extremely scarce and not even a publication on this topic for post-COVID-19 medications to date. In the current study, we investigated the genetic variations associated with COVID-19 and post-COVID-19 therapies by using whole genome sequencing data of the 1000 Vietnamese Genomes Project (1KVG) in comparison with other populations retrieved from the 1000 Genomes Project Phase 3 (1KGP3) and the Genome Aggregation Database (gnomAD). Moreover, we also evaluated the risk of drug interactions in comorbid COVID-19 and post-COVID-19 patients based on pharmacogenomic profiles of drugs using a computational approach. For COVID-19 therapies, variants related to the response of two causal treatment agents (tolicizumab and ritonavir) and antithrombotic drugs are common in the Vietnamese cohort. Regarding post-COVID-19, drugs for mental manipulations possess the highest number of clinical annotated variants carried by Vietnamese individuals. Among the superpopulations, East Asian populations shared the most similar genetic structure with the Vietnamese population, whereas the African population showed the most difference. Comorbid patients are at an increased drug-drug interaction (DDI) risk when suffering from COVID-19 and after recovering as well due to a large number of potential DDIs which have been identified. Our results presented the population-specific understanding of the pharmacogenomic aspect of COVID-19 and post-COVID-19 therapy to optimize therapeutic outcomes and promote personalized medicine strategy. We also partly clarified the higher risk in COVID-19 patients with underlying conditions by assessing the potential drug interactions.

Copy number variations of cytochrome P450 genes in Kinh Vietnamese.

Background: The cytochrome P450 (CYP450) family is well known as a major group of drug metabolizing enzymes. The polymorphism of CYP450 genes is the main factor having an impact on the interindividual difference in drug response, including drug efficacy and drug safety. The single nucleotide polymorphism (SNPs) of Vietnamese Kinh has been widely studied, but information about the copy number variations (CNVs) of other CYP450 genes is still unknown. Objective: To identify the CNV variability of CYP450 in 154 healthy unrelated Kinh Vietnamese, except eCYP2D6, which was previously reported. Methods: Multiplex Ligation-Dependent Probe Amplification (MLPA) was applied for determination of copy number of 10 CYP450 genes. Later, PCR or quantitative PCR (qPCR) was used to confirm the detected CNVs in randomly chosen subjects. Results: Of the 154 subjects, along with CYP2D6, 4 other CYP450 genes showed CNVs including duplications (CYP1B1), deletions (CYP2A6 and CYP2C9), and both duplications and deletions (CYP2E1). Among these, CYP2A6 exhibited the greatest frequency of CNVs compared with other CYP450, in which CYP2A6Del accounted for 11%. Meanwhile, allele CYP2E1Del showed the lowest frequency with only 0.3%. Conclusions: The present study provides new insight into CYP450 CNVs in the Kinh Vietnamese cohort. Our data have contributed to genetic profiling of CYP450 CNVs in Vietnam, which would be helpful for facilitating implementation of pharmacogenetics in drug dosing adjustment in Vietnam.

CD40LG mutations in Vietnamese patients with X-linked hyper-IgM syndrome; catastrophic anti-phospholipid syndrome as a new complication.

BACKGROUND: X-linked hyper-IgM syndrome (XHIGM) is a rare primary immunodeficiency caused by CD40 ligand defects. METHODS: We identified three patients with XHIGM in Ho Chi Minh City, Vietnam. Whole-exome sequencing, immunological analyses and western blot were performed to investigate phenotypic and genotypic features. RESULTS: Despite showing symptoms typical of XHIGM, including recurrent sinopulmonary infections, oral ulcers and otitis media, the diagnosis was significantly delayed. One patient developed anti-phospholipid syndrome, which has been documented for the first time in XHIGM syndrome. Two patients had elevated IgM levels and all of them had low IgG levels. Exome sequencing revealed mutations in the CD40LG gene: one novel splicing mutation c.156+2T>A and two previously characterised mutations (non-frameshift deletion c.436_438delTAC, stop-gain c.654C>A). Due to these mutations, the CD40 ligand was not expressed in any of the three patients, as demonstrated by western blot analysis. CONCLUSION: This is the first report of XHIGM syndrome in Vietnam indicates that an effective diagnostic strategy, such as sequencing analysis, contributes to reliable diagnosis and subsequent therapy.

Seasonal, spatial variation, and pollution sources of heavy metals in the sediment of the Saigon River, Vietnam.

The current study was conducted to (1) examine seasonal and spatial distribution of heavy metals and metalloid in sediment from the Saigon River and (2) apportion and quantify their pollution sources. Ninety-six sediment samples were taken in the rainy and dry season on 13 sampling sites, distributed over the lower reaches of the River, to analyze for exchangeable concentration of 11 heavy metals and metalloid (Al, B, Cd, Co, Fe, In, Mn, Ni, Pb, Sr, and Zn), pH, EC, organic carbon content, and particle-size distribution. Generally, the concentration of 11 elements was ranked in the order Mn > Al > Fe > Zn > Sr > In > B > Ni > Co > Pb > Cd. Hierarchical cluster analysis grouped 13 sampling sites into two parts based on the similar concentration of the 11 elements. Three-way analysis of variance showed that the total exchangeable concentration of 11 elements was significantly higher in the rainy season than in the dry season and in the upper part than in the lower part of the river. Principal component analysis/factor analysis and correlation analysis revealed that three pollution sources (PS) may contribute to enriching the 11 examined elements in the sediment. These sources included (PS1) from catchment through water erosion over natural areas, explaining 83%, (PS2) mixed sources from catchment through water erosion over agricultural fields and inside Ho Chi Minh City, accounting for 6%, and (PS3) mixed sources from lowland areas, explaining 7.8% of the total variance of the elements. In brief, the sediment concentration of 11 metals and metalloid varied with season and space and three major pollution sources from river catchment, inside Ho Chi Minh City, and lowland contributively enriched the elements in the sediment of the River.

Assessment and source quantification of heavy metal(loid)s in surface water using multivariate analyses from the Saigon River, Vietnam.

The metal concentration in surface water of a river could be affected by season, position, and oceanic process such as tide. The current study aimed to (1) examine the heavy metal(loid) concentration in surface water from the Saigon River as affected by the combination of season, tide, and position and (2) apportion and quantify pollution sources. Ninety-six surface water samples were collected from 13 sites on the River in four campaigns (rainy season + ebb tide, rainy season + flood tide, dry season + ebb tide, and dry season + flood tide). Eight heavy metal(loid)s (Al, B, Bi, Fe, Mn, Pb, Sr, and Zn) were measured and subjected to multivariate analyses. Three-way ANOVA showed that in the rainy season, the total concentration of the metal(loid)s (TCM) in two tides was not clearly different from each other while in the dry season the TCM was significantly higher during the ebb tide than during the flood tide. Principal component analysis/factor analysis and Pearson correlation matrix showed that the TCM could be derived from three main sources, grouped into anthropogenic activities such as industrial, agricultural, and domestic wastes from inside Ho Chi Minh city, and natural origins from lowland area and acid sulfate soil. Three pollution sources explained 70% and 68% of the total variance of TCM in the rainy and dry seasons, respectively. In brief, the metal(loid) concentration was significantly affected by the season and tide and the pollution sources could be derived from inside Ho Chi Minh City and from lowland areas beyond the river estuary.