1.A multi-omics-empowered framework for precision diagnosis and treatment of lysosomal diseases.
Nguyen Thi Hai YEN ; Nguyen Tran Nam TIEN ; Nguyen Quang THU ; Franklin DUCATEZ ; Wladimir MAUHIN ; Olivier LIDOVE ; Soumeya BEKRI ; Abdellah TEBANI ; Nguyen Phuoc LONG
Journal of Pharmaceutical Analysis 2025;15(10):101274-101274
Lysosomal diseases (LDs) are a group of rare inherited disorders belonging to inborn metabolism errors. LDs are characterized by the excessive storage of undegraded substrates, most often due to the enzymatic deficiency resulting from disease-causing gene variants. LDs lead to dysregulated cellular pathways and imbalanced molecular homeostasis and can affect multiple organs and tissues. Despite being rare, LDs account for a significant incidence when considered collectively. Due to complex molecular and genetic fingerprints, considerable challenges in LD management must be overcome. Diagnosis can be significantly delayed due to the broad and nonspecific clinical manifestations and the lack of specific biomarkers. Available treatments fail to fully stop the disease progression and can alter the disease's typical phenotypes with novel manifestations. Therefore, a paradigm shift is crucial to better understand LDs and provide actionable insights. Herein, we comprehensively review the literature to demonstrate that multi-omics approaches are promising for pathophysiology elucidation, biomarker discovery, and precision therapy in LDs. We recommend adopting longitudinal study designs integrated with a multi-omics-empowered framework to facilitate mechanistic delineation, biomarker discovery, and treatment development. Relevant approaches exploring the association between LDs and common neurodegenerative disorders are also discussed, paving a potential path for improved therapeutic development and ultimately improving the patient's quality of life.
2.Within-household SARS-CoV-2 transmission and vaccine effectiveness in the first three COVID-19 school outbreaks in northern Viet Nam, September–December 2021
Trang Thu Vu ; Tu Huy Ngo ; Khanh Cong Nguyen ; Vu Thi Lan ; Cu Thi Bich Hanh ; Le Hong Son ; Huyen Thi Nguyen ; Hien Thi Nguyen ; Nghia Duy Ngu ; Duong Nhu Tran ; Duc-Anh Dang ; Florian Vogt ; Thai Quang Pham
Western Pacific Surveillance and Response 2024;15(3):19-30
Objective: The risk of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from schoolchildren to their household and the protective effects of vaccination in these settings remain poorly understood. We assessed the transmission dynamics of schoolchildren with SARS-CoV-2 within their households and the protective effects of coronavirus disease (COVID-19) vaccination among household members in Viet Nam.
Methods: We estimated the attack rate, vaccine effectiveness and adjusted risk ratio (aRR) of factors associated with SARS-CoV-2 transmission to household contacts of children confirmed to have COVID-19 who attended three schools in Ha Nam, Phu Tho and Thanh Hoa provinces between September and December 2021 using multivariable regression with household-level random effects.
Results: This retrospective cohort study included 157 children infected with SARS-CoV-2 and their 540 household contacts. The attack rate among household contacts was 24.6% (133/540). Overall, vaccine effectiveness among household contacts was 39% (95% confidence interval [CI]: -1 to -63), higher among males than females and higher in adults aged >40 years. COVID-19 transmission was greater among female household contacts compared with males (aRR: 1.35, 95% CI: 0.94 to 1.95), although not statistically significant, and highest among those aged 19–39 years (aRR: 2.51, 95% CI: 1.50 to 4.21). Fully vaccinated household contacts had significantly lower infection risk (aRR: 0.46, 95% CI: 0.26 to 0.84).
Discussion: We found substantial onward transmission of SARS-CoV-2 from schoolchildren to household members, and older people were more likely to be protected by vaccination. We recommend that schoolchildren and all household members living with schoolchildren receive at least two doses of a COVID-19 vaccine. Recognizing the role of schoolchildren in the onward transmission of COVID-19 is an important lesson learned by Viet Nam that can help not only in managing other outbreaks but also in protecting schoolchildren by predicting the progress of the outbreak and preparing for a timely response.
3.Symptoms, Mental Health, and Quality of Life Among Patients After COVID-19 Infection: A Cross-sectional Study in Vietnam
Hai Nguyen THANH ; Duc Cap MINH ; Hien Hoang THU ; Duc Nguyen QUANG
Journal of Preventive Medicine and Public Health 2024;57(2):128-137
Objectives:
This study was conducted to characterize the symptoms, mental health, quality of life (QoL), and associated factors following the coronavirus disease 2019 (COVID-19) infection.
Methods:
This cross-sectional study included 394 participants previously infected with COVID-19 in Ho Chi Minh City, Vietnam. Mental health was assessed using the 21-item Depression, Anxiety, and Stress Scale (DASS-21). Participants self-reported health-related QoL was measured with the EuroQol 5-Dimension 5-Level (EQ-5D-5L) scale.
Results:
Among the participants, 76.4% reported experiencing at least one symptom following COVID-19 infection. The most common symptoms were fatigue (42.1%), cognitive dysfunction (42.9%), and hair loss (27.9%). According to the DASS-21 results, the proportions of depression, anxiety, and stress were 28.7%, 26.4%, and 20.6%, respectively. The mean scores on the EQ-5D-5L and the EuroQol Visual Analog Scale were 0.94±0.11 and 84.20±13.11, respectively. Regarding QoL issues, the highest proportion of participants (32.7%) reported experiencing anxiety or depression, followed by pain or discomfort (25.4%). Multivariable logistic regression analysis revealed that factors associated with the presence of symptoms following COVID-19 infection included female (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.65 to 4.91) and having QoL issues (OR, 3.25; 95% CI, 1.71 to 6.19).
Conclusions
The study investigated the prevalence rates of various symptoms following COVID-19 infection. These findings underscore the need to prioritize comprehensive care for individuals recovering from COVID-19 and to implement strategies to mitigate the long-term impact of the disease on mental health and QoL.
4.Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management.
Nguyen Quang THU ; Nguyen Tran Nam TIEN ; Nguyen Thi Hai YEN ; Thuc-Huy DUONG ; Nguyen Phuoc LONG ; Huy Truong NGUYEN
Journal of Pharmaceutical Analysis 2024;14(1):16-38
The spread of tuberculosis (TB), especially multidrug-resistant TB and extensively drug-resistant TB, has strongly motivated the research and development of new anti-TB drugs. New strategies to facilitate drug combinations, including pharmacokinetics-guided dose optimization and toxicology studies of first- and second-line anti-TB drugs have also been introduced and recommended. Liquid chromatography-mass spectrometry (LC-MS) has arguably become the gold standard in the analysis of both endo- and exo-genous compounds. This technique has been applied successfully not only for therapeutic drug monitoring (TDM) but also for pharmacometabolomics analysis. TDM improves the effectiveness of treatment, reduces adverse drug reactions, and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window. Based on TDM, the dose would be optimized individually to achieve favorable outcomes. Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs, aiding in the discovery of potential biomarkers for TB diagnostics, treatment monitoring, and outcome evaluation. This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades. Besides, we discussed the advantages and disadvantages of this technique in practical use. The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted. Lastly, we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies (pharmacometrics, drug and vaccine developments, machine learning/artificial intelligence, among others) to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.
5.Porcine epidemic diarrhea viruses from Vietnam: isolation, characterization, and neutralizing activity
Van Tan DO ; Quang Lam TRUONG ; Hoai Thu DAO ; Thi Lan NGUYEN ; Minna SHIN ; Kyeong Ryeol SHIN ; Tae-Wook HAHN
Korean Journal of Veterinary Research 2023;63(2):e18-
Porcine epidemic diarrhea (PED) is characterized by acute enteritis, watery diarrhea, weight loss, dehydration, and death, with high mortality in neonatal piglets. In this study, 3 virus isolates collected in Vietnam between 2016 and 2017 were propagated successfully in Vero cells at high virus titers. Sequence analysis of the full-length spike (S) gene showed that all 3 isolates belong to genogroup 2b, which is closely related to other prevalent Asian strains. A comparison of the amino acid sequence revealed a 98.19% to 99.13% homology with the Vietnam isolates circulating during 2013–2015, suggesting that field PED viruses (PEDVs) are evolving continuously. Experiments in animals showed that the antisera from guinea pigs immunized with the vaccine strain resulted in higher levels (5 log2) of neutralizing antibodies against the homologous strain and a relatively moderate level of neutralizing antibodies against the field isolates. This finding would be helpful in selecting a PEDV strain for vaccine development.
7.Assessment of In vitro Antioxidant, Antidiabetic and Cytotoxic Activities of Sphaeranthus africanus Extracts
Tran Thi HUYEN ; Julien DUJARDIN ; Nguyen Thi THU HUONG ; Chung Thi MY DUYEN ; Nguyen Hoang MINH ; Ha Quang THANH ; Dao Tran MONG ; Ly Hai TRIEU ; Nguyen Mai TRUC TIEN ; Mai Thanh CHUNG ; Nguyen Nhat MINH ; Nguyen Thi NGOC DAN ; Huynh LOI
Natural Product Sciences 2023;29(2):98-103
Sphaeranthus africanus is commonly used as a traditional remedy for sore throats and pain treatment in Vietnam. The aerial parts have been studied for its anti-inflammatory and anti-proliferative properties. However, the antioxidant and antidiabetic potential of the plant has not been explored. In this work, hydrophilic extracts of the plant's aerial parts were prepared in order to investigate its antioxidant and anti-diabetic properties. Also, the cytotoxicity of the root was evaluated and compared to that of the aerial parts. All of the extracts inhibited lipid peroxidation with IC 50 values ranging from 2.05 to 3.56 µg/mL, indicating substantial antioxidant activity. At an IC 50 value of 4.80 μg/mL, the 50% ethanol extract exhibited the most potent inhibition of α-glucosidase. The cytotoxic activity of root extracts is 2 to 5-fold less than that of the aerial parts. Nevertheless, dichloromethane and ethyl acetate extracts of the root demonstrated a selective effect on leukemia cells, with no harm towards the normal HEK-293 cell line. This work provides a scientific support for the antioxidant and antidiabetic activity of the plant. Hence, it may find a promising material for the development of novel antioxidant and antidiabetic agents. More research can be conducted on the phytochemistry and anticancer activities of the plant’s root.
8.Isolation and Cytotoxic Potency of Endophytic Fungi Associated with Dysosma difformis, a Study for the Novel Resources of Podophyllotoxin
Hoa Thi TRAN ; Giang Thu NGUYEN ; Hong Ha Thi NGUYEN ; Huyen Thi TRAN ; Quang Hong TRAN ; Quang Ho TRAN ; Ngoc Thi NINH ; Phat Tien DO ; Ha Hoang CHU ; Ngoc Bich PHAM
Mycobiology 2022;50(5):389-398
Endophytic fungi are promising sources for the production of podophyllotoxin-an important anticancer compound, replacing depleted medical plants. In this study, the endophytes associated with Dysosma difformis-an ethnomedicinal plant species were isolated to explore novel sources of podophyllotoxin. Fifty-three endophytic fungi were isolated and identified by morphological observation and ITS-based rDNA sequencing, assigning them to 27 genera in 3 divisions. Fusarium was found the most prevalent genus with a colonization frequency of 11.11%, followed by Trametes (9.26%) and Penicillium (7.41%). Phylogenetic trees were constructed for the endophytic fungi community in two collection sites, Ha Giang and Lai Chau, revealing the adaptation of the species to the specific tissues and habitats. Cytotoxic activity of endophytic fungal extracts was investigated on cancer cell lines such as SK-LU-1, HL-60, and HepG2, demonstrating strong anti-cancer activity of six isolates belonging to Penicillium, Trametes, Purpureocillium, Aspergillus, and Ganoderma with IC 50 value of lower than 10 10 µg/mL. The presence of podophyllotoxin was indicated in Penicillium, Trametes, Aspergillus and for the first time in Purpureocillium and Ganoderma via high-performance liquid chromatography, which implied them as a potential source of this anticancer compound.
9.Systematic sequencing of imported cases leads to detection of SARS-CoV-2 B.1.1.529 (Omicron) variant in central Viet Nam
Do Thai Hung ; Nguyen Bao Trieu ; Do Thi Thu Thuy ; Allison Olmsted ; Trinh Hoang Long ; Nguyen Duc Duy ; Huynh Kim Mai ; Bui Thi Thu Hien ; Nguyen Van Van ; Tran Van Kiem ; Vo Thi Thuy Trang ; Nguyen Truong Duy ; Ton That Thanh ; Huynh Van Dong ; Philip L Gould ; Matthew R Moore
Western Pacific Surveillance and Response 2022;13(4):82-85
As authorities braced for the arrival of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infrastructure investments and government directives prompted action in central Viet Nam to establish capacity for genomic surveillance sequencing. From 17 November 2021 to 7 January 2022, the Pasteur Institute in Nha Trang sequenced 162 specimens from 98 150 confirmed SARS-CoV-2 cases in the region collected from 8 November to 31 December 2021. Of these, all 127 domestic cases were identified as the B.1.617.2 (Delta) variant, whereas 92% (32/35) of imported cases were identified as the B.1.1.529 (Omicron) variant, all among international flight passengers. Patients were successfully isolated, enabling health-care workers to prepare for additional cases. Most (78%) of the 32 Omicron cases were fully vaccinated, suggesting continued importance of public health and social measures to control the spread of new variants.
10.Isolation, characterization and neutralizing activity of porcine epidemic diarrhea viruses from Vietnam
Van Tan DO ; Quang Lam TRUONG ; Hoai Thu DAO ; Thi Lan NGUYEN ; Jini KIM ; Tae-Wook HAHN
Korean Journal of Veterinary Research 2021;61(3):e23-
Porcine epidemic diarrhea (PED) is characterized by acute enteritis, watery diarrhea, weight loss, dehydration, and death with high mortality in neonatal piglets. In this study, 3 virus isolates collected in Vietnam between 2016 and 2017 were successfully propagated in Vero cells at high virus titers. Sequence analysis of the full-length spike (S) gene revealed that all 3 isolates belong to genogroup 2a, which is closely related to other prevalent Asian strains. Amino acid sequence comparisons revealed 98.19% to 99.13% homology with the Vietnam isolates circulating during 2013–2015, suggesting that field PED viruses (PEDVs) evolve continuously. Experiments in animals demonstrated that antisera from guinea pigs immunized with the vaccine strain resulted in higher levels (5 log2) of neutralizing antibody against the homologous strain, and showed a relatively lower level of neutralizing antibody against the field isolates. This finding would be helpful in choosing a PEDV strain for vaccine development.


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