Mucosal TLR5 activation controls healthspan and longevity.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Bio-guided isolation of alpha-glucosidase inhibitory compounds from Vietnamese liverwort Marchantia polymorpha: in vitro and in silico studies.

Bio-guided isolation was applied to Vietnamese Marchantia polymorpha L. to find alpha-glucosidase inhibition. Fifteen compounds were isolated and structurally determined, including two new compounds, marchatoside (7) and marchanol (8), along with thirteen known compounds: marchantin A (1), isoriccardin C (2), riccardin C (3), marchantin K (4), lunularin (5), 3R-(3,4-dimethoxybenzyl)-5,7-dimethoxyphthalide (6), vitexilactone (9), 12-oleanene-3-one (10), 3,11-dioxoursolic acid (11), ursolic acid (12), artemetin (13), kaempferol (14), and quercetin (15). The structures of these compounds were determined through extensive spectroscopic analyses (1D and 2D NMR, HRESIMS, and ECD) and by comparisons to the existing literature. There are five types of carbon skeleton, including bibenzyl (1-5), 3-benzylphthalide (6 and 7), diterpenoid (8 and 9), triterpenoid (10-12), and flavonoid (13-15). Compounds 6-12 were reported for the first time within the genus Marchantia. Compounds 1-12 were evaluated for their alpha-glucosidase inhibition. Among them, 1-5 and 10-12 displayed potent inhibition, with IC50 values ranging from 28.9 to 130.6 µM, compared to the positive control acarbose 330.9 µM. A kinetic study and molecular docking were also performed to understand the mechanism.

Implementation of point-of-care testing of C-reactive protein concentrations to improve antibiotic targeting in respiratory illness in Vietnamese primary care: a pragmatic cluster-randomised controlled trial.

BACKGROUND: In previous trials, point-of-care testing of C-reactive protein (CRP) concentrations safely reduced antibiotic use in non-severe acute respiratory infections in primary care. However, these trials were done in a research-oriented context with close support from research staff, which could have influenced prescribing practices. To better inform the potential for scaling up point-of-care testing of CRP in respiratory infections, we aimed to do a pragmatic trial of the intervention in a routine care setting. METHODS: We did a pragmatic, cluster-randomised controlled trial at 48 commune health centres in Viet Nam between June 1, 2020, and May 12, 2021. Eligible centres served populations of more than 3000 people, handled 10-40 respiratory infections per week, had licensed prescribers on site, and maintained electronic patient databases. Centres were randomly allocated (1:1) to provide point-of-care CRP testing plus routine care or routine care only. Randomisation was stratified by district and by baseline prescription level (ie, the proportion of patients with suspected acute respiratory infections to whom antibiotics were prescribed in 2019). Eligible patients were aged 1-65 years and visiting the commune health centre for a suspected acute respiratory infection with at least one focal sign or symptom and symptoms lasting less than 7 days. The primary endpoint was the proportion of patients prescribed an antibiotic at first attendance in the intention-to-treat population. The per-protocol analysis included only people who underwent CRP testing. Secondary safety outcomes included time to resolution of symptoms and frequency of hospitalisation. This trial is registered with ClinicalTrials.gov, NCT03855215. FINDINGS: 48 commune health centres were enrolled and randomly assigned, 24 to the intervention group (n=18 621 patients) and 24 to the control group (n=21 235). 17 345 (93·1%) patients in the intervention group were prescribed antibiotics, compared with 20 860 (98·2%) in the control group (adjusted relative risk 0·83 [95% CI 0·66-0·93]). Only 2606 (14%) of 18 621 patients in the intervention group underwent CRP testing and were included in the per-protocol analysis. When analyses were restricted to this population, larger reductions in prescribing were noted in the intervention group compared with the control group (adjusted relative risk 0·64 [95% CI 0·60-0·70]). Time to resolution of symptoms (hazard ratio 0·70 [95% CI 0·39-1·27]) and frequency of hospitalisation (nine in the intervention group vs 17 in the control group; adjusted relative risk 0·52 [95% CI 0·23-1·17]) did not differ between groups. INTERPRETATION: Use of point-of-care CRP testing efficaciously reduced prescription of antibiotics in patients with non-severe acute respiratory infections in primary health care in Viet Nam without compromising patient recovery. The low uptake of CRP testing suggests that barriers to implementation and compliance need to be addressed before scale-up of the intervention. FUNDING: Australian Government, UK Government, and the Foundation for Innovative New Diagnostics.

Indicuen, a new hopane from Parmotrema indicum Hale growing in Vietnam.

One new hopane-type triterpene, indicuen (1), along with eight known compounds (2-9) were isolated from the n-hexane extract of the lichen Parmotrema indicum Hale. The chemical structures of isolated compounds were identified by interpretation of their spectroscopic data (1D, 2D NMR and HRESIMS) combined with DFT-NMR chemical shift calculations and subsequent assignment of DP4+ probabilities and by comparison with the literature. Indicuen represents for a rare hopane bearing a 1-carboxyethyl substituent at C-21 in lichens. Compounds 1-3 and 5-8 were evaluated for α-glucosidase inhibition and cytotoxicity against K562 and HepG2 cancer cell lines. Compounds 1, 5 and 7 exhibited moderate α-glucosidase inhibition with IC50 values of 201.1, 156.3 and 187.4 µM, respectively. Compound 1 also showed weak cytotoxicity toward K562 cell line while others showed no activity.

Lasibidoupins A and B, two new compounds from the stems of Lasianthus bidoupensis V.S. Dang & Naiki.

From the Lasianthus bidoupensis stems, two new compounds, including one new 9,10-anthraquinone, lasibidoupin A (1), and one new 6,7-benzocoumarin, lasibidoupin B (2), together with one known compound, 11-O-methyldamnacanthol (3) were isolated using chromatographic method. Their structures were determined by extensive HRMS, and NMR assignments. Compound 3 was reported for the first time from this species. New compounds (1 & 2) were tested for the cytotoxicity against three human cancer cell lines (MCF-7, HeLa, and NCI-H460) by SRB assay. As results, 1 & 2 exhibited significant cytotoxic activity against all cancer cell lines (IC50 ranged from 0.058 ± 0.003 to 0.177 ± 0.014 µM).

Assessment of pesticide use and pesticide residues in vegetables from two provinces in Central Vietnam.

Pesticide residue in food, especially in vegetables, is one of the important parameters to assess food safety. This study evaluates the pesticide use in vegetables from two provinces in Central Vietnamand and present data on pesticides detected in vegetables sampled from the sites. The potential health risk associated with the contamination of four commonly used pesticides in different vegetables is also discussed. Both household surveys and monitoring campaigns were conducted. The survey showed that improper pesticide application, storage, and waste disposal prevailed at the study sites. Only 20% of the respondent were aware of pesticide toxicity. As a result, pesticides were detected in 81% out of 290 vegetable samples collected at harvesting time. Up to 23% of samples had pesticide residues above the Maximum Residue Limit values. The highest total pesticide concentration quantified in vegetables in Thua Thien Hue was 11.9 mg/kg (green onions), and in Quang Binh was 38.6 mg/kg (mustard greens). Median residue levels of individual pesticides in vegetables ranged from 0.007 to 0.037 mg/kg. Among the ten target pesticides, cypermethrin, difenoconazole, and fenobucarb were detected at the highest frequencies (72%, 41%, and 37%, respectively). Pesticide residues varied between seasons at both study provinces. Pesticide contamination in the wet season was significantly higher than in the dry season. This study also discovered a potential health risk associated with fipronil residues in vegetables in Thua Thien Hue province. The paper provides recommendations for mitigation measures (both technological and social) in reducing potential health risks linked to pesticide use in vegetables in the region.

Berberine-loaded liposomes for oral delivery: Preparation, physicochemical characterization and in-vivo evaluation in an endogenous hyperlipidemic animal model.

Berberine (BBR) is a plant-origin quaternary isoquinoline alkaloid presenting exogenous cholesterol lowering and anti-hyperlipidemia therapeutic effects. The aim of this study was to design and generate BBR-loaded proliposomes (PLs) as solid templates for high-dose liposomes and consequently, to enhance the oral bioavailability and therapeutic effect of BBR. An air-suspension coating (layering) method was used for generating BBR-loaded PLs. The size, distribution size, morphology, and entrapment efficiency (EE) of the final reconstituted liposomes were assessed. The oral bioavailability and endogenous cholesterol lowering effects of BBR loaded in liposomes were investigated in rats and mice, respectively. The BBR-loaded PLs showed a smooth BBR-embedded film around micron-scale carrier particles (mannitol). The reconstituted BBR-loaded liposomes had a nano-scale average size (116.6 ± 5.8 nm), narrow size distribution (polydispersity index, PDI 0.269 ± 0.038), and high EE (87.8 ± 1.0%). The oral bioavailability of reconstituted BBR-loaded liposomes at a dose of 100 mg/kg in rats was increased even 628% compared to that obtained with pure BBR (according to 90% confidence interval). The BBR-loaded liposomes at the daily oral dose 100 mg/kg in P-407- reduced total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C) in hyperlipidemic mice by 15.8%, 38.2%, and 57.0%, respectively.

Knowledge about COVID-19 vaccine and vaccination in Vietnam: A population survey.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccine acceptance is essential in controlling the virus. Vaccine knowledge influences vaccine acceptance and understanding this is vital in planning immunization strategies. OBJECTIVES: This study aimed to examine the public COVID-19 vaccine knowledge levels and predictors of low knowledge levels in Vietnam. METHODS: A cross-sectional, community-based survey was conducted between April 16 and July 16, 2021. To examine the community knowledge levels regarding the vaccine essentialness and efficacy, a self-administered questionnaire was developed and comprised 7 questions with 5 Likert scale responses corresponding to the levels of agreement or disagreement with the provided statements and scores ranging from 0 to 4. An individual's knowledge score above the mean score of all participants was defined as "acceptable" and that below was defined as "low." RESULTS: Among 1708 respondents, the mean age was 34.3 ± 13.4 years, 942 (55.2%) were females, and 797 (46.7%) had acceptable knowledge levels. Age (adjusted odds ratio [AOR] 0.984 [95% CI 0.972-0.995], P = 0.005) and being vaccinated against COVID-19 (0.653 [0.431-0.991], P = 0.045) were inversely associated with lower knowledge levels. Those with a Gapminder income of $8 to < $15 per day (1.613 [1.117-2.329], P = 0.001), $2 to < $8 (2.093 [1.313-3.335], P = 0.002), and < $2 (3.341 [1.951-5.722], P < 0.001), less than a high school education (4.214 [1.616-10.988], P = 0.003), and nonclinical professionals and nonhealth lecturers (1.83 [1.146-2.922], P = 0.01) were positively associated with lower knowledge levels. CONCLUSION: To ensure a successful vaccine rollout, it is crucial to improve community knowledge about vaccine essentialness and efficacy. Those who are at young age, who have low income or education levels, and working in nonclinical and nonhealth education fields should be the target of the intervention programs. Community education programs may benefit from using those who have been immunized as role models.

Two new phenolic compounds from the lichen Parmotrema cristiferum growing in Vietnam.

Two new phenolic compounds, cristiferides A-B (1-2) together with six known compounds, 2,4-dihydroxyphthalide (3), lecanoric acid (4), orsellinic acid (5), 5-chloroorsellinic acid (6), methyl haematommate (7), and methyl ß-orsellinate (8) were isolated from the lichen Parmotrema cristiferum (Taylor) Hale (Parmeliaceae). The structures of isolated compounds were identified from its spectroscopic data and by comparison with the literatures. Compounds 1-3 and 6-8 were evaluated for alpha-glucosidase inhibition. Compounds 2 and 7 revealed potent activity with IC50 values of 72.66 µM and 48.73 µM, respectively.