Therapeutic efficacy of pyronaridine-artesunate (Pyramax) in treating Plasmodium vivax malaria in the central highlands of Vietnam.

The emergence and spread of chloroquine-resistant Plasmodium vivax have necessitated the assessment of alternative blood schizonticidal drugs. In Vietnam, chloroquine-resistant P. vivax malaria has been reported. In an open-label, single-arm trial, the safety, tolerability, and efficacy of pyronaridine-artesunate (Pyramax, PA) was evaluated in Dak Nong province, Vietnam. A 3-day course of PA was administered to adults and children (≥20 kg) infected with P. vivax. Patients also received primaquine (0.25 mg/kg daily for 14 days). PA was well tolerated with transient asymptomatic increases in liver transaminases. The per-protocol proportion of patients with day 42 PCR-unadjusted adequate clinical and parasitological response was 96.0% (95% CI, 84.9%-99.0%, n = 48/50). The median parasite clearance time was 12 h (range, 12-36 h), with a median fever clearance time of 24 h (range, 12-60 h). Single nucleotide polymorphisms (SNPs) as potential genetic markers of reduced drug susceptibility were analyzed in three putative drug resistance markers, Pvcrt-o, Pvmdr1, and PvK12. Insertion at position K10 of the Pvcrt-o gene was found in 74.6% (44/59) of isolates. Pvmdr1 SNPs at Y976F and F1076L were present in 61% (36/59) and 78% (46/59), respectively. Amplification of Pvmdr1 gene (two copies) was found in 5.1% (3/59) of parasite samples. Only 5.1% (3/59) of isolates had mutation 552I of the PvK12 gene. Overall, PA rapidly cleared P. vivax blood asexual stages and was highly efficacious in treating vivax malaria, with no evidence of artemisinin resistance found. PA provides an alternative to chloroquine treatment for vivax malaria in Vietnam. CLINICAL TRIALS: This study is registered with the Australian New Zealand Clinical Trials Registry as ACTRN12618001429246.

Acute invasive fungal rhinosinusitis in post-COVID-19 patients in Vietnam.

BACKGROUND: Acute invasive fungal rhinosinusitis (AIFR) is a potentially lethal infection commonly found in immunocompromised patients. It is considered the most aggressive subtype of fungal sinusitis and can lead to severe morbidity and mortality. There was a significant increase in the incidence of AIFR in post-COVID-19 patients compared to AIFR cases before the COVID-19 pandemic. This study aimed to describe the clinical presentation of AIFR associated with COVID-19 illness. METHODS: A retrospective study included 22 patients diagnosed with AIFR with a recent COVID-19 infection. RESULTS: The most frequent disease associated with AIFR was diabetes mellitus (95.5%). The mycological analysis identified infection caused by Aspergillus species in 72.7% of patients. Along with stabilizing hemodynamic parameters and controlling any comorbidities, all patients in the present study underwent combined surgical debridement followed by antifungal medications. The overall survival rate was 72.7%. The chance of developing a fatal outcome was significantly higher if meningitis presented initially (odds ratio 35.63, p < 0.05). CONCLUSION: The presence of meningitis upon initial diagnosis is related to a significantly higher chance of developing a fatal outcome and should be considered, especially in AIFR patients previously treated for COVID-19 infections. Early diagnosis, early use of antifungal agents, aggressive surgical debridement, and control of comorbid conditions remain crucial in managing AIFR.

Asterosaponins from the starfish Protoreaster nodosus.

Five asterosaponins (1-5), including one new compound named protonodososide (1), were isolated from the methanol extract of the starfish Protoreaster nodosus, after subjecting to various chromatographic separations. The structural elucidation was confirmed by careful analysis of the 1D, 2D NMR, and HR ESI QTOF mass spectra. The cytotoxicity of isolated compounds was evaluated on five human cancer cell lines including HepG2, KB, MCF7, LNCaP, and SK-Mel2.

Pyronaridine-Artesunate (Pyramax) for Treatment of Artemisinin- and Piperaquine-Resistant Plasmodium falciparum in the Central Highlands of Vietnam.

The rise in Plasmodium falciparum resistance to dihydroartemisinin-piperaquine in Vietnam justifies the need to evaluate alternative artemisinin-based combination therapies. Between July 2018 and October 2019, a single-arm trial of pyronaridine-artesunate (Pyramax, PA) was conducted in Dak Nong province, Vietnam. PA (3-day course) was administered to adults and children infected with P. falciparum. PA was well tolerated by the participants. The proportion of patients with Day 42 PCR-corrected adequate clinical and parasitological response was 95.2% (95% confidence interval [CI], 82.3 to 98.8, n = 40/42) for treating falciparum malaria. The median parasite clearance half-life was 6.7 h (range, 2.6 to 11.9) and the median parasite clearance time was 72 h (range, 12 to 132) with 44.9% (22/49) of patients having positive blood films at 72 h. The two patients that recrudesced had comparable Day 7 blood pyronaridine concentrations (39.5 and 39.0 ng/ml) to the 40 patients who did not recrudesce (median 43.4 ng/ml, 95% CI, 35.1 to 54.9). Ring-stage and piperaquine survival assays revealed that of the 29 P. falciparum isolates collected from the patients before PA treatment, 22 (75.9%) had reduced susceptibility to artemisinins and 17 (58.6%) were resistant to piperaquine. Genotyping confirmed that 92.0% (46/50) of falciparum patients were infected with parasites bearing the Pfkelch13 C580Y mutation associated with artemisinin resistance. Of these, 56.0% (28/50) of the isolates also had multiple copies of the plasmepsin 2/3 genes responsible for piperaquine resistance. Overall, PA was effective in treating P. falciparum in the Central Highlands of Vietnam. (This study has been registered at AustralianClinicalTrials.gov.au under trial ID ACTRN12618001429246.).

Dendrodoristerol, a cytotoxic C20 steroid from the Vietnamese nudibranch mollusk Dendrodoris fumata.

Using various chromatographic separations, four steroids including one new C20 steroid namely dendrodoristerol (1), were isolated from the Vietnamese nudibranch mollusk Dendrodoris fumata. The structure elucidation was confirmed by combination of spectroscopic experiments including 1D and 2D NMR, HR QTOF MS, and CD. Compound 1 was found to exhibit significant in vitro cytotoxic activity against six human cancer cell lines as HL-60, KB, LU-1, MCF-7, LNCaP, and HepG2. In addition, 1 induced HL-60 cancer cell death by apoptosis and necrosis.

Polycyclic aromatic hydrocarbons (PAHs) in dry tea leaves and tea infusions in Vietnam: contamination levels and dietary risk assessment.

The total mean ∑[Formula: see text] in samples were from 75.3 to 387.0 ng/g dry weight (d.w) and showed high value in black dry tea, followed by herbal, oolong, and green tea. The mean ∑[Formula: see text] (a combination of benz[a]anthracene, chrysene, benzo[b]fluoranthene, and benzo[a]pyrene) values were 54.3 ng/g, 16.4 ng/g, 14.2 ng/g, and 6.6 ng/g for black, herbal, green, and oolong teas, respectively. Concentration for benzo[a]pyrene (BaP) was from 0.4 to 35.8 ng/g, and the BaP equivalent concentration values ranged from 0.3 to 48.1 ng/g. There was only 1 black tea sample that BaP concentration exceeded the maximum level according to European Union (EU) standards. Tea samples marketed in Vietnam showed insignificant difference with the samples from other origins by same analytical method. Black teas showed high PAHs contents in dry tea samples but the released percentage of sum of PAHs from tea-to-tea infusion was lower than that in other tea type samples. The released percentages of PAH4 from tea-to-tea infusion were 40.7, 15.4, and 1.9 for green, herbal, and black tea. High temperature in black tea manufacturing processes might reduce essential oil content in tea that might effect on the PAHs partially release into the infusion. Indeed, based on EU regulations, we may conclude that tea consumers are safe in risk of exposure to PAHs obtained from teas.

Anthraquinone and Butenolide Constituents from the Crinoid Capillaster multiradiatus.

Seven anthraquinones including two new compounds namely capillasterquinones A and B (1 and 2) and one new butenolide namely capillasterolide (8) were isolated and structurally elucidated from the crinoid Capillaster multiradiatus. The inhibitory effect of compounds 1-8 on lipopolysaccharide (LPS)-induced nitric oxide (NO) production as well as inhibition of 1 on expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) proteins in RAW264.7 cells were also evaluated. As the obtained results, capillasterquinone A (1) showed strong NO production inhibitory activity with an IC50 of 5.89±0.11 µM. In addition, compound 1 reduced the LPS-induced iNOS and COX-2 expressions in a dose-dependent manner.

The roles of, activities of, and competencies for, community nursing services in rural Vietnam: Implications for policy decisions.

Community health workforce plays a vital role in providing primary health care services as per the needs of residents; however, few studies have examined how nurses work within commune health centers (CHCs). Using qualitative methods including interviews and focus group discussions with key stakeholders, this study explores the roles, activities, and competencies required of community nursing services in rural districts within Vietnam. Two primary roles were identified: CHC nursing and family nursing. For the latter, in addition to providing people with general health care and health communication, they were expected to also deliver psychological care. CHC nursing fulfilled more roles and required four specific competencies: clinical care, communication, management, and planning/coordination activities. Despite these various roles serving people within a community, few ongoing efforts at either the local or national level are aimed at supporting these nurses. The study highlights the need for policy decisions via either developing a new job position policy or adapting the existing policy by integrating new roles into the existing positions of CHC nurses in Vietnam.

Two new guaiane sesquiterpene lactones from the aerial parts of Artemisia vulgaris.

Two new guaiane sesquiterpene lactones, vulgarolides A and B (1 and 2), were isolated from Artemisia vulgaris aerial parts using various chromatographic separations. The structure elucidation was performed by combination of spectroscopic experiments including 1D and 2D NMR, HR ESI MS, and CD. Their in vitro cytotoxic activities against five human cancer cell lines were also evaluated using SRB method.

Cytotoxic triterpene diglycosides from the sea cucumber Stichopus horrens.

Using various chromatographic separation techniques, eight triterpene diglycosides (1-8), including four new compounds namely stichorrenosides A-D (1-4), were isolated from a methanol extract of the Vietnamese sea cucumber S. horrens. Their structures were elucidated based on spectroscopic analyses, including HR ESI MS, 1D and 2D NMR. Their in vitro cytotoxic activity against five human cancer cell lines, Hep-G2 (hepatoma cancer), KB (epidermoid carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2 (melanoma), was evaluated using SRB methods. Stichorrenoside D (4), stichoposide A (5), and 3ß-O-[ß-d-xylopyranosyl-(1→2)-ß-d-xylopyranosyl]-23S-acetoxyholost-7-ene (7) showed strong cytotoxicity on all five tested cancer cell lines, whereas significant effect was observed for stichorrenoside C (3) and stichoposide B (6).

Triterpene saponins and megastigmane glucosides from Camellia bugiamapensis.

Two new triterpene saponins, camelliosides I and J (1 and 2), two new megastigmane glycosides, camellistigosides A and B (3 and 4), and two known megastigmane glycosides, icariside B1 (5) and (6S,9R)-roseoside (6), were isolated from a methanol extract of the Camellia bugiamapensis leaves using various chromatographic separation techniques. Their structures were elucidated based on spectroscopic analyses, including HR ESI MS, CD, 1D and 2D NMR. Their inhibitory effects on LPS-induced NO production in RAW264.7 cells were evaluated. This is the first report of the chemical constituents and biological activity of C. bugiamapensis.

Flavonoid glycosides from Barringtonia acutangula.

Using various chromatographic separation techniques, ten flavonoid glycosides, including six new compounds namely barringosides A-F (1-6), were isolated from a methanol extract of the Barringtonia acutangula leaves. The structure elucidation was confirmed by spectroscopic analyses, including 1D and 2D NMR, and HR ESI MS. Their inhibitory effects on LPS-induced NO production in RAW264.7 cells were also evaluated. Among the isolated compounds, quercetin 3-O-ß-d-(6-p-hydroxybenzoyl)galactopyranoside (9) showed significant effect with an IC50 of 20.00±1.68µM. This is the first report of these flavonoid glycosides from Barringtonia genus and their inhibition on LPS-induced NO production in RAW264.7 cells was reported here for the first time.

Cytotoxic Steroids from the Vietnamese Soft Coral Sinularia leptoclados.

Fifteen steroids, including two new compounds, leptosteroid (1) and 5,6ß-epoxygorgosterol (2), were isolated and structurally elucidated from the Vietnamese soft coral Sinularia leptoclados. Their cytotoxic effect against a panel of eight human cancer cell lines was evaluated using sulforhodamine B (SRB) method. Significant cytotoxicity against hepatoma cancer (HepG2, IC50=21.13±0.70 µM) and colon adenocarcinoma (SW480, IC50=28.65±1.53 µM) cell lines were observed for 1 and against acute leukemia (HL-60, IC50=20.53±2.26 µM) and SW480 (IC50=26.61±1.59 µM) for ergost-5-en-3ß,7ß-diol (8). In addition, 3ß,7ß-dihydroxyergosta-5,24(28)-diene (13) showed significant cytotoxic activity on all tested cell lines with IC50 values ranging from 13.45±1.81 to 29.01±3.21 µM.

Cytotoxic Steroids from the Vietnamese Soft Coral Sinularia conferta.

Twelve steroids, including five new compounds 1-5, were isolated and structurally elucidated from a methanol extract of the Vietnamese soft coral Sinularia conferta. Their cytotoxic effects against three human cancer cell lines, lung carcinoma (A-549), cervical adenocarcinoma (HeLa), and pancreatic epithelioid carcinoma (PANC-1), were evaluated using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assays. Among isolated compounds, 10 exhibited potent cytotoxic effects on all three tested cell lines with IC50 values of 3.64±0.18, 19.34±0.42, and 1.78±0.69 µM, respectively.

Steroid glycosides from the starfish Pentaceraster gracilis.

Using combined chromatographic separations, two new steroid glycosides namely pentacerosides A (1) and B (2), and four known compounds were isolated from the methanol extract of the starfish Pentaceraster gracilis. Their structures were determined on the basis of spectroscopic data (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, ROESY, and FT-ICR-MS) and by comparing obtained results to the literature values. Among the isolated compounds, only maculatoside (5) showed significant cytotoxic effect against Hep-G2 (IC50 = 16.75 ± 0.69 µM) and SK-Mel2 (IC50 = 19.44 ± 1.45 µM) cell lines and moderate effect on KB (IC50 = 36.53 ± 0.78 µM), LNCaP (IC50 = 39.75 ± 3.34 µM), and MCF7 (IC50 = 47.34 ± 7.01 µM) cell lines.

Steroid Constituents from the Soft Coral Sinularia nanolobata.

Six steroids (1-6), including the two new compounds 3ß,4α-dihydroxyergosta-5,24(28)-diene (1) and 24(S),28-epoxyergost-5-ene-3ß,4α-diol (2), were isolated from the methanol extract of the Vietnamese soft coral Sinularia nanolobata. Their structures were elucidated by spectroscopic methods including one and two dimensional (1D- and 2D)-NMR, Fourier transform ion cyclotron resonance (FT-ICR)-MS, and circular dichroism (CD). Compound 2 exhibited moderate cytotoxicity against the acute leukemia (HL-60) cell line with IC50 value of 33.53±4.25 µM and weak effect on the hepatoma cancer (HepG2) and colon adenocarcinoma (SW480) cell lines with IC50 values of 64.35±7.00 and 71.02±4.00 µM, respectively.

Further Highly Hydroxylated Steroids from the Vietnamese Starfish Archaster typicus.

Eight highly hydroxylated steroids (1-8), including three new compounds as sodium salts of (24S)-5α-cholestane-3ß,4ß,5,6α,7ß,8,14,15α,24-nonaol 6-sulfate (1), (24E)-5α-cholest-24-ene-26-yde-3ß,6α,8,14,15α-pentaol 15-sulfate (2), and 5α-cholest-3ß,6α,8,14,15α,24,25,26-octaol 15-sulfate (3), were isolated and elucidated from the methanol extract of the Vietnamese starfish Archaster typicus. The structure elucidation was done by spectroscopic methods including one and two dimensional (1D-, 2D-)NMR and Fourier transform ion cyclotron resonance (FT-ICR)-MS. The isolated compounds can be used as chemical markers for taxonomic identification of the starfish A. typicus.

Pyrrole Oligoglycosides from the Starfish Acanthaster planci Suppress Lipopolysaccharide-Induced Nitric Oxide Production in RAW264.7 Macrophages.

Two new pyrrole oligoglycosides, plancipyrrosides A and B (1 and 2), were isolated from methanol extract of the Vietnamese starfish Acanthaster planci using various chromatographic procedures. Their structures were elucidated by spectroscopic methods including one and two dimensional (1D- and 2D)-NMR and Fourier transform ion cyclotron resonance (FT-ICR)-MS. The finding of 1 and 2 represents the third case of pyrrole oligoglycosides obtaining reported to date. Moreover, plancipyrroside B (2) exhibits a potent inhibitory effect on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW264.7 cells with IC50 of 5.94±0.34 µM, whereas plancipyrroside A (1) shows this inhibitory activity with IC50 of 16.61±1.85 µM.

Steroid constituents from the soft coral Sinularia microspiculata.

A methanol extract of the soft coral Sinularia microspiculata revealed five sterols, including two new compounds. Using combined chromatographic and spectroscopic experiments, the new compounds were found to be 7-oxogorgosterol (1) and 16α-hydroxysarcosterol (2). Their structures were determined on the basis of spectroscopic data ((1)H and (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, NOESY, and FT-ICR-MS) and by comparing obtained results to the values indicated in previous studies. Among the isolated compounds, 3 showed weak cytotoxic effects against HL-60 (IC50  =  89.02  ±  9.93 µM) cell line, whereas 5 was weakly active against HL-60 (IC50  =  82.80  ±  13.65 µM) and SK-Mel2 (IC50  =  72.32  ±  1.30 µM) cell lines.

In vitro anti-inflammatory components isolated from the carnivorous plant Nepenthes mirabilis (Lour.) Rafarin.

CONTEXT: Nepenthes mirabilis (Lour.) Rafarin (Nepenthaceae) is a carnivorous plant used as a folk medicine in the treatment of jaundice, hepatitis, gastric ulcers, ureteral stones, diarrhea, diabetes, and high blood pressure. Neither the phytochemical content nor biological activities of N. mirabilis have been reported. OBJECTIVE: The anti-inflammatory activity from the N. mirabilis methanolic extract led to the isolation of compounds (1-26). MATERIALS AND METHODS: Chromatographic methods were used to isolate compounds from the methanol extract of N. mirabilis branches and leaves. The anti-inflammatory activity of these isolated compounds was investigated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) using ELISA. Primary BMDCs were used to examine the production of pro-inflammatory cytokines (IL-12 p40, IL-6, and TNF-α, at concentrations of 0.1, 0.2, and 1.0 µM) as compared with a positive control, SB203580 (1.0 µM). MTT assays showed that isolated compounds (1-26) did not exhibit significant cytotoxicity at concentrations up to 20.0 µM. RESULTS: Compound 9 showed potent inhibition of IL-12 p40, IL-6, and TNF-α production (IC50 = 0.17 ± 0.02, 0.46 ± 0.01, and 8.28 ± 0.21 µM, respectively). Compound 4 showed potent inhibition of IL-12 p40 and IL-6 production (IC50 = 1.17 ± 0.01 and 2.15 ± 0.04 µM). In addition, IL-12 p40 inhibition by naphthalene derivatives (1-7, 9, and 10), phenolic compounds (11-15), lupeone (18), and flavonoids (22, 25, and 26) was more potent than with the positive control. The isolated compounds exhibited little and/or no inhibitory effects on TNF-α production in LPS-stimulated BMDCs. DISCUSSION AND CONCLUSION: Taken together, these data suggest that the isolated components have significant inhibitory effects on pro-inflammatory cytokine production and warrant further study concerning their potential medicinal use.