Research on chemical constituents, anti-bacterial and anti-cancer effects of components isolated from Zingiber officinale Roscoe from Vietnam

Ginger, a commonly used spice and medicinal herb, is an abundant source of bioactive compounds. However, the utilization of ginger in the pharmaceutical industry is still moderate and not commensurate with the potential of the Vietnamese horticulture industry, mainly due to a lack of information about the quality of input materials. In this study, we compared the volatile compounds of gingers collected from 13 provinces of Vietnam using GC/MS and GC-FID analysis to provide a basis for selecting and standardizing input materials. Furthermore, ginger essential oil from Ben Tre province of Vietnam exhibited significant antibacterial activity particularly in inhibiting Gram-positive bacteria, including S. aureus and S. epidermidis, with inhibition zones of 30.00 ± 1.41 and 24.67 ± 3.30 mm, respectively. However, no significant inhibition was observed against Gram-negative bacteria P. aeruginosa and E. coli. We also isolated 5 non-volatile compounds from ginger extract, namely 6-shogaol (1), quercetin (2), rutin (3), beta-sitosterol (4) and beta-sitosterol-3-O-beta-D-glucopyranoside (5). Among them, compounds 1–3 displayed cytotoxicity against Hep3B, SK-LU-1, MCF-7, SK-LU-1, SW480 and HepG2 tumour cell lines, with an IC50 values ranging between 62.7 ± 2.1 and 97.6 ± 1.1 µM, using Ellipticine as a positive control. Compounds 4 and 5 showed cytotoxicity against Hep3B and HepG2 tumor cells, with the IC50 values ranging between 21.5 ± 5.1 and 46.9 ± 3.7 µM but did not exhibit any significant cytotoxicity against SW480 and SK-LU-1 cells. Compound 4 also demonstrated middling cytotoxicity against the MCF7 cell line, with an IC50 value of 43.6 ± 5.1 µM. These findings suggest further applications of Vietnamese ginger for the treatment of infectious and cancer-related diseases

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Helicobacter pylori Infection and Peptic Ulcer Disease in Symptomatic Children in Southern Vietnam: A Prospective Multicenter Study

Background: Helicobacter pylori (H. pylori) remains a major cause of gastroduodenal diseases. We aimed to evaluate the burden of this infection, particularly peptic ulcer disease in Vietnamese children. Methods: We enrolled consecutive children referred for esophagogastroduodenoscopy at two tertiary children’s hospitals in Ho Chi Minh City, from October 2019 to May 2021. Children treated with proton pump inhibitors during the last two weeks or antibiotics for four weeks, and those having a previous or interventional endoscopy were excluded. H. pylori infection was diagnosed with either a positive culture or positive histopathology combined with a rapid urease test, or with a polymerase chain reaction of the urease gene. The study was approved by the Ethics Committee and written informed consent/assent was obtained. Results: Among 336 enrolled children aged 4–16 (mean: 9.1 ± 2.4 years; 55.4% girls), H. pylori infection was positive in 80%. Peptic ulcers were detected in 65 (19%), increasing with age, and 25% with anemia. cagA+ strains were detected at a higher rate in children with ulcers. Conclusions: Prevalence of H. pylori and peptic ulcers is high among symptomatic Vietnamese children. It is crucial to have a program for early detection of H. pylori to reduce ulcer risk and gastric cancer later

Development of Blueberry-Derived Extracellular Nanovesicles for Immunomodulatory Therapy

Over the past decade, there has been a significant expansion in the development of plant-derived extracellular nanovesicles (EVs) as an effective drug delivery system for precision therapy. However, the lack of effective methods for the isolation and characterization of plant EVs hampers progress in the field. To solve a challenge related to systemic separation and characterization in the plant-derived EV field, herein, we report the development of a simple 3D inner filter-based method that allows the extraction of apoplastic fluid (AF) from blueberry, facilitating EV isolation as well as effective downstream applications. Class I chitinase (PR-3) was found in blueberry-derived EVs (BENVs). As Class I chitinase is expressed in a wide range of plants, it could serve as a universal marker for plant-derived EVs. Significantly, the BENVs exhibit not only higher drug loading capacity than that reported for other EVs but also possess the ability to modulate the release of the proinflammatory cytokine IL-8 and total glutathione in response to oxidative stress. Therefore, the BENV is a promising edible multifunctional nano-bio-platform for future immunomodulatory therapies

Bovine extracellular vesicles contaminate human extracellular vesicles produced in cell culture conditioned medium when ‘exosome-depleted serum’ is utilised

Extracellular vesicles (EVs) are important intercellular communication messengers. Half of the published studies in the field are in vitro cell culture based in which bovine serum in various concentrations and forms is used to facilitate the production of extracellular vesicles. ‘Exosome depleted serum’ is the type of bovine serum most widely used in the production of human EVs. Herein, we demonstrate that, despite the initial caution raised in 2014 about the persistence of bovine EVs, ‘exosome depleted serum’ was still used in 46% of publications on human or rodent EVs between 2015 and 2019. Using nanoparticle tracking analysis combined with detergent lysis of vesicles as well as bovine CD9 ELISA, we show that there were approximately 5.33 x 107/mL of bovine EVs remaining in the ‘exosome depleted serum’. Importantly, the ‘exosome depleted serum’ was relatively enriched in small EVs by approximately 2.7-fold relative to the large EVs compared to that in the original serum. Specifically, the percentage of small EVs in total vesicles had increased from the original 48% in the serum before ultracentrifugation to 92% in the ‘exosome depleted serum’. Furthermore, the pervasive bovine EVs carried over by the ‘exosome depleted serum’, even when the lowest concentration (0.5%) was used in cell culture, resulted in a significant contamination of human EVs in cell culture conditioned medium. Our findings indicate that the use ‘exosome depleted serum’ in cell culture-based studies may introduce artefacts into research examining the function of human and rodent EVs, in particular those involving EV miRNA. Thus, we appeal to the researchers in the EV field to seriously reconsider the practice of using ‘exosome depleted serum’ in the production of human and other mammalian EVs in vitro.</p

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921