Effect of chronic administration of ostruthin on depression-like behavior in chronically stressed mice.

We have previously shown that a single dose of a TREK-1 channel activator, ostruthin, exhibited antidepressant and anxiolytic effects in acute behavioral test models in mice. To assess the potential clinical application, it is essential to evaluate the effects of long-term administration of ostruthin in a chronically stressed mouse model, which is considered to be similar to the clinical condition of major depression in humans. Here, we tested the effects of a single and a 7-day administration of ostruthin on mice that were subjected to chronic unpredictable mild stress (CUMS). A single administration of ostruthin showed antidepressive effects in the tail suspension and forced swim tests of CUMS-treated mice. Unexpectedly, the 7-day administration exhibited only insignificant antidepressive and anxiolytic effects. The 7-day regimen did not affect food intake or body-weight gain, suggesting the absence of apparent cytotoxicity. The mice receiving the 7-day administration had significantly lower blood concentrations of ostruthin compared to those receiving a single dose, suggesting an upregulation of drug-metabolizing activities. These findings suggest that there is a need for stable TREK-1 channel activators that are not affected by drug metabolism.

Pentacyclic triterpenes from the leaves of Camellia hakodae Ninh.

Nine pentacyclic triterpene derivatives including new 3-O-cis-p-coumaroyl trichadenic acid B (1) and two new ursane-type triterpene derivatives, 11α,12-[1-(methyl)-2-(4-hydroxy-3-methoxyphenyl)ethane-1,2-dioxy]-urs-12-ene-3ß-ol (2) and 11α,12-[2-(methyl)-1-(4-hydroxy-3-methoxyphenyl)ethane-1,2-dioxy]-urs-12-ene-3ß-ol (3) were isolated from the leaves of Camellia hakodae Ninh., along with six known compounds (4-9). This is the first report on pentacyclic triterpenoids from this species. New compounds 1-3 and compound 7 were tested for cytotoxic activity against four human cancer cell lines (KB; Hep-G2; Lu; MCF-7) using the MTT assay to show moderate activity.

Novel human STING activation by hydrated-prenylated xanthones from Garcinia cowa.

OBJECTIVES: We investigate the anticancer activity and human stimulator of interferon genes pathway activation by a new hydrated-prenylated tetraoxygenated xanthone, garcicowanone I (1) and two known xanthones (2 and 3) that were isolated from the root bark of Garcinia cowa Roxb. ex Choisy. METHODS: The anticancer activity of each compound was evaluated by sulforhodamine B assay in immortalized cancer cell lines. Stimulator of interferon genes pathway activation was assessed by western blot analysis using human THP-1-derived macrophages. The production of pro-inflammatory cytokines from these macrophages was also evaluated via enzyme-linked immunosorbent assay. KEY FINDINGS: Both compounds 1 and 3 displayed moderate inhibitory effects on the cancer cells, including a cisplatin-resistant cell line, with IC50 values in the range of 10-20 µM. All three xanthones activated the stimulator of interferon genes, as evidenced by phosphorylation of tank-binding kinase 1, the stimulator of interferon genes protein and interferon regulatory factor 3. Furthermore, treatment of these macrophages with compounds 1-3 led to the production of pro-inflammatory cytokines, including interleukin 6, tumour necrosis factor α and interleukin 1ß. CONCLUSIONS: In conclusion, the isolated xanthones, including the novel garcicowanone I, displayed promising anticancer and immunomodulatory activity that warrants further research.

The Complete Mitochondrial Genome and Phylogenetic Analyses of To Chicken in Vietnam.

Indigenous chicken breeds have both cultural significance and economic value since they possess unique genetic characteristics that enable them to adapt to the local environment and contribute to biodiversity, food security, and sustainable agriculture in Vietnam. To (Tò in Vietnamese) chicken, a Vietnamese indigenous chicken breed, is popularly raised in Thai Binh province; however, little known is about the genetic diversity of this breed. In this study, we sequenced the complete mitochondrial genome of To chicken for a better understanding of the diversity and origin of the breed. The results of sequencing showed that the mitochondrial genome of To chicken spans a total length of 16,784 base pairs and comprises one non-coding control region (known as the displacement-loop (D-loop) region), two ribosomal RNA genes, 13 protein-coding genes, and 22 transfer RNA genes. The phylogenetic tree analyses and estimated genetic distances based on 31 complete mitochondrial genome sequences indicated that To chicken has a close genetic distance with the Laotian native chicken breed, Lv'erwu breed in China, and Nicobari black and Kadaknath breeds in India. The result of the current study might be important for conservation, breeding, and further genetic studies of To chicken.

Neuroprotective Effects of Ethanol Extract of Polyscias fruticosa (EEPF) against Glutamate-Mediated Neuronal Toxicity in HT22 Cells.

In traditional herbal medicine, the Polyscias fruticosa has been frequently used for the treatment of ischemia and inflammation. Oxidative stress mediated by elevated glutamate levels cause neuronal cell death in ischemia and various neurodegenerative diseases. However, so far, the neuroprotective effects of this plant extract against glutamate-mediated cell death have not been investigated in cell models. The current study investigates the neuroprotective effects of ethanol extracts of Polyscias fruticosa (EEPF) and elucidates the underlying molecular mechanisms of EEPFs relevant to neuroprotection against glutamate-mediated cell death. The oxidative stress-mediated cell death was induced by 5 mM glutamate treatment in HT22 cells. The cell viability was measured by a tetrazolium-based EZ-Cytox reagent and Calcein-AM fluorescent dye. Intracellular Ca2+ and ROS levels were measured by fluorescent dyes, fluo-3 AM and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. Protein expressions of p-AKT, BDNF, p-CREB, Bax, Bcl-2, and apoptosis-inducing factor (AIF) were determined by western blot analysis. The apoptotic cell death was measured by flow cytometry. The in vivo efficacy of EEPF was evaluated using the Mongolian gerbil mouse by surgery-induced brain ischemia. EEPF treatment showed a neuroprotective effect against glutamate-induced cell death. The EEPF co-treatment reduced the intracellular Ca2+ and ROS and apoptotic cell death. Furthermore, it recovered the p-AKT, p-CREB, BDNF, and Bcl-2 levels decreased by glutamate. The EEPF co-treatment suppressed the activation of apoptotic Bax, the nuclear translocation of AIF, and mitogen-activated protein kinase (MAPK) pathway proteins (ERK1/2, p38, JNK). Further, EEPF treatment significantly rescued the degenerative neurons in the ischemia-induced Mongolian gerbil in vivo model. EEPF exhibited neuroprotective properties that suppress glutamate-mediated neurotoxicity. The underlying mechanism of EEPF is increasing the level of p-AKT, p-CREB, BDNF, and Bcl-2 associated with cell survival. It has therapeutic potential for the treatment of glutamate-mediated neuropathology.

Six New Polyoxygenated Xanthones from Garcinia cowa and Their Neuroprotective Effects on Glutamate-Mediated Hippocampal Neuronal HT22 Cell Death.

Six new polyoxygenated xanthones, garcicowanones F-H (1-3), norcowanol A-B (4-5), and garcinone F (6) along with twelve known compounds 7-18 were obtained from the latex of Garcinia cowa Roxb. ex Choisy. All new compounds have a 1,3,7-trioxygenated or 1,3,6,7-tetraoxygenated xanthone nucleus and differ from majority of xanthones from G. cowa by hydrated side chains. Compounds 1, 7, 8 and 18 exhibited significant neuroprotective effects on glutamate-mediated hippocampal neuronal HT22 cell death. In particular, compound 1 exhibited the most potent neuroprotective effect with >80 % cell viability in the concentration range of 2.9-115 µM. Further studies on compound 1 showed that it decreased cellular Ca2+ influx and inhibits cellular reactive oxygen species generation in HT22 cells. A Western blot analysis showed that MAPK phosphorylation, Bax, and AIF translocation dramatically increased upon treatment with 5 mM glutamate and decreased upon a co-treatment with compound 1.

Microencapsulation of Hibiscus sabdariffa L. Calyx Anthocyanins with Yeast Hulls.

Yeast hulls, due to their specific thin mannoprotein layer and high content of ß-glucan, constitute a promising material to stabilise the colour of anthocyanins. This study evaluates the potential of yeast hulls on the freeze-drying encapsulation of anthocyanins-rich extract from Hibiscus sabdariffa L. calyx with comparison to maltodextrin microcapsules. The moisture content (5.28-16.38%), water activity (< 0.039-0.307) and hygroscopicity (17.50-25.99 g/100 g) of obtained powders were evaluated. The stability of encapsulated anthocyanins, monitored through the total anthocyanin content, was evaluated with the pH differential method immediately after production and after a 10-week storage under different conditions of temperature (5 or 37 °C), humidity (45 or 85% RH), in presence or absence of light. The colour parameters (a, b*, L*, C*, H°, ΔE*) of powders were measured. The results indicated that yeast-hulls showed a good ability to protect anthocyanin against the influence of temperature, light, moisture compared to freeze-dried anthocyanins-rich extracts (p < 0.05). Yeast hulls protected anthocyanin better than maltodextrin under high humidity conditions (p < 0.05).

The protective effect of rural life on mite sensitization disappears among urban migrants in the South of Vietnam.

BACKGROUND: Rapid urbanization combined with rural migration to urban areas in southern Vietnam could be risk factors for allergen sensitization, contributing to chronic respiratory diseases (CRD). We aimed to evaluate the prevalence of mite sensitization and its relation to house dust characteristics among rural and urban native and migrating populations with CRD. METHODS: Rural (n = 19) and urban (n = 46) dwellings were defined on the basis of a home typology. Controls were western Belgian houses (n = 14). Besides the house characteristics, both endotoxin and mite allergens were measured in the settled dusts. The sensitization to mite allergens was defined by positive skin prick test (SPT) and concentration of specific IgE (sIgE)≥ 0.7 U/mL. The prevalence of mite sensitization was evaluated among 610 patients with CRD and compared according to both their home types and places of birth and residences. RESULTS: The concentration of endotoxin (but not mite allergen) was higher in rural compared to urban dusts (440 (95%CI: 314-566) versus 170 (95%CI: 115-226) EU/mg; p < 0.0001). The prevalence of positive sIgE to Der p1 and Der p2 was significantly lower in rural (9% and 5%) compared to urban (15% and 9%) population, consistent with the positive SPT to mite (14% and 21%, respectively). Among the urban migrants, the risk of mite sensitization (SPT) was higher compared to the rural natives (OR: 1.79 (1.02-3.15), p < 0.05) and not different to the urban ones (OR: 1.35 (0.82-2.23) p NS). CONCLUSION: In Vietnam, associated with higher endotoxin (but not allergen) dust concentrations, the risk of mite sensitization was lower in rural compared to the native urban population, but this protective effect could disappear among rural to urban migrants.

Stress, anxiety and depression in clinical nurses in Vietnam: a cross-sectional survey and cluster analysis.

BACKGROUND: Hospital nurses are exposed to various work-related factors that may be associated with increased risk of developing different mental disorders. Empirical evidence on the prevalence and correlates of individual mental health problems such as stress, anxiety and depression is widely reported, while a combined pattern of these conditions is unknown. This study aims to examine the co-occurrence of stress, anxiety and depression among clinical nurses, and to explore socio-demographic characteristics of, and working conditions experienced by, nurses that may be associated with these three mental health conditions. METHODS: A cross-sectional study was implemented in one tertiary hospital in Hanoi city, Vietnam, from May to September 2015. A self-reported questionnaire including a short version of the Depression, Anxiety and Stress scale 21 items and questions on demographic and work-related characteristics was delivered to 787 registered nurses. 600 completed questionnaires was used in the final analysis (76.2% response rate). The two-step clustering analysis was performed to identify sub groups. Chi square test and post hoc ANOVA analysis with Bonferroni correction were used to examine differences in psychological status, demographic characteristics and working conditions among the clusters (two-tailed p < 0.05). RESULTS: The prevalence of self-reported stress, anxiety and depression were 18.5%, 39.8% and 13.2%, respectively. 45.3% participants reported symptoms of at least one mental disorder, 7.3% had all three. Nurses in the first cluster (high prevalence of mental disorders), had high task demand and conflict at work with low job control and reward. The second cluster nurses (moderate percentage of mental strain) were significantly older and in marital relationship, high task demand and job control, and presence of chronic diseases. The lowest proportion of self-perceived mental disorders were observed in the cluster three who were younger and had fewer years of services, moderate task demand and low job control and better physical health in comparison with those in the other two clusters (p < 0.05). CONCLUSIONS: Stress, anxiety and depression were prevalent among clinical nurses. Heterogeneity in demographic characteristics and working conditions were observed across clusters with different patterns of mental disorders. Institutional effort should be emphasized to support nurses in their career development to reduce psychological strains.

Encapsulation of Hibiscus sabdariffa L. anthocyanins as natural colours in yeast.

Hibiscus sabdariffa extracts, a rich source of anthocyanin, were subjected to encapsulation in yeast cells. An encapsulation yield (EY) of 208 µg/100 mg of cells and an encapsulation efficiency (EE) of 27%, were reached after optimisation of the ratios (0.5 g wet yeast cells for 5 ml of anthocyanin extracts at 1 g·L-1) and with 10% of ethanol. The storage stability of encapsulated pigments was investigated in water and buffer pH 1.5 at 5 & 37 °C for 10 days and 90 °C for 30 min. The percentage of loss of colour was determined by colourimetry assays. The microparticles made of yeast with or without heat treatment exhibited different protecting effects (P < 0.01). At 37 °C, the percentage of loss of colour in water was of 2.5% for heat-treated and 36.5% for non-treated yeast microparticles, suggesting that yeast enzymes would be responsible for the loss of anthocyanin during storage. These results are confirmed by the percentage of loss of colour which was far lower in conditions of low enzymatic activity: 3.1% at 5 °C for non-heat-treated cells in water. The pH of solvent had also an important effect on the degradation of encapsulated anthocyanin; in buffer at pH 1.5 and 37 °C with the non-heat-treated cells, the degradation decreased strongly to 9.4% compared with 36.5% in water. These results show that yeast cells are a good mean of encapsulation of pigments for a colouring purpose and that they provide anthocyanins a good protection as long as their enzymes are inactivated.

Prevalence of Self-Treatment Practice and Related Factors Among Workers Aged 15 to 60 Years in Chi Linh Town, Hai Duong Province, Vietnam.

Self-treatment is particularly prevalent in Vietnam. However, the prevalence of this practice among the working population is unclear. This study aims to describe the prevalence of self-treatment and related factors among workers aged 15 to 60 years in the suburban area of Chi Linh, Hai Duong, Vietnam. Secondary data of 3128 respondents was retrieved from the CHILILAB HDSS 2016 survey for analysis using logistic regression with a significance level of .05. Results show that 47.5% of respondents treated themselves at least once during one previous year. While rural residence and the presence of acute health symptoms and chronic diseases significantly associate with the choice of self-treatment among all investigated workers, lower education level and health insurance status only significantly relate to this practice among the formally employed workers. The findings imply the need for specific measures to manage self-treatment practices among different groups of workers.

Gambogic acid induces apoptotic cell death in T98G glioma cells.

Gambogic acid (GA), a natural product with a xanthone structure, has a broad range of anti-proliferative effects on cancer cell lines. We evaluated GA for its cytotoxic effects on T98G glioblastoma cells. GA exhibited potent anti-proliferative activity and induced apoptosis in T98G glioblastoma cells in a dose-dependent manner. Incubation of cells with GA revealed apoptotic features including increased Bax and AIF expression, cytochrome c release, and cleavage of caspase-3, -8, -9, and PARP, while Bcl-2 expression was downregulated. Furthermore, GA induced reactive oxygen species (ROS) generation in T98G cells. Our results indicate that GA increases Bax- and AIF-associated apoptotic signaling in glioblastoma cells.

Secreted M-ficolin anchors onto monocyte transmembrane G protein-coupled receptor 43 and cross talks with plasma C-reactive protein to mediate immune signaling and regulate host defense.

Although transmembrane C-type lectins (CLs) are known to initiate immune signaling, the participation and mechanism of action of soluble CLs have remained enigmatic. In this study, we found that M-ficolin, a conserved soluble CL of monocyte origin, overcomes its lack of membrane-anchor domain by docking constitutively onto a monocyte transmembrane receptor, G protein-coupled receptor 43 (GPCR43), to form a pathogen sensor-cum-signal transducer. On encountering microbial invaders, the M-ficolin-GPCR43 complex activates the NF-κB cascade to upregulate IL-8 production. We showed that mild acidosis at the local site of infection induces conformational changes in the M-ficolin molecule, which provokes a strong interaction between the C-reactive protein (CRP) and the M-ficolin-GPCR43 complex. The collaboration among CRP-M-ficolin-GPCR43 under acidosis curtails IL-8 production thus preventing immune overactivation. Therefore, we propose that a soluble CL may become membrane-associated through interaction with a transmembrane protein, whereupon infection collaborates with other plasma protein to transduce the infection signal and regulate host defense. Our finding implies a possible mechanism whereby the host might expand its repertoire of immune recognition-cum-regulation tactics by promiscuous protein networking. Furthermore, our identification of the pH-sensitive interfaces of M-ficolin-CRP provides a powerful template for future design of potential immunomodulators.