Ethanolic extract from fruiting bodies of Cordyceps militaris HL8 exhibits cytotoxic activities against cancer cells, skin pathogenic yeasts, and postharvest pathogen Penicillium digitatum.

Cordyceps militaris is a well-known medicinal mushroom in Asian countries. This edible fungus has been widely exploited for traditional medicine and functional food production. C. militaris is a heterothallic fungus that requires both the mating-type loci, MAT1-1 and MAT1-2, for fruiting body formation. However, recent studies also indicated two groups of C. militaris, including monokaryotic strains carrying only MAT1-1 in their genomes and heterokaryotic strains harboring both MAT1-1 and MAT1-2. These strain groups are able to produce fruiting bodies under suitable cultivating conditions. In previous work, we showed that monokaryotic strains are more stable than heterokaryotic strains in fruiting body formation through successive culturing generations. In this study, we report a high cordycepin-producing monokaryotic C. militaris strain (HL8) collected in Vietnam. This strain could form normal fruiting bodies with high biological efficiency and contain a cordycepin content of 14.43 mg/g lyophilized fruiting body biomass. The ethanol extraction of the HL8 fruiting bodies resulted in a crude extract with a cordycepin content of 69.15 mg/g. Assays of cytotoxic activity on six human cancer cell lines showed that the extract inhibited the growth of all these cell lines with the IC50 values of 6.41-11.51 µg/mL. Notably, the extract significantly reduced cell proliferation and promoted apoptosis of breast cancer cells. Furthermore, the extract also exhibited strong antifungal activity against Malassezia skin yeasts and the citrus postharvest pathogen Penicillium digitatum. Our work provides a promising monokaryotic C. militaris strain as a bioresource for medicine, cosmetics, and fruit preservation.

Investigation of the mechanism of action of chemical constituents of celery seed against gout disease using network pharmacology, molecular docking, and molecular dynamics simulations.

Celery (Apium graveolens L.) has long been considered as a potential herbal medicine for the prevention and treatment of gout. However, the relationship between the chemical constituents and pharmacological activities of this medicinal plant has not been fully investigated yet. Therefore, this study aims to apply network pharmacology, molecular docking and molecular dynamics to explore the relationship between the chemical constituents of celery seed and its biological effects in the treatment of gout. Network pharmacology was built and analyzed based on the data collected from GeneCards, OMIM databases and SwissTargetPrediction web server using Cytoscape 3.9.0 software. The GO and KEGG pathway analysis of the potential targets of celery seed related to gout disease was performed using the ShinyGO v0.75 app. Molecular docking and molecular dynamics were carried out using Autodock vina and NAMD 2.14 software, respectively. The network analysis identified 16 active compounds and thirteen key targets of celery seed in the treatment of gout. The GO analysis and the KEGG pathway enrichment analysis suggested that the mechanism of action of the chemical constituents of celery seed might be involved in several pathways, notably the PI3K-Akt signaling pathway, Ras signaling pathway, and HIF-1 signaling pathway, respectively. Molecular docking and molecular dynamics revealed that apiumetin might be an important chemical that plays a key role in the pharmacological effect of celery seed. These results might be useful to select the Q-markers to control the quality of the products from celery seeds.Communicated by Ramaswamy H. Sarma.

Finding and treating both tuberculosis disease and latent infection during population-wide active case finding for tuberculosis elimination.

In recognition of the high rates of undetected tuberculosis in the community, the World Health Organization (WHO) encourages targeted active case finding (ACF) among "high-risk" populations. While this strategy has led to increased case detection in these populations, the epidemic impact of these interventions has not been demonstrated. Historical data suggest that population-wide (untargeted) ACF can interrupt transmission in high-incidence settings, but implementation remains lacking, despite recent advances in screening tools. The reservoir of latent infection-affecting up to a quarter of the global population -complicates elimination efforts by acting as a pool from which future tuberculosis cases may emerge, even after all active cases have been treated. A holistic case finding strategy that addresses both active disease and latent infection is likely to be the optimal approach for rapidly achieving sustainable progress toward TB elimination in a durable way, but safety and cost effectiveness have not been demonstrated. Sensitive, symptom-agnostic community screening, combined with effective tuberculosis treatment and prevention, should eliminate all infectious cases in the community, whilst identifying and treating people with latent infection will also eliminate tomorrow's tuberculosis cases. If real strides toward global tuberculosis elimination are to be made, bold strategies are required using the best available tools and a long horizon for cost-benefit assessment.

FAS and SREBP-1c Inhibition via AMPK Activation in HepG2 Cells by Biovip, Tox-off, and Traphanoside GO1 from Glinus oppositifolius.

Glinus oppositifolius is an endemic herbaceous plant found in tropical Asian countries and is native in Vietnam. It is used in traditional folk medicine because of its flavor and antiseptic and laxative effects. In the current research, the effects of Tox-off, Biovip, and the purified compounds isolated from G. oppositifolius in the previous study were evaluated on the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK)-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC) in C2C12 myoblasts. In addition, the most potent active compounds, traphanoside-GO1 (TRA-GO1) and TRA-GO5 have validated the reduction of fatty acid synthase (FAS) and sterol regulatory element binding protein (SREBP)-1c in HepG2 cells. We found that Tox-off and Biovip significantly increased the phosphorylation of AMPK and ACC in C2C12 myoblasts. Furthermore, TRA-GO1 and TRA-GO5 significantly increased the AMPK activation and phosphorylation of its downstream substrate ACC in a concentration-dependent way compared to the dimethyl sulfoxide (DMSO) control. Besides, the protein level of FAS and SREBP-1c decreased by TRA-GO1 and TRA-GO5 in a concentration-dependent manner. Taken together, our results showed that the increased AMPK and ACC phosphorylation by active components of G. oppositifolius may activate the AMPK signaling pathways, which are useful for the anti-obesity and its related metabolic disorders.

Optimization of ß-Cyclodextrin-Assisted Extraction of Apigenin and Luteolin from Chrysanthemum indicum L. Using Response Surface Methodology Combined with Different Optimization Algorithms and Evaluation of Its Antioxidant Capacity.

Cyclodextrins and their derivatives have shown successful applications in extracting active compounds from medicinal plants. However, the use of ß-cyclodextrin derivatives for extracting apigenin and luteolin from Chrysanthemum indicum L. remains unexplored. Additionally, the application of nature-inspired optimization algorithms in optimizing extraction conditions has been limited. Therefore, this study was performed with the aims of optimizing the extraction of apigenin and luteolin from C. indicum with the assistance of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) using response surface methodology combined with various optimization algorithms, including desirability function approach, genetic algorithm, particle swarm optimization, and firefly algorithm. The results showed that the optimal conditions obtained by the four algorithms were consistent, with an extraction time of 60 min, HP-ß-CD concentration of 30 mg/mL, and a solvent-to-solid ratio of 24 mg/mL. At these conditions, the apigenin and luteolin contents were 1.362±0.008 and 8.724±0.117 mg/g, respectively. The results also showed that HP-ß-CD-assisted extraction exhibited significantly higher apigenin and luteolin contents compared to conventional solvent. Comparable results were also yielded from the antioxidant assay. Our study suggested that the nature-inspired optimization algorithms might be potential options in enhancing the effectiveness of the traditional response surface methodology for the optimization of extraction of natural products.

Investigate the anaerobic degradation of high-acetone latex wastewater with magnetite supplement.

This study evaluated the effects of acetone on the anaerobic degradation of synthetic latex wastewater, which was simulated from the wastewater of the deproteinized natural rubber production process, including latex, acetate, propionate, and acetone as the main carbon sources, at a batch scale in 5 cycles of a total of 60 days. Fe3O4 was applied to accelerate the treatment performance from cycle 3. Acetone was added in concentration ranges of 0%, 0.05%, 0.1%, 0.15%-included latex, and 0.15%-free latex (w/v). In the Fe3O4-free cycles, for latex-added vials, soluble chemical oxygen demand (sCOD) was removed at 43.20%, 43.20%, and 12.65%, corresponding to the input acetone concentrations varying from 0.05% to 0.15%, indicating the interference of acetone for COD reduction. After adding Fe3O4, all flasks reported a significant increase in COD removal efficiency, especially for acetone-only and latex-only vials, from 36.9% to 14.30%-42.95% and 83.20%, respectively. Other highlighted results of COD balance showed that Fe3O4 involvement improved the degradation process of acetate, propionate, acetone, and the other COD parts, including the intermediate products of latex reduction. Besides, during the whole batch process, the order of reduction priority of the carbon sources in the synthetic wastewater was acetate, propionate and acetone. We also found that the acetate concentration appeared to be strongly related to reducing other carbon sources in natural rubber wastewater. Microbial community analysis revealed that protein-degrading bacteria Bacteroidetes vadinHA17 and Proteinniphilum and methylotrophic methanogens might play key roles in treating simulated deproteinized-natural-rubber wastewater.

The effect of pH on the phenolic content and antioxidant properties of three different mustard extracts.

Mustard seeds are cultivated worldwide due to their substantial agronomic value of their high protein, oil, and phenolic content. The latter bioactive compounds give mustard seeds various applications in the food and pharmaceutical industries, as antimicrobial, antioxidant, and chemoprotective agents. By modifying the pretreatment and extraction conditions, a significant improvement in the quantity and quality of these crucial compounds was obtained. Based on the electrostatic interactions between the solvents and the extracts, an alternative green extraction procedure was used on three varieties of mustard seeds (Oriental, black, and yellow). Preliminary results demonstrated an interesting trend in which the isoelectric pH value affected the antioxidant activity of the extracts. A number of different antioxidant assays together with total phenolic content (TPC) and total flavonoid content (TFC) were conducted on the three different mustard seeds as affected by different combinations of times and pHs. With the exception of metal ion chelation assay, the other antioxidant methods, including ferric reducing/antioxidant power assay, 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging assay and ABTS•+ scavenging assay, significantly (p < 0.05) increased with the pretreatment time for all three pH levels studied. Interestingly, the TPC significantly increased (p < 0.05) with the lower pH level treatments. The highest TPC (2040.32 ± 360.12 mg/g dry weight basis) was obtained from yellow mustard seed under neutral treatment. Conversely, TFC showed no significant differences among the different pretreatment time conditions closer to the neutral pH. PRACTICAL APPLICATION: The usage of food-based solvents with the assistance of a home-scale pressurized wet extraction model represents a green technology that can contribute to a wide variety of applications. This method significantly improved the phenolic content, flavonoid content, and antioxidant potential of the mustard extracts, thus making water the most promising extracted solvent.

Therapeutic effects of a standardized-flavonoid Diospyros kaki L.f. leaf extract on transient focal cerebral ischemia-induced brain injury in mice.

This study aimed to investigate the neuroprotective and therapeutic effects of Diospyros kaki L.f. leaves (DK) on transient focal cerebral ischemic injury and underlying mechanisms using a middle cerebral artery occlusion (MCAO) model of mice. The animals received the MCAO operation on day 0. The daily administrations of DK (50 and 100 mg/kg, p.o) and edaravone (6 mg/kg, i.v), a reference drug with radical scavenging activity, were started 7 days before (pre-treatment) or immediately after the MCAO operation (post-treatment) and continued during the experimental period. Histochemical, biochemical, and neurological changes and cognitive performance were evaluated. MCAO caused cerebral infarction and neuronal cell loss in the cortex, striatum, and hippocampus in a manner accompanied by spatial cognitive deficits. These neurological and cognitive impairments caused by MCAO were significantly attenuated by pre- and post-ischemic treatments with DK and edaravone, suggesting that DK, like edaravone, has therapeutic potential for cerebral ischemia-induced brain damage. DK and edaravone suppressed MCAO-induced changes in biomarkers for apoptosis (TUNEL-positive cell number and cleaved caspase-3 protein expression) and oxidative stress (glutathione and malondialdehyde contents) in the brain. Interestingly, DK, but not edaravone, mitigated an increase in blood-brain permeability and down-regulation of vascular endothelial growth factor protein expression caused by MCAO. Although the exact chemical constituents implicated in the effects of DK remain to be clarified, the present results indicate that DK exerts neuroprotective and therapeutic activity against transient focal cerebral ischemia-induced injury probably by suppressing oxidative stress, apoptotic process, and mechanisms impairing blood-brain barrier integrity in the brain.

Green composites based on volcanic red algae Cyanidiales, cellulose, and coffee waste biomass modified with magnetic nanoparticles for the removal of methylene blue.

In this paper, green nanocomposites based on biomass and superparamagnetic nanoparticles were synthesized and used as adsorbents to remove methylene blue (MB) from water with magnetic separation. The adsorbents were synthesized through the wet co-precipitation technique, in which iron-oxide nanoparticles coated the cores based on coffee, cellulose, and red volcanic algae waste. The procedure resulted in materials that could be easily separated from aqueous solutions with magnets. The morphology and chemical composition of the nanocomposites were characterized by SEM, FT-IR, and XPS methods. The adsorption studies of MB removal with UV-vis spectrometry showed that the adsorption performance of the prepared materials strongly depended on their morphology and the type of the organic adsorbent. The adsorption studies presented the highest effectiveness in neutral pH with only a slight effect on ionic strength. The MB removal undergoes pseudo-second kinetics for all adsorbents. The maximal adsorption capacity for the coffee@Fe3O4-2, cellulose@Fe3O4-1, and algae@Fe3O4-1 is 38.23 mg g-1, 41.61 mg g-1, and 48.41 mg g-1, respectively. The mechanism of MB adsorption follows the Langmuir model using coffee@Fe3O4 and cellulose@Fe3O4, while for algae@Fe3O4 the process fits to the Redlich-Peterson model. The removal efficiency analysis based on UV-vis adsorption spectra revealed that the adsorption effectiveness of the nanocomposites increased as follows: coffee@Fe3O4-2 > cellulose@Fe3O4-1 > algae@Fe3O4-1, demonstrating an MB removal efficiency of up to 90%.

Immunomodulatory effects of graded levels of docosahexaenoic acid (DHA) in common carp (Cyprinus carpio) - In vitro and in vivo approaches.

The D-series resolvins formed from docosahexaenoic acid (DHA) work as anti-inflammatory mediators indicating the role of this long-chain polyunsaturated fatty acid in the immune system of mammals. However, such information is still limited in fish. The current study was conducted to evaluate the immunomodulatory effects of graded levels of DHA in common carp Cyprinus carpio by in vitro and in vivo approaches. In the in vitro experiment, the head kidney leukocytes isolated from common carp (body weight = 120.3 ± 12.4 g) were exposed to DHA at 0, 15, and 75 µM (corresponding to DHA0, DHA15, and DHA75) for 1 h; the cells were then immediately exposed to lipopolysaccharides (LPS) at a dose of 10 µg/ml for 4 or 24 h to stimulate the pro-inflammatory responses. The expression of several target genes involved in the inflammatory response (tlr4, nfkb, il-1, il-6, pge2, pla2, nf-kbi, il-10, and tgf-ß1) and cytoprotection (hsp70, gpx1, and prdx3) was then assessed by RT-qPCR. Results showed that the pro-inflammatory response induced by LPS was confirmed through the upregulations of il-1 and il-6 expressions in the DHA0 group after 4 h of LPS exposure. The downregulations of il-6 in DHA15 and DHA75 cells after 4 h of LPS exposure compared to DHA0 indicated that the free DHA supplementation in the cell culture medium induced an anti-inflammatory response. Decreases of il-10 and nf-kbi expression were also observed in DHA-treated groups and the highest expression of hsp70 in DHA75 cells. In the in vivo experiment, common carp juveniles (21.7 ± 0.9 g) were fed to apparent satiation with a diet supplemented with DHA at 0, 6, and 20 g/kg for 8 weeks. After the feeding trial, the fish were challenged with Aeromonas veronii at 2.1 × 107 CFU/ml and the fish mortality was then recorded during 14 days. At the end of the feeding trial and the second day of bacterial infection, fish blood samples were collected for haematological parameters while liver and head kidney were used for assaying different immune variables. Results showed that the DHA supplementation in fish diet did not influence the fish growth and other husbandry parameters. The lowest value of fish mortality was recorded in DHA20-fed fish. The positive effects of DHA-supplemented diets were also found in myeloperoxidase (MPO), glutathione (GSH), and catalase (CAT) activities. In conclusion, the results suggest that DHA is able to modulate the inflammatory response in the immune celsl at a dose of 75 µM/mL and to boost disease resistance in common carp fed on a diet supplemented with DHA at 20 g/kg of feed.

The Pivotal Role of Neuropeptide Crosstalk from Ventromedial-PACAP to Dorsomedial-Galanin in the Appetite Regulation in the Mouse Hypothalamus.

We have previously shown that pituitary adenylate cyclase-activating polypeptide (PACAP) in the ventromedial hypothalamus (VMH) enhances feeding during the dark cycle and after fasting, and inhibits feeding during the light cycle. On the other hand, galanin is highly expressed in the hypothalamus and has been reported to be involved in feeding regulation. In this study, we investigated the involvement of the VMH-PACAP to the dorsomedial hypothalamus (DMH)-galanin signaling in the regulation of feeding. Galanin expression in the hypothalamus was significantly increased with fasting, but this increment was canceled in PACAP-knockout (KO) mice. Furthermore, overexpression of PACAP in the VMH increased the expression of galanin, while knockdown (KD) of PACAP in the VMH decreased the expression of galanin, indicating that the expression of galanin in the hypothalamus might be regulated by PACAP in the VMH. Therefore, we expressed the synaptophysin-EGFP fusion protein (SypEGFP) in PACAP neurons in the VMH and visualized the neural projection to the hypothalamic region where galanin was highly expressed. A strong synaptophysin-EGFP signal was observed in the DMH, indicating that PACAP-expressing cells of the VMH projected to the DMH. Furthermore, galanin immunostaining in the DMH showed that galanin expression was weak in PACAP-KO mice. When galanin in the DMH was knocked down, food intake during the dark cycle and after fasting was decreased, and food intake during the light cycle was increased, as in PACAP-KO mice. These results indicated that galanin in the DMH may regulate the feeding downstream of PACAP in the VMH.

Auricular Acupressure Effect on Autonomic Responses Evoked by a Cold Pressor Test in Healthy Volunteers: A Pilot Study.

Objective: This pilot study was conducted to investigate changes in the pulse rate and blood pressure in healthy volunteers after applying auricular acupressure at the "heart acupoint." Methods: A total of 120 healthy volunteers with hemodynamic indexes within normal limits were randomly allocated into 4 groups to receive auricular acupressure treatment either at the heart acupoint of the left or the right, or in both ears, and one control group without applying auricular acupressure. Results: Before the application of auricular acupressure, there were no statistical differences in pulse rate and blood pressure increments among the four groups during the first cold pressor test. In groups in which auricular pressure was applied, the pulse rate was significantly reduced after the application of auricular acupressure in three groups; however, no statistically significant difference was detected among the groups. Changes in blood pressure were not statistically significant in or among the different groups after applying auricular acupressure. The average recorded pulse rate values during the second cold pressor test (after auricular acupressure) were significantly lower compared to the corresponding values taken during the first cold pressor test (before auricular acupressure) (p < 0.05); however, pulse rate increments during the two cold pressor tests (with and without auricular acupressure) were similar (p > 0.05). Conclusions: These findings suggest that auricular acupressure could be used as an adjunctive nonpharmacological method for reducing the pulse rate.

Immune responses and acute inflammation in common carp Cyprinus carpio injected by E.coli lipopolysaccharide (LPS) as affected by dietary oils.

Eicosanoids, resolvins, and lipoxins formed from long-chain polyunsaturated fatty acids (LC-PUFAs) are the main lipid mediators in the inflammatory processes explaining the influence of dietary lipid sources on the immune system. The current study aimed to determine the effects of dietary plant oils instead of fish oil or LC-PUFA supplementation in these oils on fish immune and inflammatory responses under normal and LPS-stimulated conditions. Six iso-nitrogenous (ranging from 30.4 to 31.1%) and iso-lipidic (from 11.2 to 11.6%) diets were formulated using three oil sources: cod liver oil (CLO, as fish oil control); linseed oil (LO, rich in α-linolenic acid, ALA); sesame oil (SO, rich in linoleic acid, LA); a blend of LO and SO (SLO, v:v 1:1); and two pure plant oil diets supplemented with docosahexaenoic acid, DHA (SO + DHA, SOD) or arachidonic acid, ARA (LO + ARA, LOA). Fish were fed the experimental diets to satiation for 42 days. On day 43, they were injected with E.coli lipopolysaccharide (LPS) at 100 µg/fish. Fish plasma and tissues such as head kidney and liver were collected on day 42 and one day after LPS injection (day 44) for humoral immune variables and gene expression analyses, respectively. After 42 days of feeding, no influences of dietary oils were found on fish survival, growth, feed utilization, and humoral immune responses. On the other hand, LPS injection significantly stimulated immune responses and induced an acute inflammation in common carp through an increase of the complement activity and the up-regulation of genes involved in the innate immune system (c2), pro-inflammatory response (tlr-4, tnf-α, il-1, il-6, il-8, and cxc), eicosanoid metabolism (pla2, cox-1, 5-lox, and pge2), and anti-inflammatory response (tgf-ß1 and nf-fki). Further, the expression of hsp70 was stimulated by LPS injection. The effects of dietary oil sources were observed after LPS injection, with a significant modification in the expression of almost all candidate genes. The highest pro-inflammatory responses induced by LPS were observed in CLO-fed fish while the mixture of plant oils (SLO) and LC-PUFA-supplemented diets induced significantly higher modulations in anti-inflammatory responses (il-10 and nf-kbi), general stress status (hsp70), and cytoprotection (gpx-1) compared to fish oil control and other pure plant oil groups. In conclusion, the immune response of common carp has been modified by the dietary fat sources. The fish oil-based diet supported an increase of the pro-inflammatory responses while the mixture of plant oil or LC-PUFA supplemented diets improved the anti-inflammatory responses and cytoprotection.

Application of multivariate linear regression models for selection of deep eutectic solvent for extraction of apigenin and luteolin from Chrysanthemum indicum L.

INTRODUCTION: Among a variety of compounds presented in chrysanthemum, apigenin and luteolin are the two main components that play a major role in numerous biological activities of this herb. OBJECTIVES: We aimed to obtain linear models showing the dependence of the yield of extraction of apigenin and luteolin on the composition of deep eutectic solvent and investigate the extraction of these two ingredients from Chrysanthemum indicum L. METHODS: Two models showing the dependence of luteolin and apigenin concentrations on the composition of the solvent were established using a multilinear regression algorithm and were applied to screen 119 different solvents. After that, the extraction process was optimized using response surface methodology and an artificial neural network. Apigenin and luteolin were recovered from the extract by the combination of distillation and addition of water. RESULTS: The screening results on 119 solvents revealed that choline chloride-acetic acid (1:4) was the most suitable deep eutectic solvent. It was showed that both response surface methodology and the artificial neural network could accurately determine the optimal conditions of extraction of apigenin and luteolin from C. indicum L., including time of extraction (65 minutes), temperature of extraction (90°C) and water content (20%). By the combination of distillation and addition of water, apigenin and luteolin could be effectively recovered from the deep eutectic solvent extract with a recovery rate of over 80%. CONCLUSIONS: Deep eutectic solvent could be used as an effective green alternative to the conventional solvents for the extraction of bioactive compounds from plants.

Anti-inflammatory norclerodane diterpenoids and tetrahydrophenanthrene from the leaves and stems of Dioscorea bulbifera.

Chemical investigation of the leaves and stems of Dioscorea bulbifera resulted in isolation of 10 compounds, including three new norclerodane diterpenoids, diosbulbiferins A (1) and B (2) and diosbulbiferinoside A (3), and one new natural congener, diosbulbiferin C (4), along with one new tetrahydrophenanthrene, diosbulbinone (8). Their structures were elucidated by comprehensive analyses of spectroscopic methods, including NMR and mass spectra. The absolute configurations of compounds 1-3 and 8 were deduced by time-dependent density functional theory (TD-DFT) electronic circular dichroism (ECD) spectroscopic analyses. In addition, cytotoxic effects against MCF-7, HepG2, and SK-Mel-2 cancer cells and in vitro anti-inflammatory effects of the isolated compounds in LPS-stimulated BV2 microglial cells were also reported.

Efficacy of Two Regimens for Colon Cleansing Using Polyethylene Glycol 4000: A Randomized Open Label Trial.

AIM: To compare effectiveness, safety and tolerance of two colon cleansing regimens using polyethylene glycol 4000 (PEG) in children. METHODS: Prospective, randomized, open clinical trial carried out in 129 children, 3 to 18 years old undergoing colonoscopy. Patients were randomized into two groups, 64 children received PEG with electrolyte (50 mL/kg) and oral bisacodyl (PEG+B group) or 65 other children received PEG with electrolyte (70 mL/kg) and glycerol enema (PEG+G group). RESULTS: Both regimens showed a good colon cleansing effectiveness with the percentage of successful cleansing being 93.8% for PEG+B regimen and 89.1% for PEG+G regimen (P=0.51). There was no statistically significant difference between the pre-regimen and post-regimen laboratory values. The rates of nausea (65.6% vs 31.3%; P<0.001) and bloating (50% vs 17.2%; P<0.001) of PEG+G group were significantly higher than that of PEG+B group. CONCLUSION: Both regimens had good efficacy and safety for colon cleansing in children. The tolerance of PEG+B regimen was better.

Pretreatment with 6-Gingerol Ameliorates Sepsis-Induced Immune Dysfunction by Regulating the Cytokine Balance and Reducing Lymphocyte Apoptosis.

Sepsis is characterized by an initial net hyperinflammatory response, followed by a period of immunosuppression, termed immunoparalysis. During this immunosuppressive phase, patients may have difficulty eradicating invading pathogens and are susceptible to life-threatening secondary hospital-acquired infections. Due to progress in antimicrobial treatment and supportive care, most patients survive early sepsis. Mortality is more frequently attributed to subsequent secondary nosocomial infections and multiorgan system failure. 6-Gingerol is the major pharmacologically active component of ginger. Although it is known to exhibit a variety of biological activities, including anti-inflammation and antioxidation, the role of 6-gingerol in sepsis-induced immune dysfunction remains elusive. Thus, we investigated whether 6-gingerol improves septic host response to infections during sepsis. 6-Gingerol-treated mice showed significantly lower mortality in polymicrobial sepsis induced by cecal ligation and puncture LPS via enhanced bacterial clearance in the peritoneum, blood, and organs (liver, spleen, and kidney) and inhibited the production of TNF-α and IL-6 in TLR2 and/or TLR4-stimulated macrophages. In addition, we demonstrated that survival improvement of secondary infection following septic insult was associated with an initial response of enhanced neutrophil numbers and function at the infection site, reduced apoptosis of immune cells, and a shift from a T helper cell type 2 (Th2) to a T helper cell type 1 (Th1) cytokine balance in the hypoinflammation phase. Our overall findings suggest that 6-gingerol potentially restores sepsis-induced immune dysfunction by shifting the balance of Th1/Th2 and by regulating apoptosis of immune cells.

29-Norlupane-1ß-hydroxy-3,20-dione, a new norlupane triterpenoid from the twigs and leaves of Phyllanthus acidus.

A new norlupane triterpenoid, 29-norlupane-1ß-hydroxy-3,20-dione (1), along with ten known compounds, 29-norlup-1-ene-3,20-dione (2), phyllanthol (3), phyllanthone (4), glochidone (5), lupeol (6), lupeone (7), 4-hydroxybenzoic acid (8), 4-hydroxybenzaldehyde (9), phyllane A (10) and methyl ß-orsellinate (11) were isolated the twigs and leaves of Phyllanthus acidus. The structure of 1 was identified by interpretation of their spectroscopic data and comparison with those reported in the literature. In addition, all isolated compounds 1-11 were evaluated for their antioxidant activity.

Pro- and anti-inflammatory responses of common carp Cyprinus carpio head kidney leukocytes to E.coli LPS as modified by different dietary plant oils.

Dietary lipids could modify fatty acid (FA) composition in fish tissues. Long chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid (ARA), eicosapentaneoic acid (EPA) and docosahexaenoic acid (DHA) are able to modulate the immune status in fish through an inflammatory process but their availability may be limited when fish are exclusively fed plant oils. This study was conducted to evaluate how to maximise the utilisation of dietary plant oil for an efficient inflammatory response in common carp head kidney leukocytes (HKLs) exposed to a gram-negative bacterial endotoxin, Escherichia coli lipopolysaccharides (LPS). HKLs were isolated from fish fed cod liver oil (CLO), linseed oil (LO), sesame oil (SO) a blend of SO and LO (SLO, v:v 1:1), and these plant oil diets supplemented with DHA (SO + DHA, SOD) or ARA (LO + ARA, LOA) for 6 weeks. Cells were then exposed to LPS at a dose of 10 µg/mL for 4 and 24 h. Peroxidase activity, total Ig, and NO levels were measured in the culture medium, while cells were used for expression analyses of candidate genes in pattern recognition (tlr-4), eicosanoid metabolism (pge2, 5-lox), pro-inflammatory (il-1, il-6, il-8, tnf-α, nf-kb, inos, cxc), anti-inflammatory (il-10, nf-kbi, tgf-ß1) responses, and cytoprotective (gpx-1, prdx-3) processes. Results showed that LPS induced significantly inflammatory responses, evidenced by a high level of almost all the targeted humoral immune parameters and/or gene expression. Expression of inflammatory cytokines and other inflammatory mediators was upregulated after 4 h-LPS exposure and reverted to basal levels after 24 h. HKLs from fish fed SLO, LOA, or SOD diet exhibited a more efficient regulation of acute inflammatory processes than those fed CLO diet. The results indicate that the immune competence of fish fed plant oil mixture was comparable to the one of fish fed fish oil diet. Moreover, the supplementation of ARA or DHA induced similar immunomodulation in common carp.

Provider Perspectives on Integration of Substance Use Disorder and HIV Care in Vietnam: A Qualitative Study.

UNAIDS recommends integration of medications for substance use disorders (SUD) with HIV care to improve HIV outcomes. Yet, integration of HIV and SUD services remains limited in many countries. The objective of this study was to assess provider perceptions of care integration in Vietnam. Qualitative interviews were conducted with 43 providers (nurses, physicians, counselors, pharmacists, and clinic managers) in 8 HIV clinics in northern Vietnam, 2013-2015. Providers identified five themes informing HIV and SUD treatment integration: (1) treatment for alcohol use disorder is often neglected compared to other SUD treatment; (2) structural challenges must be addressed to increase integration feasibility; (3) workforce limitations; (4) societal and healthcare stigmatization of SUD; and (5) providers' conflicting views regarding integration challenges. The experience of providers in Vietnam may be useful to other countries attempting to integrate HIV and SUD services.