Crosstalk between Heme Oxygenase-1 and Iron Metabolism in Macrophages: Implications for the Modulation of Inflammation and Immunity.

Heme oxygenase-1 (HO-1) is an enzyme that catalyzes the degradation of heme, releasing equimolar amounts of carbon monoxide (CO), biliverdin (BV), and iron. The anti-inflammatory and antioxidant properties of HO-1 activity are conferred in part by the release of CO and BV and are extensively characterized. However, iron constitutes an important product of HO-1 activity involved in the regulation of several cellular biological processes. The macrophage-mediated recycling of heme molecules, in particular those contained in hemoglobin, constitutes the major mechanism through which living organisms acquire iron. This process is finely regulated by the activities of HO-1 and of the iron exporter protein ferroportin. The expression of both proteins can be induced or suppressed in response to pro- and anti-inflammatory stimuli in macrophages from different tissues, which alters the intracellular iron concentrations of these cells. As we discuss in this review article, changes in intracellular iron levels play important roles in the regulation of cellular oxidation reactions as well as in the transcriptional and translational regulation of the expression of proteins related to inflammation and immune responses, and therefore, iron metabolism represents a potential target for the development of novel therapeutic strategies focused on the modulation of immunity and inflammation.

Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis?

Multiple sclerosis is an autoimmune treatable but not curable disease. There are a multiplicity of medications for multiple sclerosis therapy, including a class entitled disease-modifying drugs that are mainly indicated to reduce the number and severity of disease relapses. Not all patients respond well to these therapies, and minor to severe adverse effects have been reported. Vitamin D, called sunshine vitamin, is being studied as a possible light at the end of the tunnel. In this review, we recapitulated the similar immunopathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis, the immunomodulatory and neuroprotective potential of vitamin D and the state-of-art concerning its supplementation to multiple sclerosis patients. Finally, based on our and other groups' experimental findings, we analyzed the need to consider the relevance of the route and the different time-point administration aspects for a more rational indication of this vitamin to multiple sclerosis patients.

Volatile profiling and UHPLC-QqQ-MS/MS polyphenol analysis of Passiflora leschenaultii DC. fruits and its anti-radical and anti-diabetic properties.

Twenty-four phenolic compounds including daidzein, epicatechin and artepillin C were identified in Passiflora leschenaultii DC. fruit by UHPLC-QqQ-MS/MS analysis. The aroma profile has been studied using the HS-SPME/GC-MS which revealed 67 volatile compounds including 13 terpenes, 18 alcoholics, 15 esters, ketones and phenolic acids. Further, the proximate composition, anti-radical and anti-diabetic activities of fruit pulp were also determined. The fresh fruit pulp of P. leschenaultii registered higher total phenolic (691.90 mg GAE/g extract) and tannin (313.81 mg GAE/g extract) contents and it also exhibited maximum DPPH (IC50 of 6.69 µg/ml) and ABTS+ (9760.44 µM trolox equivalent/g extract) scavenging activities. The fresh fruit pulp showed a strong inhibition towards the α-Amylase and α-Glucosidase (IC50 of 32.20 and 19.81 µg/mL, respectively) enzymes. Thus, the work stipulates that phenolic compounds rich P. leschenaultii fruit can serve as a potential nutraceutical, antioxidative and anti-diabetic agent in food and pharmaceutical formulations.

Chemical characterization of four Brazilian brown propolis: An insight in tracking of its geographical location of production and quality control.

The aim of this work was to undertake a detailed analysis on chemical constituents of brown propolis, originating from four different states (Bahia, Minas Gerais, Paraná and Sergipe) of Brazil. The volatile profile was determined by using HS-SPME-GC-MS along with the determination of total phenolic compounds content, flavonoids and antioxidant activity. A total of 315 volatile compounds were identified, however, several of them have not been reported so far in the Brazilian brown propolis. The terpenes represented the major class with 40.92-84.66% of the total area in the chromatograms. PCA analysis of the majority of compounds successfully indicated the volatile profile of each propolis sample according to their geographical origin. The analysis of volatile compounds and its characterization also varied significantly and confirmed that these depended on the geographical area of collection of propolis. The data generated in this work may help in establishing criteria for quality control and tracking the specific region of propolis production in different states of Brazil.

Electrochemical degradation of the antibiotic ciprofloxacin in a flow reactor using distinct BDD anodes: Reaction kinetics, identification and toxicity of the degradation products.

The performances of distinct BDD anodes (boron doping of 100, 500 and 2500 ppm, with sp3/sp2 carbon ratios of 215, 325, and 284, respectively) in the electrochemical degradation of ciprofloxacin - CIP (0.5 L of 50 mg L-1 in 0.10 M Na2SO4, at 25 °C) were comparatively assessed using a recirculating flow system with a filter-press reactor. Performance was assessed by monitoring the CIP and total organic carbon (TOC) concentrations, oxidation intermediates, and antimicrobial activity against Escherichia coli as a function of electrolysis time. CIP removal was strongly affected by the solution pH (kept fixed), flow conditions, and current density; similar trends were obtained independently of the BDD anode used, but the BDD100 anode yielded the best results. Enhanced mass transport was achieved at a low flow rate by promoting the solution turbulence within the reactor. The fastest complete CIP removal (within 20 min) was attained at j = 30 mA cm-2, pH = 10.0, and qV = 2.5 L min-1 + bypass turbulence promotion. TOC removal was practically accomplished only after 10 h of electrolysis, with quite similar performances by the distinct BDD anodes. Five initial oxidation intermediates were identified (263 ≤ m/z ≤ 348), whereas only two terminal oxidation intermediates were detected (oxamic and formic acids). The antimicrobial activity of the electrolyzed CIP solution was almost completely removed within 10 h of electrolysis. The characteristics of the BDD anodes only had a marked effect on the CIP removal rate (best performance by the least-doped anode), contrasting with other data in the literature.

Optimization of the electrochemical degradation process of the antibiotic ciprofloxacin using a double-sided ß-PbO2 anode in a flow reactor: kinetics, identification of oxidation intermediates and toxicity evaluation.

The electrochemical degradation of ciprofloxacin-CIP (50 mg L-1 in 0.10 mol L-1 Na2SO4) was investigated using a double-sided Ti-Pt/ß-PbO2 anode in a filter-press flow reactor, with identification of oxidation intermediates and follow-up of antimicrobial activity against Escherichia coli. The effect of solution pH, flow rate, current density, and temperature on the CIP removal rate was evaluated. All of these parameters did affect the CIP removal performance; thus, optimized electrolysis conditions were further explored: pH = 10, qV = 6.5 L min-1, j = 30 mA cm-2, and θ = 25 °C. Therefore, CIP was removed within 2 h, whereas ~75% of the total organic carbon concentration (TOC) was removed after 5 h and then, the solution no longer presented antimicrobial activity. When the electrochemical degradation of CIP was investigated using a single-sided boron-doped diamond (BDD) anode, its performance in TOC removal was similar to that of the Ti-Pt/ß-PbO2 anode; considering the higher oxidation power of BDD, the surprisingly good comparative performance of the Ti-Pt/ß-PbO2 anode was ascribed to significantly better hydrodynamic conditions attained in the filter-press reactor used with this electrode. Five initial oxidation intermediates were identified by LC-MS/MS and completely removed after 4 h of electrolysis; since they have also been determined in other degradation processes, there must be similarities in the involved oxidation mechanisms. Five terminal oxidation intermediates (acetic, formic, oxamic, propionic, and succinic acids) were identified by LC-UV and all of them (except acetic acid) were removed after 10 h of electrolysis.

Effect of freeze- and spray-drying on physico-chemical characteristics, phenolic compounds and antioxidant activity of papaya pulp.

The effect of freeze- and spray-drying on physico-chemical characteristics, phenolics compounds and antioxidant activity of papaya pulp was investigated. The frozen pulp was freeze dried at - 62 °C during 48 h. Papaya pulp with 14% DE maltodextrin was also dried in a spray dryer. The organic acids, sugars, color, total soluble solids, pH, carotenoids, phenolic and flavonoid compounds, and antioxidant capacity values were determined. The changes in color, pH and lycopene were negligible. However, lower retention (86.5%) of vitamin C and sugars (glucose-79.7% and fructose-66.1%) was observed in spray dried products. Phenolic and flavonoid compounds were identified and quantified in dried papaya products by UHPLC-QqQ-MS/MS. Spray dried products presented a higher retention of phenolic and flavonoid compounds compared to the freeze dried products. Despite some variations in the parameters studied, the use of freeze- and spray-drying has proven viable options for the drying of papaya pulp.

Development and characterization of microencapsules containing spray dried powder obtained from Brazilian brown, green and red propolis.

The aim of this study was to obtain dried powders from the brown, green and red varieties of the Brazilian propolis by spray drying, using gum arabic and maltodextrin as encapsulating materials. Propolis microparticles were evaluated for particle size, X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), moisture, water activity, solubility, hygroscopicity, encapsulation efficiency, total phenolic content, flavonoids and antioxidant activity (DPPH, ABTS+, FRAP, ORAC). Bioactive compounds were determined by UPHLC-QqQ-MS/MS. The results showed that the microparticles presented spherical forms, smooth surfaces, amorphous characteristics, low water activity, moisture and hygroscopicity, high solubility, good encapsulation efficiency, good antioxidant activity, although a reduction in total phenolics and flavonoids from the non-encapsulated propolis. The most important compounds in propolis powders were artepillin C, kaempferide, p-coumaric acid, luteolin, chlorogenic acid, kaempferol and caffeic acid. Spray-drying of propolis is a viable option to increase its use in food and pharmaceutical applications.

UHPLC-QqQ-MS/MS identification, quantification of polyphenols from Passiflora subpeltata fruit pulp and determination of nutritional, antioxidant, α-amylase and α-glucosidase key enzymes inhibition properties.

The diabetic key enzymes inhibition, nutritional, antioxidant activity and bioactive compounds identification of Passiflora subpeltata fruit pulp were investigated. Fifteen polyphenolic compounds including protocatechuic acid, ferulic acid, vanillic acid, epicatechin, p-coumaric acid, cinnamic acid, eriodictyol and quercetin-3-glucoside were identified in the pulp of this species by using UHPLC-QqQ-MS/MS analysis. The total carbohydrates and crude protein contents in fruit pulp were 2.62 mg glucose equivalent/g sample fruit pulp and 8.80 mg BSA equivalent/g sample fruit pulp, respectively. The fresh fruit pulp of P. subpeltata contained high total phenolic (724.76 mg GAE/g sample) content and it revealed very high DPPH• (IC50 of 5.667 µg/mL) and ABTS+• (6794.96 µM trolox equivalent/g sample) scavenging activities. In the key enzymes assays useful for diabetic inhibition the fresh fruit pulp characterized maximum inhibition of α-amylase and α-glucosidase IC50 of 18.69 and 32.63 µg/mL, respectively. Thus, these results lead to conclude that this fruit specie could be very useful source in nutraceutical products preparations for Type 2 diabetic suffering humans.

Evidence of insulin-dependent signalling mechanisms produced by Citrus sinensis (L.) Osbeck fruit peel in an insulin resistant diabetic animal model.

Citrus sinensis (L.) Osbeck is extensively cultivated worldwide and one of the most consumed fruits in the world. We evaluated the therapeutic properties of the methanol extract from Citrus sinensis fruit peel (CSMe) in high-fat diet-fed streptozotocin-induced insulin-resistant diabetic rats. Body weight, food intake, and water consumption were analysed. Biochemical and molecular biologic indices, and the expression of insulin receptor-induced signalling molecules were assessed to identify possible mechanisms. In addition, we conducted histology of pancreatic and adipose tissues. UHPLC-MS/MS analysis showed the presence of 17 dietary phenolics at substantial concentrations. High-fat diet-fed streptozotocin-induced diabetic rats administered CSMe (50 and 100 mg/kg) had reduced fasting blood glucose (56.1% and 55.7%, respectively) and plasma insulin levels (22.9% and 32.7%, respectively) compared with untreated diabetic control rats. CSMe reversed the biochemical abnormalities in diabetic rats, showed cytoprotective activity, and increased the intensity of the positive immunoreactions for insulin in pancreatic islets. CSMe treatment increased the expression of PPARγ in the adipose tissue and signalling molecules GLUT4 and insulin receptor. Our data suggest that CSMe could optimize glucose uptake of adipose tissues through the insulin-dependent signalling cascade mechanism and it should be investigated in the management of individuals with type 2 diabetes mellitus.

Toward sustainable environmental quality: Identifying priority research questions for Latin America.

The Global Horizon Scanning Project (GHSP) is an innovative initiative that aims to identify important global environmental quality research needs. Here we report 20 key research questions from Latin America (LA). Members of the Society of Environmental Toxicology and Chemistry (SETAC) LA and other scientists from LA were asked to submit research questions that would represent priority needs to address in the region. One hundred questions were received, then partitioned among categories, examined, and some rearranged during a workshop in Buenos Aires, Argentina. Twenty priority research questions were subsequently identified. These research questions included developing, improving, and harmonizing across LA countries methods for 1) identifying contaminants and degradation products in complex matrices (including biota); 2) advancing prediction of contaminant risks and effects in ecosystems, addressing lab-to-field extrapolation challenges, and understanding complexities of multiple stressors (including chemicals and climate change); and 3) improving management and regulatory tools toward achieving sustainable development. Whereas environmental contaminants frequently identified in these key questions were pesticides, pharmaceuticals, endocrine disruptors or modulators, plastics, and nanomaterials, commonly identified environmental challenges were related to agriculture, urban effluents, solid wastes, pulp and paper mills, and natural extraction activities. Several interesting research topics included assessing and preventing pollution impacts on conservation protected areas, integrating environment and health assessments, and developing strategies for identification, substitution, and design of less hazardous chemicals (e.g., green chemistry). Finally, a recurrent research need included developing an understanding of differential sensitivity of regional species and ecosystems to environmental contaminants and other stressors. Addressing these critical questions will support development of long-term strategic research efforts to advance more sustainable environmental quality and protect public health and the environment in LA. Integr Environ Assess Manag 2018;14:344-357. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Evaluation of bioactive compounds potential and antioxidant activity in some Brazilian exotic fruit residues.

The agroindustrial residues have been recognized as important sources of some prominent chemical compounds and hence a viable strategy of obtaining bioactive compounds could be applied to them. The present study was aimed to investigate the presence of bioactive compounds and the antioxidant activity of some Brazilian exotic fruits (achachairu, araçá-boi, bacaba) residues. The antioxidant capacity of fruit residues was evaluated by ORAC, FRAP and ABTS assays. The contents of total phenolic compounds, flavonoids, chlorophylls and carotenoids were determined. The identification and quantification of the phenolic compounds were performed by using the UHPLC-QqQ-MS/MS system. The compounds cinnamic acid, p-coumaric acid, epicatechin and quercetin were identified and quantified in all fruits residues. The residue with the highest antioxidant capacity was bacaba for ORAC (15,285.51±20.38µmolTE/100g) and FRAP (16,916.37±10.01µmolTE/100g) assays, as well as total phenolic compounds in its methanolic extract (1537.45±73.35mgGAE/100g).

Evaluation of bioactive compounds potential and antioxidant activity of brown, green and red propolis from Brazilian northeast region.

The aim of the present study was to determine the contents of bioactive compounds present in brown, green and red species of propolis cultivated in the Brazilian northeast states of Alagoas and Sergipe. The contents of phenolic compounds, flavonoids and antioxidant activity (DPPH, ABTS+, FRAP, ORAC) were determined. Identification and quantification of phenolic and flavonoid compounds were performed by using UHPLC-QqQ-MS/MS system. The results revealed high contents of total phenolics and flavonoids. Among the three species, the antioxidant potential had higher capacity in the red propolis. The presence of some of bioactive compounds viz. acacetin, artepellin C, eriodictyol, gallic acid, isorhamnetin, protocatechuic acid, vanillin and vanillic acid in Brazilian red propolis is reported for the first time in this work. Positive correlation between total phenolics versus the FRAP and ORAC methods was established which led to conclusion that antioxidant activity of propolis is mainly due to its phenolic compounds.

Cytokines in the management of rotavirus infection: A systematic review of in vivo studies.

OBJECTIVE: Rotavirus is a leading cause of childhood diarrhoea. Rotavirus vaccines are effective against severe rotavirus gastroenteritis, but have lower efficacy in low income countries in Africa. Anti-rotavirus treatment is not available. This study reviews the literature of animal studies evaluating whether cytokine mediated pathways of immune activation could improve rotavirus therapy. METHODS: We performed a systematic review of articles in English published from 2010 to 2016 reporting agents with in vivo antirotavirus activity for the management of rotavirus infection. The search was carried in PubMed, EMBASE, Scopus and Web of Science. Animal experiments where cytokines were investigated to assess the outcome of rotavirus therapy were included. RESULTS: A total of 869 publications were identified. Of these, 19 pertained the objectives of the review, and 11 articles described the effect of probiotics/commensals on rotavirus infection and immune responses in animals. Eight further in vivo studies evaluated the immunomodulating effects of herbs, secondary metabolites and food-derived products on cytokine responses of rotavirus-infected animals. Studies extensively reported the regulatory roles for T-helper (Th)1 (interferon gamma (IFN-γ), interleukin (IL)-2, IL-12) and Th2 (IL-4, IL-6, IL-10) cytokines responses to rotavirus pathogenesis and immunity, inhibiting rotavirus infection through suppression of inflammation by viral inhibition. CONCLUSION: Th1 and Th2 cytokines stimulate the immune system, inhibiting rotavirus binding and/or replication in animal models. Th1/Th2 cytokine responses have optimal immunomodulating effects to reduce rotavirus diarrhoea and enhance immune responses in experimental rotavirus infection.

Simultaneous determination of fluoroquinolones in environmental water by liquid chromatography-tandem mass spectrometry with direct injection: A green approach.

This work describes an on-line multi-residue method for simultaneous quantification of ciprofloxacin, enrofloxacin, gemifloxacin, moxifloxacin, norfloxacin and ofloxacin in superficial and wastewater samples. For that, an octyl restricted-access media bovine serum albumin column (RAM-BSA C8) was used for sample clean-up, enrichment and analysis with quantitation carried out by tandem mass spectrometry. For water samples volumes of only 500µL the method provided good selectivity, extraction efficiency, accuracy, and precision with quantification limits in the order of 20-150ngL(-1). Out of the six fluoroquinolones only ciprofloxacin (195ngL(-1)) and norfloxacin (270ngL(-1)) were quantified in an influent sample of the wastewater treatment plant (WWTP) of São Carlos (SP, Brazil). None were found in the superficial water samples analyzed. The capability of injecting native sample in an automated mode provides high productivity and represents a greener approach in environmental sample analysis.

Enantiomeric resolution of albendazole sulfoxide by semipreparative HPLC and in vitro study of growth inhibitory effects on human cancer cell lines.

Analytical and semipreparative high performance liquid chromatography methods using polysaccharide-based chiral stationary phases were developed for the enantiomeric resolution of albendazol sulfoxide. The enantioseparation of this compound was evaluated with four chiral stationary phases: cellulose and amylose tris(3,5-dimethylphenylcarbamate), amylose tris[(S)-1-phenylethylcarbamate] and amylose tris(3,5-dimethoxyphenylcarbamate), under three elution conditions: normal, reversed-phase and polar organic mode. The influences of the mobile phase and of the structure of the chiral stationary phase on the enantiomeric separation are discussed. The best chiral performances were achieved on an amylose tris(3,5-dimethylphenylcarbamate) phase under normal (R(s)=4.96) and polar organic mode (R(s)=2.60 and 3.09). A polar organic condition using methanol as mobile phase offered shorter retention factors (k(1)=0.34) and was scaled up to semipreparative HPLC to obtain milligram quantities of both albendazole sulfoxide enantiomers for further in vitro studies. Optical rotation and circular dichroism of both enantiomers of albendazole sulfoxide was determined. The compounds ABZ, ABZ-SO, (R)-(+)-ABZ-SO and (S)-(-)-ABZ-SO were all evaluated regarding their capacity to inhibit the in vitro growth of three human tumor cell lines: MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma). In addition, the effect of the (R)-(+)-ABZ-SO compound in the cell cycle profile and apoptosis of MCF-7 cells were also studied. Results indicated that compound ABZ was the most potent regarding cell growth inhibition and that the (+)-(R)-ABZ was a more potent inhibitor of cell growth than the (S)-(-)-ABZ-SO, particularly in the MCF-7 cell line. In addition, the (R)-(+)-ABZ-SO significantly increased the levels of apoptosis of the MCF-7 cells.