Regional Variation of Erythropoiesis-Stimulating Agent Hyporesponsiveness in the Global Daprodustat Dialysis Study (ASCEND-D).

INTRODUCTION: Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) affects 10-15% of the chronic dialysis population. We explored baseline characteristics and predictors of ESA hyporesponsiveness in a global randomized cardiovascular outcomes study comparing an investigational hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), daprodustat, with conventional ESA treatment. METHODS: ASCEND-D (NCT02879305) recruited 2,964 chronic dialysis patients receiving ESA treatment (standardized to weekly intravenous [IV] epoetin) who were iron replete at baseline. The primary ESA hyporesponsiveness definition was an ESA Resistance Index (ERI, ESA units/kg/week/hemoglobin g/L) ≥2 or IV standardized ESA dose ≥450 units/kg/week. Predictors of ESA hyporesponsiveness were determined using a multivariable regression model. Alternative hyporesponder definitions were explored. RESULTS: Using the primary definition, 354 (12%) patients were ESA hyporesponsive. Geographic region, notably Latin America, lower baseline body mass index and transferrin saturation, younger age, lower albumin concentration, and a higher baseline IV iron dose were identified as strongly associated (p < 0.001) with ESA hyporesponsiveness. Additional predictors of ESA hyporesponsiveness included female sex (p = 0.010), history of heart failure (p = 0.035), longer dialysis vintage (p = 0.077), smoking status (p = 0.247), aspirin use (p = 0.121), and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use (p = 0.214). CONCLUSION: This is the first global HIF-PHI study to report prespecified definitions and predictors of ESA hyporesponsiveness. While most of the predictors identified in our study have been previously reported, geographic region stands out as an unexpected finding, meriting further investigation.

Integration of agricultural residues as biomass source to saccharification bioprocess and for the production of cellulases from filamentous fungi.

The production of second-generation bioethanol has several challenges, among them finding cheap and efficient enzymes for a sustainable process. In this work, we analyzed two native fungi, Cladosporium cladosporioides and Penicillium funiculosum, as a source of cellulolytic enzyme production, and corn stover, wheat bran, chickpeas, and bean straw as a carbon source in two fermentation systems: submerged and solid fermentation. Corn stover was selected for cellulase production in both fermentation systems, because we found the highest enzymatic activities when carboxymethyl cellulase activity (CMCase) was assessed using CMC as substrate. C. cladosporioides showed the highest CMCase activity (1.6 U/mL), while P. funiculosum had the highest filter paper activity (Fpase) (0.39 U/mL). The ß-glucosidase activities produced by both fungi were similar in submerged fermentation using corn stover as substrate. Through in-gel zymography, three polypeptides with cellulolytic activities were identified in each fungus: with molecular weights of ~ 38, 45 and 70 kDa in C. cladosporioides and ~ 21, 63 and 100 kDa in P. funiculosum. The best results for saccharification (10.11 g/L of reducing sugars) of diluted acid pretreated corn stover were obtained after 36 h of the hydrolytic process at pH 5 and 50 °C using the enzyme extract of P. funiculosum. This is the first report of cellulase identification in C. cladosporioides and the saccharification of corn stover using enzymes of this fungus. Enzymatic extracts of C. cladosporioides and P. funiculosum obtained from low-cost lignocellulosic biomass have great potential for use in the production of second-generation bioethanol.

Phenolic composition of tomato varieties and an industrial tomato by-product: free, conjugated and bound phenolics and antioxidant activity.

The aim of this study was to isolate, identify and quantify soluble free phenolics, conjugated acid-hydrolysable phenolics (AHP) and alkaline-hydrolysable phenolics, and bound phenolics (BP) fractions from two tomato varieties (saladette and grape) and an industrial tomato by-product, as well as, to determine their antioxidant capacity. Phenolic composition was determined using Folin-Ciocalteu's method and HPLC-DAD. AHP were predominant in grape and saladette tomato extracts (91.47 ± 17.28 mg gallic acid equivalents (GAE) per g dry extract (DE) and 57.41 ± 8.80 mg GAE per g DE, respectively), while BP form was predominant in tomato by-product (51.30 ± 10.91 GAE per g DE). AHP extract of grape tomato presented the highest antioxidant capacity by DPPH assay (252.35 ± 42.55 µmol trolox equiv (TE) per g DE). In the case of ORAC assay, AHP fractions from both grape (1005.19 ± 138.52 µmol TE per g DE) and saladette tomatoes (804.16 ± 131.45 µmol TE per g DE), and BP fraction from by-product (852.40 ± 71.46 µmol TE per g DE) showed the highest ORAC values. Caffeic acid was the most abundant phenolic acid and it was found mainly in its conjugated forms. Naringenin was the most abundant flavonoid and it was mainly detected in bound form. Our analysis allowed a better characterization of phenolic compounds in whole tomato and by-product, remarking the importance of the fractionation. The valorization of the industrial tomato by-product, through the use of its different fractions of phenolic antioxidant compounds, could generate additional income to the tomato industry and reduce the waste disposal problem.

Bioactive compounds and antioxidant activity in scalded Jalapeño pepper industrial byproduct (Capsicum annuum).

Bioactive compounds and antioxidant activity were evaluated from industrial Jalapeño pepper byproducts and simulated non processed byproducts from two Mexican states (Chihuahua and Sinaloa) to determine their value added potential as commercial food ingredients. Aqueous 80% ethanol produced about 13% of dry extract of polar compounds. Total phenolic content increased and capsaicin and dihydrocapsaicin decreased on scalding samples (80 °C, 2 min) without affecting ascorbic acid. The major phenolic compounds, rutin, epicatechin and catechin comprised 90% of the total compounds detected by HPLC of each Jalapeño pepper byproducts. ORAC analysis showed that the origin and scalding process affected the antioxidant activity which correlated strongly with capsaicin content. Although scalding decreased capsaicinoids (up to 42%), phenolic content by (up to 16%), and the antioxidant activity (variable). Jalapeño pepper byproduct is a good source of compounds with antioxidant activity, and still an attractive ingredient to develop useful innovative products with potential food/non-food applications simultaneously reducing food loss and waste.

Phenolic content and antioxidant and antimutagenic activities in tomato peel, seeds, and byproducts.

The phenolic content and antioxidant and antimutagenic activities from the peel and seeds of different tomato types (grape, cherry, bola and saladette type), and simulated tomato industrial byproducts, were studied. Methanolic extracts were used to quantify total phenolic content, groups of phenolic compounds, antioxidant activities, and the profile of phenolic compounds (by HPLC-DAD). Antimutagenic activity was determined by Salmonella typhimurium assay. The total phenolic content and antioxidant activity of tomato and tomato byproducts were comparable or superior to those previously reported for whole fruit and tomato pomace. Phenolic compounds with important biological activities, such as caffeic acid, ferulic acid, chlorogenic acids, quercetin-3-ß-O-glycoside, and quercetin, were quantified. Differences in all phenolic determinations due to tomato type and part of the fruit analyzed were observed, peel from grape type showing the best results. Positive antimutagenic results were observed in all samples. All evaluated materials could be used as a source of potential nutraceutical compounds.

Mercado y actividad físico-deportiva: la salud y la apariencia física como valores de cambio / Mercado e atividade física esportiva: a saúde e a aparência física como valores de mudança / The market, sports, and physical activity: health and physical appearance as values of exchange

En este trabajo se analiza la influencia que ejerce el mercado en la actividad físico-deportiva, misma que en la actualidad aparece asociada con una mayor atención sobre el cuerpo. Evidencias documentales y empíricas muestran que a través de la actividad físico-deportiva, el mercado impone, entre otros aspectos, las ventajas de la apariencia legítima dirigidas a fortalecer las relaciones interpersonales y la supremacía del atractivo físico como parámetro de aceptabilidad social y como medida del valor de cambio entre los individuos.

In this paper we analyzed the influence of the market in physical activity and sport, which currently appears associated with greater attention to the human body. Document analysis and empirical evidence show that through physical activity and sport, the market asserts the advantages of an ideal/legitimate appearance for strengthening interpersonal relationships and for advancing the supremacy of physical attractiveness both as a parameter of social acceptability and a measure of value of exchange between individuals.

Este trabalho analisa a influência que exerce o mercado na atividade física esportiva, mesmo que na atualidade apareça associada como uma atenção destinada ao corpo. Evidências documentadas e empíricas mostram que através da atividade física esportiva o mercado impõe entre outros aspectos, vantagens da aparência legítima dirigida ao fortalecimento das relações interpessoais e supremacia do atrativo físico, como parâmetro de aceitação social e como medida de valor de transformação entre os indivíduos.

Modification of the amaranth 11S globulin storage protein to produce an inhibitory peptide of the angiotensin I converting enzyme, and its expression in Escherichia coli.

Amarantin is the predominant seed storage protein from amaranth. It shows a high content of essential amino acids, making this protein important from a nutritional viewpoint. The protein has two disulfide linked subunits: acidic and basic. Acidic subunit has the potential as a functional and nutraceutical protein, and it is structurally a good candidate for modification. In order to improve its functionality, the primary structure was modified in the third variable region of globulins 11S, by inserting four Val-Tyr antihypertensive peptides in tandem. The designed plasmid was expressed in Escherichia coli Origami (DE3) and then the expressed protein was purified. Mass spectrometry analysis was used to corroborate the identity of the protein by peptide mass fingerprinting; also, the modified peptide was fragmented and sequenced by mass spectrometry, corroborating thus the inserted residues. The hydrolyzed protein showed a high inhibitory activity of the angiotensin converting enzyme (IC(50) 0.064 mg ml(-1)); it was nearly eightfold more active than the nonmodified protein. In spite that the nonmodified subunit is less active, its activity is comparable with other hydrolyzed proteins reported as high active inhibitors. The expressed and purified subunit after its engineered modification, may be useful for preventing hypertension and for other medical purposes.

One-step purification and structural characterization of a recombinant His-tag 11S globulin expressed in transgenic tobacco.

Amarantin, an 11S globulin, is one of the most important storage proteins of amaranth seeds, with relevant nutritional-functional and nutraceutical characteristics. Its cDNA was cloned in-frame with a sequence encoding a polyhistidine tag and expressed under the direction of a 35S promoter in transgenic tobacco seeds. The presence of a (His)(6) tag on the polypeptide permitted a high-yield single-step purification using immobilized metal-ion affinity chromatography and rapid characterization. Purified His-tag amarantin accounted for up to 5% of total soluble seed protein. Biochemical characterization indicated that purified His-tag amarantin migrated with the expected molecular weight (53 kDa) and was correctly processed into an acidic polypeptide (32 kDa) with isoelectric point (pI) of 5.58 and a basic polypeptide (21 kDa) with pI of 9.24, linked by a disulfide bridge. Moreover, His-tag amarantin was assembled into both homo- and hetero-hexameric 11S structures. These results show that the His tag did not change the biochemical and physicochemical properties of amarantin. The strategy presented here for rapid and high-yield expression and purification procedure should facilitate structure-function studies for this nutritional protein.