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Salinity has a strong influence on microorganisms distribution patterns and consequently on the relevance of photoheterotrophic metabolism, which since the discovery of proteorhodopsins is considered the main contributor to solar energy capture on the surface of the oceans. Solar salterns constitute an exceptional system for the simultaneous study of several salt concentrations, ranging from seawater, the most abundant environment on Earth, to saturated brine, one of the most extreme, which has been scarcely studied. In this study, pigment composition across the salinity gradient has been analyzed by spectrophotometry and RP-HPLC, and the influence of salinity on microbial diversity of the three domains of life has been evaluated by a metataxonomic study targeting hypervariable regions of 16S and 18S rRNA genes. Furthermore, based on the chlorophyll a and retinal content, we have estimated the relative abundance of rhodopsins and photosynthetic reaction centers, concluding that there is a strong correlation between the retinal/chlorophyll a ratio and salinity. Retinal-based photoheterotrophy is particularly important for prokaryotic survival in hypersaline environments, surpassing the sunlight energy captured by photosynthesis, and being more relevant as salinity increases. This fact has implications for understanding the survival of microorganisms in extreme conditions and the energy dynamics in solar salter ponds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The prevalence of obesity increases alarmingly every year mostly due to external factors such as high-fat and high-refined sugar intake associated with a sedentary lifestyle. It triggers metabolic disorders such as insulin resistance, hyperlipemia, non-alcoholic fatty liver disease, chronic inflammation, oxidative stress, and gut microbiota dysbiosis. The aim of this study was to evaluate the beneficial effects of a combined intervention with caloric restriction, nutraceutical intake, and a mixed training protocol on oxidative stress, inflammation, and gut dysbiosis derived from the development of obesity in a C57BL6/J mouse experimental model of diet-induced obesity (4.6 Kcal/g diet, 45% Kcal as fat, and 20% fructose in the drinking fluid). The nutraceutical was formulated with ethanolic extracts of Argania spinosa pulp (10%) and Camelina sativa seeds (10%) and with protein hydrolysates from Psoralea corylifolia seeds (40%) and Spirodela polyrhiza whole plants (40%). The combination of nutraceutical and exercise decreased the animals' body weights and inflammatory markers (TNFα, IL-6, and resistin) in plasma, while increasing gene expression of cat , sod2 , gsta2 , and nqo1 in the liver. Obese animals showed lower β-diversity of microbiota and a higher Firmicutes/Bacteroidetes ratio vs. normocaloric controls that were reversed by all interventions implemented. Dietary inclusion of a nutraceutical with high antioxidant potential combined with an exercise protocol can be beneficial for bodyweight control and improvement of metabolic status in patients undergoing obesity treatment.

Anemonia sulcata may be a source of marine natural products (MNPs) due to the antioxidant and antitumor activity of its crude homogenates shown in vitro in colon cancer cells. A bioguided chromatographic fractionation assay of crude Anemonia sulcata homogenates with and without its symbiont Symbiodinium was performed to characterize their bioactive composition and further determine their biological potential for the management of colorectal cancer (CRC). The 20% fractions retained the in vitro antioxidant activity previously reported for homogenates. As such, activation of antioxidant and detoxifying enzymes was also evaluated. The 40% fractions showed the greatest antiproliferative activity in T84 cells, synergistic effects with 5-fluoruracil and oxaliplatin, overexpression of apoptosis-related proteins, cytotoxicity on tumorspheres, and antiangiogenic activity. The predominantly polar lipids and toxins tentatively identified in the 20% and 40% fractions could be related to their biological activity in colon cancer cells although further characterizations of the active fractions are necessary to isolate and purify the bioactive compounds.

Aims: The study of molecular mechanisms related to obesity and associated pathologies like type 2-diabetes and non-alcoholic fatty liver disease requires animal experimental models in which the type of obesogenic diet and length of the experimental period to induce obesity deeply affect the metabolic alterations. Therefore, this study aimed to test the influence of aging along a rat model of diet-induced obesity in gene expression of the hepatic transcriptome., Main Methods: A high-fat/high-fructose diet to induce obesity was used. Mid- (13 weeks) and long-term (21 weeks) periods were established. Caloric intake, bodyweight, hepatic fat, fatty acid profile, histological changes, antioxidant activity, and complete transcriptome were analyzed., Key Findings: Excess bodyweight, hepatic steatosis and altered lipid histology, modifications in liver antioxidant activity, and dysregulated expression of transcripts related to cell structure, glucose & lipid metabolism, antioxidant & detoxifying capacity were found. Modifications in obese and control rats were accounted for by the different lengths of the experimental period studied., Significance: Main mechanisms of hepatic fat accumulation were de novo lipogenesis or altered fatty acid catabolism for mid- or long-term study, respectively. Therefore, the choice of obesity-induction length is a key factor in the model of obesity used as a control for each specific experimental design., Competing Interests: Declaration of competing interest At the time of submission, the authors have no competing interests (financial, professional or personal) that are relevant to the submitted work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Legumes are a highly nutritious source of plant protein, fiber, minerals and vitamins. However, they also contain several bioactive compounds with significant potential benefits for human health. The objectives of this study were to evaluate the antioxidant, antitumor and chemopreventive activity of functional extracts from legumes using raw and germinated flours of six legume species of commercial interest. The methodology carried out consisted on the development of protein hydrolysates, assessment of their antioxidant capacity and in vitro tests on T84, HCT15 and SW480 colorectal cancer (CRC) cell lines. Our results showed a high antitumor activity of protein hydrolysate from M. sativa . Likewise, when combined with 5-Fluorouracile (5-Fu), there was a synergistic effect using extract concentrations from 50 to 175 µg/mL and 5-Fu concentrations from 1.5 to 5 µM. Similarly, the induction effect on detoxifying enzymes by the extracts of M. sativa , germinated V. faba Baraca × LVzt1 and V. narbonensis , which produced a higher induction rate than the positive control sulforaphane (10 µM), should be highlighted. Therefore, incorporating these enzymes into the diet could provide nutritional effects, as well as play an effective role in cancer chemoprevention and therapy.

Amorphous calcium phosphate nanoparticles (ACP NPs) exhibit excellent biocompatibility and biodegradability properties. ACP NPs were functionalized with two coumarin compounds (esculetin and euphorbetin) extracted from Euphorbia lathyris seeds (BC-ACP NPs) showing high loading capacity (0.03% and 0.34% (w/w) for esculetin and euphorbetin, respectively) and adsorption efficiency (2.6% and 33.5%, respectively). BC-ACP NPs, no toxic to human blood cells, showed a more selective cytotoxicity against colorectal cancer (CRC) cells (T-84 cells) (IC50, 71.42 µg/ml) compared to non-tumor (CCD18) cells (IC50, 420.77 µg/ml). Both, the inhibition of carbonic anhydrase and autophagic cell death appeared to be involved in their action mechanism. Interestingly, in vivo treatment with BC-ACPs NPs using two different models of CRC induction showed a significant reduction in tumor volume (62%) and a significant decrease in the number and size of polyps. A poor development of tumor vasculature and invasion of normal tissue were also observed. Moreover, treatment increased the bacterial population of Akkermansia by restoring antioxidant systems in the colonic mucosa of mice. These results show a promising pathway to design innovative and more efficient therapies against CRC based on biomimetic calcium phosphate NPs loaded with natural products., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The association of obesity with changes in bone mass is not clear. Obese individuals tend to have an increased bone mineral density, but other studies have shown that obesity is a major risk factor for fractures. The mechanisms of bone response during a weight loss therapy as well as the possible osteoprotective effect of exercise should be analyzed. The aim of this study was to test the effects of a weight-loss program based on the combination of caloric restriction and/or a mixed training protocol on different parameters of bone morphology and functionality in a DIO rat model. Three stages were established over a 21-week period (obesity induction 0-12 w, weight loss intervention 12-15 w, weight maintenance intervention 15-21 w) in 88 male Sprague Dawley rats. Bone microarchitecture, total mineral and elemental composition, and bone metabolism parameters were assessed. Weight loss interventions were associated to healthy changes in body composition, decreasing body fat and increasing lean body mass. On the other hand, obesity was related to a higher content of bone resorption and inflammatory markers, which was decreased by the weight control interventions. Caloric restriction led to marked changes in trabecular microarchitecture, with a significant decrease in total volume but no changes in bone volume (BV). In addition, the intervention diet caused an increase in trabeculae number and a decrease in trabecular spacing. The training protocol increased the pore diameter and reversed the changes in cortical porosity and density of BV induced by the high protein diet at diaphysis level. Regarding the weight-maintenance stage, diminished SMI values indicate the presence of more plate-like spongiosa in sedentary and exercise groups. In conclusion, the lifestyle interventions of caloric restriction and mixed training protocol implemented as weight loss strategies have been effective to counteract some of the deleterious effects caused by a dietary induction of obesity, specifically in trabecular bone morphometric parameters as well as bone mineral content.

Basil is an aromatic herb with a high concentration of bioactive compounds. The oil extracted from its seeds is a good source of α-linolenic acid (ALA) and also provides substantial amounts of linoleic acid (LA). This study aimed to test the bioavailability of the oil derived from basil seeds and its effects on different physiological parameters using 7-15% dietary inclusion levels. Furthermore, the assimilation of LA and ALA and their transformation in long-chain polyunsaturated fatty acids (LC-PUFAs) have been studied. Digestive utilization of total fat from basil seed oil (BSO) was high and similar to that of olive oil used as a control. Consumption of BSO resulted in increased LA and ALA levels of the plasma, liver, and erythrocyte membrane. In addition, the transformation of LA to arachidonic acid (ARA) was decreased by the high dietary intake of ALA which redirected the pathway of the Δ-6 desaturase enzyme towards the transformation of ALA into eicosapentaenoic acid (EPA). No alterations of hematological and plasma biochemical parameters were found for the 7 and 10% dietary inclusion levels of BSO, whereas a decrease in the platelet count and an increase in total- and HDL-cholesterol as well as plasma alkaline phosphatase (ALP) were found for a 15% BSO dose. In conclusion, BSO is a good source of ALA to be transformed into EPA and decrease the precursor of the pro-inflammatory molecule ARA. This effect on the levels of EPA in different tissues offers potential for its use as a dietary supplement, novel functional food, or a constituent of nutraceutical formulations to treat different pathologies.

The emergence of adverse effects and resistance to colorectal cancer (CRC) current therapies calls for the development of new strategies aimed at both preventing and treating. In this context, functional extracts from Brassicaceae family contains abundant bioactive compounds directly related to a positive effect on human health including cancer. The main objective of this systematic review is to compile all recent studies that analyzed the in vitro antiproliferative activity of functional extracts or isolated molecules from the Brassicaceae family against CRC. A total of 711 articles published between January 2011 and May 2021 were identified. Of them, 68 met our inclusion criteria. Different standardized protocols using variable parts of plants of the Brassicaceae family resulted in diverse bioactive extracts and/or compounds. Most of them were related to isothiocyanates, which showed significant antitumor activity against CRC. These in vitro studies provide an excellent guide to direct research on the applications of plants of the Brassicaceae family to the prevention of this type of tumor. The extracts and molecules with demonstrated activity against CRC should be tested in vivo and in clinical trials to determine their usefulness in the prevention of this cancer to reduce its global incidence., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Continuous improvements in morphological and histochemical analyses of Apis mellifera could improve our understanding of the anatomy and physiology of these insects at both the cellular and tissue level. In this work, two different approaches have been performed to add new data on the abdomen of worker bees: (i) Micro-computed tomography (Micro-CT), which allows the identification of small-scale structures (micrometers) with adequate/optimal resolution and avoids sample damage and, (ii) histochemical multi-staining with Periodic Acid-Schiff-Alcian blue, Lactophenol-Saphranin O and pentachrome staining to precisely characterize the histological structures of the midgut and hindgut. Micro-CT allowed high-resolution imaging of anatomical structures of the honeybee abdomen with particular emphasis on the proventriculus and pyloric valves, as well as the connection of the sting apparatus with the terminal abdominal ganglia. Furthermore, the histochemical analyses have allowed for the first-time description of ventricular telocytes in honeybees, a cell type located underneath the midgut epithelium characterized by thin and long cytoplasmic projections called telopodes. Overall, the analysis of these images could help the detailed anatomical description of the cryptic structures of honeybees and also the characterization of changes due to abiotic or biotic stress conditions.

Nannochloropsis gaditana is a microalga with interesting nutritional and functional value due to its high content of protein, polyunsaturated fatty acids, and bioactive compounds. However, the hardness of its cell wall prevents accessibility to these components. This work aimed to study the effect of a treatment to increase the fragility of the cell wall on the bioavailability of its nutrients and functional compounds. The antioxidant and antiproliferative capacity of functional extracts from treated and untreated N. gaditana was assessed, and the profile of bioactive compounds was characterized. Furthermore, to study the effect of treatment on its nutrient availability and functional capacity, an in vivo experiment was carried out using a rat experimental model and a 20% dietary inclusion level of microalgae. Functional extracts from treated N. gaditana exhibited higher antioxidant activity than the untreated control. Furthermore, the treated microalga induced hypoglycemic action, higher nitrogen digestibility, and increased hepatic antioxidant activity. In conclusion, N. gaditana has interesting hepatoprotective, antioxidant, and anti-inflammatory potential, thus proving itself an ideal functional food candidate, especially if the microalga is treated to increase the fragility of its cell wall before consumption.

Euphorbia lathyris seeds have been used to treat various medical conditions. We previously reported that ethanolic extract from the defatted seed of Euphorbia lathyris (EE) (variety S3201) possesses a potent in vitro antitumor activity against colon cancer (CRC) cell lines. However, the effects of EE on CRC in vivo models and its possible preventive activity have not been elucidated. The aim of this study is to develop an in vivo study to corroborate its efficacy. For this purpose, two tumor induction models have been developed. In orthotopic xenograft model, it has been shown that EE reduces tumor size without hematological toxicity. The ethanolic extract induced an intense apoptosis in tumors mediated by caspase 3. Using the Azoxymethane/Dextran Sulfate Sodium model, a reduction of dysplastic polyps has been demonstrated, showing its preventive power. Furthermore, EE promoted the presence of an eubiotic microbiotal environment in the mucosa of the colon and induced an increase in antioxidant enzyme activity. This fact was accompanied by a modulation of cytokine expression that could be related to its protective mechanism. Therefore, although further experiments will be necessary to determine its applicability in the treatment of CRC, ES could be a new prevention strategy as well as treatment for this type of tumor, being a powerful candidate for future clinical trials., (Copyright © 2022. Published by Elsevier Masson SAS.)

Colon cancer is the fourth leading cause of cancer deaths around the world. Despite advances in understanding its etiology and in diagnosis and treatment, new therapeutic strategies are still required. In this sense, the Solanaceae and Cucurbitaceae families have been widely used to treat various pathologies, including cancer, for their bioactive components. The objective of this systematic review was to analyze the antitumor activity of the bioactive components present in extracts from Solanaceae and Cucurbitaceae families using different in in vitro models of colon cancer. 241 publications have been identified (published from January 2008 to January 2020) from different electronic data base. 44 articles were included, 26 of which examined the Solanaceae family. The antitumor activity exhibited by this family was due to the withanolide-type steroid compounds they harbor. 18 articles were related to the Cucurbitaceae family. This family is characterized by their production of cucurbitacin-type triterpenoid compounds and their derivatives, which confer antitumor activity. In conclusion, the different genera belonging to both families are an important source of bioactive compounds with relevant activity against colon cancer. More experimental and in vivo studies will be required to corroborate their antitumor activity and to leverage them in future clinical practice.

Moringa oleifera, Tropaeolum tuberosum and Annona cherimola are medicinal plants traditionally used in Ecuador. However, their therapeutic properties are not completely known. We analyzed chromatographically ethanolic extracts of the seeds of M. oleifera, A. cherimola and the tubers of T. tuberosum; all presented a high content of polyphenols. The extract of A. cherimola showed the highest antioxidant activity and M. oleifera had the highest capacity to enhance the activity of detoxifying enzymes such as glutathione S-transferase and quinone oxidoreductase. The antitumor effect of these extracts was evaluated in vitro with colorectal cancer (CRC) cell lines T84, HCT-15, SW480 and HT-29, as well as with cancer stem cells (CSCs). A. cherimola and M. oleifera extracts presented the lowest IC 50 in T-84 and HCT-15 (resistant) cells, respectively, as well as the highest level of inhibition of proliferation in multicellular tumor spheroids of HCT-15 cells. The inhibitory effect on CSCs is noteworthy because in vivo, these cells are often responsible for cancer recurrences and resistance to chemotherapy. Moreover, all extracts showed a synergistic activity with 5-Fu. The antiproliferative mechanism of the extracts was related to overexpression of caspases 9, 8 and 3 and increased production of reactive oxygen species. In addition, we observed cell death by autophagy in M. oleifera and T. tuberosum extracts. Therefore, these ethanolic extracts are excellent candidates for future molecular analysis of the presence of bioactive compounds and in vivo studies which could improve colon cancer therapy., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: The study goal was to examine whether there are sex-related differences in the incidence of ventricular arrhythmias and mortality in CRT-defibrillator (CRT-D) recipients., Background: Few studies have evaluated sex-related benefits of cardiac resynchronization therapy (CRT). Moreover, data on sex-related differences in the occurrence of ventricular tachyarrhythmias in this population are limited., Methods: A multicenter retrospective study was conducted in 460 patients (355 male subjects and 105 female subjects) from the UMBRELLA (Incidence of Arrhythmia in Spanish Population With a Medtronic Implantable Cardiac Defibrillator Implant) national registry. Patients were followed up through remote monitoring after the first implantation of a CRT-D during a median follow-up of 2.2 ± 1.0 years. Sex differences were analyzed in terms of ventricular arrhythmia-treated incidence and death during the follow-up period, with a particular focus on primary prevention patients., Results: Baseline New York Heart Association functional class was worse in women compared with that in men (67.0% of women in New York Heart Association functional class III vs. 49.7% of men; p = 0.003), whereas women had less ischemic cardiac disease (20.8% vs. 41.7%; p < 0.001). Female sex was an independent predictor of ventricular arrhythmias (hazard ratio: 0.40; 95% confidence interval: 0.19 to 0.86; p = 0.020), as well as left ventricular ejection fraction and nonischemic cardiomyopathy. Mortality in women was one-half that of men, although events were scarce and without significant differences (2.9% vs. 5.6%; p = 0.25)., Conclusions: Women with left bundle branch block and implanted CRT have a lower rate of ventricular tachyarrhythmias than men. All-cause mortality in patients is, at least, similar between female and male subjects., Competing Interests: FUNDING SUPPORT AND AUTHOR DISCLOSURES The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Obesity is critically associated with the development of insulin resistance and related cardiovascular and kidney diseases. Several strategies for weight loss have been developed but most of them exhibit a post-intervention rebound effect. Here, we aimed to design combined weight-loss strategies of caloric restriction, physical exercise, and administration of a CB1 receptor blocker to inhibit food intake that also accomplish the objectives of lost-weight maintenance and improvement of cardiovascular and renal function. Diet-induced obesity (DIO) was generated in Sprague Dawley rats for 12 weeks to test the effects of single or combined strategies (i.e. caloric restriction, mixed training protocol, and/or administration of appetite suppressant) on caloric intake, body weight, cardiovascular and renal functionality resulting from a weight-loss intervention period of 3 weeks followed by 6 weeks of weight maintenance. Consumption of a high-fat diet (HFD) caused a significant increase in body weight (5th week of the experimental period) and led to the development of insulin resistance, cardiovascular, and renal alterations. The different interventions tested, resulted in a significant body weight loss and improved glucose metabolism, aerobic capacity, electrocardiographic parameters, vascular expression of adhesion molecules and inflammatory mediators, and renal functionality, reaching values similar to the control normocaloric group or even improving them. Successful maintenance of lost weight was achieved along a 6-week maintenance period in addition to adequate health status. In conclusion, the weight-loss and maintenance intervention strategies tested were efficient at reversing the obesity-related alterations in body weight, glucose metabolism, aerobic capacity, cardiovascular and renal functionality. The beneficial action was very consistent for caloric restriction and physical exercise, whereas administration of a CB1 receptor blocker complemented the effects of the prior interventions in some parameters like body weight or aerobic capacity, and showed specific actions in renal status, increasing glomerular filtration rate and diuresis. Overall, the novelty of our study relies on the easy implementation of combined strategies for effective weight management that resulted in significant health benefits.

The seeds of Euphorbia lathyris have been used in traditional medicine to treat various medical conditions. However, neither all of their active biocompounds nor the molecular mechanisms underlying their therapeutic effects have been described. A new ethanolic extract of defatted flour from mature seeds of Euphorbia lathyris showed a high total polyphenol content and significant antioxidant activity. Chromatographic analysis showed that esculetin, euphorbetin, gaultherin, and kaempferol-3-rutinoside were the most abundant polyphenolic bioactive compounds. Antiproliferative assays showed a high and selective antitumor activity against colon cancer cell lines (T84 and HCT-15). In addition, a significant antiproliferative activity against glioblastoma multiforme cells was also demonstrated. Its mechanism of action to induce cell death was mediated by the overexpression of caspases 9, 3, and 8, and by activation of autophagy. Interestingly, a reduction in the migration capacity of colon cancer cells and a significant antiangiogenic effect on human umbilical vein endothelial cells were also demonstrated. Finally, the extract significantly reduced the subpopulations of cancer stem cells. This extract could be the basis to develop new therapeutic strategies for the treatment of colon cancer, although further experiments will be necessary to determine its in vivo effects.

Recently, invertebrate marine species have been investigated for the presence of natural products with antitumor activity. We analyzed the invertebrate Anemonia sulcata with (W) and without (W/O) the presence of its microalgal symbiont Symbiodinium as a source of bioactive compounds that may be applied in the therapy and/or prevention of colorectal cancer (CRC). Animals were mechanically homogenized and subjected to ethanolic extraction. The proximate composition and fatty acid profile were determined. In addition, an in vitro digestion was performed to study the potentially dialyzable fraction. The antioxidant and antitumor activity of the samples and the digestion products were analyzed in CRC cells in vitro. Our results show a high concentration of polyunsaturated fatty acid in the anemone and a great antioxidant capacity, which demonstrated the ability to prevent cell death and a high antitumor activity of the crude homogenates against CRC cells and multicellular tumor spheroids, especially W/O symbiont. These preliminary results support that Anemonia sulcata could be a source of bioactive compounds with antioxidant and antitumor potential against CRC and that the absence of its symbiont may enhance these properties. Further studies will be necessary to define the bioactive compounds of Anemonia sulcata and their mechanisms of action.

Purpose: Functional and structural changes in cardiovascular and renal systems resulting from obesity and metabolic syndrome represent a severe risk to human health. Lifestyle interventions such as combining healthy diet with adequate physical exercise protocols are good strategies to manage these pathologies. In this research, the effects of lentil protein hydrolysate administration, combined or not with a mixed training protocol, on insulin resistance, cardiovascular and renal functionality were studied in the obese Zucker rat experimental model., Methods: Thirty-two rats (16 lean and 16 obese subdivided in sedentary and trained animals) were administered lentil protein hydrolysate, whereas another 32 subdivided in the same experimental design were administered placebo. The experiment lasted for 8 weeks. At the end of the experimental period, insulin resistance and different parameters of cardiovascular and renal functionality were measured., Results: The individual or combined interventions with lentil protein hydrolysate and mixed training protocol were efficient at counteracting some of the metabolic, cardiovascular and renal alterations characterizing the obese Zucker rat. Specifically, lentil protein hydrolysate decreased hyperphagia, amplitude of QRS complex, plasma ACE and selectin E expression in aorta, while increasing urinary volume and pH. Exercise showed beneficial actions on HOMA-IR, QRS amplitude, QTc interval, urinary volume, kidney weight and Mn-SOD activity. Interestingly, most of the mentioned benefits of exercise were more consistent when protein hydrolysate was also administered., Conclusion: The interesting synergies between the two interventions assessed qualify them as alternative therapeutic strategies to treat cardiovascular and kidney diseases associated to the metabolic syndrome.

Obesity is critically related with the development of metabolic and pathophysiological alterations among which non-alcoholic fatty liver disease (NAFLD) is of especial relevance. Although there are numerous strategies to successfully treat obesity, the prevention of weight regain still remains challenging for individuals who have undergone weight loss programs. In such context, diet and physical activity are considered essential for the regulation of body weight and lipid metabolism. In this study, rats were fed a high-fat diet (HFD) to induce obesity and alterations in hepatic lipid metabolism. Obese rats were then treated with single or combined strategies of caloric restriction, physical exercise, and/or pharmacological treatment with an appetite suppressant, to lose weight, reverse the obesity-related alterations in hepatic morphology and lipid metabolism and maintain the beneficial effects of the interventions used. HFD induced excess body weight, hepatic steatosis, altered fatty acid profile, dysregulated gene expression of lipogenic and lipolytic enzymes, as well as plasma markers of liver damage, and modifications in liver antioxidant enzyme activity. Such alterations were ameliorated by caloric restriction in combination with a mixed training protocol and/or food-intake inhibitor administration during a weight loss intervention period of 3 weeks, and the beneficial effects remained after 6 weeks of weight maintenance, with some interesting interactions observed. In conclusion, weight loss strategies assayed were efficient at correcting the obesogenic action of a HFD and related alterations in hepatic functionality through different molecular mechanisms. The beneficial effects were also evident along the post-intervention maintenance period to avoid body weight regain., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The use of legumes as functional foods has gained increasing attention for the prevention and treatment of the so called non-communicable diseases that are highly prevalent worldwide. In this regard, biotechnological approaches for the enhancement of legumes' nutritional and functional value have been extensively employed. In the present study, the process of germination increased several parameters of mung bean ( Vigna radiata L.) functionality, including extract yield, total phenolic content and in vitro antioxidant capacity. In addition, 3-day-germinated mung bean proved to be an interesting source of dietary essential minerals and exhibited a greater variety of polyphenolic compounds compared to raw mung bean. These properties resulted in enhanced cytoprotective features of the 3-day mung bean extracts against radical oxygen species in human colorectal (HT29) and monocyte (U937) cell lines. Moreover, the antiproliferative effects were tested in different colon cancer cell lines, T84 and drug-resistant HCT-18, as well as in a non-tumor colon CCD-18 line. Altogether, our results demonstrate that the germination process improves the mung bean's nutritional value and its potential as a functional food.

Cowpea (Vigna unguiculata) is among the most cultivated legumes, with interesting agronomic and environmental properties, and great potential as a nutritious food. The nutritional value of cowpea can be improved by technological processing. In this study, we showed that natural fermentation improved bioavailability of protein, amino acids, and dietary essential minerals from cowpea in growing rats, thus strengthening its potential value as functional food or food supplement. Forty Wistar albino rats (48 ± 1.8 g), were fed one of four experimental diets ( n = 10 rats per diet): casein, raw cowpea, fermented cowpea or fermented and autoclaved cowpea. Despite lower growth indices of raw and fermented cowpea protein (PER, FTI) than casein, fermentation enhanced apparent digestibility of arginine, leucine, lysine, methionine, phenylalanine, tyrosine, and valine, and true digestibility of essential amino acids, except for tyrosine and valine, compared to raw cowpea. On the other hand, autoclaving of fermented cowpea flour decreased apparent, as did true digestibility of sulfur amino acids. Regarding the nutritive utilization of dietary essential minerals, Vigna unguiculata was a good source of available P, Mg, and K, while fermentation significantly improved the availability of P. Overall, cowpea was a good source of digestible essential amino acids and minerals and fermentation significantly improved its nutritional value that was not further enhanced by autoclaving.

Obesity, metabolic syndrome, and renal injury are considered risk factors for type 2 diabetes, as well as kidney disease. Functional and structural changes in the kidney as consequence of obesity and metabolic syndrome may lead to impaired mineral metabolism in what is known as chronic kidney disease-mineral and bone disorder. Lifestyle interventions such as physical activity are good strategies to manage these pathologies and therefore, prevent the loss of kidney functionality and related complications in mineral metabolism. In this study, we have used 40 male Zucker rats that were randomly allocated into four different experimental groups, two of them (an obese and a lean one) performed an aerobic interval training protocol, and the other two groups were sedentary. At the end of the experimental period (8 wk), urine, plasma, and femur were collected for biochemical and mineral composition analysis, whereas the kidney was processed for histological studies. The obese rats exhibited albuminuria, glomerulosclerosis, and hypertrophy in glomeruli and renal tubule in some areas, together with alterations in mineral content of plasma but not of femur. The training protocol prevented the generation of albuminuria and glomerulosclerosis, showing a significant action on plasma and bone mineral levels. Therefore, the specific training protocol used in this study was able to prevent the development of diabetic nephropathy and affected the metabolism of certain minerals.

Clinical and animal studies have suggested efficacies of common bean (Phaseolus vulgaris) consumption on weight loss. Fermentation of common bean-derived dietary fiber by gut microbiota is proposed to mitigate obesity; however, the mechanism of action is unclear. The objective of this study was to investigate whether and how fecal fermentation of common bean-derived dietary fiber impacts adipogenesis in a cell model. Dietary fiber was generated by in vitro digestion of cooked, lyophilized common bean flour, followed by anaerobic fermentation with the use of fresh feces from healthy mice without antibiotics treatment. The murine 3T3-L1 cells were induced to differentiate in the presence of the fermentation products. Treatment of the fecal fermentation products inhibited adipocyte differentiation and lipid accumulation in a dose- and time-dependent manner. The fermentation products decreased (P<.05) protein levels of two key transcription factors for adipogenesis, CCAAT/enhancer binding protein α and peroxisome proliferator-activated receptor γ by 79-92% and 78-90%, respectively, and one of their downstream targets fatty acid binding protein 4 by 49-86% and 63-98% at protein and mRNA levels, respectively, during the time course. In contrast, the fermentation products increased (P<.05) levels of two proteins promoting energy expenditure, peroxisome proliferator-activated receptor δ (71-91%) on days 2 and 4 and mitochondrial uncoupling protein 2 (1.1-1.2 fold) on days 4-8. Altogether, fecal fermentation of dietary fiber derived from in vitro digestion of common bean temporally and dose-dependently inhibits adipogenesis and key adipogenic transactivators, but activates two energy expenditure proteins in 3T3-L1 cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction and Objectives: Fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator are susceptible to antitachycardia pacing (ATP) termination. Some manufacturers allow programming 2 ATP bursts: before charging (BC) and during (DC) charging. The aim of this study was to describe the safety and effectiveness of ATP BC and DC for fast ventricular tachycardias in the ventricular fibrillation zone in patients with an implantable cardioverter-defibrillator in daily clinical practice., Methods: Data proceeded from the multicenter UMBRELLA trial, including implantable cardioverter-defibrillator patients followed up by the CareLink monitoring system. Fast ventricular tachycardias in the ventricular fibrillation zone until a cycle length of 200ms with ATP BC and/or ATP DC were included., Results: We reviewed 542 episodes in 240 patients. Two ATP bursts (BC/DC) were programmed in 291 episodes (53.7%, 87 patients), while 251 episodes (46.3%, 153 patients) had 1 ATP burst only DC. The number of episodes terminated by 1 ATP DC was 139, representing 55.4% effectiveness (generalized estimating equation-adjusted 60.4%). There were 256 episodes terminated by 1 or 2 ATP (BC/DC), representing 88% effectiveness (generalized estimating equation-adjusted 79.3%); the OR for ATP effectiveness BC/DC vs DC was 2.5, 95%CI, 1.5-4.1; P <.001. Shocked episodes were 112 (45%) for ATP DC vs 35 (12%) for ATP BC/DC, representing an absolute reduction of 73%. The mean shocked episode duration was 16seconds for ATP DC vs 19seconds for ATP BC/DC (P=.07)., Conclusions: The ATP DC in the ventricular fibrillation zone for fast ventricular tachycardia is moderately effective. Adding an ATP burst BC increases the overall effectiveness, reduces the need for shocks, and does not prolong episode duration., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Metabolic syndrome is a cluster of metabolic alterations characterized by central obesity, dyslipidemia, elevated plasma glucose, insulin resistance (IR) and non-alcoholic fatty liver disease (NAFLD). In this study, a combined intervention of a lentil protein hydrolysate and a mixed training protocol was assessed in an animal experimental model of genetic obesity and metabolic syndrome. Thirty-two male obese and 32 lean Zucker rats were divided into eight different experimental groups. Rats performed a mixed exercise protocol or had a sedentary lifestyle and were administered a lentil protein hydrolysate or placebo. Daily food intake, weekly body weight gain, plasma parameters of glucose and lipid metabolisms, body composition, hepatic weight, total fat content and fatty acid profile, as well as gene expression of lipogenic and lipolytic nuclear transcription factors and their target genes were measured. Obese Zucker rats exhibited higher body and liver weight and fat content than did their lean counterparts. Such alterations were related to modifications in aerobic capacity, plasma biochemical parameters of glucose and lipid metabolisms, hepatic fatty acid profile and gene expression of nuclear transcription factors SREBP1c, PPARα, LXR and associated lipogenic and lipolytic enzymes. The interventions tested did not affect body weight gain but improved aerobic capacity, reduced hepatomegalia and steatosis associated with NAFLD and relieved the adverse effects produced by this condition in glucose and lipid metabolisms through the modulation in the expression of different genes involved in diverse metabolic pathways.

Metabolic syndrome (MetS) is a group of related metabolic alterations that increase the risk of developing non-alcoholic fatty liver disease (NAFLD). Several lifestyle interventions based on dietary treatment with functional ingredients and physical activity are being studied as alternative or reinforcement treatments to the pharmacological ones actually in use. In the present experiment, the combined treatment with mung bean ( Vigna radiata ), a widely used legume with promising nutritional and health benefits that was included in the experimental diet as raw or 4 day-germinated seed flour, and aerobic interval training protocol (65-85% VO₂ max) has been tested in lean and obese Zucker rats following a 2 × 2 × 2 (2 phenotypes, 2 dietary interventions, 2 lifestyles) factorial ANOVA (Analysis of Variance) statistical analysis. Germination of V. radiata over a period of four days originated a significant protein hydrolysis leading to the appearance of low molecular weight peptides. The combination of 4 day-germinated V. radiata and aerobic interval training was more efficient compared to raw V. radiata at improving the aerobic capacity and physical performance, hepatic histology and functionality, and plasma lipid parameters as well as reverting the insulin resistance characteristic of the obese Zucker rat model. In conclusion, the joint intervention with legume sprouts and aerobic interval training protocol is an efficient treatment to improve the alterations of glucose and lipid metabolism as well as hepatic histology and functionality related to the development of NAFLD and the MetS., Competing Interests: The authors declare no conflict of interest.

The benefits of exercise on bone density, structure and turnover markers are rather controversial. The present study aimed to examine the effects of hypertrophy exercise (HE) on bone. 20 male Wistar rats were randomly distributed in 2 experimental groups, one performing HE and the other untrained over 12 weeks. Plasma parameters, bone mineral content, bone mineral density (BMD), structure, and trabecular and cortical microarchitecture were measured. Femur Mg content was 12% higher (p<0.001), whereas femur length, dry weight, P content, and aminoterminal propeptides of type I procollagen were lower in the HE group (all, p<0.05). Total BMD and cortical/subcortical BMD were higher (both, p<0.01), whereas total cross-sectional and trabecular areas were lower (both, p<0.001), and cortical area and thickness were lower in the HE (both, p<0.05). Trabecular connectivity density, number, mean density of total and bone volume were higher in the HE (all, p<0.05). Cortical volume fraction and the mean density of total volume of the diaphysis were lower, whereas the cortical volume density was higher in the HE (all, p<0.05). This HE protocol may have beneficial effect on cancellous bone microarchitecture, but it induces low bone formation and is associated with hypogonadism in growing male rats. However, this type of training might be inefficient to maintain appropriate cortical thickness., Competing Interests: Conflict of interest: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Weight loss is a public health concern in obesity-related diseases such as metabolic syndrome, and the protein level of the diets seem to be crucial for the development and maintenance of bone. The nature of exercise and whether exercise in combination with moderately high-protein dietary interventions could protect against potential bone mass deficits remains unclear., Objectives: To investigate the effects of a moderately high-protein diet and interval aerobic training combined with strength-endurance exercise (IASE) protocol on bone status, and to assess potential interaction effects (i.e. diet*IASE)., Methods: Male Zucker fatty rats were randomized distributed into 4 groups (n=8): normoprotein+sedentary; normoprotein+exercise; moderately high-protein+sedentary, and moderately high-protein+exercise. Training groups conducted an IASE program, 5days/week for 2months. Markers of bone metabolism were measured in plasma. Parameters of bone mass and 3D outcomes for trabecular and cortical bone microarchitecture were assessed by micro-computed tomography., Results: Femur length, plasma osteocalcin, sclerostin, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand, insulin, leptin, PTH, uric acid and urinary phosphorus levels were lower in the moderately high-protein compared to the normoprotein groups (all, p<0.05), whereas plasma alkaline phosphatase, aspartate aminotransferase, alanine transaminase, and urinary uric acid concentrations, and cortical total volume (TV) and bone volume (BV) were higher in the moderately high-protein (all, p<0.01). Final body weight and alkaline phosphatase levels were lower in the exercise compared to the sedentary (both, p<0.05), whereas femur length and weight, aminoterminal propeptides of type I procollagen and C-terminal telopeptides of type I collagen concentrations, and cortical TV and BV were higher in the exercise compared to the sedentary groups (all, p<0.05)., Conclusion: The combination of interventions may be effective to enhance trabecular bone microarchitecture and BMD, and has a partial impact on cortical bone in obese rats. Nevertheless, they do not induce any alteration on the bone turnover markers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CNVs) in SCN5A in BrS patients, and the role of CNVs in BrS-minor genes is a completely unexplored field., Methods: 220 BrS patients with negative genetic results were studied to detect CNVs in SCN5A. 63 cases were also screened for CNVs in BrS-minor genes. Studies were performed by Multiplex ligation-dependent probe amplification or Next-Generation Sequencing (NGS)., Results: The detection rate for CNVs in SCN5A was 0.45% (1/220). The detected imbalance consisted of a duplication from exon 15 to exon 28, and could potentially explain the BrS phenotype. No CNVs were found in BrS-minor genes., Conclusion: CNVs in current BrS-related genes are uncommon among BrS patients. However, as these rearrangements may underlie a portion of cases and they undergo unnoticed by traditional sequencing, an appealing alternative to conventional studies in these patients could be targeted NGS, including in a single experiment the study of SNVs, indels and CNVs in all the known BrS-related genes., Competing Interests: Author RB received funding from FerrerInCode, a commercial company, for this study. Author CF-C received funding from Gendiag SL, a commercial company, for this study. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Legume consumption plays a pivotal role in the prevention and treatment of the metabolic syndrome (MetS). This systematic review aimed to highlight the beneficial effects of legume interventions for the prevention and/or improvement of parameters related to the MetS and the implicated metabolic pathways so far reported. The methodology involved a search in four electronic databases (Medline, Web of Science, Scopus, Cochrane Library) from January 2007 to December 2014, considering as descriptors 'Metabolic Syndrome' and 'Fabaceae' and adequately adjusting the equation in each one of them. In total, forty-one studies were finally included. The majority of the studies described a regulating effect on glucose and lipid metabolism due to legume administration, whereas effects on blood pressure and renal parameters are not fully described. Regarding the metabolic pathways involved, they include the up-regulation of genes related to β-oxidation and acetyl-CoA degradation and the down-regulation of glycolytic and lipogenesis genes, as well as those associated with the acetyl-CoA synthesis. The ameliorating effects of legume consumption on the alterations associated with the MetS are clearly reported and coincide with changes in the expression of protein and genes involved in lipid and glucose metabolism. More research needs to be conducted including more legume species that are highly consumed as part of a healthy dietary pattern.

The purpose of this study was to investigate the effects of interval aerobic training combined with strength exercise in the same training session on body composition, and glycaemic and lipid profile in obese rats. Sixteen lean Zucker rats and sixteen obese Zucker rats were randomly divided into exercise and sedentary subgroups (4 groups, n = 8). Exercise consisted of interval aerobic training combined with strength exercise in the same training session. The animals trained 60 min/day, 5 days/week for 8 weeks. Body composition, lipid and glycaemic profiles and inflammatory markers were assessed. Results showed that fat mass was reduced in both lean and obese rats following the exercise training (effect size (95% confidence interval (CI)) = 1.8 (0.5-3.0)). Plasma low-density lipoprotein-cholesterol and fasting glucose were lower in the exercise compared to the sedentary groups (d = 2.0 (0.7-3.2) and 1.8 (0.5-3.0), respectively). Plasma insulin was reduced in exercise compared to sedentary groups (d = 2.1 (0.8-3.4)). Some exercise × phenotype interactions showed that the highest decreases in insulin, homeostatic model assessment-insulin resistance, fasting and postprandial glucose were observed in the obese + exercise group (all, P < 0.01). The findings of this study suggest that interval aerobic training combined with strength exercise would improve body composition, and lipid and glycaemic profiles, especially in obese rats.

Background: Different types of ventricular arrhythmias (monomorphic ventricular tachycardia [VT], polymorphic VT, or ventricular fibrillation) can be detected by implantable cardiac defibrillators (ICDs) in fast VT zone. The efficacy of antitachycardia pacing (ATP) depends on the type of the treated arrhythmia. We hypothesized that an automatic algorithm based on morphological affinity of ICD far-field electrograms during tachycardia can predict ATP success and the need of shock., Methods: The algorithm was evaluated on ventricular arrhythmias recorded in CareLink ICD remote monitoring system (Medtronic Inc., Minneapolis, MN, USA). Patients were selected if first ATP programmed was a burst of eight pulses at 88% coupling interval and if a far-field electrogram was available. The algorithm calculated a stability coefficient (SC) for all their stored ATP-treated fast ventricular arrhythmia (VA) episodes (LC 200-300 ms), analyzing the morphology homogeneity of the last eight recorded far-field electrograms before ventricular arrhythmias detection., Results: Inclusion criteria were fulfilled by 717 patients from 29 centers. Three hundred and twenty fast VA were recorded in 103 patients. A higher SC was observed in episodes terminated with the first-ATP (0.78 [0.72-0.84] vs 0.74 [0.60-0.84]; P = 0.006). These differences were especially marked among the 62 episodes of very fast VA (CL ≤250 ms) (0.77 [0.74-0.85] vs 0.64 [0.51-0.8]; P = 0.006). In the multivariate analysis, a SC > 70% was independently associated with a higher likelihood of first-ATP success (odds ratio [OR] = 2.5; [95% confidence interval (CI) = 1.4-4.5], P = 0.001) and a lower need of shock (OR = 0.37; [95% CI = 0.2-0.7], P = 0.002)., Conclusion: This automatic algorithm (stability coefficient) shows that ATP therapy response can be predicted in fast ventricular arrhythmias through morphology evaluation., (© 2016 Wiley Periodicals, Inc.)

Stanozonol (ST) is a synthetic derivative of testosterone; it has anabolic/androgenic activity, increasing both the turnover of trabecular bone and the endocortical apposition of bone. The present study aimed to examine the effects of ST on bone status in rats by bone mineral content, markers of formation and resorption, bone density, and structural and microarchitectural parameters. Twenty male Wistar rats were randomly distributed into two experimental groups corresponding to placebo or ST administration, which consisted of weekly intramuscular injections of 10 mg/kg body weight of ST. Plasma parameters were analyzed by immunoassay. Bone mineral content was determined by spectrophotometry. Bone mineral density (BMD) and structural parameters were measured by peripheral quantitative computed tomography, and trabecular and cortical microarchitecture by micro-computed tomography. Plasma Ca, Mg, and alkaline phosphatase were higher, and urinary Ca excretion, corticosterone, and testosterone concentrations lower in the ST group. Femur Ca content was higher and P content was lower in the ST, whereas osteocalcin, aminoterminal propeptides of type I procollagen, and C-terminal telopeptides of type I collagen were lower. Total cross-sectional, trabecular, and cortical/subcortical areas were lower in the ST. No differences were observed on BMD and area parameters of the diaphysis as well as on trabecular and cortical microarchitecture. The use of ST increases bone mineralization, ash percentage, and Ca and Mg content in femur. In spite of an absence of changes in BMD, geometric metaphyseal changes were observed. We conclude that ST alters bone geometry, leads to low bone turnover, and thus may impair bone quality.

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P < 0.0001) and suffered significant alterations in plasma lipid profile, area under the curve after oral glucose overload (P < 0.0001), liver histology and functionality, and antioxidant status. The AIT protocol reduced the severity of alterations related to glucose and lipid metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

Objective: to study the effect of co-inoculation with Ensifer meliloti and Halomonas maura of the leguminous Medicago sativa L., on growth, nutritional and functional value, grown under salinity conditions., Methods: plants of M. sativa were grown in a solution with a mixture of salts (CaSO4, MgCl, NaCl and NaHCO 3) and were co-inoculated with its specific rhizobium and the halophilic moderated bacterium H. maura. Different physiologic parameters were determined, as well as, nitrogen and minerals content. Furthermore, an assay of in vitro digestibility was carried out., Results: salinity had a negative effect on the plants; however, co-inoculation increased yield, nitrogen content, total minerals, Ca and Mg. Moreover, physiologic parameters as water potential and leghemoglobin content in fresh nodules were higher compared to those of plants inoculated only with E. meliloti. Both, salinity and bacterial treatment with E. meliloti and H. maura increased the antioxidant capacity of the legume, in dialyzates and retentates collected after an in vitro digestibility assay., Conclusion: co-inoculation of plants with E. meliloti and H. maura could improve the alfalfa yield under specific salinity conditions, increasing the nutritional and functional value of the plants. M. sativa could be considered in the formulations of nutritional supplements for the human diet., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

We analyzed the effects of high-intensity exercise (HIE) and anabolic androgenic steroids (AAS) on brain redox status. 40 male Wistar rats were randomly distributed in 4 experimental groups (n=10) with or without HIE and with or without weekly Stanozolol administration. Thiobarbituric acid-reactive substances (TBARs) and protein carbonyl content (PCC) were assessed. Total superoxide dismutase (tSOD), manganese superoxide dismutase (Mn-SOD), copper/zinc superoxide dismutase (CuZn-SOD) and catalase (CAT) activities were measured. Finally, protein expression levels of glutathione peroxidase (GPx), NAD(P)H dehydrogenase, Quinone 1 (NQO1), NF-E2-Related Factor 2 (Nrf2), glial fibrillary acidic protein (GFAP), nuclear factor kappa β p65 (NF-κβ) and signal transducer and activator of transcription 3 were determined. Brain PCC concentrations were lower in the HIE groups compared to the untrained controls, whereas CAT activity was higher (both, p<0.01). Both HIE and AAS groups exhibited higher expression levels of GFAP and GPx, but lower NQO1 levels (all, p<0.05). There were increased expression levels of NF-κβ in the AAS groups (p<0.01). In addition, there was increased expression of Nrf2 in the HIE groups (p<0.001). HIE*AAS interactions were found on TBARs content and GFAP expression, with HIE downregulating and upregulating AAS-mediated increases in TBARs and GFAP, respectively (p<0.05). Overall, HIE appeared to reduce the AAS-mediated negative effect on brain redox status., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Brugada syndrome (BrS) is a rare genetic cardiac arrhythmia that can lead to sudden cardiac death in patients with a structurally normal heart. Genetic variations in SCN5A can be identified in approximately 20-25% of BrS cases. The aim of our work was to determine the spectrum and prevalence of genetic variations in a Spanish cohort diagnosed with BrS., Methodology/principal Findings: We directly sequenced fourteen genes reported to be associated with BrS in 55 unrelated patients clinically diagnosed. Our genetic screening allowed the identification of 61 genetic variants. Of them, 20 potentially pathogenic variations were found in 18 of the 55 patients (32.7% of the patients, 83.3% males). Nineteen of them were located in SCN5A, and had either been previously reported as pathogenic variations or had a potentially pathogenic effect. Regarding the sequencing of the minority genes, we discovered a potentially pathogenic variation in SCN2B that was described to alter sodium current, and one nonsense variant of unknown significance in RANGRF. In addition, we also identified 40 single nucleotide variations which were either synonymous variants (four of them had not been reported yet) or common genetic variants. We next performed MLPA analysis of SCN5A for the 37 patients without an identified genetic variation, and no major rearrangements were detected. Additionally, we show that being at the 30-50 years range or exhibiting symptoms are factors for an increased potentially pathogenic variation discovery yield., Conclusions: In summary, the present study is the first comprehensive genetic evaluation of 14 BrS-susceptibility genes and MLPA of SCN5A in a Spanish BrS cohort. The mean pathogenic variation discovery yield is higher than that described for other European BrS cohorts (32.7% vs 20-25%, respectively), and is even higher for patients in the 30-50 years age range.

Introduction: An empirical sequence of burst antitachycardia pacing (ATP) is effective in terminating fast ventricular tachycardias (FVT) in patients with implantable cardioverter-defibrillators (ICDs). We aimed to determine whether multiple ATP bursts for termination of FVT results in shock reduction compared to a single ATP burst., Methods and Results: We analyzed data from the Umbrella trial, a multicenter prospective observational study of ICD patients followed by the CareLink Monitoring System. We compared the safety and effectiveness of a single ATP burst (Group 1) with a strategy of successive ATP sequences (Group 2) for termination of FVT episodes (cycle lengths 250-320 milliseconds) before shock therapy. Over a mean follow-up of 35 months, a total of 650 FVT episodes were detected in 154 patients (mean cycle length: 299 ± 18 milliseconds). Effectiveness of the first burst ATP in Group 1 was 73% and shocks were required in 27% of episodes. Effectiveness of the first burst ATP in Group 2 was 77%, and this increased to 91% with the third or successive ATP bursts. Shocks were required in 9% of episodes in group 2, representing a 67% reduction in the need of high-energy shocks. Median duration of FVT episodes and mortality in both groups were similar. Multivariate analysis indicated that programming multiple ATP bursts (OR 3.4, 95%CI 1.7-6.8, P = 0.001) was an independent predictor of ATP effectiveness., Conclusion: This study provides first evidence that a strategy of multiple burst ATP sequences for termination of FVT episodes leads to a clinically meaningful reduction in the need for shocks., (© 2015 Wiley Periodicals, Inc.)

Crosstalk may occur between cannabinoids and other systems controlling appetite, since cannabinoid receptors are present in hypothalamic circuits involved in feeding regulation, and likely to interact with orexin. In this study, an immunohistochemical approach was used to examine the effect of the intracerebroventricular administration of cannabinoid receptor inverse agonist AM 251 on orexin neuropeptide in the hypothalamic system. AM-activated neurons were identified using c-Fos as a marker of neuronal activity. The results obtained show that AM 251 decreases orexin A immunoreactivity, and that it increases c-Fos-immunoreactive neurons within the hypothalamus when compared with the vehicle-injected control group. We also studied the effects of subchronic intraperitoneal administration of AM 251 on food intake, body weight, and protein utilization. The administration of AM 251 at 1, 2, or 5 mg/kg led to a significant reduction in food intake, along with a significant decrease in the digestive utilization of protein in the groups injected with 1 and 2 mg/kg. There was a dose-related slowdown in weight gain, especially at the doses of 2 and 5 mg/kg, during the initial days of the trial. The absence of this effect in the pair-fed group reveals that any impairment to digestibility was the result of administering AM 251. These data support our conclusion that hypothalamic orexigenic neuropeptides are involved in the reduction of appetite and mediated by the cannabinoid receptor inverse agonist. Furthermore, the subchronic administration of AM 251, in addition to its effect on food intake, has significant effects on the digestive utilization of protein.

Background: The antioxidant capacity and hypolipidaemic effects of Vigna unguiculata, as well as their potential improvement by different fermentation and thermal processes were studied using in vitro and in vivo methods., Results: Phenolic content and reducing capacity of legume acetone extract were significantly increased by different fermentation processes, and by the thermal treatment of fermented legume flours. TBARS inhibiting capacity was increased by fermentation but not by thermal treatment. A higher ability to decrease Cu(2+)/H2O2-induced electrophoretic mobility of LDL was found in fermented when compared to raw legume extracts, and a higher protective effect on short term metabolic status of HT-29 cells was found for raw and lactobacillus-fermented Vigna followed by naturally fermented Vigna extracts. Significant improvements in plasma antioxidant capacity and hepatic activity of antioxidant enzymes were observed in rats that consumed fermented legume flours when compared to the untreated legume or a casein-methionine control diet. In addition, liver weight and plasma levels of cholesterol and triglycerides were also positively affected by untreated or naturally fermented Vigna., Conclusion: V. unguiculata has demonstrated its potential as a functional food with interesting antioxidant and lipid lowering properties, which can be further augmented by fermentation processes associated or not to thermal processing., (© 2014 Society of Chemical Industry.)

The use of enriched Se isotopes as tracers has provided important information on Se metabolism. However, selenium isotopes are expensive and difficult to obtain. A simple and cheap strategy based on the production of [(77)Se]-methylselenocysteine ([(77)Se]-MeSeCys) when preparing sauerkraut in the presence of [(77)Se]-selenite was developed. The resulting [(77)Se]-MeSeCys was used for evaluating the metabolic transformation of MeSeCys in Wistar rats, by feeding them with an AIN-93 M diet containing 20 % sauerkraut enriched in [(77)Se]-MeSeCys. Organs (liver, kidney, brain, testicles, and heart) were obtained after seven days of treatment and subjected to total selenium and selenium-speciation analysis by high-performance liquid chromatography coupled with isotope-dilution-analysis inductively-coupled-plasma mass spectrometry (HPLC-IDA-ICP-MS). Analysis of (77)Se-labeled organs revealed a prominent increase (more than 100 % Se-level enhancement) of selenium in the kidney and heart, whereas in the liver selenium concentration only increased by up to 20 % and it remained constant in the brain and testicles. (77)Se-enriched-sauerkraut supplementation does not alter the concentration of other essential elements in comparison to controls except for in the heart and kidney, in which selenium was positively correlated with Mg, Zn, Cu, and Mo. HPLC-ICP-MS analysis of hydrolyzed extracts after carbamidomethylation of the (77)Se-labeled organs revealed the presence of [(77)Se]-SeCys and an unknown Se-containing peak, the identity of which could not be verified by electrospray-ionization (ESI)-MS-MS. Low amounts of [(77)Se]-MeSeCys were found in (77)Se-labeled liver and kidney extracts, suggesting the incorporation of this selenium species in its intact form.

Introduction: It is well established that soy protein diets as well as aerobic exercise could promote antioxidant capacity and consequently reduce free radicals overproduction on brain. However, little is know regarding to the high-protein diets and high intensity exercise on oxidative stress production. The aim of this study was to analyse the effects of high-protein diets and high-intensity exercise (HIE) on brain oxidative stress markers., Materials and Methods: A total of 40 male Wistar rats were randomly distributed in 4 experimental groups (n=10): normal-protein or high-protein diets with or without HIE for an experimental period of 12 weeks. Main oxidative damage markers in brain such as thiobarbituric acid-reactive substances (TBARs) and protein carbonyl content (PCC) were assessed. In addition, brain manganese superoxide dismutase (Mn-SOD), cooper/ zinc superoxide dismutase (CuZn-SOD) and catalase (CAT) antioxidant enzymes activity, and protein level of Nuclear factor erythroid 2 related factor 2 (Nrf2) were measured., Results and Discussion: Brain TBARs, PCC, tSOD, Mn-SOD, CuZn-SOD and CAT levels were higher in the high-protein compared to the normal-protein groups (all, p., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

Different dietary protein sources can promote different renal statuses. We examined the effects of whey protein (WP) and soy protein (SP) intake on plasma, urinary, and morphological renal parameters in rats. One hundred and twenty Wistar rats were randomly distributed into 2 experimental groups fed with either WP or SP diets over 12 weeks. These diets were based on commercial WP or SP isolates. The urinary calcium content was higher in the WP diet compared to the SP diet group (P<.001) whereas the urinary citrate level was lower (P<.001). The urinary pH was more acidic in the WP diet group compared to the SP diet group (P<.001); however, no differences were observed between the groups for any of the renal morphological parameters analyzed (all, P>.05) or other plasma renal markers such as albumin or urea concentrations. The increase of acid and urinary calcium and the lower urinary citrate level observed in the WP diet group could increase the incidence of nephrolithiasis compared to the SP diet group. Despite the WP showed poorer acid-base profile, no significant morphological renal changes were observed. These results suggest that the use of SP instead of WP appears to promote a more alkaline plasma and urinary profile, with their consequent renal advantages.

We investigated the renal effects of a high-intensity exercise (HIE) program based on strength training. 20 Wistar rats were randomly assigned to 2 experimental groups performing HIE or control over 12 weeks. Urinary volume, pH, citrate and calcium, and plasma urea, total proteins, creatinine, albumin, lactate dehydrogenase, creatine kinase (CK), calcium, magnesium, corticosterone and testosterone were measured. We also studied renal morphology with the Fibrosis HR(®) software. Plasma urea and CK concentrations were higher in the HIE compared to the control group (p < 0.05), whereas plasma creatinine was lower (p < 0.01). Plasma corticosterone was higher (p < 0.05) and testosterone lower (p < 0.01) in the HIE group. Except for the higher urinary volume found in the HIE group (p < 0.05), no differences between groups were observed in the rest of urinary parameters analyzed. Renal interstitial connective tissue was ~30% higher in the HIE group (p < 0.05). Glomerular tufts and mesangial areas were also higher in the HIE group (all, p < 0.05). No differences between groups were observed in the glomerular area. Overall, HIE promoted a worse morphological renal profile that might be associated with a higher risk for incidence of kidney disease in the long-term. The stress induced by the type of exercise performed could be on the basis of this worse morphological renal status., (© Georg Thieme Verlag KG Stuttgart · New York.)

This study examined the effects of the dietary amount and source of protein on bone status in rats. 140 male Wistar rats aged 8 weeks were randomly allocated to 4 groups (n = 35) fed normal-protein (NP, 10% richness) or high-protein (HP, 45% richness) diets based on whey protein (WP) or soy protein (SP) sources for 12 weeks. Plasma urea was 46% higher for the HP compared to the NP diet (p < 0.001). Urinary calcium was 65% higher for the HP compared to the NP and 60% higher for the WP compared to the SP diets (all, p < 0.001). Urinary pH was 8% more acidic in the HP compared to the NP diet (p < 0.001) and 4% in the WP compared to the SP diet (p < 0.01). The plasma osteocalcin concentration was 19% higher for the NP compared to the HP (p < 0.05) and 25% for the SP compared to the WP diets (p < 0.01). Femur ash, metaphyseal and diaphyseal cross-sectional, trabecular and cortical areas were 3% higher in the HP compared to the NP diet (all, p < 0.05). Femur diaphyseal periosteal and endocortical perimeters were also 3% higher in the HP compared to the NP diet (both, p < 0.01). Groups fed the SP diet showed 2% higher femur ash percentage, 7% higher calcium content (both, p < 0.001), and 3% higher diaphyseal cortical area and thickness (both, p < 0.05) than those fed the WP diet. Some interactions were found, such as the greater effects of the SP diet on decreasing the higher plasma urea concentration promoted by the intake of the HP diet (p < 0.001). Under adequate Ca intake, HP diets could better maintain bone properties than NP diets, even with increasing some acidity markers, which could be reduced by the intake of SP sources.

Background and Objective: Recent research suggests that cannabinoid receptor CB1 antagonists can affect appetite and body weight gain, although their influence on other parameters related to metabolic syndrome is not well documented. The present study was designed to assess the effects of chronic treatment with the CB1 receptor inverse agonist AM 251 (3 mg/kg for 3 weeks) in obese and lean Zucker rats on parameters related to metabolic syndrome., Materials and Methods: Four groups of rats were used: lean Zucker rats, untreated obese Zucker rats, AM 251-treated obese Zucker rats and a pair-fed obese Zucker rat experimental group which received the same amount of food as that consumed by the animals treated with AM251. Food intake, body weight gain, energy expenditure, plasma biochemical parameters, leptin, insulin and hepatic status markers were analysed., Results: Daily injection of AM 251 in obese Zucker rats produced a marked and sustained decrease in daily food intake and body weight and a considerable increase in energy expenditure in comparison with untreated obese Zucker rats. AM 251 administration to obese rats significantly reduced plasma levels of glucose, leptin, AST, ALT, Gamma GT, total bilirubin and LDL cholesterol whereas HDL cholesterol plasma levels increased. The results also showed a decrease in liver/weight body ratio and total fat content in the liver. The main effects of AM251 (3 mg/kg) found in this study were not observed in pair-fed obese animals, highlighting the additional beneficial effects of treatment with AM 251. The results obtained in obese rats can be interpreted as a decrease in leptin and insulin resistance, thereby improving glucose and lipid metabolism, alleviating the steatosis present in the metabolic syndrome and thus favourably modifying plasma levels of hepatic biomarkers., Conclusion: Our results indicate that the cannabinoid CB1 inverse agonist AM 251 represents a promising therapeutic strategy for the treatment of obesity and metabolic syndrome., (© 2013.)

Introduction: Vitamin A deficiency can result from malnutrition, malabsorption of vitamin A, impaired vitamin metabolism associated with liver disease, or chronic debilitating diseases like HIV infection or cancer., Background & Aims: Cannabis administration has been described as a palliative symptom management therapy in such pathological stages. Therefore, this research aimed to study the effects of acute administration of cannabidiol (CBD) or thetrahydrocannabinol (THC) on the levels of retinol in plasma and in the liver, and biochemical parameters related to lipid and glucose metabolism (cholesterolaemia, triglyceridemia and glycemia) in a rat experimental model of vitamin A deficiency., Methods: The experimental animal model of Vitamin A deficiency was developed during a 50-day experimental period in which rats consumed a vitamin A-free diet. Cannabidiol (10 mg/kg body weight) or thetrahydrocannabinol (5 mg/kg body weight) were administered intraperitoneally 2 hours prior to sacrifice of the animals., Results: The nutritional deficiency caused a significant decrease in plasmatic and liver contents of retinol and biochemical parameters of glycemic, lipidic, and mineral metabolism. Acute intraperitoneal administration of Cannabidiol and thetrahydrocannabinol did not improve the indices of vitamin A status in either control or vitamin A-deficient rats. However, it had a significant effect on specific biochemical parameters such as glucose, triglycerides, and cholesterol., Conclusion: Under our experimental conditions, the reported effects of cannabinoid administration on certain signs of nutritional vitamin A deficiency appeared to be mediated through mechanisms other than changes in retinol metabolism or its mobilization after the acute administration of such compounds., (Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.)

Background: Quercetin is a natural polyphenolic compound currently under study for its ergogenic capacity to improve mitochondrial biogenesis. Sedentary mice have exhibited increased endurance performance, but results are contradictory in human models., Methods: We examined the effects of six weeks of endurance training and quercetin supplementation on markers of endurance performance and training in a rodent model. Rats were randomly assigned to one of the following groups: placebo+sedentary (PS), quercetin+sedentary (QS), placebo+endurance training (PT) and quercetin+endurance training (QT). Quercetin was administered at a dose of 25 mg/kg on alternate days. During six weeks of treatment volume parameters of training were recorded, and after six weeks all groups performed a maximal graded VO2 max test and a low-intensity endurance run-to-fatigue test., Results: No effects were found in VO2 peak (p>0.999), nor in distance run during low-intensity test, although it was 14% greater in QT when compared with PT (P = 0.097). Post-exercise blood lactate was increased in QT when compared with PT (p=0.023) and also in QS compared with PS (p=0.024)., Conclusions: This study showed no effects in VO2 peak, speed at VO2 peak or endurance time to exhaustion after six weeks of quercetin supplementation compared with placebo in trained rats. Quercetin was show to increase blood lactate production after high-intensity exercise.

Introduction: Dietary protein amount and source, hypertrophy resistance training (RT) and anabolicandrogenic steroids (AAS) may affect body weight and plasma and hepatic lipid profile., Material and Methods: 157 adult male Wistar rats were randomly distributed in 16 experimental groups resulting in: normal-protein (NP) or high-protein (HP) diets, whey or soy-protein diets, with or without RT and with or without AAS, for 3 months., Results and Discussion: Final body weight was lower in the RT and AAS groups compared to sedentary and non- AAS groups, respectively (all, p<0.001). Plasma total cholesterol (TC) was lower for the HP compared to the NP diets, for the whey compared to the soy-protein diets and for the AAS compared to the non-AAS groups (all, p<0.001). Plasma HDL-cholesterol was higher in the RT groups (p<0.05) but lower for the AAS groups (p<0.001), the HP and the soy-protein diets (p<0.05). Plasma triglycerides (TAG) were lower for the HP diet (p<0.001), for the RT (p=0.002) and the non-AAS groups (p=0.001). Liver TC was lower for the NP (p<0.01), for the soyprotein (p<0.05) and for the AAS groups (p<0.001). Liver TAG were lower for the whey-protein diet (p<0.001), RT and non-AAS groups (both, p<0.05). Some interactions were found, such as the greater effect of AAS on reducing body weight of rats that performed RT or ingested a HP diet (all, p<0.05). HDL-cholesterol was higher when RT was combined with HP diets (p=0.010) or non-AAS and when HP diets were combined with non-AAS (both,p<0.001). Groups that combined RT with non-AAS administration obtained the lowest hepatic TAG (p<0.05)., Conclusion: Among all the interventions tested, AAS was the factor that most negatively affected plasma and hepatic lipid profile, whereas HP diets and RT could benefit lipid profile, especially when combined., (Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.)