Suchergebnisse

Here, we present new original data on the effects of strawberry consumption on body weight and liver status of aged rats. Wistar rats aged 19–21 months were fed a strawberry enriched diet prepared by substituting 15% of the total calories with freeze-dried strawberry powder for two months. Body weight, plasma biomarkers of liver injury (alanine transferase, aspartate aminotransferase and alkaline phosphatase) and liver histological analysis were assessed. These data indicate that strawberry supplementation did not interfere with normal animal maintenance and with liver structure and functionality. For further details and experimental findings please refer to the article "Strawberry consumption improves agingassociated impairments, mitochondrial biogenesis and functionality through the AMP-Activated Protein Kinase signaling cascade" in FOOD CHEMISTRY (Giampieri et al., 2017). ; European Union (EU) 679303

The Papillon–Lefèvre syndrome (PLS) is a rare autosomal recessive disorder caused by mutations in the Cathepsin C (CTSC) gene, characterized by periodontitis and palmoplantar hyperkeratosis. The main inflammatory deficiencies include oxidative stress and autophagic dysfunction. Mitochondria are the main source of reactive oxygen species; their impaired function is related to skin diseases and periodontitis. The mitochondrial function has been evaluated in PLS and mitochondria have been targeted as a possible treatment for PLS. We show for the first time an important mitochondrial dysfunction associated with increased oxidative damage of mtDNA, reduced CoQ10 and mitochondrial mass and aberrant morphologies of the mitochondria in PLS patients. Mitochondrial dysfunction, determined by oxygen consumption rate (OCR) in PLS fibroblasts, was treated with CoQ10 supplementation, which determined an improvement in OCR and a remission of skin damage in a patient receiving a topical administration of a cream enriched with CoQ10 0.1%. We provide the first evidence of the role of mitochondrial dysfunction and CoQ10 deficiency in the pathophysiology of PLS and a future therapeutic option for PLS. ; Andalusian regional government (Grupo de Investigación Junta de Andalucía) CTS113

The NLRP3-inflammasome complex has emerged as an important component of inflammatory processes in metabolic dysfunction induced by high-caloric diets. In this study, we investigate the molecular mechanisms by which NLRP3 inhibition may attenuate diet-induced cardiac injury. Here we show the cardiac damage induced by high sugar diet (HSD), high fat diet (HFD) or high sugar/fat diet (HSFD) over 15 weeks. Genetic ablation of NLRP3 protected against this damage by autophagy induction and apoptotic control. Furthermore, NLRP3 inhibition by the selective small molecule MCC950 resulted in similar autophagy induction and apoptotic control in hearts after diets. These data were reproduced in THP-1 cells treated with MCC950 and cultured in media supplemented with serum from mice dosed with MCC950 and fed with diets. NLRP3 inhibition exerted beneficial metabolic, and autophagic adaptations in hearts from obesogenic diets. The inhibition of NLRP3 activation may hold promise in the treatment of metabolic and cardiovascular diseases. ; Andalusian regional government (Grupo de Investigacion Junta de Andalucia) CTS113 ; Junta de Andalucia PI-0036-2014

Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on lipid metabolism by modulating several downstream-signaling components. The main objective of the present work was to evaluate the in vitro effect of a methanolic strawberry extract on AMPK and its possible repercussion on lipid metabolism in human hepatocellular carcinoma cells (HepG2). For such purpose, the lipid profile and the expression of proteins metabolically related to AMPK were determined on cells lysates. The results demonstrated that strawberry methanolic extract decreased total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides levels (up to 0.50-, 0.30-, and 0.40-fold, respectively) while it stimulated the p-AMPK/AMPK expression (up to 3.06-fold), compared to the control. AMPK stimulation led to the phosphorylation and consequent inactivation of acetyl coenzyme A carboxylase (ACC) and inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the major regulators of fatty acids and cholesterol synthesis, respectively. Strawberry treatment also entailed a 4.34-, 2.37-, and 2.47-fold overexpression of LDL receptor, sirtuin 1 (Sirt1), and the peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC-1α), respectively, compared to control. The observed results were counteracted by treatment with compound C, an AMPK pharmacological inhibitor, confirming that multiple effects of strawberries on lipid metabolism are mediated by the activation of this protein. ; European Union (EU) 679303

Conventional cardiovascular risk factors (CVRF) are accepted to identify asymptomatic individuals with high risk of acute myocardial infarction (AMI). However, AMI affects many patients previously classified at low risk. New biomarkers are needed to improve risk prediction. We propose to evaluate the NLRP3-inflammasome complex as a potential CVR indicator in healthy males and post-AMI patients and compare both groups by known CVRFs. We included 109 men with no history of cardiovascular disease (controls) and 150 AMI patients attending a cardiac rehabilitation program. AMI patients had higher mean of BMI and waist circumference than the controls. However, high percentages of the controls had a high BMI and a waist circumference >95 cm. The controls also had higher systolic blood pressure (P>0.001), total and LDLcholesterol, dietary nutrient and calorific intake. Fuster BEWAT Score (FBS) correlated more closely than Framingham risk score (FRS) with most CVRF, groups. However, only the FBS showed a correlation with inflammasome cytokine IL-1β. Several conventional CVRFs were significantly better in AMI patients; however, this group also had higher mRNA expression of the inflammasome gene NLRP3 and lower expression of the autophagy gene MAP-LC3. The controls had high levels of CVRF, probably reflecting unhealthy lifestyle. FBS reflects the efficiency of strategies to induce lifestyle changes such as cardiac rehabilitation programs, and could provide a sensitive evaluation cardiovascular risk. These results lead to the hypothesis that NLRP3- inflammasome and associated IL-1β release have potential as CVR biomarkers, particularly in post-AMI patients with otherwise low risk scores. ; Andalusian regional government (Grupo de Investigacion Junta de Andalucia) CTS113 Consejeria de Salud de la Junta de Andalucia: PI-0036-2014

Mediterranean countries have lower rates of mortality from cardiovascular disease and cancer than Northern European or other Western countries. This has been attributed, at least in part,tothe so-called Mediterranean diet, which is composed of specific local foods, including olive oil. Traditionally, many beneficial properties associated with this oil have been ascribed to its high oleic acid content. Today, it is clear that many of the beneficial effects of ingesting virgin olive oil are due to its minor compounds. This review summarizes the existing knowledge concerning the chemistry, pharmacokinetics, and toxicology of hydroxytyrosol, a minor compound of virgin olive oil, as well as this compound's importance for health. The main findings in terms of its beneficial effects in cardiovascular disease and cancer, including its properties against inflammation and platelet aggregation, are emphasized. New evidence and strategies regarding the use of hydroxytyrosol as a natural drug for the prevention and treatment of diseases with high incidences in Western countries are also presented. ; Excelentisima Diputacion de Jaen, CEAS Foundation 30.C0.244500 ; Junta de Andalucia PI-0210/2007 ; Spanish Government AP2005-144

While NLRP3‐inflammasome has been implicated in cardiovascular diseases, its role in physiological cardiac aging is largely unknown. During aging, many alterations occur in the organism, which are associated with progressive impairment of metabolic pathways related to insulin resistance, autophagy dysfunction, and inflammation. Here, we investigated the molecular mechanisms through which NLRP3 inhibition may attenuate cardiac aging. Ablation of NLRP3‐inflammasome protected mice from age‐related increased insulin sensitivity, reduced IGF‐1 and leptin/adiponectin ratio levels, and reduced cardiac damage with protection of the prolongation of the agedependent PR interval, which is associated with atrial fibrillation by cardiovascular aging and reduced telomere shortening. Furthermore, old NLRP3 KO mice showed an inhibition of the PI3K/AKT/mTOR pathway and autophagy improvement, compared with old wild mice and preserved Nampt‐mediated NAD+ levels with increased SIRT1 protein expression. These findings suggest that suppression of NLRP3 prevented many age‐associated changes in the heart, preserved cardiac function of aged mice and increased lifespan. ; Andalusian regional government; Consejería de Salud de la Junta de Andalucia, Grant/ Award Number: PI‐0036‐2014; Ministerio de economía y competitividad, Grant/Award Number: SAF2017‐84494‐C2‐1‐R

Periodontal disease is an inflammatory disease with high prevalence in adults that leads to destruction of the teeth-supporting tissues. Periodontal therapy has been traditionally directed at reduction of the bacterial load to a level that encourages health-promoting bacteria and maintenance of oral-hygiene. The role of nutrition in different chronic inflammatory diseases has been the subject of an increasing body of research in the last decades. In this sense, there has been an important increase in the volume of research on role of nutrition in periodontitis since the diet has known effects on the immune system and inflammatory cascades. Minerals play a key role in all these processes due to the multiple pathways where they participate. To clarify the role of the different minerals in the establishment, progression and/or treatment of this pathology, a systemically review of published literature cited in PubMed until May 2016 was conducted, which included research on the relationship of these elements with the onset and progression of periodontal disease. Among all the minerals, calcium dietary intake seems important to maintain alveolar bone. Likewise, dietary proportions of minerals that may influence its metabolism also can be relevant. Lastly, some observations suggest that all those minerals with roles in immune and/or antioxidant systems should be considered in future research. ; Alfonso Varela-López is recipient of a "Contrato Puente" from the University of Granada. Authors acknowledge to the University of Granada and the Autonomous Government of Andalusia for partial support of the research team. Francesca Giampieri was supported by a Fondazione Umberto Veronesi Fellowship.

The risk of different oral problems (root caries, tooth mobility, and tooth loss) can be increased by the presence of periodontal disease, which has also been associated with a growing list of systemic diseases. The presence of some bacteria is the primary etiology of this disease; a susceptible host is also necessary for disease initiation. In this respect, the progression of periodontal disease and healing of the periodontal tissues can be modulated by nutritional status. To clarify the role of lipids in the establishment, progression, and/or treatment of this pathology, a systematic review was conducted of English-written literature in PubMed until May 2016, which included research on the relationship of these dietary components with the onset and progression of periodontal disease. According to publication type, randomized-controlled trials, cohort, case-control and cross-sectional studies were included. Among all the analyzed components, those that have any effect on oxidative stress and/or inflammation seem to be the most interesting according to current evidence. On one hand, there is quite a lot of information in favor of a positive role of n-3 fatty acids, due to their antioxidant and immunomodulatory effects. On the other hand, saturated fat-rich diets increase oxidative stress as well the as intensity and duration of inflammatory processes, so they must be avoided. ; Alfonso Varela-López is recipient of a fellowship of FPU program from the Spanish Ministry of Education. Authors acknowledge to the University of Granada and the Autonomous Government of Andalusia for partial support of the research team.

Purpose: Metabolomics is the comprehensive global study of metabolites in biological samples. In this retrospective pilot study we explored whether serum metabolomic profile can discriminate the presence of human breast cancer irrespective of the cancer subtype. Methods: Plasma samples were analyzed from healthy women (n = 20) and patients with breast cancer after diagnosis (n = 91) using a liquid chromatographymass spectrometry platform. Multivariate statistics and a Random Forest (RF) classifier were used to create a metabolomics panel for the diagnosis of human breast cancer. Results: Metabolomics correctly distinguished between breast cancer patients and healthy control subjects. In the RF supervised class prediction analysis comparing breast cancer and healthy control groups, RF accurately classified 100% both samples of the breast cancer patients and healthy controls. So, the class error for both group in and the out-of-bag error were 0. We also found 1269 metabolites with different concentration in plasma from healthy controls and cancer patients; and basing on exact mass, retention time and isotopic distribution we identified 35 metabolites. These metabolites mostly support cell growth by providing energy and building stones for the synthesis of essential biomolecules, and function as signal transduction molecules. The collective results of RF, significance testing, and false discovery rate analysis identified several metabolites that were strongly associated with breast cancer. Conclusions: In breast cancer a metabolomics signature of cancer exists and can be detected in patient plasma irrespectively of the breast cancer type. ; Spanish Ministry of Economy and Competitiveness, Institute Carlos III (FIS grant) PI14/00328 ; Generalitat de Catalunya 2014SGR168 ; FEDER funds from the European Union ('Una manera de hacer Europa')

María D. Navarro-Hortal is a FPU fellow from the Spanish Ministry of Educación y Formación Profesional. The research group was partially supported by the Visiting Scholar Program from the University of Granada. The authors acknowledge Nutraceutical Translations for English language editing of this manuscript. ; Increasing evidence connects periodontitis with a variety of systemic diseases, including metabolic syndrome, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). The proposal of this study was to evaluate the role of diets rich in saturated fat and cholesterol in some aspects of periodontal diseases in a lipopolysaccharide (LPS)-induced model of periodontal disease in rabbits and to assess the influence of a periodontal intervention on hyperlipidemia, atherosclerosis, and NAFLD progression to non-alcoholic steatohepatitis. Male rabbits were maintained on a commercial standard diet or a diet rich in saturated fat (3% lard w/w) and cholesterol (1.3% w/w) (HFD) for 40 days. Half of the rabbits on each diet were treated 2 days per week with intragingival injections of LPS from Porphyromonas gingivalis. Morphometric analyses revealed that LPS induced higher alveolar bone loss (ABL) around the first premolar in animals receiving standard diets, which was exacerbated by the HFD diet. A higher score of acinar inflammation in the liver and higher blood levels of triglycerides and phospholipids were found in HFD-fed rabbits receiving LPS. These results suggest that certain dietary habits can exacerbate some aspects of periodontitis and that bad periodontal health can contribute to dyslipidemia and promote NAFLD progression, but only under certain conditions. ; Ministry of Education, Culture and Sport (Spain) ; Spanish Government ; Traslados Temporales FPU (University of Kings College of London)

The application of metallic nanoparticles (materials with size at least in one dimension ranging from 1 to 100 nm) as a new therapeutic tool will improve the diagnosis and treatment of diseases. The mitochondria could be a therapeutic target to treat pathologies whose origin lies in mitochondrial dysfunctions or whose progression is dependent on mitochondrial function. We aimed to study the subcellular distribution of 2–4 nm iron nanoparticles and its effect on mitochondrial DNA (mtDNA), mitochondrial function, and autophagy in colorectal cell lines (HT-29). Results showed that when cells were exposed to ultra-small iron nanoparticles, their subcellular fate was mainly mitochondria, affecting its respiratory and glycolytic parameters, inducing the migration of the cellular state towards quiescence, and promoting and triggering the autophagic process. These effects support the potential use of nanoparticles as therapeutic agents using mitochondria as a target for cancer and other treatments for mitochondria-dependent pathologies. ; Government of Asturias through the Science, Technology and Innovation Plan (PCTI) - FEDER funds FC-GRUPIN-IDI/2018/000242 ; Spanish Ministry of Economy, Industry and Competitiveness (MINECO) CTQ2016-80069-C 2-1R RTI2018-094605-B-I00

Periodontal disease, a relevant public health problem worldwide, is generally considered a common pathology of elderly people. In this respect, there is agreement about that nutritional status may be a modifying factor in the progression and healing of the periodontal tissues. Vitamins have been recommended as nutraceuticals for prevention and treatment of some pathological conditions, such as cardiovascular diseases, obesity or cancer. Thus, a systematic approach to determining how the different vitamin type could ameliorate periodontal risks or improve periodontal health is necessary to further the understanding of the potential benefits and risks of vitamins supplementation use. For this, a systematic review of English-written literature in PubMed until February 2018, which included both human and animal research on the relationship of each vitamin with periodontal disease, was conducted. Among all the analyzed vitamins those with antioxidant capacity and effects on immune system seem to be useful for prevention or improvement of periodontal disease, as well as those implicated in bone metabolism. In the first case, there are quite information in favor of various vitamins, mainly vitamin C, that is the most studied. In the second case, vitamin D seems to have the most relevant role. ; Authors acknowledge to the University of Granada and the Autonomous Government of Andalusia for partial support of the research team. Francesca Giampieri was supported by a Fondazione Umberto Veronesi Fellowship. Alfonso Varela-López is recipient of a postdoctoral fellowship from the Foundation Alfonso Martin Escudero. María D. Navarro-Hortal has enjoyed a Research Initiation Scholarship for undergraduate students of the University of Granada's Own Plan during the 2016–2017 academic year and a Student Collaboration Grant for Research in University Departments for the academic year 2017–2018, from the Spanish Ministry of Education, Culture and Sports, 2017/2018 call.

An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources. ; Spanish Government AGL2008-01057 ; Autonomous Government of Andalucia AGR832 ; German Research Foundation (DFG) ; Generalitat Valenciana APOSTD/2012/021

María Dolores Navarro-Hortal is a FPU fellow from the Spanish Ministry of Ciencia, Innovación y Universidades. We acknowledge Nutraceutical Translations for English language editing of this manuscript. ; Beeswax is useful for the beekeeping sector but also for the agro-food, pharmaceutical or cosmetics sectors. Frequently, this bee product is contaminated with pesticides reducing its utility and causing the decline in its market. This study aimed to prove the effectiveness of an industrial-scale decontamination method in removing acaricides from beeswax. Chlorfenvinphos and coumaphos decrease was higher than 90%, whereas tau fluvalinate decrease was only 30%. No changes were observed in the beeswax content of hydrocarbons and monoesters, whereas a decrease in the concentrations of Ca, Fe, Zn, Hg, Mn and P, and an increase in the concentrations of As and Si were found after the decontamination. Filtration reduced total phenolics, flavonoids and the antioxidant capacity of the lipophilic extract. These results demonstrate that the industrial method used was as effective as the method previously tested on a laboratory scale. The study also contributes to a better knowledge and characterization of beeswax, specially related to trace and ultra-trace elements and antioxidant capacity. Moreover, it offers the chance to further develop a method to effectively detect wax adulterations based on the chemical elements profile. ; The present study was partially funded by the "National Beekeeping Aid Program (Programa Nacional de Ayudas a la Apicultura)", cofounded by the European Union and assigned to Spanish FEGA and FEAGA agencies (2016).