Pleiotropic Biological Effects of Dietary Phenolic Compounds and their Metabolites on Energy Metabolism, Inflammation and Aging

The authors would like to thank to the Ministry of Science, Innovation and Universities (RTI2018-096724-B-C22). The author M.d.C.V.-A. is grateful acknowledges to the Ministry of Science, Innovation and Universities, University of Granada and AGR274 group for the contract (5450). Also, the authors are grateful to the University of Granada for a “Contrato Puente” postdoctoral contracts (Á.F.-O. and S.P.-M.) and a “Perfeccionamiento de Doctores” postdoctoral contract (M.d.l.L.C.-G.).Dietary phenolic compounds are considered as bioactive compounds that have effects in different chronic disorders related to oxidative stress, inflammation process, or aging. These compounds, coming from a wide range of natural sources, have shown a pleiotropic behavior on key proteins that act as regulators. In this sense, this review aims to compile information on the effect exerted by the phenolic compounds and their metabolites on the main metabolic pathways involved in energy metabolism, inflammatory response, aging and their relationship with the biological properties reported in high prevalence chronic diseases. Numerous in vitro and in vivo studies have demonstrated their pleiotropic molecular mechanisms of action and these findings raise the possibility that phenolic compounds have a wide variety of roles in different targets.Ministry of Science, Innovation and Universities (RTI2018-096724-B-C22)University of Granada and AGR274 group for the contract (5450

LC-MS and Spectrophotometric Approaches for Evaluation of Bioactive Compounds from Peru Cocoa By-Products for Commercial Applications

Peru is one of the main areas where there are large cocoa crops with special relevance to the economy of this country. In fact, cocoa is a major, economically important, international crop which has been linked to several benefits, such as anti-allergenic, anti-atherogenic, anti-inflammatory, anti-microbial, anti-oxidant, anti-thrombotic, cardioprotective and vasodilatory properties, relating to its bioactive compound content. However, in cocoa industrial processing, several residues or wastes, which are commonly discarded generating a negative impact on the environment, are produced in large amounts. Some of the cocoa by-products, which go underutilized, could be a good source of bioactive compounds with high utility for the development of innovative products in nutraceutical, medical or pharmaceutical industries. For this reason, the aim of this study is to qualitatively determine the phytochemical composition of husk and bean extracts from different cocoa-growing areas and processes from Peru by high performance liquid chromatography coupled to mass spectrometry. Furthermore, we aim to evaluate their phenolic and flavan-3-ol contents and antioxidant capacities for the purpose of highlighting the potential of cocoa by-products from these cultivars as functional ingredients. In total, 49 chemical compounds were detected in the analyzed extracts. Comparing both husks and beans, bean extracts were characterized by high content in flavonoids whereas husk extracts had a higher content of phenolic acids. The presence of these compounds together with the bioactivity results suggest that these matrices may be further studied for their revaluation in the development of high added-value products in nutraceutical, medical, and pharmaceutical industries.Ministry of Science, Innovation and Universities RTI2018-096724-B-C22Spanish Ministry of Economy and Competitiveness (MINECO) BES-2016-076618Ministry of Science, Innovation and UniversitiesAGR274 group 5450University of Granad

Risk factors in the development of breast cancer, state of Mexicoº

Introducción: El cáncer de mama es una de las patología más frecuentes de la mujer y con gran impacto en la sociedad. Los factores de riesgo más estudiados han sido los hormonales, los genéticos y los ambientales, aunque también los hábitos tóxicos, el sobrepeso y la obesidad; como factores protectores, por el contrario, la lactancia materna y la actividad física. Objetivo: Conocer los factores de riesgo de las mujeres con cáncer de mama en nuestro grupo de estudio. Material y métodos: Se realizó un estudio de casos y controles en 115 mujeres diagnosticadas con cáncer de mama y en 115 mujeres sanas que acudieron al centro Oncológico de ISSEMyM en el periodo enero-diciembre del año 2011. Se recogieron datos sobre la historia familiar de cáncer, de los antecedentes personales, así como de los estilos de vida y de la determinación del Índice de Masa Corporal (IMC). El riesgo fue estimado con modelos multivariados de regresión logística y chi cuadrada. Resultados: Se encontró un riesgo mayor de padecer cáncer de mama a las mujeres con sobrepeso y obesidad, que no desarrollaban ejercicio alguno y con un menor índice de lactancia materna. No se encontraron diferencias significativas entre el cáncer de mama y los hábitos tóxicos. Conclusiones: En nuestro estudio, el cáncer de mama se relaciona con el sobrepeso, la obesidad y la inactividad física. La lactancia materna, practicada durante los primeros meses de vida del bebé, se manifestó como un factor protector de padecer esta enfermedad.Introduction: Breast cancer is one of the most frequent diseases in women today, and its social impact is devastating. The risk factors focused on in recent research are mainly hormonal, genetic, and environmental though toxic habits, overweight, and obesity have also been studied. In contrast, protective factors against breast cancer include breastfeeding and daily exercise. Objective: To ascertain the risk factors for the women with breast cancer in our study sample. Material and methods: A study of cases and controls was performed on 115 women diagnosed with breast cancer and on 115 healthy women, who had been patients at the National Cancer Institute ISSEMYM in Mexico from January to December 2011. Information was collected from the women in the sample pertaining to their family history of cancer, personal background, life style, and body mass index (BMI). Breast cancer risk was estimated with multivariate logistic regression models and the chi-square test. Results: It was found that there was a greater risk of breast cancer in overweight or obese women who did not do any physical exercise and either who had breastfed their children for a very short time or who had not breastfed them at all. No significant differences were found between breast cancer and toxic habits. Conclusions: The results of our study found a direct relation between breast cancer and overweight, obesity, and physical inactivity. Breastfeeding during the first months of the babyís life was found to be a protective factor against breast cancer

Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors

Circadian rhythm synchronizes each body function with the environment and regulates physiology. Disruption of normal circadian rhythm alters organismal physiology and increases disease risk. Recent epidemiological data and studies in model organisms have shown that maternal circadian disruption is important for offspring health and adult phenotypes. Less is known about the role of paternal circadian rhythm for offspring health. Here, we disrupted circadian rhythm in male mice by night-restricted feeding and showed that paternal circadian disruption at conception is important for offspring feeding behavior, metabolic health, and oscillatory transcription. Mechanistically, our data suggest that the effect of paternal circadian disruption is not transferred to the offspring via the germ cells but initiated by corticosterone-based parental communication at conception and programmed during in utero development through a state of fetal growth restriction. These findings indicate paternal circadian health at conception as a newly identified determinant of offspring phenotypes

The occurrence of tarsal injuries in male mice of C57BL/6N substrains in multiple international mouse facilities.

Dislocation in hindlimb tarsals are being observed at a low, but persistent frequency in group-housed adult male mice from C57BL/6N substrains. Clinical signs included a sudden onset of mild to severe unilateral or bilateral tarsal abduction, swelling, abnormal hindlimb morphology and lameness. Contraction of digits and gait abnormalities were noted in multiple cases. Radiographical and histological examination revealed caudal dislocation of the calcaneus and partial dislocation of the calcaneoquartal (calcaneus-tarsal bone IV) joint. The detection, frequency, and cause of this pathology in five large mouse production and phenotyping centres (MRC Harwell, UK; The Jackson Laboratory, USA; The Centre for Phenogenomics, Canada; German Mouse Clinic, Germany; Baylor College of Medicine, USA) are discussed

The International Mouse Phenotyping Consortium (IMPC): a functional catalogue of the mammalian genome that informs conservation.

The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of mammalian gene function by producing and phenotyping a knockout mouse line for every protein-coding gene. To date, the IMPC has generated and characterised 5186 mutant lines. One-third of the lines have been found to be non-viable and over 300 new mouse models of human disease have been identified thus far. While current bioinformatics efforts are focused on translating results to better understand human disease processes, IMPC data also aids understanding genetic function and processes in other species. Here we show, using gorilla genomic data, how genes essential to development in mice can be used to help assess the potentially deleterious impact of gene variants in other species. This type of analyses could be used to select optimal breeders in endangered species to maintain or increase fitness and avoid variants associated to impaired-health phenotypes or loss-of-function mutations in genes of critical importance. We also show, using selected examples from various mammal species, how IMPC data can aid in the identification of candidate genes for studying a condition of interest, deliver information about the mechanisms involved, or support predictions for the function of genes that may play a role in adaptation. With genotyping costs decreasing and the continued improvements of bioinformatics tools, the analyses we demonstrate can be routinely applied

Streptozotocin-induced beta-cell damage, high fat diet, and metformin administration regulate Hes3 expression in the adult mouse brain

Diabetes mellitus is a group of disorders characterized by prolonged high levels of circulating blood glucose. Type 1 diabetes is caused by decreased insulin production in the pancreas whereas type 2 diabetes may develop due to obesity and lack of exercise;it begins with insulin resistance whereby cells fail to respond properly to insulin and it may also progress to decreased insulin levels. The brain is an important target for insulin, and there is great interest in understanding how diabetes affects the brain. In addition to the direct effects of insulin on the brain, diabetes may also impact the brain through modulation of the inflammatory system. Here we investigate how perturbation of circulating insulin levels affects the expression of Hes3, a transcription factor expressed in neural stem and progenitor cells that is involved in tissue regeneration. Our data show that streptozotocin-induced beta-cell damage, high fat diet, as well as metformin, a common type 2 diabetes medication, regulate Hes3 levels in the brain. This work suggests that Hes3 is a valuable biomarker helping to monitor the state of endogenous neural stem and progenitor cells in the context of diabetes mellitus

Towards frailty biomarkers:Candidates from genes and pathways regulated in aging and age-related diseases

Objective: Use of the frailty index to measure an accumulation of deficits has been proven a valuable method for identifying elderly people at risk for increased vulnerability, disease, injury, and mortality. However, complementary molecular frailty biomarkers or ideally biomarker panels have not yet been identified. We conducted a systematic search to identify biomarker candidates for a frailty biomarker panel. Methods: Gene expression databases were searched (http://genomics.senescence.info/genes including GenAge, AnAge, LongevityMap, CellAge, DrugAge, Digital Aging Atlas) to identify genes regulated in aging, longevity, and age-related diseases with a focus on secreted factors or molecules detectable in body fluids as potential frailty biomarkers. Factors broadly expressed, related to several \u201challmark of aging\u201d pathways as well as used or predicted as biomarkers in other disease settings, particularly age-related pathologies, were identified. This set of biomarkers was further expanded according to the expertise and experience of the authors. In the next step, biomarkers were assigned to six \u201challmark of aging\u201d pathways, namely (1) inflammation, (2) mitochondria and apoptosis, (3) calcium homeostasis, (4) fibrosis, (5) NMJ (neuromuscular junction) and neurons, (6) cytoskeleton and hormones, or (7) other principles and an extensive literature search was performed for each candidate to explore their potential and priority as frailty biomarkers. Results: A total of 44 markers were evaluated in the seven categories listed above, and 19 were awarded a high priority score, 22 identified as medium priority and three were low priority. In each category high and medium priority markers were identified. Conclusion: Biomarker panels for frailty would be of high value and better than single markers. Based on our search we would propose a core panel of frailty biomarkers consisting of (1) CXCL10 (C-X-C motif chemokine ligand 10), IL-6 (interleukin 6), CX3CL1 (C-X3-C motif chemokine ligand 1), (2) GDF15 (growth differentiation factor 15), FNDC5 (fibronectin type III domain containing 5), vimentin (VIM), (3) regucalcin (RGN/SMP30), calreticulin, (4) PLAU (plasminogen activator, urokinase), AGT (angiotensinogen), (5) BDNF (brain derived neurotrophic factor), progranulin (PGRN), (6) \u3b1-klotho (KL), FGF23 (fibroblast growth factor 23), FGF21, leptin (LEP), (7) miRNA (micro Ribonucleic acid) panel (to be further defined), AHCY (adenosylhomocysteinase) and KRT18 (keratin 18). An expanded panel would also include (1) pentraxin (PTX3), sVCAM/ICAM (soluble vascular cell adhesion molecule 1/Intercellular adhesion molecule 1), defensin \u3b1, (2) APP (amyloid beta precursor protein), LDH (lactate dehydrogenase), (3) S100B (S100 calcium binding protein B), (4) TGF\u3b2 (transforming growth factor beta), PAI-1 (plasminogen activator inhibitor 1), TGM2 (transglutaminase 2), (5) sRAGE (soluble receptor for advanced glycosylation end products), HMGB1 (high mobility group box 1), C3/C1Q (complement factor 3/1Q), ST2 (Interleukin 1 receptor like 1), agrin (AGRN), (6) IGF-1 (insulin-like growth factor 1), resistin (RETN), adiponectin (ADIPOQ), ghrelin (GHRL), growth hormone (GH), (7) microparticle panel (to be further defined), GpnmB (glycoprotein nonmetastatic melanoma protein B) and lactoferrin (LTF). We believe that these predicted panels need to be experimentally explored in animal models and frail cohorts in order to ascertain their diagnostic, prognostic and therapeutic potential

Reorganización de los centros de capacitación de la Asociación Fe y Alegría tomo I Diagnóstico

La Asociación Fé y Alegria cuenta con centros de capacitación y cada uno de ellos tiene como objetivo primordial la reorganización de dichos centros, que consiste en el rediseño de los planes de estudios de los sistemas de control administrativo

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function