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Dierssen-Sotos T.,CIBER ISCIII | Dierssen-Sotos T.,University of Cantabria | Gomez-Acebo I.,CIBER ISCIII | Gomez-Acebo I.,University of Cantabria | And 45 more authors.
Preventive Medicine | Year: 2017

The potential protective effect of renin–angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65 years group (OR = 0.65 95%CI (0.48–0.89)) and to a lesser degree to men (OR = 0.81 95%CI (0.66–0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65 years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65 years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location. © 2017 Elsevier Inc.


Robles-Vera I.,University of Granada | Toral M.,University of Granada | Romero M.,University of Granada | Romero M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | And 6 more authors.
Current Hypertension Reports | Year: 2017

Purpose of Review: The present review focuses in the hypertension-associated changes in the microbiota and the current insights regarding the impact of probiotics on blood pressure in animal models and in human hypertensive patients. Recent Findings: Gut dysbiosis in hypertension is characterized by (i) the gut microbioma that is less diverse and less rich with an increased Firmicutes/Bacteroidetes ratio and (ii) a decrease in acetate- and butyrate-producing bacteria and an increase in lactate-producing bacterial populations. The meta-analysis of the human studies supports that supplementation with probiotics reduces blood pressure. The mechanism of this antihypertensive effect of probiotics and its protective effect on endothelial function has not been fully elucidated. Summary: Further investigations are needed to clarify if the effects of probiotic bacteria result from the changes in the gut microbiota and its metabolic by-products; the restoration of the gut barrier function; and the effects on endotoxemia, inflammation, and renal sympathetic nerve activity. © 2017, Springer Science+Business Media New York.


Molina-Molina J.-M.,University of Granada | Molina-Molina J.-M.,CIBER ISCIII | Molina-Molina J.-M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Real M.,University of Granada | And 10 more authors.
Food and Chemical Toxicology | Year: 2014

Zearalenone (ZEN) is a well-known mycotoxin present in numerous agricultural products. Humans and animals are therefore at a risk of exposure to zearalenone through consumption of contaminated food. After intake, ZEN is reduced to α- and β-zearalenol (α-ZEL and β-ZEL), zearalanone (ZAN), and α- and β-zearalanol (α-ZAL and β-ZAL). Although their estrogenicity has been well characterized, much less is known about their interaction with other nuclear receptors. This study was undertaken to investigate interactions of ZEN and its five metabolites, with the human androgen receptor (hAR) and estrogen receptor alpha (hERα). Their ability to induce hAR-mediated reporter gene expression was examined in androgen-sensitive PALM cells, whereas the effects on hERα function were assessed in MCF-7 cells using the E-Screen bioassay. We confirm that ZEN and its metabolites are full agonists for hERα and demonstrate that all six compounds tested possess hAR-mediated antagonistic activity in PALM cells, in which ZAN, α-ZAL, and β-ZAL were the most effective hAR antagonists. Overall, the observed estrogenic and anti-androgenic potencies of ZEN and its metabolites suggest that these compounds may interfere with the endocrine system by various modes of action and that further investigation is warranted into their role as endocrine disrupters in animals and humans. © 2014 Elsevier Ltd.


Lope V.,Carlos III Institute of Health | Lope V.,CIBER ISCIII | Lope V.,Cancer Epidemiology Research Group | De Larrea N.F.,Carlos III Institute of Health | And 51 more authors.
PLoS ONE | Year: 2016

Background: Sex hormones play a role in gastric cancer and colorectal cancer etiology, however, epidemiological evidence is inconsistent. This study examines the influence of menstrual and reproductive factors over the risk of both tumors. Methods: In this case-control study 128 women with gastric cancer and 1293 controls, as well as 562 female and colorectal cancer cases and 1605 controls were recruited in 9 and 11 Spanish provinces, respectively. Population controls were frequency matched to cases by age and province. Demographic and reproductive data were directly surveyed by trained staff. The association with gastric, colon and rectal cancer was assessed using logistic and multinomial mixed regression models. Results: Our results show an inverse association of age at first birth with gastric cancer risk (fiveyear trend: OR = 0.69; p-value = 0.006). Ever users of hormonal contraception presented a decreased risk of gastric (OR = 0.42; 95%CI = 0.26-0.69), colon (OR = 0.64; 95%CI = 0.48-0.86) and rectal cancer (OR = 0.61; 95%CI = 0.43-0.88). Postmenopausal women who used hormone replacement therapy showed a decreased risk of colon and rectal tumors. A significant interaction of educational level with parity and months of first child lactation was also observed. Conclusion: These findings suggest a protective role of exogenous hormones in gastric and colorectal cancer risk. The role of endogenous hormones remains unclear. Copyright © 2016 Lope et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Real M.,University of Granada | Real M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Molina-Molina J.-M.,University of Granada | Molina-Molina J.-M.,CIBER ISCIII | And 9 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2015

Medicinal plants are widely used for the treatment of diseases and for the development of new drugs. This study was designed to determine the presence of hormone-like activities dependent on the activation of human estrogen receptor alpha (hERa) and/or androgen receptor (hAR) in methanol extracts prepared from three medicinal plants historically and currently used for therapeutic purposes: Ginkgo biloba leaves (GBL), Elettaria cardamomum seeds (ECS) and Plantago ovata seeds (POS). After a solid–liquid extraction (SLE) step, their effects on hERa function were assessed in MCF-7 breast cancer cells using the E-Screen bioassay, and their ability to induce hAR-mediated reporter gene expression was evaluated using the androgen-sensitive stable prostatic PALM cell line. Unlike POS extracts, GBL and ECS extracts showed estrogenic (0.07 and 0.20 nM E2Eq mg–1, respectively) and anti-estrogenic (0.01 and 0.02 μM ICI182780Eq mg–1, respectively) activities. ECS extracts evidenced androgenic activity (0.30 nM R1881Eq mg–1) and POS extracts anti-androgenic activity (22.30 μM ProcEq mg–1). According to these findings, these plant extracts may interfere with the endocrine system via one or more hormonal receptors, and further investigation is warranted into their role as endocrine disrupters in humans. © 2015 Taylor & Francis.


Romero M.,University of Granada | Romero M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Toral M.,University of Granada | Gomez-Guzman M.,University of Granada | And 9 more authors.
Food and Function | Year: 2016

The effects of chronic consumption of oleuropein-enriched (15% w/w) olive leaf extract (OLE) on blood pressure, endothelial function, and vascular oxidative and inflammatory status in spontaneously hypertensive rats (SHR) were evaluated. Ten Wistar Kyoto rats (WKY) and twenty SHR were randomly assigned to three groups: a control WKY group, a control SHR group and a SHR group treated with OLE (30 mg kg-1) for 5 weeks. Long-term administration of OLE reduced systolic blood pressure, heart rate, and cardiac and renal hypertrophy. OLE treatment reversed the impaired aortic endothelium-dependent relaxation to acetylcholine observed in SHR. OLE restored aortic eNOS phosphorylation at Ser-1177 and Thr-495 and increased eNOS activity. OLE eliminated the increased aortic superoxide levels, and reduced the elevated NADPH oxidase activity, as a result of reduced NOX-1 and NOX-2 mRNA levels in SHR. OLE reduced the enhanced vascular TLR4 expression by inhibition of mitogen-activated protein kinase (MAPK) signaling with the subsequent reduction of proinflammatory cytokines. In conclusion, OLE exerts antihypertensive effects on genetic hypertension related to the improvement of vascular function as a result of reduced pro-oxidative and pro-inflammatory status. © The Royal Society of Chemistry 2016.


Rodriguez-Barranco M.,University of Granada | Rodriguez-Barranco M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | Lacasana M.,University of Granada | Lacasana M.,Institute Investigacion Biosanitaria Of Granada Ibsgranada | And 12 more authors.
Environmental Research | Year: 2014

This study assessed the association between cadmium exposure and neuropsychological development in children from a region with high industrial and mining activities in southwestern Spain. We conducted a cross-sectional study with 261 children aged 6-9 years between January and March 2012. Cadmium exposure was measured in urine and hair of children, and neuropsychological development was assessed with the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) and with three computerized tests from the Behavioral Assessment and Research System (BARS): Reaction Time Test (RTT), Continuous Performance Test (CPT) and Selective Attention Test (SAT). Multivariate linear regression models, adjusted for potential confounders, were used to estimate the association between neuropsychological development and cadmium exposure measured in urine and hair samples. Geometric means of urine and hair cadmium levels were 0.75. μg/g creatinine and 0.01. μg/g, respectively. We observed that doubling of levels of cadmium in urine was associated with a reduction of two points (95% CI: -3.8 to -0.4) in the Full-Scale intelligence quotient (IQ) in boys. By domains, association was statistically significant for Verbal Comprehension ( β=-2.0; p=0.04) and close to the significance level for Perceptual Reasoning ( β=-1.8; p=0.06). Among girls, only Verbal Comprehension showed suggestive associations with cadmium exposure ( β=-1.7; p=0.06). Cadmium exposure is associated with cognitive delays in boys in our region. Our results provide additional evidence of the neurotoxic effect of low-level postnatal cadmium exposure among children, and support the hypothesis of differences between sexes in the neurotoxic effect of metals on children. © 2014 Elsevier Inc.

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