21 research outputs found

    Association between circulating levels of sex steroid hormones and esophageal adenocarcinoma in the FINBAR Study

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    Funding: The study was supported by NIH Intramural Research Program, National Cancer Institute; Cancer Focus Northern Ireland (formerly the Ulster Cancer Foundation); the Northern Ireland R&D office; and the Health Research Board, Ireland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

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    Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

    Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

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    There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

    Adjusted<sup>a</sup> odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between circulating metabolite concentrations and esophageal adenocarcinoma incidence, in the FINBAR Study: 2002‚Äď2004.

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    <p>Adjusted<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0190325#t002fn001" target="_blank"><sup>a</sup></a> odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between circulating metabolite concentrations and esophageal adenocarcinoma incidence, in the FINBAR Study: 2002‚Äď2004.</p

    Interaction of the Human Prostacyclin Receptor and the NHERF4 Family member Intestinal and Kidney Enriched PDZ Protein (IKEPP)

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    Prostacyclin and its I Prostanoid receptor, the IP, play central roles in haemostasis and in re-endothelialization in response to vascular injury. Herein, Intestinal and Kidney Enriched PDZ Protein (IKEPP) was identified as an interactant of the human (h) IP mediated through binding of PDZ domain 1 (PDZD1) and, to a lesser extent, PDZD2 of IKEPP to a carboxyl-terminal Class I ‚ÄėPDZ ligand‚Äô within the hIP. While the interaction is constitutive, agonist-activation of the hIP leads to cAMP-dependent protein kinase (PK) A and PKC- phosphorylation of IKEPP, coinciding with its increased interaction with the hIP. Ectopic expression of IKEPP increases functional expression of the hIP, enhancing its ligand binding and agonist-induced cAMP generation. Originally thought to be restricted to renal and gastrointestinal tissues, herein, IKEPP was also found to be expressed in vascular endothelial cells where it co-localizes and complexes with the hIP. Furthermore, siRNA-disruption of IKEPP expression impaired hIP-induced endothelial cell migration and in vitro angiogenesis, revealing the functional importance of the IKEPP:IP interaction within the vascular endothelium. Identification of IKEPP as a functional interactant of the IP reveals novel mechanistic insights into the role of these proteins within the vasculature and, potentially, in other systems where they are co-expressed.Science Foundation IrelandDG - 10/10/1

    Distribuição das espécies de corais azooxantelados na plataforma e talude continental superior do sul do Brasil Distribution of deep-sea azooxanthellate scleractinians from southern Brazilian waters

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    Dentre os organismos registrados para √°guas profundas (> 100 m) no sul do Brasil, podemos destacar os corais azooxantelados pertencentes a ordem Scleractinia. Atrav√©s de an√°lises estat√≠sticas, identifica√ß√£o de esp√©cimes depositados em cole√ß√Ķes cient√≠ficas, e compila√ß√£o de todos os registros pret√©ritos destes cnidarios ocorrentes no sul e parte do sudeste do Brasil, foi poss√≠vel constatar que as coordenadas abrangidas no presente estudo representam uma √°rea de transi√ß√£o entre os corais azooxantelados ocorrentes ao norte e as esp√©cies mais caracter√≠sticas das zonas polares, principalmente em rela√ß√£o √†s esp√©cies solit√°rias. Com a an√°lise da distribui√ß√£o batim√©trica, foi observado um significativo aumento no n√ļmero de esp√©cies entre o setor de plataforma externa e 500 m de profundidade. Finalizando, foi realizada a an√°lise de agrupamento, o que permitiu discriminar a forma√ß√£o de 6 bi√≥topos das associa√ß√Ķes de corais azooxantelados para a √°rea de estudo. Desta forma, apresentamos a primeira tentativa de se compreender a distribui√ß√£o desta pouco conhecida fauna da plataforma e talude continental superior, entre 24¬ļS e 34¬ļS.<br>Amongst organisms reported in deep waters (> 100 m) from southern Brazil, the azooxanthellate scleractinians are of particular importance due to their capacity to form habitats which attract many species of invertebrates and vertebrates. Through statistical analysis of distribution, identification of specimens deposited in scientific collections, and revision of all preterite records of azooxanthellate scleractinians from southern and part of southeastern coast of Brazil, was noted that the coordinates covered by the present study represent an transitional distributional area between the Caribbean and marginal Antarctic fauna, especially for the solitary species. From a vertical distribution analysis, an increase in the number of species in the sector between the external continental shelve and 500 m depth was observed. A grouping analysis was performed, allowing the discrimination of 6 association biotopes of corals. Thus, we present the first attempt to understand the distribution of this fauna from the continental shelf and continental slope of southern Brazil, between 24¬įS and 34¬įS