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

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

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

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Ciencia Odontológica 2.0

Libro que muestra avances de la Investigación Odontológica en MéxicoEs para los integrantes de la Red de Investigación en Estomatología (RIE) una enorme alegría presentar el segundo de una serie de 6 libros sobre casos clínicos, revisiones de la literatura e investigaciones. La RIE está integrada por cuerpos académicos de la UAEH, UAEM, UAC y UdeG

Central proliferation and neurogenesis is impaired in type 2 diabetes and prediabetes animal models

This is an open-access article distributed under the terms of the Creative Commons Attribution License.Type 2 diabetes (T2D) is an important risk factor to suffer dementia, including Alzheimer's disease (AD), and some neuropathological features observed in dementia could be mediated by T2D metabolic alterations. Since brain atrophy and impaired neurogenesis have been observed both T2D and AD we analyzed central nervous system (CNS) morphological alterations in the db/db mice (leptin receptor KO mice), as a model of long-term insulin resistance and T2D, and in C57Bl6 mice fed with high fat diet (HFD), as a model of diet induced insulin resistance and prediabetes. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. We also detected increased neurogenesis and cell proliferation rates in young db/db mice when compared with control littermates. Our study shows that metabolic parameters serve as predictors of both atrophy and altered proliferation and neurogenesis in the CNS. Moreover in the cortex, atrophy, cell proliferation and neurogenesis were significantly correlated. Our data suggest that T2D may underline some of the pathological features observed in the dementia process. They also support that blood glucose control in elderly patients could help to slow down dementia evolution and maybe, improve its prognosis. © 2014 Ramos-Rodriguez et al.RYC-2008-02333, Junta de Andalucia, Proyectos de Excelencia (P11-CTS-7847), Instituto de Salud Carlos III and FEDER (European Union), cofinanced by Fondo Europeo de Desarrollo Regional ‘‘Una manera de hacer Europa’’ PI12/00675 (Monica Garcia-Alloza) IC-C: RYC-2011-08101, ISCIII Subdirección General de Evaluación y Fomento de la Investigación, Spain (PS09/00671), Europe-FP7 Marie Curie grant (IRG-247835).Peer Reviewe

Brain atrophy in db/db mice.

<p><b>A</b>) Brain weight was significantly reduced is db/db mice as disease progressed. At 4 weeks of age brains were significantly smaller in Control and db/db mice, when compared with adult brains. As T2D worsened a significant reduction in brain weight was observed in 14 and 26 weeks of age db/db mice, whereas no effect of prediabetes was observed in HFD treated mice [F_(7,31) = 23.70, **p<0.01 vs. Control 14 and 26 weeks, C57 RD and C57 HFD]. <b>B</b>) Cortical thickness affected as disease progressed and specific cortical areas were significantly reduced. Frontal cortex was thinner in db/db mice by 14 weeks of age and this effect was worsened by 26 weeks of age [F_(7,337) = 11.683, **p<0.01 vs. Control 14 weeks, Control 26 weeks, Control and db/db 4 weeks, RD and HFD treated mice]. A similar profile was observed in the parietal cortex and a progressive thinning effect was observed in db/db mice [F_(7,161) = .34, **p<0.01 vs. Control 14 weeks, Control 26 weeks, Control and db/db 4 weeks, RD and HFD treated mice]. Temporal cortex was only affected in 26 weeks db/db mice when compared with the rest of the groups [F_(7,250) = 114.232, **p<0.01 vs. Control and db/db 4 weeks, RD and HFD treated mice]. <b>C</b>) A similar profile was observed in the hippocampus, although thinning effect was detected at later stages. A significant reduction in dental gyrus thickness was only detectable in db/db mice at 26 weeks of age [F(7,118) = 1.11, *p = 0.47 vs. Control 26 weeks]. Hippocampal CA2 thickness was also significantly reduced in db/db 26 weeks [F(7,116) = 2.313, *p = 0.30 vs. Control 26 weeks]. Although a reduction in CA3 thicknes was observed in db/db mice at 14 weeks of age, differences only reached statistical significance in db/db 26 weeks mice [F(7,115) = 2.970, **p = 0.007 vs. RD and HFD treated mice]. <b>D</b>) Illustrative example of cortical thinning in db/db and control mice at 4, 14 and 26 weeks of age. Scale bar: 500 µm.</p

Body weight, glucose and insulin levels in 4, 14 and 26 weeks db/db and Control mice as well as in 26 weeks C57Bl6 mice after 18 weeks fed with HFD.

<p>Metabolic parameters including body weight, glucose and insulin levels were determined at the end of the experiments. Differences were detected by one-way ANOVA followed by Tuckey b or Tamhane tests as required. When we compared all groups under study we observed a significant increase in body weight as age progressed, and even higher body weights were observed in overweight mice (db/db 14 weeks old mice, db/db 26 weeks old mice and HFD treated mice), when compared to the rest of the groups [F_(7,35) = 63.03, **p<0.01 vs. Control 14 weeks, Control 26 weeks, RD and 4 weeks old mice (db/db and Control), ††<0.01 vs. Control and db/db 4 weeks]. Glucose levels were significantly higher in db/db mice both at 14 and 26 weeks of age when compared with the rest of the groups [F_(7,35) = 74.36, **p<0.01 vs. Control 14 weeks, Control 26 weeks, RD, HFD and 4 weeks old mice (db/db and Control)]. Increased insulin levels were observed in db/db 4 weeks mice, although these differences did not reach statistical significance. Significant hyperinsulinemia was observed in db/db 14 weeks and db/db 26 weeks whereas statistically higher levels were observed in HFD treated mice [F_(7,35) = 11.498, **p<0.01 vs. Control 14 weeks, Control 26 weeks, RD and 4 weeks old mice (db/db and Control), ††p<0.01 vs. rest of the groups].</p