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

Multi-Agent Reinforcement Learning in Network Management

Abstract. This paper outlines research in progress intended to contribute to the autonomous management of networks, allowing policies to be dynamically adjusted and aligned to application directives according to the available resources. Many existing management approaches require static a priori policy deployment but our proposal goes one step further modifying initially deployed policies by learning from the system behaviour. We use a hierarchical policy model to show the connection of high level goals with network level configurations. We also intend to solve two important and mostly forgotten issues: the system has multiple goals some of them contradictory and we will show how to overcome it; and, some current works optimize one network element but being unaware of other participants; instead, our proposed scheme takes into account various social behaviours, such as cooperation and competition among different elements

Elasticity assessment of electrospun nanofibrous vascular grafts: a comparison with femoral ovine arteries

Development of successful small-diameter vascular grafts constitutes a real challenge to biomaterial engineering. In most cases these grafts fail in-vivo due to the presence of a mechanical mismatch between the native vessel and the vascular graft. Biomechanical characterization of real native vessels provides significant information for synthetic grafts development. Electrospun nanofibrous vascular grafts emerge as a potential tailor made solution to this problem. PLLA-electrospun nanofibrous tubular structures were prepared and selected as model bioresorbable grafts. An experimental setup, using gold standard and high resolution ultrasound techniques, was adapted to characterize in vitro the Poly(L-lactic acid) (PLLA) electrospun structures. The grafts were subjected to near physiologic pulsated pressure conditions, following the pressure-diameter loop approach and the criteria stated in the international standard for cardiovascular implants-tubular vascular prostheses. Additionally, ovine femoral arteries were subjected to a similar evaluation. Measurements of pressure and diameter variations allowed the estimation of dynamical compliance (C%, 10-2 mmHg) and the pressure-strain elastic modulus (EPe, 106 dyn cm-2) of the abovementioned vessels (grafts and arteries). Nanofibrous PLLA showed a decrease in %C (1.38 ± 0.21, 0.93 ± 0.13 and 0.76 ± 0.15) concomitant to an increase in EPe (10.57 ± 0.97, 14.31 ± 1.47 and 17.63 ± 2.61) corresponding to pressure ranges of 50 to 90 mmHg, 80 to 120 mmHg and 100 to 150 mmHg, respectively. Furthermore, femoral arteries exhibited a decrease in %C (8.52 ± 1.15 and 0.79 ± 0.20) and an increase in EPe (1.66 ± 0.30 and 15.76 ± 4.78) corresponding to pressure ranges of 50-90 mmHg (elastin zone) and 100-130 mmHg (collagen zone). Arterial mechanics framework, extensively applied in our previous works, was successfully used to characterize PLLA vascular grafts in vitro, although its application can be directly extended to in vivo experiences, in conscious and chronically instrumented animals. The specific design and construction of the electrospun nanofibrous PLLA vascular grafts assessed in this work, showed similar mechanical properties as the ones observed in femoral arteries, at the collagen pressure range.Fil: Suarez Bagnasco, D.. Universidad de la República. Facultad de Ciencias; UruguayFil: Montini Ballarin, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Cymberknop, Leandro Javier. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; ArgentinaFil: Balay, G.. Universidad de la República. Facultad de Ciencias; UruguayFil: Negreira, C.. Universidad de la República. Facultad de Ciencias; UruguayFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Armentano, Ricardo Luis. Universidad Tecnológica Nacional; Argentina. Universidad de la República; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Elasticity response of electrospun bioresorbable small-diameter vascular grafts: Towards a biomimetic mechanical response

The elasticity response of synthetic vascular grafts is very important for the grafts long term success. Natural arteries possess a characteristic response to internal pressure, known as J-curve. Mimicking this feature is believed to be the path to obtain a vascular graft that does not fail over time. In this work, two synthetic bioresorbable polymers were selected to design small-diameter vascular grafts (SDVGs) based on their biomimetic mechanical response. Poly(L-lactic acid) (PLLA) was chosen for its similar response to collagen and a segmented poly(ester urethane) (PHD) was used to introduce elastomeric properties through its elastin-like behavior. A bilayered electrospun conduit with two different PLLA/PHD blends was fabricated by mimicking the natural collagen-to-elastin ratio in the media and adventitia layers. The biomimetic mechanical response, compliance and elastic modulus were studied under pulsated pressure conditions. The grafts nanofibrous morphology as well as its layered structure resulted in properties promising for bypass applications.Fil: Montini Ballarin, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Suárez Bagnasco, Diego. Universidad de la República; UruguayFil: Cymberknop, Leandro Javier. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; ArgentinaFil: Balay, Guillermo. Universidad de la República; UruguayFil: Caracciolo, Pablo Christian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Negreira, Carlos. Universidad de la República; UruguayFil: Armentano, Ricardo Luis. Universidad Tecnológica Nacional. Facultad Regional Buenos Aires; ArgentinaFil: Abraham, Gustavo Abel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin

Direct effect of ghrelin on leptin production by cultured rat white adipocytes.

OBJECTIVE: Because ghrelin is known to stimulate adipogenesis, we tested whether ghrelin could contribute to the maintenance of homeostasis, directly affecting rat white adipocyte leptin production. RESEARCH METHODS AND PROCEDURES: Isolated retroperitoneal adipocytes were cultured for 0.5 to 48 hours without (baseline) or with (0.001 to 1 nM) ghrelin alone or in combination with insulin (0.01 to 10 nM) or dexamethasone (1 to 100 nM). Adipocytes were also incubated with ghrelin and inhibitors either of RNA (actinomycin D) or protein synthesis (cycloheximide) or with several concentrations (10 to 1000 nM) of a specific ghrelin antagonist. When cultures were terminated, we evaluated adipocyte leptin secretion and ob mRNA expression. RESULTS: Our data indicate that ghrelin directly enhanced adipocyte leptin release and ob mRNA expression, that the leptin-releasing activity of ghrelin was additive to the action of both insulin and dexamethasone and was abrogated by protein synthesis inhibitors, and that effects of ghrelin on adipocyte ob mRNA expression and release were blocked by coincubation with the specific growth hormone secretagogue receptor 1a antagonist. DISCUSSION: Our study supports the ability of ghrelin to enhance white adipose tissue leptin production by a direct receptor-mediated effect. This activity of ghrelin could play a potentially significant role in rapid restoration of homeostasis after food intake