Reduced proliferation of endothelial colony-forming cells in unprovoked venous thromboembolic disease as a consequence of endothelial dysfunction

Background Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). Methods and results Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20−50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated β-galactosidase (SA-β-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP). Conclusions As compared with controls, ECFC-ECs from individuals with VTD have higher oxidative stress, proliferation stress, cellular senescence, and low proliferative potential. These findings suggest that patients with a history of VTD are ECFC-ECs dysfunctional that could be associated to permanent risk for new thrombotic events

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

Epistemología Y Trabajo Social Tomo II

Epistemología y Trabajo Social Tomo II, surge de la necesidad\ua0de continuar analizando desde la disciplina de Trabajo Social\ua0y el problema de la construcción del conocimiento, ya que aunque los\ua0antecedentes de la reflexión epistemológica se remiten a unos\ua0cuantos siglos, no es así para el caso de Trabajo Social (ACANTTS).\ua0Está obra colectiva, es el resultado de las reflexiones y discusiones\ua0colegidas desarrolladas en el Primero y Segundo Seminario\ua0organizados por la Academia Nacional de Investigación en Trabajo\ua0Social. Sus colaboraciones son análisis de los problemas y\ua0necesidades sociales, reflexiones sobre el objeto de estudio del\ua0Trabajo Social; contribuciones teóricas y metodológicas productos\ua0de los procesos de investigación que los trabajadores sociales\ua0aplican a nivel nacional. La construcción del conocimiento, requiere del proceso epistemológico tanto en la interrelación objeto/sujeto como en la investigación/intervención. La reflexión sobre el objeto de estudio y los elementos subjetivos a los problemas inherentes a la realidad, aportan al desarrollo de la disciplina la explicación y la actuación ante los problemas y necesidades sociales. La obra al mismo tiempo que se constituye como una muestra de los intereses profesionales de los investigadores de la disciplina de Trabajo Social en México, ha permitido deconstruir prácticas y construir discursos en una reflexión epistemológica centrada en paradigmas, teorías y modelos, así como de la manera como estos sustentan la investigación y la intervención, y al mismo tiempo muestra algunos de los ámbitos de intervención prioritarios en las condiciones sociales actuales

Effect of plasma and supernatants on the proliferative potential of ECFC-ECs obtained from peripheral blood of controls and patients with VTD.

<p>(A) The figure shows the number of ECFC-ECs in controls and patients with VTD at passage 4 after stimulation with plasma obtained from controls and patients with VTD. (B) Results of the 24-h incubation of supernatants and ECFC-ECs from VTD patients and controls. Results are expressed as mean ± standard deviation of three independent experiments, *P ≤0.05, **P ≤0.05.</p

Expression of ROS in ECFC-ECs obtained from blood of controls and patients with VTD.

<p>Mean fluorescence intensity (MFI) emitted by 2’,7’-dichlorofluorescein (DCF) in ECFC-ECs from peripheral blood samples of controls and patients with VTD in passage 4. MFI was expressed as percentage being 100% the value obtained by ECFC-ECs from controls. The results are expressed as mean ± standard deviation of three independent experiments *P = 0.012.</p

Relative expression of ephrin-B2 and Eph-B4 genes in ECFC-ECs from peripheral blood of controls and patients with VTD.

<p><b>(</b>A) mRNA expression of ephrin-B2 (639 bp), Eph-B4 (251 bp) and RPS18 (240 bp) as housekeeping gene in peripheral blood samples from controls and from patients with VTD. (B) Densitometric analysis of ephrin-B2 and (C) Eph-B4 evaluated in positive controls (HUVECs and PAECs) in ECFC-ECs of controls and patients with VTD. Results are expressed as mean ± standard deviation of three independent experiments in passage 4. *P = 0.017, **P = 0.01. Expression of the proteins Ephrin-B2 (D) and Eph-B4 (E), was evaluated by confocal inmunofluorescence microscopy.</p

Apoptosis in ECFC-ECs obtained from peripheral blood of controls and patients with VTD.

<p>The figure shows the percentage of ECFC-EC annexin V-FITC positive (A) and the presence of DNA damage evaluated by the expression of γH2AX histone by immunofluorescence (B) as well as flow cytometry analysis (C), in passage 4. Results are expressed as mean ± standard deviation of three independent experiments. *P = 0.002 for annexin expression.</p

Identification of ECFCs obtained from peripheral blood from controls and patients with VTD.

<p>Representative photomicrograph (40X magnification) of colonies formed by ECFCs in cultures of MNCs obtained from peripheral blood after 14 days in culture. (A) controls and (B) patients with history of VTD.</p