Damage-associated molecular patterns (DAMPs) are endogenous molecules that are released into the extracellular space under conditions of activation, cellular stress, or tissue damage. These molecules are recognized by pattern-recognition receptors (PRRs) and can induce inflammation and immune responses in the absence of infection. An increasing number of DAMPs have been linked to the pathogenesis of many auto-immune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis, and systemic sclerosis (SSc); as they promote the maturation/activation of different immune cells and pro-inflammatory cytokines production associated with these diseases. Several studies suggest that the loss of tolerance to self-antigens in these diseases could be due to continuous exposure to DAMPs. Thus, understanding the mechanisms of sterile inflammation triggered by DAMPs is important to elucidate novel therapeutic strategies for the treatment of various auto-immune diseases through inhibition or modulation the expression of these molecules. To this end, this review describes different DAMPs, their molecular characteristics, their modifications, and the receptors through which they activate an immune response while considering their role in the pathogenesis of various auto-immune diseases.
The European and African contribution to the pre-existing Native American background has influenced the complex genetic pool of Colombia. Because colonisation was not homogeneous in this country, current populations are, therefore, expected to have different proportions of Native American, European and African ancestral contributions. The aim of this work was to examine 11 urban admixed populations and a Native American group, called Pastos, for 32 X chromosome indel markers to expand the current knowledge concerning the genetic background of Colombia. The results revealed a highly diverse genetic background comprising all admixed populations, harbouring important X chromosome contributions from all continental source populations. In addition, Colombia is genetically sub-structured, with different proportions of European and African influxes depending on the regions. The samples from the North Pacific and Caribbean coasts have a high African ancestry, showing the highest levels of diversity. The sample from the South Andean region showed the lowest diversity and significantly higher proportion of Native American ancestry than the other samples from the North Pacific and Caribbean coasts, Central-West and Central-East Andean regions, and the Orinoquian region. The results of admixture analysis using X-chromosomal markers suggest that the high proportion of African ancestry in the North Pacific coast was primarily male driven. These men have joined to females with higher Native American and European ancestry (likely resulting from a classic colonial asymmetric mating type: European male x Amerindian female). This high proportion of male-mediated African contributions is atypical of colonial settings, suggesting that the admixture occurred during a period when African people were no longer enslaved. In the remaining regions, the African contribution was primarily female-mediated, whereas the European counterpart was primarily male driven and the Native American ancestry contribution was not gender biased.
Mazorra (2020) Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule, OncoImmunology, 9:1, 1762465,
Background: Elevated levels of circulating microparticles (MPs) and molecules of the complement system have been reported in patients with systemic lupus erythematosus (SLE). Moreover, microparticles isolated from patients with SLE (SLE-MPs) contain higher levels of damage-associated molecular patterns (DAMPs) than MPs from healthy controls (CMPs). We hypothesize that the uptake of MPs by monocytes could contribute to the chronic inflammatory processes observed in patients with SLE. Therefore, the aim of this study was to evaluate the expression of activation markers, production of proinflammatory mediators, and activation of the NF-κB signaling pathway in monocytes treated with CMPs and SLE-MPs. Methodology: Monocytes isolated from healthy individuals were pretreated or not with pyrrolidine dithiocarbamate (PDTC) and cultured with CMPs and SLE-MPs. The cell surface expression of CD69 and HLA-DR were evaluated by flow cytometry; cytokine and eicosanoid levels were quantified in culture supernatants by Cytokine Bead Array and ELISA, respectively; and the NF-κB activation was evaluated by Western blot and epifluorescence microscopy. Results: The cell surface expression of HLA-DR and CD69, and the supernatant levels of IL-6, IL-1β, PGE2, and LTB4 were higher in cultures of monocytes treated with SLE-MPs than CMPs. These responses were blocked in the presence of PDTC, a pharmacological inhibitor of the NF-κB pathway, with concomitant reduction of IκBα and cytoplasmic p65, and increased nuclear translocation of p65. Conclusions: The present findings indicate that significant uptake of SLE-MPs by monocytes results in activation, production of inflammatory mediators, and triggering of the NF-κB signaling pathway.
Objectives Characterize children's and adolescent's exposure of Digital Marketing (DM) and identify DM strategies of advertised food and beverages Methods This was a cross-sectional study. We used a crowdsourcing strategy to recruit children and adolescents around Mexico. Those with home access to Wi-Fi, with mobile capacity to record their habitual internet usage, and with abilities to upload their videos of exposure in a cloud were included. Once the videos were received, we performed a content analysis using the protocol for Monitoring of Marketing of Unhealthy Products to Children and Adolescents of the World Health Organization (Europe Office). The protocol and template were adapted to the Mexican context and then piloted in a sample of 20 children. We included an item to explore if COVID was used as a marketing strategy. Data was captured in an excel spreadsheet and then transferred to Stata 14. Results We received 45 minutes of internet exposure recordings from 348 children and adolescents. Overall, 45% of children and adolescents were exposed to food and beverage DM. Most of the DM was made of unhealthy food categories: fast food 17%, sweet snacks 10%, cakes and pastries 7%, among others. From the food and beverage advertising (f&b ads) 38% had at least one element to attract children, and 43% attracted adolescents. Brand characters were displayed on 10% of the ads; while licensed characters were displayed on 3.6%. We found that COVID19 was mentioned or illustrated in 3% of the f&b ads and that 67% f&b ads included an incentive to purchase or consume; such as: a person eating the product, or a f&b product served on a plate ready to eat. Conclusions A restriction of unhealthy food and beverage digital marketing aimed at children and adolescents should be considered in the current Mexican advertising regulation. Funding Sources This project was funded by UNICEF México and Bloomberg Philanthropies. The presenting author was funded by CONACYT México and was awarded with the Healthy Food Policy Fellowship.
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