p38γ and p38δ as biomarkers in the interplay of colon cancer and inflammatory bowel diseases

descripción no proporcionada por scopusThis research was funded by the MCIN/AEI/10.13039/501100011033 (PID2019-108349RB100 and SAF2016-79792R) to AC and JJSE; Villum Foundation, grant no. 13152 to KA; by Agencia Estatal de Investigación (PID2019-104867RBI00/AEI/10.13039/501100011033) and the Instituto de Salud Carlos III- Fondo Europeo de Desarrollo Regional (CIBERONC/CB16/12/00273 and ICI20/00057) to AM and AB. PF received MCIN FPI fellowship (BES-2017-080139)

Alternative p38MAPKs as biomarkers in the interplay of colon cancer and inflammatory bowel diseases

Trabajo presentado en el 44º Congreso Nacional de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM), celebrado en Málaga (España) del 06 al 09 de septiembre de 2022.Chronic inflammation in inflammatory bowel disease (IBD) is a risk factor for Colorectal cancer (CRC) development, but our understanding of this interplay at a molecular level is still limited. p38γ and p38δ, are central in the development of mouse colitis-associated CRC (CAC) by modulating the inflammatory immune response. However, their implication in human CRC and IBD is not well defined. In this study we perform an integrative analysis of p38γ and p38δ mRNA and protein expression and activation in human patients; using human CRC derived organoids and plasma samples, as well as data from different human CRC and IBD mRNA databases. We found that, p38δ levels were decreased, whereas p38γ expression and phosphorylation were significantly increased in CRC compared to normal colon samples. This increase correlated with the expression of genes implicated in inflammation. Examine of p38γ/p38δ in IBD patients showed that p38γ mRNA and protein levels were increased in Crohn’s disease and ulcerative colitis patients. Contrary, p38δ mRNA was significantly decreased. We also investigated the expression of miRNAs, miR-128-2, miR133a and miR-155, implicated in inflammation and cancer development. In mouse model of colitis and CAC, miR128-2 level was regulated by p38γ/p38δ. In the plasma of IBD and CRC patients, miR128-2 was increased compared to healthy donors, and this correlated with p38γ and p38δ levels. Our results show an opposite regulation of p38γ and p38δ in both CRC and IBD; and suggest that p38γ acts as a link between colitis and CRC by favouring an inflammatory environment that promotes tumour development. We provided evidence that p38γ/p38δ, together with miR-128-2, can be useful as biomarkers, and as potential treatment targets, for colitis and early-stage CRC

A comprehensive collection of chicken cDNAs

AbstractBirds have played a central role in many biological disciplines, particularly ecology, evolution, and behavior. The chicken, as a model vertebrate, also represents an important experimental system for developmental biologists, immunologists, cell biologists, and geneticists. However, genomic resources for the chicken have lagged behind those for other model organisms, with only 1845 nonredundant full-length chicken cDNA sequences currently deposited in the EMBL databank. We describe a large-scale expressed-sequence-tag (EST) project aimed at gene discovery in chickens (http://www.chick.umist.ac.uk). In total, 339,314 ESTs have been sequenced from 64 cDNA libraries generated from 21 different embryonic and adult tissues. These were clustered and assembled into 85,486 contiguous sequences (contigs). We find that a minimum of 38% of the contigs have orthologs in other organisms and define an upper limit of 13,000 new chicken genes. The remaining contigs may include novel avian specific or rapidly evolving genes. Comparison of the contigs with known chicken genes and orthologs indicates that 30% include cDNAs that contain the start codon and 20% of the contigs represent full-length cDNA sequences. Using this dataset, we estimate that chickens have approximately 35,000 genes in total, suggesting that this number may be a characteristic feature of vertebrates

Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity

Fundació la Marató de TV3 (GrantNumber(s): 20133431; Grant recipient(s): Ana Cuenda) Wellcome Trust (GrantNumber(s): 97377, 102705; Grant recipient(s): GORDON D. BROWN) Ministerio de Economía y Competitividad (GrantNumber(s): SAF2016-79792-R, SAF2014- 52009-R, SAF2013-45331-R; Grant recipient(s): Ana Cuenda, SUSANA ALEMANY) Medical Research Council (GrantNumber(s): MR/N006364/1; Grant recipient(s): GORDON D. BROWN) ERC Consolidator Grant (GrantNumber(s): 310372; Grant recipient(s): Mihai Netea)Peer reviewedPublisher PD

Characterization in vitro and in vivo of a pandemic H1N1 influenza virus from a fatal case

Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32).Funding Statement: This work was supported by Instituto de Salud Carlos III (Programa especial de investigación sobre la gripe pándemica GR09/0023, GR09/0040, GR09/0039) and Ciber de Enfermedades Respiratorias. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

p38 Signalling Pathway

© 2021 by the authors.p38 Mitogen activated protein kinases (p38MAPK) are a highly evolutionary conserved group of protein kinases, which are central for cell adaptation to environmental changes as well as for immune response, inflammation, tissue regeneration, and tumour formation [...]This research was funded by grants from the Spanish Ministerio of Ciencia e Innovación (MICINN) (SAF2016-79792R, PID2019-108349RB-I00).Peer reviewe

Signalling Pathways in Embryonic Development

The formation of a complex multicellular organism from a single cell is one of the most amazing processes of biology. Embryonic development is characterised by the careful regulation of cellular behaviours such that cells proliferate, migrate, differentiate and form tissues at the correct place and time. These processes are genetically controlled and depend both on the history of cells, their lineage, and on the activities of signalling pathways, which coordinate the cell interactions leading to organogenesis. The aim of the Frontiers research topic “Signalling pathways in embryonic development” has been to provide a forum for experts in cell and developmental biology to share recent advances in the field of signalling during embryonic development. Sixteen articles in a variety of formats are united in this Topic, offering a valuable collection for researchers looking for an update in the knowledge of signalling pathways operating during embryogenesis. The works, focused mainly on vertebrates, explore different aspects of this theme from cell communication to organ formation and have implications for areas as distant as evolution or pathology. Understanding developmental signalling pathways is important for several reasons. It gives us information about basic mechanisms of cell function and interactions needed for morphogenesis and organogenesis. It uncovers the basis of congenital malformations, since errors at any step of cell signalling during development are a major cause of defects. This fundamental insight gives us clues to understand the mechanisms operating in evolution that explain diversity in form and function. And finally, it allows the identification of possible causes of disease in the adult organism (such as cancer or degenerative diseases) pinpointing possible targets for therapeutic approaches