Heme oxygenase-1 as a modulator of intestinal inflammation development and progression

Indexación: Scopus.Heme Oxygenase 1 (HMOX1) is an enzyme that catalyzes the reaction that degrades the heme group contained in several important proteins, such as hemoglobin, myoglobin, and cytochrome p450. The enzymatic reaction catalyzed by HMOX1 generates Fe2+, biliverdin and CO. It has been shown that HMOX1 activity and the by-product CO can downmodulate the damaging immune response in several models of intestinal inflammation as a result of pharmacological induction of HMOX1 expression and the administration of non-toxic amounts of CO. Inflammatory Bowel Diseases, which includes Crohn's Disease (CD) and Ulcerative Colitis (UC), are one of the most studied ailments associated to HMOX1 effects. However, microbiota imbalances and infections are also important factors influencing the occurrence of acute and chronic intestinal inflammation, where HMOX1 activity may play a major role. As part of this article we discuss the immune modulatory capacity of HMOX1 during IBD, as well during the infections and interactions with the microbiota that contribute to this inflammatory disease. © 2018 Sebastián, Salazar, Coronado-Arrázola, Schultz, Vallejos, Berkowitz, álvarez-Lobos, Riedel, Kalergis and Bueno.https://www.frontiersin.org/articles/10.3389/fimmu.2018.01956/ful

Magnetic enhancement of Co0.2_{0.2}Zn0.8_{0.8}Fe2_2O4_4 spinel oxide by mechanical milling

We report the magnetic properties of mechanically milled Co$_{0.2}$Zn$_{0.8}$Fe$_2$O$_4$ spinel oxide. After 24 hours milling of the bulk sample, the XRD spectra show nanostructure with average particle size $\approx$ 20 nm. The as milled sample shows an enhancement in magnetization and ordering temperature compared to the bulk sample. If the as milled sample is annealed at different temperatures for the same duration, recrystallization process occurs and approaches to the bulk structure on increasing the annealing temperatures. The magnetization of the annealed samples first increases and then decreases. At higher annealing temperature ($\sim$ 1000$^{0}$C) the system shows two coexisting magnetic phases {\it i.e.}, spin glass state and ferrimagnetic state, similar to the as prepared bulk sample. The room temperature M\"{o}ssbauer spectra of the as milled sample, annealed at 300$^{0}$C for different durations (upto 575 hours), suggest that the observed change in magnetic behaviour is strongly related with cations redistribution between tetrahedral (A) and octahedral (O) sites in the spinel structure. Apart from the cation redistribution, we suggest that the enhancement of magnetization and ordering temperature is related with the reduction of B site spin canting and increase of strain induced anisotropic energy during mechanical milling.Comment: 14 pages LaTeX, 10 ps figure

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Parent and child mental health trajectories April 2020 to May 2021: strict lockdown versus no lockdown in Australia

Objective To control a second-wave COVID-19 outbreak, the state of Victoria in Australia experienced one of the world's first long and strict lockdowns over July-October 2020, while the rest of Australia experienced 'COVID-normal' with minimal restrictions. We (1) investigate trajectories of parent/child mental health outcomes in Victoria vs non-Victoria and (2) identify baseline demographic, individual and COVID-19-related factors associated with mental health trajectories. Methods Online community sample of 2004 Australian parents with rapid repeated assessment over 14 time-points over April 2020 to May 2021. Measures assessed parent mental health (Depression, Anxiety and Stress Scales-21), child depression symptoms (13-item Short Mood and Feelings Questionnaire) and child anxiety symptoms (four items from Brief Spence Children's Anxiety Scale). Results Mental health trajectories shadowed COVID-19 infection rates. Victorians reported a peak in mental health symptoms at the time of the second-wave lockdown compared to other states. Key baseline predictors, including parent and child loneliness (standardized regression coefficient [β] = 0.09-0.46), parent/child diagnoses (β = 0.07-0.21), couple conflict (β = 0.07-0.18) and COVID-19 stressors, such as worry/concern about COVID-19, illness and loss of job (β = 0.12-0.15), predicted elevated trajectories. Effects of predictors on parent and child mental health trajectories are illustrated in an online interactive app for readers (https://lingtax.shinyapps.io/CPAS_trend/). Conclusion Our findings provide evidence of worse trajectories of parent and child mental health symptoms at a time coinciding with a second COVID-19 outbreak involving strict lockdown in Victoria, compared to non-locked states in Australia. We identified several baseline factors that may be useful in detecting high-risk families who are likely to require additional support early on in future lockdowns.Elizabeth M Westrupp, Christopher J Greenwood, Matthew Fuller-Tyszkiewicz, Craig A Olsson, Emma Sciberras, Antonina Mikocka-Walus ... et al