Influence of lipids and obesity on haemorheological parameters in patients with deep vein thrombosis

It is not well established whether haemorheological alterations constitute independent risk factors for deep vein thrombosis (DVT).We have determined in 149 DVT patients and in 185 control subjects the body mass index (BMI), the haemorheological profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen (Fg), erythrocyte aggregation (EA), erythrocyte deformability (ED) and plasma lipids. In the crude analysis BMI, Fg, PV, EA, triglycerides (TG) and ApoB were statistically higher and HDL cholesterol (HDL-Chol) statistically lower in DVT patients than in controls. No differences in BV and ED were observed.After BMI adjustment, Fg, PV and EA remained statistically higher in DVT cases than in controls (P=0.013; P=0.012; P=0.013; P=0.028, respectively). When the risk of DVT associated with these variables (using cut-offs that corresponded to the mean plus one SD of the control group) was estimated, EA>8.2 and PV>1.28 mPa.s were significantly associated with DVT even further adjustment for lipids and obesity (OR=2.78, P=0.004; OR=1.91, P=0.024, respectively). However, PV did not remain statistically significant after additional adjustment for Fg.When we consider together all the analyzed variables in order to control every variable for each other,TG>175 mg/dl (OR=3,2,P=0.004) and BMI>30 kg/m2 (OR=3.5, P=0.003), were also independently associated with a greater risk of DVT. Our results suggest that increased EA constitute an independent risk factor for DVT. However, when associated to hyperlipidaemia and obesity it further increases thrombotic [email protected]

Chromatin regulation by Histone H4 acetylation at Lysine 16 during cell death and differentiation in the myeloid compartment

Histone H4 acetylation at Lysine 16 (H4K16ac) is a key epigenetic mark involved in gene regulation, DNA repair and chromatin remodeling, and though it is known to be essential for embryonic development, its role during adult life is still poorly understood. Here we show that this lysine is massively hyperacetylated in peripheral neutrophils. Genome-wide mapping of H4K16ac in terminally differentiated blood cells, along with functional experiments, supported a role for this histone post-translational modification in the regulation of cell differentiation and apoptosis in the hematopoietic system. Furthermore, in neutrophils, H4K16ac was enriched at specific DNA repeats. These DNA regions presented an accessible chromatin conformation and were associated with the cleavage sites that generate the 50 kb DNA fragments during the first stages of programmed cell death. Our results thus suggest that H4K16ac plays a dual role in myeloid cells as it not only regulates differentiation and apoptosis, but it also exhibits a non-canonical structural role in poising chromatin for cleavage at an early stage of neutrophil cell death

Anti-SARS-CoV-2 IgA and IgG in Human Milk From Vaccinated Mothers After Holder Pasteurization

Breastfeeding rendered crucial for preterm infants during COVID-19 pandemic. However, the role of donated human milk (DHM) in the protection against SARS-CoV-2 infection when own mother’s milk is not available or insufficient remains unclear. Pasteurization of DHM contributes to the loss of some biological and nutritional properties of human milk. The presence of specific breast milk SARS-CoV-2 antibodies has been demonstrated in women after COVID-19 disease and after vaccination. We aimed to evaluate the impact of Holder pasteurization on vaccinated donor women’s milk and to identify the impact on the concentrations of specific immunoglobulins (Ig) against SARS-CoV-2. A prospective, observational, exploratory pilot study in lactating women (n=12) who received the complete course of mRNA-based vaccines (BioNTech/Pfizer) against SARS-CoV-2 infection was conducted. Levels of antibodies directed to structural receptor-binding domain of the SARS-CoV-2 spike protein were determined by ELISA before and after pasteurization. IgA and IgG anti-SARS-CoV-2 immunoglobulin concentrations were significantly reduced after Holder pasteurization. Interestingly, there was a negative correlation between the initial amount of anti-SARS-CoV-2 antibodies and the percentage of their recovery after the pasteurization for both isotypes. Despite the partial loss of immunoglobulins still a high percentage of antibodies remained after the pasteurization, a mean of 70.53 (3.4)% of anti-SARS-CoV-2 IgA and 81.99 (21.89)% of IgG antibodies. Our study underscores the potential relevance of breast feeding or alternatively DHM to provide babies at risk with virus-specific SARS-CoV-2 antibodies thus protecting them against COVID-19.We thank the support and guidance of M.C. Collado and C. Martinez-Costa. We thank all the families who were involved in the study during this difficult time and in the middle of the COVID-19 pandemic as well as the collaborators of the MilkCORONA study team and, the support received by the research grant from LaMarató-TV3 (ref. 31/109/202106).N

Deciphering the sex bias in housekeeping gene expression in adipose tissue: a comprehensive meta-analysis of transcriptomic studies

Abstract Background As the housekeeping genes (HKG) generally involved in maintaining essential cell functions are typically assumed to exhibit constant expression levels across cell types, they are commonly employed as internal controls in gene expression studies. Nevertheless, HKG may vary gene expression profile according to different variables introducing systematic errors into experimental results. Sex bias can indeed affect expression display, however, up to date, sex has not been typically considered as a biological variable. Methods In this study, we evaluate the expression profiles of six classical housekeeping genes (four metabolic: GAPDH, HPRT, PPIA, and UBC, and two ribosomal: 18S and RPL19) to determine expression stability in adipose tissues (AT) of Homo sapiens and Mus musculus and check sex bias and their overall suitability as internal controls. We also assess the expression stability of all genes included in distinct whole-transcriptome microarrays available from the Gene Expression Omnibus database to identify sex-unbiased housekeeping genes (suHKG) suitable for use as internal controls. We perform a novel computational strategy based on meta-analysis techniques to identify any sexual dimorphisms in mRNA expression stability in AT and to properly validate potential candidates. Results Just above half of the considered studies informed properly about the sex of the human samples, however, not enough female mouse samples were found to be included in this analysis. We found differences in the HKG expression stability in humans between female and male samples, with females presenting greater instability. We propose a suHKG signature including experimentally validated classical HKG like PPIA and RPL19 and novel potential markers for human AT and discarding others like the extensively used 18S gene due to a sex-based variability display in adipose tissue. Orthologs have also been assayed and proposed for mouse WAT suHKG signature. All results generated during this study are readily available by accessing an open web resource ( https://bioinfo.cipf.es/metafun-HKG ) for consultation and reuse in further studies. Conclusions This sex-based research proves that certain classical housekeeping genes fail to function adequately as controls when analyzing human adipose tissue considering sex as a variable. We confirm RPL19 and PPIA suitability as sex-unbiased human and mouse housekeeping genes derived from sex-specific expression profiles, and propose new ones such as RPS8 and UBB