Datasets for the validation of the "in vivo" siRNA-silencing of CD40 and for the detection of new markers of atherosclerosis progression in ApoE-deficient mice

AbstractData presented in this Data in Brief article correspond to the article "in vivo" silencing of CD40 reduces progression of experimental atherogenesis through a NFκB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis" (M. Hueso, L. De Ramon, E. Navarro, E. Ripoll, J.M. Cruzado, J.M. Grinyo, J. Torras, 2016) [1]. Here, we describe the validation of the silencing of CD40 expression with a specific siRNA in ApoE−/− mouse aortas, and its systemic effects on splenic lymphocytic subpopulations as well as on the infiltration of aortic intima by F4/80+, galectin-3+ macrophages or by NF-κB+ cells. We also show the output of a Gene Ontology and TLDA analysis which allowed the detection of potential mediators of atherosclerosis progression. We provide the scientific community with a set of genes whose expression is increased during atherosclerosis progression but downregulated upon CD40 silencing

Lipidomic Alterations in the Cerebral Cortex and White Matter in Sporadic Alzheimer’s Disease

Non-targeted LC-MS/MS-based lipidomic analysis was conducted in post-mortem human grey matter frontal cortex area 8 (GM) and white matter of the frontal lobe centrum semi-ovale (WM) to identify lipidome fingerprints in middle-aged individuals with no neurofibrillary tangles and senile plaques, and cases at progressive stages of sporadic Alzheimer's disease (sAD). Complementary data were obtained using RT-qPCR and immunohistochemistry. The results showed that WM presents an adaptive lipid phenotype resistant to lipid peroxidation, characterized by a lower fatty acid unsaturation, peroxidizability index, and higher ether lipid content than the GM. Changes in the lipidomic profile are more marked in the WM than in GM in AD with disease progression. Four functional categories are associated with the different lipid classes affected in sAD: membrane structural composition, bioenergetics, antioxidant protection, and bioactive lipids, with deleterious consequences affecting both neurons and glial cells favoring disease progression

Noncanonical immunomodulatory activity of complement regulator C4BP(β-) limits the development of lupus nephritis

Lupus nephritis is a chronic autoimmune-inflammatory condition that can lead to end-stage kidney disease. Presently available immunosuppressive treatments for lupus nephritis are suboptimal and can induce significant side effects. Recently, we characterized a novel immunomodulatory activity of the minor isoform of the classical pathway complement inhibitor, C4BP(β-). We show here that C4BP(β-) treatment prevented the development of proteinuria and albuminuria, decreased significantly the formation of anti-dsDNA antibodies and, locally, mitigated renal glomerular IgG and C3 deposition and generation of apoptotic cells. There was a consequent histological improvement and increased survival in lupus-prone mice. The therapeutic efficacy of C4BP(β-) was analogous to that of the broad-acting immunosuppressant cyclophosphamide. Remarkably, a comparative transcriptional profiling analysis revealed that the kidney gene expression signature resulting from C4BP(β-) treatment turned out to be 10 times smaller than that induced by cyclophosphamide treatment. C4BP(β-) immunomodulation induced significant downregulation of transcripts relevant to lupus nephritis indicating immunopathogenic cell infiltration, including activated T cells (Lat), B cells (Cd19, Ms4a1, Tnfrsf13c), inflammatory phagocytes (Irf7) and neutrophils (Prtn3, S100a8, S100a9). Furthermore, cytokine profiling and immunohistochemistry confirmed that C4BP(β-), through systemic and local CXCL13 downregulation, was able to prevent ectopic lymphoid structures neogenesis in aged mice with lupus nephritis. Thus, due to its anti-inflammatory and immunomodulatory activities and high specificity, C4BP(β-) could be considered for further clinical development in patients with systemic lupus erythematosus

Update on controls for isolation and quantification methodology of extracellular vesicles derived from adipose tissue mesenchymal stem cells

The research field on extracellular vesicles (EV) has rapidly expanded in recent years due to the therapeutic potential of EV. Adipose tissue human mesenchymal stem cells (ASC) may be a suitable source for therapeutic EV. A major limitation in the field is the lack of standardization of the challenging techniques to isolate and characterize EV. The aim of our study was to incorporate new controls for the detection and quantification of EV derived from ASC and to analyze the applicability and limitations of the available techniques. ASC were cultured in medium supplemented with 5% of vesicles-free fetal bovine serum. The EV were isolated from conditioned medium by differential centrifugation with size filtration (0.2 μm). As a control, non-conditioned culture medium was used (control medium). To detect EV, electron microscopy, conventional flow cytometry, and western blot were used. The quantification of the EV was by total protein quantification, ExoELISA immunoassay, and Nanosight. Cytokines and growth factors in the EV samples were measured by multiplex bead array kit. The EV were detected by electron microscope. Total protein measurement was not useful to quantify EV as the control medium showed similar protein contents as the EV samples. The ExoELISA kits had technical troubles and it was not possible to quantify the concentration of exosomes in the samples. The use of Nanosight enabled quantification and size determination of the EV. It is, however, not possible to distinguish protein aggregates from EV with this method. The technologies for quantification and characterization of the EV need to be improved. In addition, we detected protein contaminants in the EV samples, which make it difficult to determine the real effect of EV in experimental models. It will be crucial in the future to optimize design novel methods for purification and characterization of EV

Patients with Crohn's disease have longer post-operative in-hospital stay than patients with colon cancer but no difference in complications' rate

BACKGROUNDRight hemicolectomy or ileocecal resection are used to treat benign conditions like Crohn's disease (CD) and malignant ones like colon cancer (CC).AIMTo investigate differences in pre- and peri-operative factors and their impact on post-operative outcome in patients with CC and CD.METHODSThis is a sub-group analysis of the European Society of Coloproctology's prospective, multi-centre snapshot audit. Adult patients with CC and CD undergoing right hemicolectomy or ileocecal resection were included. Primary outcome measure was 30-d post-operative complications. Secondary outcome measures were post-operative length of stay (LOS) at and readmission.RESULTSThree hundred and seventy-five patients with CD and 2,515 patients with CC were included. Patients with CD were younger (median = 37 years for CD and 71 years for CC (P < 0.01), had lower American Society of Anesthesiology score (ASA) grade (P < 0.01) and less comorbidity (P < 0.01), but were more likely to be current smokers (P < 0.01). Patients with CD were more frequently operated on by colorectal surgeons (P < 0.01) and frequently underwent ileocecal resection (P < 0.01) with higher rate of de-functioning/primary stoma construction (P < 0.01). Thirty-day post-operative mortality occurred exclusively in the CC group (66/2515, 2.3%). In multivariate analyses, the risk of post-operative complications was similar in the two groups (OR 0.80, 95%CI: 0.54-1.17; P = 0.25). Patients with CD had a significantly longer LOS (Geometric mean 0.87, 95%CI: 0.79-0.95; P < 0.01). There was no difference in re-admission rates. The audit did not collect data on post-operative enhanced recovery protocols that are implemented in the different participating centers.CONCLUSIONPatients with CD were younger, with lower ASA grade, less comorbidity, operated on by experienced surgeons and underwent less radical resection but had a longer LOS than patients with CC although complication's rate was not different between the two groups