Relevance of mouse and human IBD patients-derived colon organoids to investigate intestinal macrophage differentiation.

The gastrointestinal tract is a remarkable example of complex biology, with a constant dialogue between the intestinal epithelium, in close contact with the microbiota, and the immune cells that protect the gut from infection. Organoids have revolutionized our approach to modelling the intestinal cellular compartment and have opened new avenues for unravelling the mechanisms involved in intestinal homeostasis and chronic pathogenesis such as inflammatory bowel disease. To date, few models have been established to explore the role of the colon, which is however the main site of inflammation in ulcerative colitis (UC).

Plasmacytoid dendritic cells proliferation associated with acute myeloid leukemia: phenotype profile and mutation landscape.

Neoplasms involving plasmacytoid Dendritic Cells (pDCs) include Blastic pDC Neoplasms (BPDCN) and other pDC proliferations, where pDCs are associated with myeloid malignancies: most frequently Chronic MyeloMonocytic Leukemia (CMML) but also Acute Myeloid Leukemia (AML), hereafter named pDC-AML. We aimed to determine the reactive or neoplastic origin of pDCs in pDC-AML, and their link with the CD34+ blasts, monocytes or conventional DCs (cDCs) associated in the same sample, by phenotypic and molecular analyses (targeted NGS, 70 genes). We compared 15 pDC-AML at diagnosis with 21 BPDCN and 11 normal pDCs from healthy donors.

Switching renal transplant recipients to belatacept therapy: results of a real-life gradual conversion protocol.

Conversion to belatacept immunosuppression is a therapeutic option for renal-transplant recipients with calcineurin inhibitors (CNI) toxicity, but it associates with high risk of acute rejection. Gradual conversion and serial immune monitoring with urinary chemokine CXCL9 may allow increasing safety of this maneuver. We converted kidney transplant recipients with signs of toxicity to CNI or other immunosuppressive drugs to belatacept over a 2-month period.

Do evidence summaries increase health policy-makers' use of evidence from systematic reviews? A systematic review.

Unlabelled: This review summarizes the evidence from six randomized controlled trials that judged the effectiveness of systematic review summaries on policymakers' decision making, or the most effective ways to present evidence summaries to increase policymakers' use of the evidence. This review included six randomized controlled studies. A randomized controlled study is one in which the participants are divided randomly (by chance) into separate groups to compare different treatments or other interventions.

Abnormal Circulating Levels of Metalloproteinase and Their Inhibitor in Hypertensive Patients.

Background: The aim of this study was to determine the plasmatic levels matrix metalloproteinases (MMPs): MMP-2, MMP-3, MMP-9, and their inhibitors (TIMPs): TIMP-1 and TIMP-2 in hypertensive patients and healthy subjects.

Methods: The study involved 60 hypertensive patients and 61 adult healthy controls. Pro-MMP-9 and pro-MMP-2 activity was determined by the gelatin zymography method and MMP-3, TIMP-1, and TIMP-2 levels were determined by ELISA method.

Peripheral blood levels of matrix and inflammatory mediators are elevated in Tunisian patients with acute coronary syndromes.

Background: The aim of the present study was to investigate differences of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in the peripheral blood of patients admitted with acute coronary syndrome (ACS), in correlation with the widely accepted markers of inflammatory activity, C-reactive protein, fibrinogen, and white blood cell number.

Methods: 315 patients with ACS (165 unstable angina pectoris/non-ST-elevation myocardial infarction, 150 ST-elevation myocardial infarction), 111 stable angina (SA) patients, and 296 control subjects were enrolled in the study. All biochemical analyses were carried out using a Hitachi 912 analyzer (Roche).

Upregulation of adhesion molecules on leukemia targets improves the efficacy of cytotoxic T cells transduced with chimeric anti-CD19 receptor.

T lymphocytes engineered to express chimeric antigen receptors (CARs) interact directly with cell surface molecules, bypassing MHC antigen presentation dependence. We generated human anti-CD19ζ CAR cytotoxic T lymphocytes and cytokine-induced killer cells and studied their sensitivity to the expression of adhesion molecules for the killing of primary B-lineage acute lymphoblastic leukemia (B-ALL) targets. Despite a very low basal expression of surface adhesion molecules, B-ALL blasts were lysed by the anti-CD19ζ-CAR transduced effectors as expected.

Abnormal circulating levels of matrix metalloproteinases and their inhibitors in diabetes mellitus.

Background: The aim of this study was to determine plasma levels of matrix metalloproteinases (MMPs) 2, 3, and 9 and their tissue inhibitors (TIMPs) 1 and 2 in type 2 diabetic patients (T2DM) compared to healthy subjects.

Methods: The study involved 54 patients with T2DM and 57 age and gender matched healthy adults as controls. MMPs 2 and 9 were analyzed by gelatin zymography and MMP-3 and TIMPs 1 and 2 by ELISA.

Cloned IGH VDJ targets as tools for personalized minimal residual disease monitoring in mature lymphoid malignancies; a feasibility study in mantle cell lymphoma by the Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang.

Molecular minimal residual disease (MRD) analysis is fast emerging as an essential clinical decision-making tool for the treatment and follow-up of mature B cell malignancies. Current EuroMRD consensus IGH real-time quantitative polymerase chain reaction RQ-PCR assays rely on flow cytometric assessment of diagnostic tumour burdens to construct 'normalized', patient-specific, diagnostic DNA-based MRD quantification standards. Here, we propose a new 'hybrid' assay that relies on plasmid-based quantification of patient-specific IGH VDJ targets by consensus IGH real time (RQ)-PCR, combined with EuroMRD guidelines, for MRD monitoring in lymphoid malignancies.

Age-related changes in the elastic tissue of the human aorta.

Background: Age-related arterial alterations affecting cells, matrix and biomolecules are the main culprit for initiation and progression of cardiovascular disease. The objective of this study is to gain further insights into the complex mechanism of elastic tissue ageing in human aortic blood vessels.

Methods: One hundred and nineteen human aortic tissue samples were collected from adult patients (101 males, 18 females; age 40-86 years) undergoing coronary artery bypass grafting.

Exploration of the lysis mechanisms of leukaemic blasts by chimaeric T-cells.

Adoptive transfer of specific cytotoxic T lymphocytes (CTL) and Cytokine Induced Killer Cells (CIK) following genetic engineering of T-cell receptor zeta hold promising perspective in immunotherapy. In the present work we focused on the mechanisms of anti-tumor action of effectors transduced with an anti-CD19 chimaeric receptor in the context of B-lineage acute lymphoblastic leukemia (B-ALL). Primary B-ALL blasts were efficiently killed by both z-CD19 CTL and z-CD19 CIK effectors.

Chromosomal mapping of quantitative trait loci controlling elastin content in rat aorta.

Extracellular matrix molecules such as elastin and collagens provide mechanical support to the vessel wall. In addition to its structural role, elastin is a regulator that maintains homeostasis through biologic signaling. Genetically determined minor modifications in elastin and collagen in the aorta could influence the onset and evolution of arterial pathology, such as hypertension and its complications.

CD4+ CD56+ lineage negative malignancies: a new entity developed from malignant early plasmacytoid dendritic cells.

Background And Objectives: The CD4+ CD56+ lin- immunophenotype characterizes rare malignancies, so far considered as arising from the transformation of NK progenitors, and therefore classified as blastic NK-cell leukemia/lymphoma by the WHO committee. Recently it was formally demonstrated that such malignancies do, in fact, develop from plasmacytoid dendritic cells (pDC), according to immunophenotypic and functional criteria. The clinico-biological features of this neoplasm were moreover recently summarized from a large series of 23 patients.

Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions.

The extracellular matrix provides a structural framework essential for the functional properties of vessel walls. The three dimensional organization of the extracellular matrix molecules - elastin, collagens, proteoglycans and structural glycoproteins - synthesized during fetal development - is optimal for these functions. In uninjured arteries and veins, some proteases are constitutively expressed, but through the control of their activation and/or their inhibition by inhibitors, these proteases have a very low activity and the turn-over of elastic and collagen fibers is low.

Plasmacytoid dendritic cells: from the plasmacytoid T-cell to type 2 dendritic cells CD4+CD56+ malignancies.

Recent identification of CD4(+)CD56(+) malignancies as pathological counterparts of the precursors of type 2 dendritic cells (DC2) has shed new light on a leukocyte lineage that long remained elusive. This review retraces how knowledge evolved, through careful examination and analysis of both normal lymphoid tissue and rare proliferative diseases, from plasmacytoid T cells to plasmacytoid dendritic cells (pDC) and then DC2. The functions of these cells and their key role at the crossroads of innate and cognitive immunity are also discussed.

Fibrosis of the left atria during progression of heart failure is associated with increased matrix metalloproteinases in the rat.

Objectives: The purpose of this study was to determine the pathogenic factors and molecular mechanisms involved in fibrosis of the atria.

Background: Fibrosis is an important component of the pathophysiology of atrial fibrillation, especially when the arrhythmia is associated with heart failure (HF) or atrial dilation.

Methods: We used a rat model of myocardial infarction (MI) complicated by various degrees of left ventricular dysfunction and atrial dilation to study fibrosis and matrix metalloproteinase (MMP) activity in the left atrial (LA) myocardium by means of histologic, Western blot, zymographic, and immunohistologic techniques.

Efficient model-based quantification of left ventricular function in 3-D echocardiography.

Quantitative functional analysis of the left ventricle plays a very important role in the diagnosis of heart diseases. While in standard two-dimensional echocardiography this quantification is limited to rather crude volume estimation, three-dimensional (3-D) echocardiography not only significantly improves its accuracy but also makes it possible to derive valuable additional information, like various wall-motion measurements. In this paper, we present a new efficient method for the functional evaluation of the left ventricle from 3-D echographic sequences.