Objective: Implantation of an endovascular device disrupts the homeostatic CD31:CD31 interactions among quiescent endothelial cells (ECs), platelets, and circulating leukocytes. The aim of this study was to design an endothelial-mimetic coating of nitinol and cobalt-chromium (CoCr) surfaces and stents using synthetic CD31 peptides, to promote device endothelialization and pacific integration within the arterial wall.
Methods: Peptides mimicking the domains 1 (D1) and 2 (D2) of CD31 were synthetized and immobilized onto experimental nitinol and CoCr surfaces using a three-step, dip-coating, mussel-inspired protocol using copper-free click chemistry.
Urine collection can be challenging in studies involving small rodents like mice, as the actual methods of collection are anxiogenic and constrain animal welfare while having high variability in the volume of urine collected. To improve the current methods and eventually reduce the impact on the well-being of mice, we developed an innovative 3D-printed urine collection device (UCD). This two-compartment UCD is shaped to fit in classical husbandry cages and allows urine collection by spontaneous urination from two mice housed in their own cage without cross-contamination while enabling potential social interactions.
View Article and Find Full Text PDFPerturbation of cell polarity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) progression. Scribble (SCRIB) is a well-characterized polarity regulator that has diverse roles in the pathogenesis of human neoplasms. To investigate the impact of SCRIB deficiency in PDAC development and progression, Scrib expression was genetically ablated in well-established mouse models of PDAC.
View Article and Find Full Text PDFBackground And Objectives: Sirolimus-eluting stents (SESs) have shown promise in treating intracranial atherosclerosis but concerns about potential neurotoxicity due to prolonged drug release exist. The aim of this study was to comprehensively assess the safety of SES, with a focus on neurotoxicity.
Methods: Stents (1.
Exposure to pathogens throughout a lifetime influences immunity and organ function. Here, we explore how the systemic host-response to bacterial urinary tract infection (UTI) induces tissue-specific alterations to the mammary gland. Utilizing a combination of histological tissue analysis, single cell transcriptomics, and flow cytometry, we identify that mammary tissue from UTI-bearing mice displays collagen deposition, enlarged ductal structures, ductal hyperplasia with atypical epithelial transcriptomes and altered immune composition.
View Article and Find Full Text PDFAim: To assess the prevalence of severe periodontitis based on the population-based CONSTANCES cohort using a validated self-reported questionnaire.
Materials And Methods: Individuals were selected from the adult population in France using a random sampling scheme. Analyses were restricted to those invited in 2013-2014 who completed the periodontal health questionnaire at the 2017 follow-up.
For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics.
View Article and Find Full Text PDFAims: IgE type immunoglobulins and their specific effector cells, mast cells (MCs), are associated with abdominal aortic aneurysm (AAA) progression. In parallel, immunoglobulin-producing B cells, organised in tertiary lymphoid organs (TLOs) within the aortic wall, have also been linked to aneurysmal progression. We aimed at investigating the potential role and mechanism linking local MCs, TLO B cells, and IgE production in aneurysmal progression.
View Article and Find Full Text PDFIn spite of intensive research efforts driving spectacular advances in terms of prevention and treatments, cardiovascular diseases (CVDs) remain a leading health burden, accounting for 32% of all deaths (World Health Organization. "Cardiovascular Diseases (CVDs)." WHO, February 1, 2017, https://www.
View Article and Find Full Text PDFRecurrent chromosomal rearrangements found in rhabdomyosarcoma (RMS) produce the PAX3-FOXO1 fusion protein, which is an oncogenic driver and a dependency in this disease. One important function of PAX3-FOXO1 is to arrest myogenic differentiation, which is linked to the ability of RMS cells to gain an unlimited proliferation potential. Here, we developed a phenotypic screening strategy for identifying factors that collaborate with PAX3-FOXO1 to block myo-differentiation in RMS.
View Article and Find Full Text PDFObjective: Despite recent advances in surgical and interventional techniques, knowledge on the management of carcinoid heart disease (CHD) remains limited. In a cohort of patients with liver metastases of midgut neuroendocrine tumours (NETs), we aimed to describe the perioperative management and short-term outcomes of CHD.
Methods: From January 2003 to June 2022, consecutive patients with liver metastases of midgut NETs and severe CHD (severe valve disease with symptoms and/or right ventricular enlargement) were included at Beaujon and Bichat hospitals.
Significance Statement: Kidney-derived thrombopoietin (TPO) increases myeloid cell and platelet production during antibody-mediated chronic kidney disease (AMCKD) in a mouse model, exacerbating chronic thromobinflammation in microvessels. The effect is mirrored in patients with extracapillary glomerulonephritis associated with thromboinflammation, TGF β -dependent glomerulosclerosis, and increased bioavailability of TPO. Neutralization of TPO in mice normalized hematopoiesis, reduced chronic thromboinflammation, and ameliorated renal disease.
View Article and Find Full Text PDFActivated fibroblasts in tumors, or cancer-associated fibroblasts (CAFs), have become a popular research area over the past decade. As important players in many aspects of tumor biology, with functions ranging from collagen deposition to immunosuppression, CAFs have been the target of clinical and pre-clinical studies that have revealed their potential pro- and anti-tumorigenic dichotomy. In this review, we describe the important role of CAFs in the tumor microenvironment and the technological advances that made these discoveries possible, and we detail the models that are currently available for CAF investigation.
View Article and Find Full Text PDFBackground: The first-pass complete recanalization by mechanical thrombectomy (MT) for the treatment of stroke remains limited due to the poor integration of the clot within current devices. Aspiration can help retrieval of the main clot but fails to prevent secondary embolism in the distal arterial territory. The dense meshes of extracellular DNA, recently described in stroke-related clots, might serve as an anchoring platform for MT devices.
View Article and Find Full Text PDFWe evaluated the contribution of artificial intelligence in predicting the risk of acute cellular rejection (ACR) using early plasma levels of soluble CD31 (sCD31) in combination with recipient haematosis, which was measured by the ratio of arterial oxygen partial pressure to fractional oxygen inspired (PaO/FiO) and respiratory SOFA (Sequential Organ Failure Assessment) within 3 days of lung transplantation (LTx). CD31 is expressed on endothelial cells, leukocytes and platelets and acts as a "peace-maker" at the blood/vessel interface. Upon nonspecific activation, CD31 can be cleaved, released, and detected in the plasma (sCD31).
View Article and Find Full Text PDFTrichothiodystrophy (TTD) is a rare hereditary neurodevelopmental disorder defined by sulfur-deficient brittle hair and nails and scaly skin, but with otherwise remarkably variable clinical features. The photosensitive TTD (PS-TTD) forms exhibits in addition to progressive neuropathy and other features of segmental accelerated aging and is associated with impaired genome maintenance and transcription. New factors involved in various steps of gene expression have been identified for the different non-photosensitive forms of TTD (NPS-TTD), which do not appear to show features of premature aging.
View Article and Find Full Text PDFAims: The rapid endothelialization of bare metal stents (BMS) is counterbalanced by inflammation-induced neointimal growth. Drug-eluting stents (DES) prevent leukocyte activation but impair endothelialization, delaying effective device integration into arterial walls. Previously, we have shown that engaging the vascular CD31 co-receptor is crucial for endothelial and leukocyte homeostasis and arterial healing.
View Article and Find Full Text PDFBackground: Antibody-mediated rejection (AMR) is a major cause of graft loss. The development of donor-specific antibodies (DSAs) directed against the allogeneic HLA molecules expressed by the graft also leads to accelerated arteriosclerosis. CD31 is a protein expressed on endothelial and immune cells, ensuring homeostasis at this interface.
View Article and Find Full Text PDFBackground And Purpose: Beyond aneurysmal occlusion, metallic flow diverters (FDs) can induce an adverse endovascular reaction due to the foreignness of metal devices, hampering FD endothelialization across the aneurysm neck, and arterial healing of intracranial aneurysms. Here, we evaluated the potential benefits of an FD coating mimicking CD31, a coreceptor critically involved in endothelial function and endovascular homeostasis, on the endothelialization of FDs implanted in vivo.
Methods: Nitinol FD (Silk Vista Baby) and flat disks were dip-coated with a CD31-mimetic peptide via an intermediate layer of polydopamine.