Deciphering tumour tissue organization by 3D electron microscopy and machine learning.

Despite recent progress in the characterization of tumour components, the tri-dimensional (3D) organization of this pathological tissue and the parameters determining its internal architecture remain elusive. Here, we analysed the spatial organization of patient-derived xenograft tissues generated from hepatoblastoma, the most frequent childhood liver tumour, by serial block-face scanning electron microscopy using an integrated workflow combining 3D imaging, manual and machine learning-based semi-automatic segmentations, mathematics and infographics. By digitally reconstituting an entire hepatoblastoma sample with a blood capillary, a bile canaliculus-like structure, hundreds of tumour cells and their main organelles (e.

Quality of life in colostomy patients practicing colonic irrigation: An observational study.

Aims Of The Study: The presence of colostomy has a major impact on quality of life that could potentially be improved by performing colonic irrigation (CI), yet few studies have assessed the impact of this technique on quality of life. The aim of this study was to assess the quality of life between two groups of patients having a colostomy; those practicing CI vs those not practicing CI.

Patients And Methods: The French Federation of Ostomy (FFO) members were evaluated by a self-questionnaire assessing their experience of CI.

In vitro comparison of three percutaneous atrial septal defect closure devices for endothelialisation and haemocompatibility.

Background: Percutaneous device closure of atrial septal defect (ASD) is the gold-standard treatment, but several delayed complications may occur as a result of incomplete device endothelialisation.

Aims: In this in vitro study, we compared three ASD closure devices [Nit-Occlud® ASD-R (device 1); Hyperion™ ASDO (device 2); and Amplatzer™ Septal Occluder (device 3)] in terms of the endothelialisation process, using human endothelial progenitors cells (EPCs), and haemocompatibility.

Methods: EPCs from umbilical cord blood were extracted, cultured and characterised.

CD154 Induces Interleukin-6 Secretion by Kidney Tubular Epithelial Cells under Hypoxic Conditions: Inhibition by Chloroquine.

Inflammation is a major contributor to tubular epithelium injury in kidney disorders, and the involvement of blood platelets in driving inflammation is increasingly stressed. CD154, the ligand of CD40, is one of the mediators supporting platelet proinflammatory properties. Although hypoxia is an essential constituent of the inflammatory reaction, if and how platelets and CD154 regulate inflammation in hypoxic conditions remain unclear.

New factors for protein transport identified by a genome-wide CRISPRi screen in mammalian cells.

Protein and membrane trafficking pathways are critical for cell and tissue homeostasis. Traditional genetic and biochemical approaches have shed light on basic principles underlying these processes. However, the list of factors required for secretory pathway function remains incomplete, and mechanisms involved in their adaptation poorly understood.

Correction to: Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critically ill patients?

Upon publication of the original article [1], it was noticed that the title was incorrect. Instead of 'critical', it should read 'critically', and therefore, the correct title should be.

Unconventional secretion of FABP4 by endosomes and secretory lysosomes.

An appreciation of the functional properties of the cytoplasmic fatty acid binding protein 4 (FABP4) has advanced with the recent demonstration that an extracellular form secreted by adipocytes regulates a wide range of physiological functions. Little, however, is known about the mechanisms that mediate the unconventional secretion of FABP4. Here, we demonstrate that FABP4 secretion is mediated by a membrane-bounded compartment, independent of the conventional endoplasmic reticulum-Golgi secretory pathway.

Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critically [corrected] ill patients?

Beyond haemostasis, platelets have emerged as versatile effectors of the immune response. The contribution of platelets in inflammation, tissue integrity and defence against infections has considerably widened the spectrum of their role in health and disease. Here, we propose a narrative review that first describes these new platelet attributes.

A Role for CD154, the CD40 Ligand, in Granulomatous Inflammation.

Granulomatous inflammation is a distinctive form of chronic inflammation in which predominant cells include macrophages, epithelioid cells, and multinucleated giant cells. Mechanisms regulating granulomatous inflammation remain ill-understood. CD154, the ligand of CD40, is a key mediator of inflammation.

Chitosan-based hydrogels for developing a small-diameter vascular graft: in vitro and in vivo evaluation.

Aims: Vascular grafts made of synthetic polymers perform poorly in small-diameter applications (cardiac and peripheral bypass). Chitosan is a biocompatible natural polymer that can provide a novel biological scaffold for tissue engineering development. The goal of this study was to demonstrate the biocompatibility of a novel chitosan preparation in vitro and in vivo, and to assess its potential as a scaffold for vascular applications.

CD40 signaling and hepatic steatosis: Unanticipated links.

Obesity predisposes to an increased risk of nonalcoholic fatty liver disease (NAFLD). Hepatic steatosis is the key pathological feature of NAFLD and has emerged as a metabolic disorder in which innate and adaptive arms of the immune response play a central role in disease pathogenesis. Recent studies have revealed unexpected relationships between CD40 signaling and hepatic steatosis in high fat diet rodent models.

Pregnane X-receptor promotes stem cell-mediated colon cancer relapse.

Colorectal cancer lethality usually results from post-treatment relapse in the majority of stage II-IV patients, due to the enhanced resistance of Cancer Stem Cells (CSCs). Here, we show that the nuclear receptor Pregnane X Receptor (PXR, NR1I2), behaves as a key driver of CSC-mediated tumor recurrence. First, PXR is specifically expressed in CSCs, where it drives the expression of genes involved in self-renewal and chemoresistance.

Primary prevention of peristomial hernias via parietal prostheses: A randomized, multicentric study (GRECCAR 7 trial).

Background: Peristomal hernia (PH) is a common complication of colostomy. It often leads to a decrease in the patient's quality of life. Surgical procedures for PH are difficult and present high failure and morbidity rates.

CD154 Induces Matrix Metalloproteinase-9 Secretion in Human Podocytes.

Matrix remodeling is a key feature of glomerulosclerosis secondary to diabetes or hypertension. Podocytes contribute to glomerular basement membrane (GBM) turnover by producing matrix components and matrix remodelling enzymes, including matrix metalloproteinases (MMPs). The CD40/CD154 signaling pathway modulates matrix remodeling through the synthesis of MMPs and tissue inhibitors of MMPs.

Anatomical basis of the coordination between smooth and striated urethral and anal sphincters: loops of regulation between inferior hypogastric plexus and pudendal nerve. Immuno-histological study with 3D reconstruction.

Purpose: (1) Describe both nervous pathways to the sphincters, and highlight the anatomical support of their coordination. (2) Obtain a 3D representation of this complex innervation system.

Methods: A computer-assisted anatomical dissection technique was used.

Beneficial Effect of Covalently Grafted α-MSH on Endothelial Release of Inflammatory Mediators for Applications in Implantable Devices.

Intravascular devices for continuous glucose monitoring are promising tools for the follow up and treatment of diabetic patients. Limiting the inflammatory response to the implanted devices in order to achieve better biocompatibility is a critical challenge. Herein we report on the production and the characterization of gold surfaces covalently derivatized with the peptide α-alpha-melanocyte stimulating hormone (α-MSH), with a quantifiable surface density.

Kinetic eGFR and Novel AKI Biomarkers to Predict Renal Recovery.

Background And Objectives: Prompt recognition of severe renal impairment could improve the early management of critically ill patients. We compared the value of kinetic eGFR, plasma neutrophil gelatinase-associated lipocalin (NGAL), and urine tissue inhibitor of metalloproteinase-2 and urine insulin-like growth factor-binding protein 7 ([TIMP-2]*[IGFBP7]) in predicting short-term recovery from AKI and major adverse kidney events.

Design, Setting, Participants, & Measurements: During the 6-month study period, 245 patients were admitted to our intensive care unit.

New frontiers for platelet CD154.

The role of platelets extends beyond hemostasis. The pivotal role of platelets in inflammation has shed new light on the natural history of conditions associated with acute or chronic inflammation. Beyond the preservation of vascular integrity, platelets are essential to tissue homeostasis and platelet-derived products are already used in the clinics.

Is low tie ligation truly reproducible in colorectal cancer surgery? Anatomical study of the inferior mesenteric artery division branches.

Aim: Curative surgery is the standard treatment for colorectal cancer. The ligation level of the inferior mesenteric artery (IMA) is still debated, as neither low tie (LT) nor high tie ligation (HT) has shown any benefit on the patients' overall survival. We examined whether LT is standardizable and easily reproducible from an anatomical point of view.

The best surgical approach for left colectomy: a comparative study between transverse laparotomy, midline laparotomy and laparoscopy.

Aim: To compare the early and late complications after left colectomy (LC) by left transverse laparotomy (LTL), midline laparotomy (ML) and laparoscopy (La).

Methods: From 1998 to 2003, 328 patients underwent an LC by LTL, ML or La. After matching patients for age, ASA score and indication, 159 patients were divided into three groups of 53 patients each according to the surgical approach performed.

IQ domain GTPase-activating protein 1 is involved in shear stress-induced progenitor-derived endothelial cell alignment.

Shear stress is one of mechanical constraints which are exerted by blood flow on endothelial cells (ECs). To adapt to shear stress, ECs align in the direction of flow through adherens junction (AJ) remodeling. However, mechanisms regulating ECs alignment under shear stress are poorly understood.

Doppler resistive index to reflect regulation of renal vascular tone during sepsis and acute kidney injury.

Introduction: Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance. The aim of this study was to evaluate if mean arterial pressure (MAP) is determinant of renal RI in septic, critically ill patients suffering or not from acute kidney injury (AKI).

Methods: This prospective observational study included 96 patients.