Search results for "RACE"

2017

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal genetic arrhythmia that manifests syncope or sudden death in children and young adults under stress conditions. CPVT patients often present bradycardia and sino-atrial node (SAN) dysfunction. However, the mechanism remains unclear. We analyzed SAN function in two CPVT families and in a novel knock-in (KI) mouse model carrying the RyR2R420Q mutation. Humans and KI mice presented slower resting heart rate. Accordingly, the rate of spontaneous intracellular Ca2+ ([Ca2+]i) transients was slower in KI mouse SAN preparations than in WT, without any significant alteration in the "funny" current (If ). The L-type Ca2+ current …

Macronutrient balance and micronutrient amounts through growth and development

2021

AbstractNutrition is essential for human growth, particularly in newborns and children. An optimal growth needs a correct diet, in order to ensure an adequate intake of macronutrients and micronutrients. Macronutrients are the compounds that humans consume in largest quantities, mainly classified in carbohydrates, proteins and fats. Micronutrients are instead introduced in small quantities, but they are required for an adequate growth in the pediatric age, especially zinc, iron, vitamin D and folic acid. In this manuscript we describe the most important macro and micronutrients for children’s growth.

Low-Cost Optical Mapping Systems for Panoramic Imaging of Complex Arrhythmias and Drug-Action in Translational Heart Models.

2017

[EN] Panoramic optical mapping is the primary method for imaging electrophysiological activity from the entire outer surface of Langendorff-perfused hearts. To date, it is the only method of simultaneously measuring multiple key electrophysiological parameters, such as transmembrane voltage and intracellular free calcium, at high spatial and temporal resolution. Despite the impact it has already had on the fields of cardiac arrhythmias and whole-heart computational modeling, present-day system designs precludes its adoption by the broader cardiovascular research community because of their high costs. Taking advantage of recent technological advances, we developed and validated low-cost opti…

Gut Microbiota Condition the Therapeutic Efficacy of Trastuzumab in HER2-Positive Breast Cancer.

2021

Abstract Emerging evidence indicates that gut microbiota affect the response to anticancer therapies by modulating the host immune system. In this study, we investigated the impact of gut microbiota on immune-mediated trastuzumab antitumor efficacy in preclinical models of HER2-positive breast cancer and in 24 patients with primary HER2-positive breast cancer undergoing trastuzumab-containing neoadjuvant treatment. In mice, the antitumor activity of trastuzumab was impaired by antibiotic administration or fecal microbiota transplantation from antibiotic-treated donors. Modulation of the intestinal microbiota was reflected in tumors by impaired recruitment of CD4+ T cells and granzyme B–posi…

2021

Although it is widely accepted that cancer-derived extracellular vesicles (EVs) carry DNA cargo, the association of cell-free circulating DNA (cfDNA) and EVs in plasma of healthy humans remains elusive. Using a physiological exercise model, where EVs and cfDNA are synchronously released, we aimed to characterize the kinetics and localization of DNA associated with EVs. EVs were separated from human plasma using size exclusion chromatography or immuno-affinity capture for CD9+, CD63+, and CD81+ EVs. DNA was quantified with an ultra-sensitive qPCR assay targeting repetitive LINE elements, with or without DNase digestion. This model shows that a minute part of circulating cell-free DNA is asso…

Calcium Polyphosphate Nanoparticles Act as an Effective Inorganic Phosphate Source during Osteogenic Differentiation of Human Mesenchymal Stem Cells

2019

The ability of bone-marrow-derived mesenchymal stem/stromal cells (BM-MSCs) to differentiate into osteoblasts makes them the ideal candidate for cell-based therapies targeting bone-diseases. Polyphosphate (polyP) is increasingly being studied as a potential inorganic source of phosphate for extracellular matrix mineralisation. The aim of this study is to investigate whether polyP can effectively be used as a phosphate source during the in vitro osteogenic differentiation of human BM-MSCs. Human BM-MSCs are cultivated under osteogenic conditions for 28 days with phosphate provided in the form of organic &beta

Extracellular vesicles as miRNA nano-shuttles : dual role in tumor progression

2018

[EN] Tumor-derived extracellular vesicles (EVs) have a pleiotropic role in cancer, interacting with target cells of the tumor microenvironment, such as fibroblasts, immune and endothelial cells. EVs can modulate tumor progression, angiogenic switch, metastasis, and immune escape. These vesicles are nano-shuttles containing a wide spectrum of miRNAs that contribute to tumor progression. MiRNAs contained in extracellular vesicles (EV-miRNAs) are disseminated in the extracellular space and are able to influence the expression of target genes with either tumor suppressor or oncogenic functions, depending on both parental and target cells. Metastatic cancer cells can balance their oncogenic pote…

Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance

2019

Cancer-derived extracellular vesicles (EVs) have been detected in the bloodstream and other biofluids of cancer patients. They carry various tumor-derived molecules such as mutated DNA and RNA fragments, oncoproteins as well as miRNA and protein signatures associated with various phenotypes. The molecular cargo of EVs partially reflects the intracellular status of their cellular origin, however various sorting mechanisms lead to the enrichment or depletion of EVs in specific nucleic acids, proteins or lipids. It is becoming increasingly clear that cancer-derived EVs act in a paracrine and systemic manner to promote cancer progression by transferring aggressive phenotypic traits and drug-res…

Membrane-anchored heat-shock protein 70 (Hsp70) in cancer.

2020

International audience; Hsp70 is a highly conserved and inducible heat shock protein that belongs to the HSP70 family of molecular chaperones and plays a central role in protein homeostasis. The main function of Hsp70 is to protect cells from physiological, pathological and environmental insults, as it assists an ATP-dependent manner the process of protein folding. Since Hsp70 provides critical cell survival functions, cancer cells are assumed to rely on this chaperone. Strong evidence suggests that Hsp70 is upregulated in different type of cancers and is involved in tumor growth, invasion, migration and resistance to anti-cancer therapy. Interestingly, this Hsp70 upregulation induces Hsp70…

Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1α Axis

2020

Bone disease severely affects the quality of life of over 70% of multiple myeloma (MM) patients, which daily experience pain, pathological fractures, mobility issues and an increased mortality. Recent data have highlighted the crucial role of the endoplasmic reticulum-associated unfolded protein response (UPR) in malignant transformation and tumor progression