Search results for "loi"
showing 10 items of 4617 documents
CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin
2021
Summary Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless…
Tissue factor at the crossroad of coagulation and cell signaling
2018
The tissue factor (TF) pathway plays a central role in hemostasis and thrombo-inflammatory diseases. Although structure-function relationships of the TF initiation complex are elucidated, new facets of the dynamic regulation of TF?s activities on cells continue to emerge. Cellular pathways that render TF non-coagulant participate in signaling of distinct TF complexes with associated proteases through the protease-activated receptor (PAR) family of G-protein coupled receptors. Additional coreceptors, including the endothelial protein C receptor (EPCR) and integrins, confer signaling specificity by directing subcellular localization and trafficking. We here review how TF is switchedbetween it…
Epithelium‐specific MyD88 signaling, but not DCs or macrophages, control acute intestinal infection with Clostridium difficile
2019
Infection with Clostridium difficile is one of the major causes of health care acquired diarrhea and colitis. Signaling though MyD88 downstream of TLRs is critical for initiating the early protective host response in mouse models of C. difficile infection (CDI). In the intestine, MyD88 is expressed in various tissues and cell types, such as the intestinal epithelium and mononuclear phagocytes (MNP), including DC or macrophages. Using a genetic gain-of-function system, we demonstrate here that restricting functional MyD88 signaling to the intestinal epithelium, but also to MNPs is sufficient to protect mice during acute CDI by upregulation of the intestinal barrier function and recruitment o…
CNS-localized myeloid cells capture living invading T cells during neuroinflammation
2020
Using an in vivo real-time approach, the authors show that local myeloid cells remove early CNS-invading T cells via an engulfment pathway that is dependent on N-acetyl-D-glucosamine (GlcNAc) and lectin. These results reveal a novel capacity of myeloid cells to counteract neuroinflammation.
Alzheimer's Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy
2016
Background: Alzheimer’s disease (AD) is a dementia, a neurodegenerative condition, and a protein-misfolding disease or proteinopathy, characterized by protein deposits, extracellular plaques and intracellular neurofibrillary tangles, which contain the AD’s typical pathological proteins, abnormal [1]-amyloid and hyperphosphorylated tau, respectively, and are located predominantly in the cortex of the frontal, parietal, and temporal brain lobes. What is the role of molecular chaperones in AD? Data indicate that molecular chaperones, also known as Hsp, are involved in AD, probably displaying protective roles and/or acting as pathogenic factors as it occurs in chaperonopathies in which case AD …
Aneuploidy and Ethanol Tolerance in Saccharomyces cerevisiae
2019
Response to environmental stresses is a key factor for microbial organism growth. One of the major stresses for yeasts in fermentative environments is ethanol. Saccharomyces cerevisiae is the most tolerant species in its genus, but intraspecific ethanol-tolerance variation exists. Although, much effort has been done in the last years to discover evolutionary paths to improve ethanol tolerance, this phenotype is still hardly understood. Here, we selected five strains with different ethanol tolerances, and used comparative genomics to determine the main factors that can explain these phenotypic differences. Surprisingly, the main genomic feature, shared only by the highest ethanol-tolerant st…
Ethanol Controls the Self-Assembly and Mesoscopic Properties of Human Insulin Amyloid Spherulites.
2018
Protein self-assembly into amyloid fibrils or highly hierarchical superstructures is closely linked to neurodegenerative pathologies as Alzheimer's and Parkinson's diseases. Moreover, protein assemblies also emerged as building blocks for bioinspired nanostructured materials. In both the above mentioned fields, the main challenge is to control the growth and properties of the final protein structure. This relies on a more fundamental understanding of how interactions between proteins can determine structures and functions of biomolecular aggregates. Here, we identify a striking effect of the hydration of the single human insulin molecule and solvent properties in controlling hydrophobicity/…
Rescuing monopronucleated-derived human blastocysts: a model to study chromosomal topography and fingerprinting.
2021
Objective To quantify the percentage of monopronuclear-derived blastocysts (MNBs) that are potentially useful for reproductive purposes using classic and state-of-the-art chromosome analysis approaches, and to study chromosomal distribution in the inner cell mass (ICM) and trophectoderm (TE) for intertissue/intratissue concordance comparison. Design Prospective experimental study. Setting Single-center in vitro fertilization clinic and reproductive genetics laboratory. Patient(s) A total of 1,128 monopronuclear zygotes were obtained between June 2016 and December 2018. Intervention(s) MNBs were whole-fixed or biopsied to obtain a portion of ICM and 2 TE portions (TE1 and TE2) and were subse…
The good and bad of targeting cancer-associated extracellular matrix
2017
The maintenance of tissue homeostasis requires extracellular matrix (ECM) remodeling. Immune cells actively participate in regenerating damaged tissues contributing to ECM deposition and shaping. Dysregulated ECM deposition characterizes fibrotic diseases and cancer stromatogenesis, where a chronic inflammatory state sustains the ECM increase. In cancer, the ECM fosters several steps of tumor progression, providing pro-survival and proliferative signals, promoting tumor cell dissemination via collagen fibers or acting as a barrier to impede drug diffusion. Interfering with processes leading to chronic ECM deposition, as occurring in cancer, might allow the simultaneous targeting of both pri…
Vascular pathology: Cause or effect in Alzheimer disease?
2018
Introduction: Alzheimer disease (AD) is the main cortical neurodegenerative disease. The incidence of this disease increases with age, causing significant medical, social and economic problems, especially in countries with ageing populations. Objective: This review aims to highlight existing evidence of how vascular dysfunction may contribute to cognitive impairment in AD, as well as the therapeutic possibilities that might arise from this evidence. Development: The vascular hypothesis emerged as an alternative to the amyloid cascade hypothesis as an explanation for the pathophysiology of AD. This hypothesis locates blood vessels as the origin for a variety of pathogenic pathways that lead …