A Novel Function of Na Channel β3 Subunit in Endothelial Cell Alignment Through Autophagy Modulation.

Endothelial cells (EC) play a pivotal role in vascular homeostasis. By sensing shear stress generated by blood flow, EC endorse vasculoprotection through mechanotransduction signaling pathways. Various ion channels are involved in mechanosignaling, and here, we investigated the endothelial voltage-gated Na channels (Na channels), since their mechanosensitivity has been previously demonstrated in cardiomyocytes.

Evidence of residual micellar structures in a lipid nanocapsule dispersion. A multi-technique approach.

Nanoemulsions are metastable emulsions in the nanometric range which can be obtained using low-energy processes. A decade ago, it was demonstrated that a non-negligible amount of residual surfactant micelles may coexist with the oil nanodroplets in a model oil/surfactant system. Those micelles were called "wasted" micelles as they did not participate in the formation of the nanodroplets.

Cancer/Testis Antigen 55 is required for cancer cell proliferation and mitochondrial DNA maintenance.

Cancer/Testis Antigens (CTAs) represent a group of proteins whose expression under physiological conditions is restricted to testis but activated in many human cancers. Also, it was observed that co-expression of multiple CTAs worsens the patient prognosis. Five CTAs were reported acting in mitochondria and we recently reported 147 transcripts encoded by 67 CTAs encoding for proteins potentially targeted to mitochondria.

New In Vitro Coculture Model for Evaluating Intestinal Absorption of Different Lipid Nanocapsules.

Standard models used for evaluating the absorption of nanoparticles like Caco-2 ignore the presence of vascular endothelium, which is a part of the intestinal multi-layered barrier structure. Therefore, a coculture between the Caco-2 epithelium and HMEC-1 (Human Microvascular Endothelial Cell type 1) on a Transwell insert has been developed. The model has been validated for (a) membrane morphology by transmission electron microscope (TEM); (b) ZO-1 and β-catenin expression by immunoassay; (c) membrane integrity by trans-epithelial electrical resistance (TEER) measurement; and (d) apparent permeability of drugs from different biopharmaceutical classification system (BCS) classes.

Semisynthetic Vitamin E Derivatives as Potent Antibacterial Agents against Resistant Gram-Positive Pathogens.

New 5-substituted vitamin E derivatives were semisynthesized, and their antibacterial activity against human Gram-positive and Gram-negative pathogens was evaluated. Several vitamin E analogues were active against methicillin-resistant Staphylococcus aureus (MRSA) and/or methicillin-resistant Staphylococcus epidermidis (MRSE); structure-activity relationships (SARs) are discussed. As a result, it is shown that the presence of a carboxylic acid function at the C-5 position and/or at the end of the side chain is crucial for the antibacterial activity.

Osteocyte staining with rhodamine in osteonecrosis and osteoarthritis of the femoral head.

Death of osteocytes is synonymous of bone death. Aseptic osteonecrosis of the femoral head is a lesion characterized by the death of osteocytes occurring after major vascular changes. The evolution may lead to hip osteoarthritis, which requires total hip arthroplasty in most cases.

A new glioblastoma cell trap for implantation after surgical resection.

Glioblastoma (GB) is a highly infiltrative tumor, recurring, in 90% of cases, within a few centimeters of the surgical resection cavity, even with adjuvant chemo/radiotherapy. Residual GB cells left in the margins or infiltrating the brain parenchyma shelter behind the extremely fragile and sensitive brain tissue and may favor recurrence. Tools for eliminating these cells without damaging the brain microenvironment are urgently required.

Efficacy of targeting bone-specific GIP receptor in ovariectomy-induced bone loss.

Glucose-dependent insulinotropic polypeptide (GIP) has been recognized in the last decade as an important contributor of bone remodelling and is necessary for optimal bone quality. However, GIP receptors are expressed in several tissues in the body and little is known about the direct vs indirect effects of GIP on bone remodelling and quality. The aims of the present study were to validate two new GIP analogues, called [d-Ala2]-GIP-Tag and [d-Ala2]-GIP1-30, which specifically target either bone or whole-body GIP receptors, respectively; and to ascertain the beneficial effects of GIP therapy on bone in a mouse model of ovariectomy-induced bone loss.

CLUH couples mitochondrial distribution to the energetic and metabolic status.

Mitochondrial dynamics and distribution are critical for supplying ATP in response to energy demand. CLUH is a protein involved in mitochondrial distribution whose dysfunction leads to mitochondrial clustering, the metabolic consequences of which remain unknown. To gain insight into the role of CLUH on mitochondrial energy production and cellular metabolism, we have generated CLUH-knockout cells using CRISPR/Cas9.

Glucose-dependent insulinotropic polypeptide (GIP) dose-dependently reduces osteoclast differentiation and resorption.

A role for glucose-dependent insulinotropic polypeptide (GIP) in controlling bone resorption has been suspected. However uncertainty remains to identify whether GIP act directly on osteoclasts. The aim of the present study were (i) to identify in different osteoclast differentiation models (human peripheral blood mononuclear cells-PBMC, murine bone marrow macrophage-BMM and murine Raw 264.

High fat-fed diabetic mice present with profound alterations of the osteocyte network.

Diabetes mellitus is considered to be an independent risk factor for bone fragility fractures. Reductions in bone mass, observed only with type 1 diabetes mellitus, as well as modifications of bone microarchitectures and tissue material properties are landmarks of diabetes-related bone alterations. An interesting feature observed in type 2 diabetes mellitus (T2DM) is the augmented concentration in circulating sclerostin.

Polystyrene scaffolds based on microfibers as a bone substitute; development and in vitro study.

Unlabelled: We created non-resorbable porous scaffolds of polystyrene by electrospinning usable as a bone grafting material. Aligned and random fibers were prepared with a diameter ranging from 1 to 4.5μm.

Giant axonal neuropathy-associated gigaxonin mutations impair intermediate filament protein degradation.

Giant axonal neuropathy (GAN) is an early-onset neurological disorder caused by mutations in the GAN gene (encoding for gigaxonin), which is predicted to be an E3 ligase adaptor. In GAN, aggregates of intermediate filaments (IFs) represent the main pathological feature detected in neurons and other cell types, including patients' dermal fibroblasts. The molecular mechanism by which these mutations cause IFs to aggregate is unknown.

Reversal of neuropathy phenotypes in conditional mouse model of Charcot-Marie-Tooth disease type 2E.

Mutations in the gene encoding for the neurofilament light subunit (NF-L) are responsible for Charcot-Marie-Tooth (CMT) neuropathy type 2E. To address whether CMT2E disease is potentially reversible, we generated a mouse model with conditional doxycycline-responsive gene system that allows repression of mutant hNF-LP22S transgene expression in adult neurons. The hNF-LP22S;tTa transgenic (tg) mice recapitulated key features of CMT2E disease, including aberrant hindlimb posture, motor deficits, hypertrophy of muscle fibres and loss of muscle innervation without neuronal loss.

Neuronal intermediate filaments and neurodegenerative disorders.

Intermediate filaments represent the most abundant cytoskeletal element in mature neurons. Mutations and/or accumulations of neuronal intermediate filament proteins are frequently observed in several human neurodegenerative disorders. Although it is now admitted that disorganization of the neurofilament network may be directly involved in neurodegeneration, certain type of perikaryal intermediate filament aggregates confer protection in motor neuron disease.

Real-time imaging reveals defects of fast axonal transport induced by disorganization of intermediate filaments.

Intermediate filament (IF) abnormalities frequently appear in neurodegenerative disorders, but how they may contribute to neuronal dysfunction remains unclear. Here, we examined the effects of IF disorganization on the fast axonal transport using time-lapse microscopy. We studied the axonal transport of mitochondria and lysosomes in cultured primary dorsal root ganglion (DRG) neurons derived from mice deficient for neurofilament light (NFL(-/-)), mice overexpressing peripherin (Per), and mice double transgenic Per;NFL(-/-).

Review of the multiple aspects of neurofilament functions, and their possible contribution to neurodegeneration.

Neurofilaments (NF) are the most abundant cytoskeletal component of large myelinated axons from adult central and peripheral nervous system. Here, we provide an overview of the complementary approaches, including biochemistry, cell biology and transgenic technology that were used to investigate the assembly, axonal transport and functions of NF in normal and pathological situations. Following their synthesis and assembly in the cell body, NFs are transported along the axon.

Axonal neurofilaments control multiple fiber properties but do not influence structure or spacing of nodes of Ranvier.

In the vertebrate nervous system, axon calibers correlate positively with myelin sheath dimensions and electrophysiological parameters including action potential amplitude and conduction velocity. Neurofilaments, a prominent component of the neuronal cytoskeleton, are required by axons to support their normal radial growth. To distinguish between fiber features that arise in response to absolute axon caliber and those that are under autonomous control, we investigated transgenic mice in which neurofilaments are sequestered in neuronal cell bodies.