SaO032PAPILLARY RENAL CELL CARCINOMA ORIGINATES FROM A POPULATION OF RENAL PROGENITOR CELLS AND IS PROMOTED BY ACUTE KIDNEY INJURY

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HCV derived from sera of HCV-infected patients induces pro-fibrotic effects in human primary fibroblasts by activating GLI2

Hepatitis C virus (HCV) infection is a leading cause of liver fibrosis, especially in developing countries. The process is characterized by the excess accumulation of ECM that may lead, over time, to hepatic cirrhosis, liver failure and also to hepatocarcinoma. The direct role of HCV in promoting fibroblasts trans-differentiation into myofibroblasts, the major fibrogenic cells, has not been fully clarified. In this study, we found that HCV derived from HCV-infected patients infected and directly induced the trans-differentiation of human primary fibroblasts into myofibroblasts, promoting fibrogenesis. This effect correlated with the activation of GLI2, one of the targets of Hedgehog signaling pathway previously reported to be involved in myofibroblast generation. Moreover, GLI2 activation by HCV correlated with a reduction of autophagy in fibroblasts, that may further promoted fibrosis. GLI2 inhibition by Gant 61 counteracted the pro-fibrotic effects and autophagy inhibition mediated by HCV, suggesting that targeting HH/GLI2 pathway might represent a promising strategy to reduce the HCV-induced fibrosis

Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-α

<p>Abstract</p> <p>Background</p> <p>In addition to cytotoxic mechanisms directly impacting neurons, β-amyloid (Aβ)-induced glial activation also promotes release of proinflammatory molecules that may self-perpetuate reactive gliosis and damage neighbouring neurons, thus amplifying neuropathological lesions occurring in Alzheimer's disease (AD). Palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory, analgesic, antiepileptic and neuroprotective effects. PEA is a lipid messenger isolated from mammalian and vegetable tissues that mimics several endocannabinoid-driven actions, even though it does not bind to cannabinoid receptors. Some of its pharmacological properties are considered to be dependent on the expression of peroxisome proliferator-activated receptors-α (PPARα).</p> <p>Findings</p> <p>In the present study, we evaluated the effect of PEA on astrocyte activation and neuronal loss in models of Aβ neurotoxicity. To this purpose, primary rat mixed neuroglial co-cultures and organotypic hippocampal slices were challenged with Aβ_1-42and treated with PEA in the presence or absence of MK886 or GW9662, which are selective PPARα and PPARγ antagonists, respectively. The results indicate that PEA is able to blunt Aβ-induced astrocyte activation and, subsequently, to improve neuronal survival through selective PPARα activation. The data from organotypic cultures confirm that PEA anti-inflammatory properties implicate PPARα mediation and reveal that the reduction of reactive gliosis subsequently induces a marked rebound neuroprotective effect on neurons.</p> <p>Conclusions</p> <p>In line with our previous observations, the results of this study show that PEA treatment results in decreased numbers of infiltrating astrocytes during Aβ challenge, resulting in significant neuroprotection. PEA could thus represent a promising pharmacological tool because it is able to reduce Aβ-evoked neuroinflammation and attenuate its neurodegenerative consequences.</p

Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments

The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations

Biomedical applications of polarimetric imaging contrast. Initial studies for scattering media and human tissues

Improving the visualization of dysplastic regions of uterine cervix in vivo is essential for a better identification of the locations to biopsy and a better definition of the boundaries of the anomalous regions to be surgically removed. For this purpose we propose an innovative optical technique based on multispectral full Mueller polarimetric imaging in backscattering configuration. Measurements on ex vivo samples were performed to define the best acquisition procedures and data treatments for in vivo diagnosis. As this optimization requires thorough understanding of polarimetric contrasts between healthy and anomalous tissues, we simulated the propagation of polarized light in multilayer structures representative of real tissues. These structures typically involve an uppermost layer describing the epithelium and/or superficial connective tissue, on top of a totally depolarizing lambertian surface lumping the contribution of deeper layers. The simulations were performed by using a Monte Carlo code which has been modified and adapted to our topic. We thus showed that the contribution of the cell nuclei is in fact quite small in the backscattering geometry. For connective tissue, collagen fibers were modelled as 200 nm radius scatterers. Once more this contribution alone could not reproduce the main experimental features. Very small scatterers (50 nm typical radius) have to be included to account for the Rayleigh-like polarimetric response observed in all tissues, both healthy and diseased. These scatterers may be representative of proteins, whose concentration seems to be a crucial parameter to account for the observed contrasts. In this sense, polarimetric imaging may reflect not only the tissue morphology as seen by optical microscopy, but also its physiological state, which may be a very important point for cancer detection and staging.L'amélioration de la visualisation in vivo des lésions précancéreuse (dysplasies) du col utérin est essentielle pour mieux identifier les zones à biopsier et pour optimiser la définition des limites d'exérèse chirurgicale. Dans ce but nous étudions une nouvelle technique d'imagerie polarimétrique en rétrodiffusion, que nous avons mise en oeuvre sur des échantillons ex vivo dans des configurations expérimentales variées afin d'optimiser le diagnostic in vivo. Comme cette optimisation passe par la compréhension des contrastes polarimétriques observés, nous avons réalisé de nombreuses simulations de la propagation de lumière polarisée dans des structures multicouche représentatives des tissus. Ces structures comprennent typiquement une couche comportant des diffuseurs dans une matrice homogène et représentant l'épithélium ou le tissu conjonctif superficiel, et un substrat lambertien totalement dépolarisant pour les couches plus profondes. Ces simulations ont été effectuées au moyen d'un code Monte Carlo que nous avons adapté à notre problématique. Nous avons ainsi montré que la contribution des noyaux cellulaires est très faible en rétrodiffusion. Pour le tissu conjonctif, les fibres de collagène, modélisées par des diffuseurs sphériques de 200 nm de rayon, donnent une contribution plus importante que les noyaux, mais ne reproduisent pas la réponse polarimétrique de type Rayleigh observée dans tous les tissus étudiés, qu'ils soient sains ou pathologiques. En revanche, l'inclusion de diffuseurs de taille nettement inférieure à la longueur d'onde, modélisés par des sphères de 50 nm, permet de reproduire cette réponse de manière très stable. Ces diffuseurs correspondent a priori aux protéines intracellulaires. Dans le cadre de ce modèle, les contrastes observés entre tissus sains et cancéreux s'expliquent essentiellement par une variation de la concentration de ces petits diffuseurs. Ce résultat, encore préliminaire, suggère que l'imagerie polarimétrique en rétrodiffusion peut être sensible non seulement à la morphologie, mais également à l'état physiologique du tissu, ce qui peut s'avérer important pour la détection sélective des dysplasies

Intercalation and Exfoliation Compounds of Graphite Oxide with Quaternary Phosphonium Ions DOI: 10.1021/cm504174v

Highly ordered graphite oxide intercalation compounds (GOIC) and fully disordered graphite oxide exfoliated compounds (GOEC) have been obtained, for two quaternary phosphonium salts. X-ray diffraction patterns of both GOIC and GOEC maintain the 100 and 110 reflections of GO, clearly indicating the maintenance of in-plane GO order. For GOICs, few 00l reflections (with l up to 3) appear, indicating an increase with respect to GO of crystalline order as well as an increase of spacing between GO layers from 0.84 nm up to 1.40 nm. GOIC and GOEC have been compared for their kinetics of release in aqueous solutions of a phosphonium ion, being a known antibacterial agent. GOICs exhibit pH sensitive cation release, with zero order kinetics, which could be helpful for applications requiring triggered and constant supply of active ions

A case of melanotic desmoplastic ganglioglioma

We describe a case of desmoplastic infantile ganglioglioma (DIG) in a 9-month-old boy located in the temporal lobe. Grossly the tumor was brown and superficially located. Histologically the tumor contained pigment in numerous neoplastic cells, shown to be melanosomal melanin by ultrastructural examination. Pigmented neoplasms have been reported at various sites in the central and peripheral nervous system. Previous reports on pigmented neuroepithelial tumors include neoplasms containing melanin, while others have contained neuromelanin and or lipofuscin. This case represents the first description of pigmented neoplastic cells in DIG, enlarging the spectrum of pigmented primary CNS tumors

Intercalation and exfoliation compounds of graphite oxide with quaternary phosphonium ions

Highly ordered graphite oxide intercalation compounds (GOIC) and fully disordered graphite oxide exfoliated compounds (GOEC) have been obtained, for two quaternary phosphonium salts. X-ray diffraction patterns of both GOIC and GOEC maintain the 100 and 110 reflections of GO, clearly indicating the maintenance of in-plane GO order. For GOICs, few 00l reflections (with l up to 3) appear, indicating an increase with respect to GO of crystalline order as well as an increase of spacing between GO layers from 0.84 nm up to 1.40 nm. GOIC and GOEC have been compared for their kinetics of release in aqueous solutions of a phosphonium ion, being a known antibacterial agent. GOICs exhibit pH sensitive cation release, with zero order kinetics, which could be helpful for applications requiring triggered and constant supply of active ions