AVNP2 protects against cognitive impairments induced by C6 glioma by suppressing tumour associated inflammation in rats

© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/).Glioblastoma is a kind of malignant tumour and originates from the central nervous system. In the last century, some researchers and clinician have noticed that the psychosocial and neurocognitive functioning of patients with malignant gliomas can be impaired. Many clinical studies have demonstrated that part of patients, adults or children, diagnosed with glioblastoma will suffer from cognitive deficiency during their clinical course, especially in long-term survivors. Many nanoparticles (NPs) can inhibit the biological functions of tumours by modulating tumour-associated inflammation, which provokes angiogenesis and tumour growth. As one of the best antiviral nanoparticles (AVNPs), AVNP2 is the 2nd generation of AVNP2 that have been conjugated to graphite-graphene for improving physiochemical performance and reducing toxicity. AVNP2 inactivates viruses, such as the H1N1 and H5N1influenza viruses and even the SARS coronavirus, while it inhibits bacteria, such as MRSA and E. coli. As antimicrobials, nanoparticles are considered to be one of the vectors for the administration of therapeutic compounds. Yet, little is known about their potential functionalities and toxicities to the neurotoxic effects of cancer. Herein, we explored the functionality of AVNP2 on inhibiting C6 in glioma-bearing rats. The novel object-recognition test and open-field test showed that AVNP2 significantly improved the neuro-behaviour affected by C6 glioma. AVNP2 also alleviated the decline of long-term potentiation (LTP) and the decreased density of dendritic spines in the CA1 region induced by C6. Western blot assay and immunofluorescence staining showed that the expressions of synaptic-related proteins (PSD-95 and SYP) were increased, and these findings were in accordance with the results mentioned above. It revealed that the sizes of tumours in C6 glioma-bearing rats were smaller after treatment with AVNP2. The decreased expression of inflammatory factors (IL-1β, IL-6 and TNF-α) by Western blotting assay and ELISA, angiogenesis protein (VEGF) by Western blotting assay and other related proteins (BDNF, NF-ĸB, iNOS and COX-2) by Western blotting assay in peri-tumour tissue indicated that AVNP2 could control tumour-associated inflammation, thus efficiently ameliorating the local inflammatory condition and, to some extent, inhibiting angiogenesis in C6-bearing rats. In conclusion, our results suggested that AVNP2 could have an effect on the peri-tumor environment, obviously restraining the growth progress of gliomas, and eventually improving cognitive levels in C6-bearing rats.Peer reviewedProo

Pensare l'infondato. Una lettura di Schelling a partire dal corsodel 1936 di Martin Heidegger

In his 1936 lecture-course on the Philosophical Inquiries into the Essence of Human Freedom Heidegger notices a tension towards a non-metaphysical ontology in Schelling's philosophy, and in particular in the introduction of the thought of the not-being into the one of being, of the non-ground (Un-grund) into the one of ground (Grund). What I aim to show, in the wake of Heidegger's interpretation, is how the attempt of thinking of a deity as a guarantee of the rationality of finite existence clashes, not only in the Inquiries but also in the Philosophy of Revelation, with the need to acknowledge irrational, unchosen and therefore unfounded conditions at the basis of God's manifestation: contrast, opposition, the existence of evil

La durée dans la dureté: Espaces de la mémoire et mémoires de l’espace chez Paul Ricœur

In Memory, History, Forgetting, Ricœur does not provide us with a clear definition of collective memory. In this article, we will try to show how it could nevertheless be described, based on the same text, as the capacity for recognition, by way of reciprocal attribution, memories that are engraved in temporal spaces and are shared with our neighbors and, through them, with strangers. To verify this hypothesis, we will analyse Ricœur’s reflection on architecture as public memory’s engraving into space, presented for the first time in the text “Architecture et narrativité.” Lastly, we will consider imagination and bodily memory, i.e. habit emanating from the act of inhabiting, as the conditions of possibility for the crystallization of memories in shared places.Dans La mémoire, l’histoire, l’oubli, Ricœur ne parvient pas à donner une définition claire de la mémoire collective. Dans cet article, nous cherchons à montrer comment elle se laisse néanmoins décrire, à partir de ce même texte, comme la capacité à reconnaître, à travers l’attribution réciproque, des souvenirs qui s’inscrivent dans les espaces temporels partagés avec nos proches et, à travers ces derniers, avec les étrangers. Afin d’appuyer cette hypothèse, nous analysons les réflexions de Ricœur sur l’architecture en tant qu’inscription de la mémoire publique dans l’espace, présentées pour la première fois dans le texte “Architecture et narrativité.” Deuxièmement, nous considérons l’imagination et la mémoire corporelle, à savoir l’habitude qui découle de l’acte d’habiter, comme les conditions de possibilité de la cristallisation des souvenirs dans les lieux partagés

La pensée des lieux de Paul Ricœur à l’épreuve du paysage. Un dialogue possible entre herméneutique, esthétique performative et phénoménologie

In this article, we argue that Paul Ricœur’s hermeneutics of spaces and the aesthetics vision of the landscape as a performance, based on the contemporary theories of Erika Fischer-Lichte, can integrate each other through the mediation of Mikel Dufrenne’s phenomenology of the a priori. In particular, we will show how the representations and the hermeneutics of a landscape as a peculiar “text” are essentially connected with its the pre-reflective experience, which, being made possible by the activation of precise material – and therefore historical and cultural – a priori, can be thus translated into images and words. By intertwining hermeneutics, phenomenology, and performative esthetics we will provide with a non-reductive philosophical description of a landscape, i.e., a definition that does not neglect the aspects of it suggested by its linguistic pre-comprehension and artistic representations.Dans cet article, nous soutenons que l’herméneutique des espaces de Paul Ricœur et la vision esthétique du paysage comme performance, basée sur les théories contemporaines de Erika Fischer-Lichte, peuvent être réconciliées par la médiation de la phénoménologie de l’a priori de Mikel Dufrenne. Nous montrons en particulier comment la représentation du paysage et son interprétation en tant que « texte » sont essentiellement liées à l’expérience pré-réflexive que nous en faisons. Cette expérience, rendue possible par l’activation d’a priori matériels précis – et donc historiques et culturels –  peut être ainsi traduite en images et en textes. En entrelaçant l’herméneutique, la phénoménologie et l’esthétique performative, nous proposerons une description philosophique aussi exhaustive que possible du paysage ; c’est-à-dire une définition du paysage qui ne néglige pas les aspects de ce phénomène suggérés par sa précompréhension linguistique et par ses représentations artistiques

A BMP7 variant inhibits tumor angiogenesis in vitro and in vivo through direct modulation of endothelial cell biology

Bone morphogenetic proteins (BMPs), members of the TGF-\u3b2 superfamily, have numerous biological activities including control of growth, differentiation, and vascular development. Using an in vitro co-culture endothelial cord formation assay, we investigated the role of a BMP7 variant (BMP7v) in VEGF, bFGF, and tumor-driven angiogenesis. BMP7v treatment led to disruption of neo-endothelial cord formation and regression of existing VEGF and bFGF cords in vitro. Using a series of tumor cell models capable of driving angiogenesis in vitro, BMP7v treatment completely blocked cord formation. Pre-treatment of endothelial cells with BMP7v significantly reduced their cord forming ability, indicating a direct effect on endothelial cell function. BMP7v activated the canonical SMAD signaling pathway in endothelial cells but targeted gene knockdown using shRNA directed against SMAD4 suggests this pathway is not required to mediate the anti-angiogenic effect. In contrast to SMAD activation, BMP7v selectively decreased ERK and AKT activation, significantly decreased endothelial cell migration and down-regulated expression of critical RTKs involved in VEGF and FGF angiogenic signaling, VEGFR2 and FGFR1 respectively. Importantly, in an in vivo angiogenic plug assay that serves as a measurement of angiogenesis, BMP7v significantly decreased hemoglobin content indicating inhibition of neoangiogenesis. In addition, BMP7v significantly decreased angiogenesis in glioblastoma stem-like cell (GSLC) Matrigel plugs and significantly impaired in vivo growth of a GSLC xenograft with a concomitant reduction in microvessel density. These data support BMP7v as a potent anti-angiogenic molecule that is effective in the context of tumor angiogenesis

Ganglioglioma arising in an ovarian teratoma

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Prognostic value of the TCGA molecular classification in uterine carcinosarcoma

Background: The TCGA molecular groups of endometrial carcinoma are “POLE-mutated” (POLEmut), “microsatellite-instable/mismatch repair-deficient” (MSI/MMRd), “TP53-mutated/p53-abnormal” (TP53mut/p53abn), and “no specific molecular profile” (NSMP). Objective: Prognostic assessment of the TCGA groups in uterine carcinosarcoma (UCS). Search strategy: Systematic review from January 2000 to January 2021. Selection criteria: Studies assessing the TCGA groups in UCS. Data collection and analysis: Progression-free survival (PFS) and overall survival (OS) were assessed by Kaplan–Meier and Cox analyses (reference: TP53mut/p53abn group) and compared with endometrioid and serous carcinomas (original TCGA cohort), with a significant P < 0.050. Main results: Five studies with 263 UCS were included. Compared with TP53mut/p53abn UCS, MSI/MMRd UCS showed significantly better PFS (P < 0.001) but similar OS (P = 0.788), whereas NSMP UCS showed similar PFS (P = 0.936) and OS (P = 0.240). Compared with their endometrioid/serous counterparts, NSMP and TP53mut/p53abn UCS showed significantly worse PFS (P < 0.001 and P = 0.004) and OS (P < 0.001 and P < 0.001), while MSI/MMRd UCS showed similar PFS (P = 0.595) but significantly worse OS (P < 0.001). The POLEmut group showed neither recurrences nor deaths in both the UCS and the endometrioid/serous carcinoma cohorts. Conclusion: POLEmut UCS show excellent prognosis, whereas TP53mut/p53abn and NSMP UCS show a prognosis even worse than that of TP53mut/p53abn endometrioid/serous carcinomas. The prognosis of MSI/MMRd UCS remains to be defined

Usefulness of 3T MR in surgical planning for deep brain stimulation surgery: a systematic literature review

Magnetic resonance imaging (MRI) allows direct visualization and targeting of the subthalamic nucleus (STN) and the globus pallidus interna (GPi) during deep brain stimulation (DBS) surgery for Parkinson’s disease (PD). Compared to standard 1.5T MRI, the availability of MRI machines with higher magnetic field strength, as 3T MRI, could provide surgical advantages for DBS surgery. The aim of the present systematic review was to gather the available evidence on targeting precision and accuracy, and on clinical outcome, of DBS performed using 1.5T vs. 3T MRI. The literature search yielded 289 results. After duplicate removal and title and abstract screening, 15 full-text papers were assessed, ultimately resulting in the inclusion of six studies in the present work. An improved visualization of STN with 3T MRI was described. Two studies analyzed targeting precision, finding no difference between 1.5T and 3T. Targeting accuracy was evaluated using microelectrode recording-based nucleus identification in four studies: three reported an increased accuracy using 3T MRI, and one reported no differences. Clinical outcome was assessed in three papers, and was judged similar between 1.5T and 3T-based DBS. Risk of bias from the included studies was non-negligible. In conclusion, while the use of 3T MRI can foster deep gray nuclei identification during DBS, according to the available evidence the use of 1.5T MRI remains an adequate option. Further research on this topic is needed. Clinical trial number: Not applicable

Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Endometrial Cancer: A Review on Immunohistochemistry Staining Patterns and Clinical Implications

Among the four endometrial cancer (EC) TCGA molecular groups, the MSI/hypermutated group represents an important percentage of tumors (30%), including different histotypes, and generally confers an intermediate prognosis for affected women, also providing new immunotherapeutic strategies. Immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6 and PMS2) has become the optimal diagnostic MSI surrogate worldwide. This review aims to provide state-of-the-art knowledge on MMR deficiency/MSI in EC and to clarify the pathological assessment, interpretation pitfalls and reporting of MMR status

Atypical cellular neurothekeoma (ACN) of the elderly: case report and brief review of the literature

Atypical cellular neurothekeoma (ACN) is an aggressive and rare variant of cellular neurothekeoma. Only few cases have been reported in the literature and the biological behavior seems to be uncertain. We describe the case of an ACN presenting on the scalp of an elderly man, emphasizing the cytologic features of malignancy. In addition, we provide a brief overview of the literature and discuss the differential diagnosis with other entities, and the possible diagnostic pitfalls