The ocular surface microbiota refers to the resident non-pathogenic microorganisms that colonize conjunctiva and cornea. Several studies have shown that ocular surface epithelial cells can respond selectively to specific components of ocular pathogenic bacteria by producing pro-inflammatory cytokines and, in contrast, they do not respond to non-pathogenic bacteria, thus supporting the colonization by a real microbiota. However, the analysis of the ocular microbiome composition is essential for understanding the pathophysiology of various ophthalmic diseases. In this scenario, the first studies, which used microbiological culture techniques, reported a less diverse profile of the ocular microbiota compared with that recently discovered using new molecular-based methods. Indeed, until a few years ago, the microbiota of the ocular surface appeared to be dominated by Gram-positive and a few Gram-negative bacteria, as well as some fungal strains. In contrast, genomics has nowadays detected a remarkable diversity in the ocular surface microorganisms. Furthermore, recent studies suggest that the microbiota of other areas of the body, such as the gut and oral microbiota, are involved in the pathophysiology of several ophthalmic diseases. The aim of the present study is to highlight the current evidence on the ocular surface microbiota to better understand it and to investigate its potential role in the development of ophthalmic diseases.

Among all solid tumors, the high‐grade glioma appears to be the most vascularized one. In fact, “microvascular hyperplasia” is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs) reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a “quiescent” state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo‐ and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo‐ and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Elisabetta Benedetti1, *, Andrea Antonosante1, *, Michele d’Angelo1, Loredana Cristiano1, Renato Galzio1, Damien Destouches2, 3, Tiziana Marilena Florio1, Anne Chloé Dhez1, Carlo Astarita6, Benedetta Cinque1, Alessia Fidoamore1, Floriana Rosati4, Maria Grazia Cifone1, Rodolfo Ippoliti1, Antonio Giordano5, 6, José Courty2, 3, Annamaria Cimini1, 6, 7 1Department of Life, Health and Environmental Sciences, University of L’Aquila, L’Aquila, Italy 2Department of Cell Biology, Université Paris-Est, UPEC, Créteil, France 3Laboratoire de Recherche sur la Croissance Cellulaire, la Réparation et la Régénération Tissulaires (CRRET) CNRS, Créteil, France 4Department of Life Sciences, University of Siena, Siena, Italy 5Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy 6Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology, Temple University, Philadelphia, Pennsylvania, USA 7National Institute for Nuclear Physics (INFN), Gran Sasso National Laboratory (LNGS), Assergi, Italy *These authors have contributed equally to this work Correspondence to: Annamaria Cimini, e-mail: annamaria.cimini@univaq.it José Courty, e-mail: courty@u-pec-fr Keywords: glioblastoma, autophagy, targeted therapy Received: July 15, 2015 Accepted: October 09, 2015 Published: October 19, 2015

Regenerative medicine represents a major challenge for the scientific community. The choice of the biological sources used, such as stem cells and grafts, is crucial. Stem cell therapy is mainly related to the use of mesenchymal stem cells; however, clinical trials are still needed to investigate their safety. The micrografting technique was conceived by Cicero Parker Meek in 1958. It is based on the principle that by increasing the superficial area of skin grafts and reducing the size of its particles, it is possible to cover an area larger than the original donor site. Stem cells are pluripotent cells that have the capacity to differentiate into all cell types and are self-renewing, whereas micrografts derive from a small fragment of an autologous tissue and exhibit limited differentiative potential compared with stem cells. Therefore, stem cells and micrografts cannot be considered equivalent, although in some cases they exhibit similar regenerative potential, which is the focus of this review. Last, stem cell therapies remain limited because of complex and costly processes, making them not very feasible in clinical practice, whereas obtaining micrografts is generally a one-step procedure that does not require any advanced tissue manipulation.

Cell cycle reactivation in adult neurons is an early hallmark of neurodegeneration. The lipopolysaccharide (LPS) is a well-known pro-inflammatory factor that provokes neuronal cell death via glial cells activation. The retinoblastoma (RB) family includes RB1/p105, retinoblastoma-like 1 (RBL1/p107), and retinoblastoma-like 2 (Rb2/p130). Several studies have indicated that RB proteins exhibit tumor suppressor activities, and play a central role in cell cycle regulation. In this study, we assessed LPS-mediated inflammatory effect on cell cycle reactivation and apoptosis of neuronally differentiated cells. Also, we investigated whether the LPS-mediated inflammatory response can influence the function and expression of RB proteins. Our results showed that LPS challenges triggered cell cycle reactivation of differentiated neuronal cells, indicated by an accumulation of cells in S and G2/M phase. Furthermore, we found that LPS treatment also induced apoptotic death of neurons. Interestingly, we observed that LPS-mediated inflammatory effect on cell cycle re-entry and apoptosis was concomitant with the aberrant expression of RBL1/p107 and RB1/p105. To the best of our knowledge, our study is the first to indicate a role of LPS in inducing cell cycle re-entry and/or apoptosis of differentiated neuronal cells, perhaps through mechanisms altering the expression of specific members of RB family proteins. This study provides novel information on the biology of post-mitotic neurons and could help in identifying novel therapeutic targets to prevent de novo cell cycle reactivation and/or apoptosis of neurons undergoing neurodegenerative processes.