1,721,002 research outputs found
Receptors on Autonomic Neurons and Neuroeffector Cells: Peptidergic Receptors.
Full text linkNeuropeptides are peptides involved in various nervous system functions. They are synthesized in cells as large precursor proteins, and
generally several biologically active peptides are contained in the same precursor molecule. Peptidergic signaling molecules are widely
distributed throughout the central and peripheral nervous systems and in peripheral organs. They act by neurocrine, paracrine,
autocrine and endocrine mechanisms and the same peptides may participate in inter-cellular communications through different
modalities. For instance, many peptides expressed in the enteric nervous system belong to a class of agents known as brain-gut
peptides, functioning both as neuropeptides and as gut hormones
Neuroprotective Peptides in Retinal Disease
Full text linkIn the pathogenesis of many disorders, neuronal death plays a key role. It is now assumed that neurodegeneration is caused by multiple and somewhat converging/overlapping death mechanisms, and that neurons are sensitive to unique death styles. In this respect, major advances in the knowledge of different types, mechanisms, and roles of neurodegeneration are crucial to restore the neuronal functions involved in neuroprotection. Several novel concepts have emerged recently, suggesting that the modulation of the neuropeptide system may provide an entirely new set of pharmacological approaches. Neuropeptides and their receptors are expressed widely in mammalian retinas, where they exert neuromodulatory functions including the processing of visual information. In multiple models of retinal diseases, different peptidergic substances play neuroprotective actions. Herein, we describe the novel advances on the protective roles of neuropeptides in the retina. In particular, we focus on the mechanisms by which peptides affect neuronal death/survival and the vascular lesions commonly associated with retinal neurodegenerative pathologies. The goal is to highlight the therapeutic potential of neuropeptide systems as neuroprotectants in retinal diseases
Regenerative Strategies for Retinal Neurons: Novel Insights in Non-Mammalian Model Organisms
Full text linkA detailed knowledge of the status of the retina in neurodegenerative conditions is a crucial point for the development of therapeutics in retinal pathologies and to translate eye research to CNS disease. In this context, manipulating signaling pathways that lead to neuronal regeneration offers an excellent opportunity to substitute damaged cells and, thus, restore the tissue functionality. Alternative systems and methods are increasingly being considered to replace/reduce in vivo approaches in the study of retina pathophysiology. Herein, we present recent data obtained from the zebrafish (Danio rerio) and the fruit fly Drosophila melanogaster that bring promising advantages into studying and modeling, at a preclinical level, neurodegeneration and regenerative approaches in retinal diseases. Indeed, the regenerative ability of vertebrate model zebrafish is particularly appealing. In addition, the fruit fly is ideal for regenerative studies due to its high degree of conservation with vertebrates and the broad spectrum of genetic variants achievable. Furthermore, a large part of the drosophila brain is dedicated to sight, thus offering the possibility of studying common mechanisms of the visual system and the brain at once. The knowledge acquired from these alternative models may help to investigate specific well-conserved factors of interest in human neuroregeneration after injuries or during pathologies
Morpho-functional analysis of the early changes induced in retinal ganglion cells by the onset of diabetic retinopathy: The effects of a neuroprotective strategy
Full text linkRetinal ganglion cells (RGCs) are highly susceptible to diabetes-induced metabolic stress. This study describes the early responses of RGCs to hyperglycemia and examines the effects of the neuroprotective somatostatin analog octreotide (OCT)
The Secondary Metabolite Euplotin C Induces Apoptosis-Like Death in the Marine Ciliated Protist Euplotes vannus
No full textThe sesquiterpenoid euplotin C is a secondary metabolite produced by the ciliated protist Euplotes crassus and provides a mechanism for damping populations of potential competitors. Indeed, E. crassus is virtually resistant to its own product while different non-producer species representing an unbiased sample of the marine, interstitial, ciliate diversity are sensitive. For instance, euplotin C exerts a marked disruption of different homeostatic mechanisms in Euplotes vannus. We demonstrate by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay that euplotin C quickly decreases viability and mitochondrial function of E. vannus with a very high efficacy and at micromolar potency. In addition, euplotin C induces apoptosis in E. vannus as 4,6-diamino-2-phenylindole and terminal transferase dUTP nick end labeling staining show the rapid condensation and fragmentation of nuclear material in cells treated with euplotin C. These effects occur without detectable permeabilisation or rupture of cell membranes and with no major changes in the overall morphology, although some traits, such as vacuolisation and disorganized microtubules, can be observed by transmission electron microscopy. In particular, E. vannus show profound changes of the mitochondrial ultrastructure. Finally, we also show that caspase activity in E. vannus is increased by euplotin C. These data elucidate the pro-apoptotic role of euplotin C and suggest a mechanism for its impact on natural selection
Melanoma progression is reduced by the ciliated protozoan toxin climacostol: results from in vitro and in vivo studies
Full text linkMelanoma progression is reduced by the ciliated protozoan toxin climacostol: results from in vitro and in vivo studies
Authorship:
Federico Buonanno1, Cristiana Perrotta2, Laura Guerra3, Simona Picchietti3, Anna Maria Fausto3, Enrico Marcantoni4, Simone Giorgi4, Claudio Ortenzi1, Davide Cervia2,3
1Laboratory of Protistology and Biology Education, University of Macerata, 62100 Macerata, Italy
2 Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), Università di Milano, via G.B. Grassi 74, 20157 Milano, Italy
3 Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università della Tuscia, via S. Camillo de Lellis snc, 01100 Viterbo, Italy
4School of Sciences and Technologies, Section of Chemistry, University of Camerino, 62032 Camerino, Macerata, Italy
Text:
Melanoma diagnoses have risen sharply over past decades, and despite new lines of therapy have been introduced the need for additional drugs is urgent. Previous findings from our group demonstrated that climacostol, an alkyl resorcinol produced by the ciliated protozoan Climacostomum virens, decreases the viability of five different mammalian cancer cell lines, while it was devoid of effects on endothelial cells. In order to expand these data and due to the availability of the synthetic toxin, we have further analysed different tumoral and non-tumoral cell lines, observing that viability of human and rodent tumoral cells was negatively affected by climacostol with higher potency when compared to non-tumoral cells. We then focused on the B16-F10 mouse melanoma cells, where climacostol caused a concentration-dependent reduction of viability with an EC50 of 6.3 μg/ml, and an Emax of 30 μg/ml. Flow cytometry analyses indicated that cell proliferation was effectively inhibited by climacostol, with a significant increase of apoptotic cells.The data collected prompted us to investigate the effects of climacostol on in vivo melanoma progression using a B16-F10 allograft transplantation tumor model. The results indicate that climacostol decreased tumour weight and increased the content of apoptotic cells, suggesting that the toxin may be considered for the design of cytotoxic and pro-apoptotic new drugs for melanoma therapy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Molecular mechanisms underlying apoptotic effects of euplotin C, a secondary metabolite of Euplotes crassus in a tumour cell line
No full textClimacostol, a ciliate secondary metabolite with anticancer activity: results from in vitro and in vivo studies
Full text linkClimacostol, a ciliate secondary metabolite with anticancer activity: results from in vitro and in vivo studies
Federico Buonanno1, Cristiana Perrotta2, Laura Guerra3, Simona Picchietti3, Anna Maria Fausto3, Enrico Marcantoni4, Simone Giorgi4, Claudio Ortenzi1, Davide Cervia2,3
1Laboratory of Protistology and Biology Education, University of Macerata, 62100 Macerata, Italy
2 Department of Biomedical and Clinical Sciences “Luigi Sacco” (DIBIC), Università di Milano, via G.B. Grassi 74, 20157 Milano, Italy
3 Department for Innovation in Biological, Agro-food and Forest systems (DIBAF), Università della Tuscia, via S. Camillo de Lellis snc, 01100 Viterbo, Italy
4School of Sciences and Technologies, Section of Chemistry, University of Camerino, 62032 Camerino, Macerata, Italy
Climacostol is a natural toxic secondary metabolite isolated from the freshwater ciliate Climacostomum virens and belongs to the group of resorcinolic lipids (or alkylresorcinols). Climacostol is stored in ejectable organelles (extrusomes) and it is naturally used by the ciliate for its chemical defense against predators. In addition, it was recently shown that climacostol exerts a potent antimicrobial activity against a panel of bacterial and fungal pathogens, and that it inhibits the growth of mammalian tumor cell lines in a dose-dependent manner by inducing apoptosis via intrinsic pathway. Climacostol is also able to exert a prooxidant effect, inducing plasmid DNA strand breakage and eukaryotic DNA damage in presence of Cu(II) ions. In order to expand these data and due to the availability of the synthetic toxin, we have further analyzed different tumoral and non-tumoral cell lines of the anticancer action of this compound. Cytometry analyses on the B16-F10 mouse melanoma cells indicated that cell proliferation was effectively inhibited by climacostol, with a significant increase of apoptotic cells. The data collected prompted us to investigate the effects of climacostol on in vivo melanoma progression using a B16-F10 allograft transplantation tumor model. The results indicate that climacostol decreased tumour growth and increased the content of apoptotic cells, suggesting that the toxin may be considered for the design of cytotoxic and pro-apoptotic new drugs for melanoma therapy
- …
