المؤلفون: Neviani, Paolo <1978>

مرشدي الرسالة: Spada, Gian Piero

مصطلحات موضوعية: CHIM/06 Chimica organica

الوصف: Supramolecular self-assembly represents a key technology for the spontaneous construction of nanoarchitectures and for the fabrication of materials with enhanced physical and chemical properties. In addition, a significant asset of supramolecular self-assemblies rests on their reversible formation, thanks to the kinetic lability of their non-covalent interactions. This dynamic nature can be exploited for the development of “self-healing” and “smart” materials towards the tuning of their functional properties upon various external factors. One particular intriguing objective in the field is to reach a high level of control over the shape and size of the supramolecular architectures, in order to produce well-defined functional nanostructures by rational design. In this direction, many investigations have been pursued toward the construction of self-assembled objects from numerous low-molecular weight scaffolds, for instance by exploiting multiple directional hydrogen-bonding interactions. In particular, nucleobases have been used as supramolecular synthons as a result of their efficiency to code for non-covalent interaction motifs. Among nucleobases, guanine represents the most versatile one, because of its different H-bond donor and acceptor sites which display self-complementary patterns of interactions. Interestingly, and depending on the environmental conditions, guanosine derivatives can form various types of structures. Most of the supramolecular architectures reported in this Thesis from guanosine derivatives require the presence of a cation which stabilizes, via dipole-ion interactions, the macrocyclic G-quartet that can, in turn, stack in columnar G-quadruplex arrangements. In addition, in absence of cations, guanosine can polymerize via hydrogen bonding to give a variety of supramolecular networks including linear ribbons. This complex supramolecular behavior confers to the guanine-guanine interactions their upper interest among all the homonucleobases studied. They have been subjected to intense investigations in various areas ranging from structural biology and medicinal chemistry – guanine-rich sequences are abundant in telomeric ends of chromosomes and promoter regions of DNA, and are capable of forming G-quartet based structures– to material science and nanotechnology. This Thesis, organized into five Chapters, describes mainly some recent advances in the form and function provided by self-assembly of guanine based systems. More generally, Chapter 4 will focus on the construction of supramolecular self-assemblies whose self-assembling process and self-assembled architectures can be controlled by light as external stimulus. Chapter 1 will describe some of the many recent studies of G-quartets in the general area of nanoscience. Natural G- quadruplexes can be useful motifs to build new structures and biomaterials such as self-assembled nanomachines, biosensors, therapeutic aptamer and catalysts. In Chapters 2-4 it is pointed out the core concept held in this PhD Thesis, i.e. the supramolecular organization of lipophilic guanosine derivatives with photo or chemical addressability. Chapter 2 will mainly focus on the use of cation-templated guanosine derivatives as a potential scaffold for designing functional materials with tailored physical properties, showing a new way to control the bottom-up realization of well-defined nanoarchitectures. In section 2.6.7, the self-assembly properties of compound 28a may be considered an example of open-shell moieties ordered by a supramolecular guanosine architecture showing a new (magnetic) property. Chapter 3 will report on ribbon-like structures, supramolecular architectures formed by guanosine derivatives that may be of interest for the fabrication of molecular nanowires within the framework of future molecular electronic applications. In section 3.4 we investigate the supramolecular polymerizations of derivatives dG 1 and G 30 by light scattering technique and TEM experiments. The obtained data reveal the presence of several levels of organization due to the hierarchical self-assembly of the guanosine units in ribbons that in turn aggregate in fibrillar or lamellar soft structures. The elucidation of these structures furnishes an explanation to the physical behaviour of guanosine units which display organogelator properties. Chapter 4 will describe photoresponsive self-assembling systems. Numerous research examples have demonstrated that the use of photochromic molecules in supramolecular self-assemblies is the most reasonable method to noninvasively manipulate their degree of aggregation and supramolecular architectures. In section 4.4 we report on the photocontrolled self-assembly of modified guanosine nucleobase E-42: by the introduction of a photoactive moiety at C8 it is possible to operate a photocontrol over the self-assembly of the molecule, where the existence of G-quartets can be alternately switched on and off. In section 4.5 we focus on the use of cyclodextrins as photoresponsive host-guest assemblies: αCD–azobenzene conjugates 47-48 (section 4.5.3) are synthesized in order to obtain a photoresponsive system exhibiting a fine photocontrollable degree of aggregation and self-assembled architecture. Finally, Chapter 5 contains the experimental protocols used for the research described in Chapters 2-4.

وصف الملف: application/pdf

الإتاحة: http://amsdottorato.unibo.it/2410Test/

المؤلفون: Blavier, Laurence, Nakata, Rie, Neviani, Paolo, Sharma, Khounish, Shimada, Hiroyuki, Benedicto García, Aitor, Matei, Irina, Lyden, David, DeClerck, Yves A.

مصطلحات موضوعية: exosomes, extracellular vesicles, inflammation, metastasis, microRNA, pre-metastatic niche, tumour microenvironment

الوصف: The capture of tumour-derived extracellular vesicles (TEVs) by cells in the tumour microenvironment (TME) contributes to metastasis and notably to the formation of the pre-metastatic niche (PMN). However, due to the challenges associated with modelling release of small EVs in vivo, the kinetics of PMN formation in response to endogenously released TEVs have not been examined. Here, we have studied the endogenous release of TEVs in mice orthotopically implanted with metastatic human melanoma (MEL) and neuroblastoma (NB) cells releasing GFP-tagged EVs (GFTEVs) and their capture by host cells to demonstrate the active contribution of TEVs to metastasis. Human GFTEVs captured by mouse macrophages in vitro resulted in transfer of GFP vesicles and the human exosomal miR-1246. Mice orthotopically implanted with MEL or NB cells showed the presence of TEVs in the blood between 5 and 28 days after implantation. Moreover, kinetic analysis of TEV capture by resident cells relative to the arrival and outgrowth of TEV-producing tumour cells in metastatic organs demonstrated that the capture of TEVs by lung and liver cells precedes the homing of metastatic tumour cells, consistent with the critical roles of TEVs in PMN formation. Importantly, TEV capture at future sites of metastasis was associated with the transfer of miR-1246 to lung macrophages, liver macrophages, and stellate cells. This is the first demonstration that the capture of endogenously released TEVs is organotropic as demonstrated by the presence of TEV-capturing cells only in metastatic organs and their absence in non-metastatic organs. The capture of TEVs in the PMN induced dynamic changes in inflammatory gene expression which evolved to a pro-tumorigenic reaction as the niche progressed to the metastatic state. Thus, our work describes a novel approach to TEV tracking in vivo that provides additional insights into their role in the earliest stages of metastatic progression. ; The authors would like to thank Mrs. J. Rosenberg for her help in the formatting of ...

وصف الملف: application/pdf

العلاقة: Journal of Extracellular Vesicles 12(5) : (2023) // Article ID 12326; http://hdl.handle.net/10810/61783Test

الإتاحة: https://doi.org/10.1002/jev2.12326Test
http://hdl.handle.net/10810/61783Test

المؤلفون: Poderi, Cecilia, Neira, Iago, Franchi, Paola, Mezzina, Elisabetta, Baù, Ilario, Neviani, Paolo, Lucarini, Marco

المصدر: Chemistry – A European Journal ; volume 29, issue 55 ; ISSN 0947-6539 1521-3765

الوصف: New nitroxides based on aza‐crown ethers were prepared and employed as selective sensors for the detection of inorganic and organic cations by EPR analysis of the corresponding host–guest complexes. The nitroxide unit behaves as a sensitive probe for a number of alkali and alkaline earth metal cations affording EPR spectra differing in the value of nitrogen hyperfine constants and in the appearance of splitted signals due to the non‐zero nuclear spin of some metal cation upon complexation. Owing to the remarkable EPR spectral differences between the host and the corresponding cation complex the new macrocycles are likely to act as multitasking tools to recognize several cationic species. EPR behaviour of the larger nitroxide azacrown 1 ⋅ when acting as a wheel in a radical synthetic bistable [2]rotaxane containing both secondary dialkylammonium and 1,2‐bis(pyridinium) molecular stations, was also investigated. Reversible movements of the macrocycle between the two recognition sites in the rotaxane were promptly revealed by EPR, which shows significant changes either in nitrogen coupling constant values ( a N ) or in the spectral shape in the two rotaxane co‐conformations.

الإتاحة: https://doi.org/10.1002/chem.202301508Test

المؤلفون: Sirivolu, Shreya, Peng, Chen-Ching, Neviani, Paolo, Xu, Benjamin Y., Berry, Jesse L., Xu, Liya

المصدر: International Journal of Molecular Sciences; Jun2024, Vol. 25 Issue 11, p6035, 12p

مصطلحات موضوعية: EXTRACELLULAR vesicles, AQUEOUS humor, MELANOMA, RADIATION, PARTICLE analysis, TETRASPANIN

مستخلص: Small extracellular vesicles (sEVs) have been shown to promote tumorigenesis, treatment resistance, and metastasis in multiple cancer types; however, sEVs in the aqueous humor (AH) of uveal melanoma (UM) patients have never previously been profiled. In this study, we used single particle analysis to characterize sEV subpopulations in the AH of UM patients by quantifying their size, concentration, and phenotypes based on cell surface markers, specifically the tetraspanin co-expression patterns of CD9, CD63, and CD81. sEVs were analyzed from paired pre- and post-treatment (brachytherapy, a form of radiation) AH samples collected from 19 UM patients. In post-brachytherapy samples, two subpopulations, CD63/81+ and CD9/63/81+ sEVs, were significantly increased. These trends existed even when stratified by tumor location and GEP class 1 and class 2 (albeit not significant for GEP class 2). In this initial report of single vesicle profiling of sEVs in the AH of UM patients, we demonstrated that sEVs can be detected in the AH. We further identified two subpopulations that were increased post-brachytherapy, which may suggest radiation-induced release of these particles, potentially from tumor cells. Further study of the cargo carried by these sEV subpopulations may uncover important biomarkers and insights into tumorigenesis for UM. [ABSTRACT FROM AUTHOR]

: Copyright of International Journal of Molecular Sciences is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Vannini, Ivan, Wise, Petra M, Challagundla, Kishore B, Plousiou, Meropi, Raffini, Mirco, Bandini, Erika, Fanini, Francesca, Paliaga, Giorgia, Crawford, Melissa, Ferracin, Manuela, Ivan, Cristina, Fabris, Linda, Davuluri, Ramana V, Guo, Zhiyi, Cortez, Maria Angelica, Zhang, Xinna, Chen, Lu, Zhang, Shuxing, Fernandez-Cymering, Cecilia, Han, Leng, Carloni, Silvia, Salvi, Samanta, Ling, Hui, Murtadha, Mariam, Neviani, Paolo, Gitlitz, Barbara J, Laird-Offringa, Ite A, Nana-Sinkam, Patrick, Negrini, Massimo, Liang, Han, Amadori, Dino, Cimmino, Amelia, Calin, George A, Fabbri, Muller

المصدر: Nature communications. 9(1)

الوصف: In the originally published version of this Article, the positions of the final two authors in the author list were inadvertently inverted during the production process. This error has now been corrected in both the PDF and HTML versions of the Article.

الوصول الحر: https://escholarship.org/uc/item/9bh2p48zTest

المؤلفون: Vannini, Ivan, Wise, Petra M, Challagundla, Kishore B, Plousiou, Meropi, Raffini, Mirco, Bandini, Erika, Fanini, Francesca, Paliaga, Giorgia, Crawford, Melissa, Ferracin, Manuela, Ivan, Cristina, Fabris, Linda, Davuluri, Ramana V, Guo, Zhiyi, Cortez, Maria Angelica, Zhang, Xinna, Chen, Lu, Zhang, Shuxing, Fernandez-Cymering, Cecilia, Han, Leng, Carloni, Silvia, Salvi, Samanta, Ling, Hui, Murtadha, Mariam, Neviani, Paolo, Gitlitz, Barbara J, Laird-Offringa, Ite A, Nana-Sinkam, Patrick, Negrini, Massimo, Liang, Han, Amadori, Dino, Cimmino, Amelia, Calin, George A, Fabbri, Muller

المصدر: Nature communications. 8(1)

مصطلحات موضوعية: Lung, Cell Line, Tumor, Animals, Humans, Mice, Mice, Nude, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Cyclins, MicroRNAs, Xenograft Model Antitumor Assays, Cell Proliferation, Down-Regulation, Gene Expression Regulation, Neoplastic, Up-Regulation, Base Sequence, Conserved Sequence, Genes, Tumor Suppressor, Female, RNA, Long Noncoding, Carcinogenesis, Cell Line, Tumor, Nude, Carcinoma, Non-Small-Cell Lung, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, RNA, Long Noncoding

الوصف: The transcribed ultraconserved regions (T-UCRs) encode long non-coding RNAs implicated in human carcinogenesis. Their mechanisms of action and the factors regulating their expression in cancers are poorly understood. Here we show that high expression of uc.339 correlates with lower survival in 210 non-small cell lung cancer (NSCLC) patients. We provide evidence from cell lines and primary samples that TP53 directly regulates uc.339. We find that transcribed uc.339 is upregulated in archival NSCLC samples, functioning as a decoy RNA for miR-339-3p, -663b-3p, and -95-5p. As a result, Cyclin E2, a direct target of all these microRNAs is upregulated, promoting cancer growth and migration. Finally, we find that modulation of uc.339 affects microRNA expression. However, overexpression or downregulation of these microRNAs causes no significant variations in uc.339 levels, suggesting a type of interaction for uc.339 that we call "entrapping". Our results support a key role for uc.339 in lung cancer.

الوصول الحر: https://escholarship.org/uc/item/63n6c2stTest

المؤلفون: Peng, Chen‐Ching, Im, Deborah, Sirivolu, Shreya, Reiser, Bibiana, Nagiel, Aaron, Neviani, Paolo, Xu, Liya, Berry, Jesse L.

المصدر: Journal of Extracellular Biology ; volume 1, issue 4 ; ISSN 2768-2811 2768-2811

الوصف: Aqueous humor (AH), the clear fluid in front of the eye, maintains the pressure and vitality of ocular tissues. This fluid is accessible via the clear cornea which enables use of AH as a liquid biopsy source of biomarkers for intraocular disease. Extracellular vesicles are detectable in the AH and small extracellular vesicles (sEVs) are present in the AH from adults. However, EVs in AH from pediatric eyes in vivo have never previously been explored. We know very little about the heterogeneity of AH EV populations in ocular disease. Twenty‐seven processing‐free AH samples from 19 patients across four different pediatric ocular diseases were subjected to Nanoparticle Tracking Analysis (NTA) and Single Particle‐Interferometric Reflectance Imaging Sensor (SP‐IRIS) analysis. NTA demonstrated the concentration of AH EV/EPs is 3.11 × 10 9 –1.38 × 10 10 particles/ml; the majority sized 76.8–103 nm. SP‐IRIS revealed distinct patterns of tetraspanin expression of AH sEVs. An enriched mono‐CD63+ sEV subpopulation identified in AH indicates this is a potential AH‐specific biomarker. In the setting of retinoblastoma there was a more heterogeneous population of sEVs which normalized with treatment. This suggests a potential clinical application of direct measurement of sEV subpopulations in AH samples to monitor successful tumor response to therapy.

الإتاحة: https://doi.org/10.1002/jex2.36Test

المؤلفون: Wise, Petra M., Neviani, Paolo, Riwaldt, Stefan, Corydon, Thomas Juhl, Wehland, Markus, Braun, Markus, Krüger, Marcus, Infanger, Manfred, Grimm, Daniela

المصدر: Wise , P M , Neviani , P , Riwaldt , S , Corydon , T J , Wehland , M , Braun , M , Krüger , M , Infanger , M & Grimm , D 2021 , ' Changes in Exosome Release in Thyroid Cancer Cells after Prolonged Exposure to Real Microgravity in Space ' , International Journal of Molecular Sciences , vol. 22 , no. 4 , 2132 . https://doi.org/10.3390/ijms22042132Test

مصطلحات موضوعية: Cell culture, Exosomes, Microgravity, Spaceflight, Tetraspanins, Thyroid cancer, Transmembrane pro-teins

الوصف: Space travel has always been the man’s ultimate destination. With the ability of spaceflight though, came the realization that exposure to microgravity has lasting effects on the human body. To counteract these, many studies were and are undertaken, on multiple levels. Changes in cell growth, gene, and protein expression have been described in different models on Earth and in space. Extracellular vesicles, and in particular exosomes, are important cell-cell communicators, being secreted from almost all the cells and therefore, are a perfect target to further investigate the underlying reasons of the organism’s adaptations to microgravity. Here, we studied supernatants harvested from the CellBox-1 experiment, which featured human thyroid cancer cells flown to the International Space Station during the SpaceX CRS-3 cargo mission. The initial results show differences in the number of secreted exosomes, as well as in the distribution of subpopulations in regards to their surface protein expression. Notably, alteration of their population regarding the tetraspanin surface expression was observed. This is a promising step into a new area of microgravity research and will potentially lead to the discovery of new biomarkers and pathways of cellular cross-talk.

العلاقة: https://pure.au.dk/portal/da/publications/changes-in-exosome-release-in-thyroid-cancer-cells-after-prolonged-exposure-to-real-microgravity-in-spaceTest(2ea35bbc-3806-400f-9cbd-9233a37e8f3a).html

الإتاحة: https://doi.org/10.3390/ijms22042132Test
https://pure.au.dk/portal/da/publications/changes-in-exosome-release-in-thyroid-cancer-cells-after-prolonged-exposure-to-real-microgravity-in-spaceTest(2ea35bbc-3806-400f-9cbd-9233a37e8f3a).html
http://www.scopus.com/inward/record.url?scp=85100937901&partnerID=8YFLogxKTest

المؤلفون: Silvestri, Giovannino, Trotta, Rossana, Stramucci, Lorenzo, Ellis, Justin J, Harb, Jason G, Neviani, Paolo, Wang, Shuzhen, Eisfeld, Ann-Kathrin, Walker, Christopher J, Zhang, Bin, Srutova, Klara, Gambacorti-Passerini, Carlo, Pineda, Gabriel, Jamieson, Catriona H M, Stagno, Fabio, Vigneri, Paolo, Nteliopoulos, Georgios, May, Philippa C, Reid, Alistair G, Garzon, Ramiro, Roy, Denis-Claude, Moutuou, Moutuaata M, Guimond, Martin, Hokland, Peter, Deininger, Michael W, Fitzgerald, Garrett, Harman, Christopher, Dazzi, Francesco, Milojkovic, Dragana, Apperley, Jane F, Marcucci, Guido, Qi, Jianfei, Polakova, Katerina Machova, Zou, Ying, Fan, Xiaoxuan, Baer, Maria R, Calabretta, Bruno, Perrotti, Danilo

المصدر: Silvestri , G , Trotta , R , Stramucci , L , Ellis , J J , Harb , J G , Neviani , P , Wang , S , Eisfeld , A-K , Walker , C J , Zhang , B , Srutova , K , Gambacorti-Passerini , C , Pineda , G , Jamieson , C H M , Stagno , F , Vigneri , P , Nteliopoulos , G , May , P C , Reid , A G , Garzon , R , Roy , D-C , Moutuou , M M , Guimond , M ....

الوصف: Persistence of drug-resistant quiescent leukemic stem cells (LSC) and impaired natural killer (NK) cell immune response account for relapse of chronic myelogenous leukemia (CML). Inactivation of protein phosphatase 2A (PP2A) is essential for CML-quiescent LSC survival and NK cell antitumor activity. Here we show that MIR300 has antiproliferative and PP2A-activating functions that are dose dependently differentially induced by CCND2/CDK6 and SET inhibition, respectively. MIR300 is upregulated in CML LSCs and NK cells by bone marrow microenvironment (BMM) signals to induce quiescence and impair immune response, respectively. Conversely, BCR-ABL1 downregulates MIR300 in CML progenitors to prevent growth arrest and PP2A-mediated apoptosis. Quiescent LSCs escape apoptosis by upregulating TUG1 long noncoding RNA that uncouples and limits MIR300 function to cytostasis. Genetic and pharmacologic MIR300 modulation and/or PP2A-activating drug treatment restore NK cell activity, inhibit BMM-induced growth arrest, and selectively trigger LSC apoptosis in vitro and in patient-derived xenografts; hence, the importance of MIR300 and PP2A activity for CML development and therapy.

العلاقة: https://pure.au.dk/portal/en/publications/5ef7c005-d8c1-4979-95c9-5c23640f75dfTest

الإتاحة: https://doi.org/10.1158/0008-5472.BCD-19-0039Test
https://pure.au.dk/portal/en/publications/5ef7c005-d8c1-4979-95c9-5c23640f75dfTest
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510943/pdf/nihms-1623750.pdfTest

المؤلفون: Costinean, Stefan, Sandhu, Sukhinder K, Pedersen, Irene M, Tili, Esmerina, Trotta, Rossana, Perrotti, Danilo, Ciarlariello, David, Neviani, Paolo, Harb, Jason, Kauffman, Lauren Rachel, Shidham, Aaditya, Croce, Carlo Maria

المصدر: Blood. 114(7)

مصطلحات موضوعية: Hematology, Genetics, Biotechnology, Childhood Leukemia, Pediatric Cancer, Cancer, Rare Diseases, Pediatric, Lymphoma, Aetiology, 2.1 Biological and endogenous factors, Animals, CCAAT-Enhancer-Binding Protein-beta, Cell Transformation, Neoplastic, Down-Regulation, Gene Expression Regulation, Leukemic, Inositol Polyphosphate 5-Phosphatases, Interleukin-6, Lymphoma, B-Cell, Mice, Mice, Transgenic, MicroRNAs, Phosphoric Monoester Hydrolases, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor Cells, B-Lymphoid, Signal Transduction, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Paediatrics and Reproductive Medicine, Immunology

الوصف: We showed that Emicro-MiR-155 transgenic mice develop acute lymphoblastic leukemia/high-grade lymphoma. Most of these leukemias start at approximately 9 months irrespective of the mouse strain. They are preceded by a polyclonal pre-B-cell proliferation, have variable clinical presentation, are transplantable, and develop oligo/monoclonal expansion. In this study, we show that in these transgenic mice the B-cell precursors have the highest MiR-155 transgene expression and are at the origin of the leukemias. We determine that Src homology 2 domain-containing inositol-5-phosphatase (SHIP) and CCAAT enhancer-binding protein beta (C/EBPbeta), 2 important regulators of the interleukin-6 signaling pathway, are direct targets of MiR-155 and become gradually more down-regulated in the leukemic than in the preleukemic mice. We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6rg1h7k5Test