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71.
Antonio Magrì Alessia Munzone Massimiliano Peana Serenella Medici Maria Antonietta Zoroddu Orjan Hansson Cristina Satriano Enrico Rizzarelli Diego La Mendola 《International journal of molecular sciences》2016,17(8)
Angiogenin (Ang) is a potent angiogenic factor, strongly overexpressed in patients affected by different types of cancers. The specific Ang cellular receptors have not been identified, but it is known that Ang–actin interaction induces changes both in the cell cytoskeleton and in the extracellular matrix. Most in vitro studies use the recombinant form (r-Ang) instead of the form that is normally present in vivo (“wild-type”, wt-Ang). The first residue of r-Ang is a methionine, with a free amino group, whereas wt-Ang has a glutamic acid, whose amino group spontaneously cyclizes in the pyro-glutamate form. The Ang biological activity is influenced by copper ions. To elucidate the role of such a free amino group on the protein–copper binding, we scrutinized the copper(II) complexes with the peptide fragments Ang(1–17) and AcAng(1–17), which encompass the sequence 1–17 of angiogenin (QDNSRYTHFLTQHYDAK-NH2), with free amino and acetylated N-terminus, respectively. Potentiometric, ultraviolet-visible (UV-vis), nuclear magnetic resonance (NMR) and circular dichroism (CD) studies demonstrate that the two peptides show a different metal coordination environment. Confocal microscopy imaging of neuroblastoma cells with the actin staining supports the spectroscopic results, with the finding of different responses in the cytoskeleton organization upon the interaction, in the presence or not of copper ions, with the free amino and the acetylated N-terminus peptides. 相似文献
72.
Vincenzo Vestuto Veronica Di Sarno Simona Musella Giorgio Di Dona Ornella Moltedo Isabel Maria Gomez-Monterrey Alessia Bertamino Carmine Ostacolo Pietro Campiglia Tania Ciaglia 《International journal of molecular sciences》2023,24(1)
The endoplasmic reticulum (ER) is a dynamic structure, playing multiple roles including calcium storage, protein synthesis and lipid metabolism. During cellular stress, variations in ER homeostasis and its functioning occur. This condition is referred as ER stress and generates a cascade of signaling events termed unfolded protein response (UPR), activated as adaptative response to mitigate the ER stress condition. In this regard, calcium levels play a pivotal role in ER homeostasis and therefore in cell fate regulation since calcium signaling is implicated in a plethora of physiological processes, but also in disease conditions such as neurodegeneration, cancer and metabolic disorders. A large body of emerging evidence highlighted the functional role of TRP channels and their ability to promote cell survival or death depending on endoplasmic reticulum stress resolution, making them an attractive target. Thus, in this review we focused on the TRP channels’ correlation to UPR-mediated ER stress in disease pathogenesis, providing an overview of their implication in the activation of this cellular response. 相似文献
73.
Alessia Tonoli Karla Wagner Arianna Bacchin Tamara Reiter Prof. Dr. Elisabetta Bergantino Dr. Marina S. Robescu Prof. Dr. Mélanie Hall 《Chembiochem : a European journal of chemical biology》2023,24(9):e202300146
The formal asymmetric and stereodivergent enzymatic reduction of α-angelica lactone to both enantiomers of γ-valerolactone was achieved in a one-pot cascade by uniting the promiscuous stereoselective isomerization activity of Old Yellow Enzymes with their native reductase activity. In addition to running the cascade with one enzyme for each catalytic step, a bifunctional isomerase-reductase biocatalyst was designed by fusing two Old Yellow Enzymes, thereby generating an unprecedented case of an artificial enzyme catalyzing the reduction of nonactivated C=C bonds to access (R)-valerolactone in overall 41 % conversion and up to 91 % ee. The enzyme BfOYE4 could be used as single biocatalyst for both steps and delivered (S)-valerolactone in up to 84 % ee and 41 % overall conversion. The reducing equivalents were provided by a nicotinamide recycling system based on formate and formate dehydrogenase, added in a second step. This enzymatic system provides an asymmetric route to valuable chiral building blocks from an abundant bio-based chemical. 相似文献
74.
Mabrouk Horchani Gerardo Della Sala Alessia Caso Federica DAria Germana Esposito Ilaria Laurenzana Concetta Giancola Valeria Costantino Hichem Ben Jannet Anis Romdhane 《International journal of molecular sciences》2021,22(5)
Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds. 相似文献
75.
Giuseppe Schepisi Caterina Gianni Sara Bleve Silvia De Padova Cecilia Menna Cristian Lolli Alessia Filograna Vincenza Conteduca Milena Urbini Valentina Gall Chiara Casadei Giovanni Rosti Ugo De Giorgi 《International journal of molecular sciences》2021,22(10)
Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications. 相似文献
76.
77.
Deborah Stanco Monica Boffito Alessia Bogni Luca Puricelli Josefa Barrero Gianni Soldati Gianluca Ciardelli 《International journal of molecular sciences》2020,21(22)
Defining the best combination of cells and biomaterials is a key challenge for the development of tendon tissue engineering (TE) strategies. Adipose-derived stem cells (ASCs) are ideal candidates for this purpose. In addition, controlled cell-based products adherent to good manufacturing practice (GMP) are required for their clinical scale-up. With this aim, in this study, ASC 3D bioprinting and GMP-compliant tenogenic differentiation were investigated. In detail, primary human ASCs were embedded within a nanofibrillar-cellulose/alginate bioink and 3D-bioprinted into multi-layered square-grid matrices. Bioink viscoelastic properties and scaffold ultrastructural morphology were analyzed by rheology and scanning electron microscopy (SEM). The optimal cell concentration for printing among 3, 6 and 9 × 106 ASC/mL was evaluated in terms of cell viability. ASC morphology was characterized by SEM and F-actin immunostaining. Tenogenic differentiation ability was then evaluated in terms of cell viability, morphology and expression of scleraxis and collagen type III by biochemical induction using BMP-12, TGF-β3, CTGF and ascorbic acid supplementation (TENO). Pro-inflammatory cytokine release was also assessed. Bioprinted ASCs showed high viability and survival and exhibited a tenocyte-like phenotype after biochemical induction, with no inflammatory response to the bioink. In conclusion, we report a first proof of concept for the clinical scale-up of ASC 3D bioprinting for tendon TE. 相似文献
78.
Manuela Chessa Guido Maiello Alessia Borsari Peter J. Bex 《Human-Computer Interaction》2019,34(1):51-82
The recent release of the Oculus Rift, originally developed for entertainment applications, has reignited the interest of researchers and clinicians toward the use of head-mounted-displays in basic behavioral research and physical and psychological rehabilitation. However, careful evaluation of the Oculus Rift is necessary to determine whether it can be effectively used in these novel applications. In this article we address two issues concerning the perceptual quality of the Oculus Rift. (a) Is the Oculus able to generate an acceptable degree of immersivity? In particular, is it possible to elicit the sensation of presence via the virtual stimuli rendered by the device? (b) Does the Virtual Reality experienced through the Oculus Rift induce physical discomfort? To answer these questions, we employed four virtual scenarios in three separate experiments and evaluated performance with objective and subjective outcomes. In Experiment 1 we monitored observers’ heart rate and asked them to rate their Virtual Reality experience via a custom questionnaire. In Experiment 2 we monitored observers’ head movements in reaction to virtual obstacles and asked them to fill out the Simulator Sickness Questionnaire (Kennedy et al., 1993) both before and after experiencing Virtual Reality. In Experiment 3 we compared the Oculus Rift against two other low-cost devices used in immersive Virtual Reality: the Google cardboard and a standard 3DTV monitor. Observers’ heart rate increased during exposure to Virtual Reality, and they subjectively reported the experience to be immersive and realistic. We found a strong relationship between observers’ fear of heights and vertigo experienced during one of the virtual scenarios involving heights, suggesting that observers felt a strong sensation of presence within the virtual worlds. Subjects reacted to virtual obstacles by moving to avoid them, suggesting that the obstacles were perceived as real threats. Observers did not experience simulator sickness when the exposure to Virtual Reality was short and did not induce excessive amounts of vection. Compared to the other devices the Oculus Rift elicited a greater degree of immersivity. Thus our investigation suggests that the Oculus Rift head-mounted-display is a potentially powerful tool for a wide array of basic research and clinical applications. 相似文献
79.
Kevin Neumann Sarthak Jain Alessia Gambardella Dr. Sarah E. Walker Dr. Elsa Valero Dr. Annamaria Lilienkampf Prof. Mark Bradley 《Chembiochem : a European journal of chemical biology》2017,18(1):91-95
Molecules that undergo activation or modulation following the addition of benign external small‐molecule chemical stimuli have numerous applications. Here, we report the highly efficient “decaging” of a variety of moieties by activation of a “self‐immolative” linker, by application of water‐soluble and stable tetrazine, including the controlled delivery of doxorubicin in a cellular context. 相似文献
80.