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151.
Carmen Caiazza Teresa Brusco Federica DAlessio Massimo DAgostino Angelica Avagliano Alessandro Arcucci Concetta Ambrosino Giuseppe Fiume Massimo Mallardo 《International journal of molecular sciences》2022,23(22)
STING is a transmembrane ER resident protein that was initially described as a regulator of innate immune response triggered by viral DNA and later found to be involved in a broader range of immune processes. Here, we assessed its role in the antigen presentation by generating a STING KO macrophage cell line. In the absence of STING, we observed an impaired OVA-derived SIINFEKL peptide presentation together with a decreased level of MHC-I complex on the plasma membrane, likely due to a decreased mRNA expression of β2 m light chain as no relevant alterations of the peptide-loading complex (TAPs) were found. Moreover, JAK-STAT signaling resulted in impaired STING KO cells following OVA and LPS treatments, suggesting a dampened activation of immune response. Our data revealed a new molecular role of STING in immune mechanisms that could elucidate its role in the pathogenesis of autoimmune disorders and cancer. 相似文献
152.
Paola Piscopo Valeria Manzini Roberto Rivabene Alessio Crestini Loredana Le Pera Elisabetta Pizzi Caterina Veroni Giuseppina Talarico Martina Peconi Anna Elisa Castellano Carmelo DAlessio Giuseppe Bruno Massimo Corbo Nicola Vanacore Eleonora Lacorte 《International journal of molecular sciences》2022,23(21)
The most frequently used biomarkers to support the diagnosis of Alzheimer’s Disease (AD) are Aβ42, total-Tau, and phospho-tau protein levels in CSF. Moreover, magnetic resonance imaging is used to assess hippocampal atrophy, 18F-FDG PET to identify abnormal brain metabolism, and PET imaging for amyloid deposition. These tests are rather complex and invasive and not easily applicable to clinical practice. Circulating non-coding RNAs, which are inherently stable and easy to manage, have been reported as promising biomarkers for central nervous system conditions. Recently, circular RNAs (circRNAs) as a novel class of ncRNAs have gained attention. We carried out a pilot study on five participants with AD and five healthy controls (HC) investigating circRNAs by Arraystar Human Circular RNA Microarray V2.0. Among them, 26 circRNAs were differentially expressed (FC ≥ 1.5, p < 0.05) in participants with AD compared to HC. From a top 10 of differentially expressed circRNAs, a validation study was carried out on four up-regulated (hsa_circRNA_050263, hsa_circRNA_403959, hsa_circRNA_003022, hsa_circRNA_100837) and two down-regulated (hsa_circRNA_102049, hsa_circRNA_102619) circRNAs in a larger population. Moreover, five subjects with mild cognitive impairment (MCI) were investigated. The analysis confirmed the upregulation of hsa_circRNA_050263, hsa_circRNA_403959, and hsa_circRNA_003022 both in subjects with AD and in MCI compared to HCs. We also investigated all microRNAs potentially interacting with the studied circRNAs. The GO enrichment analysis shows they are involved in the development of the nervous system, and in the cellular response to nerve growth factor stimuli, protein phosphorylation, apoptotic processes, and inflammation pathways, all of which are processes related to the pathology of AD. 相似文献
153.
Roberta Listro Alessio Malacrida Francesca Alessandra Ambrosio Giacomo Rossino Marcello Di Giacomo Valeria Cavalloro Martina Garbagnoli Pasquale Linciano Daniela Rossi Guido Cavaletti Giosu Costa Stefano Alcaro Mariarosaria Miloso Simona Collina 《International journal of molecular sciences》2022,23(21)
The insurgence of drug resistance in treating Multiple Myeloma (MM) still represents a major hamper in finding effective treatments, although over the past decades new classes of drugs, such as proteasome inhibitors and immunomodulatory drugs, have been discovered. Recently, our research team, within a Nature-Aided Drug Discovery project, isolated from Hibiscus Sabdariffa L. calyces the secondary metabolite called Hib-ester which possesses antiproliferative properties against human multiple myeloma RPMI 8226 cells, reduces migration and cell invasion and inhibits proteasome without neurotoxic effects. In the present study, we explored the chemical spaces of the hit compound Hib-ester. We explored the structure-activity relationships (SAR), and we optimized the scaffold through sequentially modifying Hib-ester subunits. Compound screening was performed based on cytotoxicity against the RPMI 8226 cells to assess the potential efficacy toward human MM. The ability of the most effective molecules to inhibit the proteasome was evaluated and the binding mode of the most promising compounds in the proteasome chymotrypsin binding pocket was deciphered through molecular modeling simulations. Compounds 13 and 14 are more potent than Hib-ester, demonstrating that our strategy was suitable for the identification of a novel chemotype for developing possible drug candidates and hopefully widening the drug armamentarium against MM. 相似文献
154.
Alessio Vizzoca Gioia Lucarini Elisabetta Tognoni Selene Tognarelli Leonardo Ricotti Lisa Gherardini Gualtiero Pelosi Mario Pellegrino Arianna Menciassi Settimio Grimaldi Caterina Cinti 《International journal of molecular sciences》2022,23(17)
Over the past few decades, finding more efficient and selective administration routes has gained significant attention due to its crucial role in the bioavailability, absorption rate and pharmacokinetics of therapeutic substances. The pulmonary delivery of drugs has become an attractive target of scientific and biomedical interest in the health care research area, as the lung, thanks to its high permeability and large absorptive surface area and good blood supply, is capable of absorbing pharmaceuticals either for local deposition or for systemic delivery. Nevertheless, the pulmonary drug delivery is relatively complex, and strategies to mitigate the effects of mechanical, chemical and immunological barriers are required. Herein, engineered erythrocytes, the Erythro–Magneto–Hemagglutinin (HA)–virosomes (EMHVs), are used as a novel strategy for efficiently delivering drugs to the lungs. EMHV bio-based carriers exploit the physical properties of magnetic nanoparticles to achieve effective targeting after their intravenous injection thanks to an external magnetic field. In addition, the presence of hemagglutinin fusion proteins on EMHVs’ membrane allows the DDS to anchor and fuse with the target tissue and locally release the therapeutic compound. Our results on the biomechanical and biophysical properties of EMHVs, such as the membrane robustness and deformability and the high magnetic susceptibility, as well as their in vivo biodistribution, highlight that this bio-inspired DDS is a promising platform for the controlled and lung-targeting delivery of drugs, and represents a valuable alternative to inhalation therapy to fulfill unmet clinical needs. 相似文献
155.
Mariarosaria De Pascali Monica De Caroli Alessio Aprile Antonio Miceli Carla Perrotta Mariolina Gullì Patrizia Rampino 《International journal of molecular sciences》2022,23(14)
Durum wheat is strongly affected by climatic constraints such as high temperatures and drought, which frequently lead to yield reduction. Damages due to high temperatures are related to plant thermotolerance, a trait determined by two components: basal and acquired thermotolerance. In this study, the effect of drought and heat stress imposed singularly or sequentially was investigated in ten durum wheat cultivars (cvs) at the physiological and molecular level. The traits analyzed were cell membrane stability, relative water content, proline content, and expression level of several genes for heat shock proteins (HSPs). Our results indicate that drought priming can induce the acquisition of thermotolerance in most cultivars already classified as able to acquire thermotolerance by heat pre-treatment. Proline accumulation was correlated to cell membrane stability, meaning that the most thermotolerant cvs were able to accumulate higher levels of proline. Acquired thermotolerance is also due to the activation of HSP gene expression; similarly, pre-treatment with water stress was able to activate HSPs expression. The results reported indicate that water stress plays an important role in inducing thermotolerance, comparable to mild heat stress pre-treatment. This is the first report on the effect of drought stress on the acquisition of thermotolerance. 相似文献
156.
Masato Ishizaka Minghao Chen Shun Narai Yoshikazu Tanaka Toyoyuki Ose Masaki Horitani Min Yao 《International journal of molecular sciences》2023,24(1)
Iron–sulfur (Fe–S) clusters are essential cofactors for enzyme activity. These Fe–S clusters are present in structurally diverse forms, including [4Fe–4S] and [3Fe–4S]. Type-identification of the Fe–S cluster is indispensable in understanding the catalytic mechanism of enzymes. However, identifying [4Fe–4S] and [3Fe–4S] clusters in particular is challenging because of their rapid transformation in response to oxidation–reduction events. In this study, we focused on the relationship between the Fe–S cluster type and the catalytic activity of a tRNA-thiolation enzyme (TtuA). We reconstituted [4Fe–4S]-TtuA, prepared [3Fe–4S]-TtuA by oxidizing [4Fe–4S]-TtuA under strictly anaerobic conditions, and then observed changes in the Fe–S clusters in the samples and the enzymatic activity in the time-course experiments. Electron paramagnetic resonance analysis revealed that [3Fe–4S]-TtuA spontaneously transforms into [4Fe–4S]-TtuA in minutes to one hour without an additional free Fe source in the solution. Although the TtuA immediately after oxidation of [4Fe–4S]-TtuA was inactive [3Fe–4S]-TtuA, its activity recovered to a significant level compared to [4Fe–4S]-TtuA after one hour, corresponding to an increase of [4Fe–4S]-TtuA in the solution. Our findings reveal that [3Fe–4S]-TtuA is highly inactive and unstable. Moreover, time-course analysis of structural changes and activity under strictly anaerobic conditions further unraveled the Fe–S cluster type used by the tRNA-thiolation enzyme. 相似文献
157.
Moataz Shaldam Alessio Nocentini Zainab M. Elsayed Tamer M. Ibrahim Rofaida Salem Ramadan A. El-Domany Clemente Capasso Claudiu T. Supuran Wagdy M. Eldehna 《International journal of molecular sciences》2021,22(20)
A new series of quinoline-based benzenesulfonamides (QBS) were developed as potential carbonic anhydrase inhibitors (CAIs). The target QBS CAIs is based on the 4-anilinoquinoline scaffold where the primary sulphonamide functionality was grafted at C4 of the anilino moiety as a zinc anchoring group (QBS 13a–c); thereafter, the sulphonamide group was switched to ortho- and meta-positions to afford regioisomers 9a–d and 11a–g. Moreover, a linker elongation approach was adopted where the amino linker was replaced by a hydrazide one to afford QBS 16. All the described QBS have been synthesized and investigated for their CA inhibitory action against hCA I, II, IX and XII. In general, para-sulphonamide derivatives 13a–c displayed the best inhibitory activity against both cancer-related isoforms hCA IX (KIs = 25.8, 5.5 and 18.6 nM, respectively) and hCA XII (KIs = 9.8, 13.2 and 8.7 nM, respectively), beside the excellent hCA IX inhibitory activity exerted by meta-sulphonamide derivative 11c (KI = 8.4 nM). The most promising QBS were further evaluated for their anticancer and pro-apoptotic activities on two cancer cell lines (MDA-MB-231 and MCF-7). In addition, molecular docking simulation studies were applied to justify the acquired CA inhibitory action of the target QBS. 相似文献
158.
Alessio Gizzi Anna Pandolfi Marcello Vasta 《International Journal for Computational Methods in Engineering Science and Mechanics》2016,17(3):143-155
Elastic-electroactive biological media are sensitive to both mechanical and electric forces. Their active behavior is often associated with the presence of reinforcing fibers and their excitation-contraction coupling is due to the interplay between the passive elastic tissue and the active muscular network. In this paper we focus on the theoretical framework of constitutive equations for viscous electroactive media. The approach is based on the additive decomposition of the Helmholtz free energy accompanied to the multiplicative decomposition of the deformation gradient in elastic, viscous and active parts. We describe a thermodynamically sound scenario that accounts for geometric and material nonlinearities. 相似文献
159.
Rick Salay Marsha Chechik Jennifer Horkoff Alessio Di Sandro 《Requirements Engineering》2013,18(2):107-128
Models are good at expressing information that is known but do not typically have support for representing what information a modeler does not know at a particular phase in the software development process. Partial models address this by being able to precisely represent uncertainty about model content. In previous work, we developed a general approach for defining partial models and using them to reason about design models containing uncertainty. In this paper, we show how to apply our approach to managing uncertainty in requirements by providing support for uncertainty capture, elaboration, and change. In particular, we address the problem of specifying uncertainty within a requirements model, refining a model as uncertainty reduces, providing meaning to traceability relations between models containing uncertainty, and propagating uncertainty-reducing changes between related models. We describe the implementation of uncertainty management within the Model Management Tool Framework and illustrate our approach using two examples. 相似文献
160.