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61.
Pter P. Lakatos Dvid rpd Kardi Anna Rita Galambos Nariman Essmat Kornl Kirly Rudolf Laufer Orsolya Geda Zoltn S. Zdori Tams Tbi Mahmoud Al-Khrasani va Szk 《International journal of molecular sciences》2022,23(17)
Current treatment approaches to manage neuropathic pain have a slow onset and their use is largely hampered by side-effects, thus there is a significant need for finding new medications. Tolperisone, a centrally acting muscle relaxant with a favorable side effect profile, has been reported to affect ion channels, which are targets for current first-line medications in neuropathic pain. Our aim was to explore its antinociceptive potency in rats developing neuropathic pain evoked by partial sciatic nerve ligation and the mechanisms involved. Acute oral tolperisone restores both the decreased paw pressure threshold and the elevated glutamate level in cerebrospinal fluid in neuropathic rats. These effects were comparable to those of pregabalin, a first-line medication in neuropathy. Tolperisone also inhibits release of glutamate from rat brain synaptosomes primarily by blockade of voltage-dependent sodium channels, although inhibition of calcium channels may also be involved at higher concentrations. However, pregabalin fails to affect glutamate release under our present conditions, indicating a different mechanism of action. These results lay the foundation of the avenue for repurposing tolperisone as an analgesic drug to relieve neuropathic pain. 相似文献
62.
Giulia Carozza Annamaria Tisi Annamaria Capozzo Benedetta Cinque Aldo Giovannelli Marco Feligioni Vincenzo Flati Rita Maccarone 《International journal of molecular sciences》2022,23(23)
Opposing dose-dependent effects of curcumin (Cur) have been documented in Retinal Pigment Epithelium (RPE); therefore, to shed the light on the mechanisms of action is crucial for ophthalmic applications. On this basis we explored new insights about the dose-dependent mechanisms triggered by Cur in human retinal pigment epithelial cells (ARPE-19). Three concentrations (0.01 mM; 0.05 mM; 0.1 mM) of Cur were tested, followed by morphological, molecular, and functional analysis of the cells. Cur 0.01 mM promotes a significant increase in cell proliferation, not affecting cell cycle progression and apoptosis; by contrast, Cur 0.05 mM and 0.1 mM block cellular proliferation and trigger S-phase cell cycle arrest without inducing apoptosis. The observation of neuronal-like morphological changes in Cur 0.05 mM and 0.1 mM were not associated with neuronal differentiation, as observed by the quantification of Neurofilament-200 and by the analysis of voltage-dependent currents by patch clamp. Evaluation of autophagic markers LC3BII and p62 revealed significant modulations, suggesting an important activation of autophagy in ARPE-19 cells treated with Cur 0.05 mM and Cur 0.1 mM; conversely, Cur 0.01 mM did not affect autophagy. Altogether, our findings show new dose-dependent mechanisms of action of Cur that suggest a wide therapeutic application in ocular diseases with different pathogenesis (i.e., proliferative vitreoretinopathy or Age-Related Macular Degeneration). 相似文献
63.
Satoru Shindo Irma Josefina Savitri Takenobu Ishii Atsushi Ikeda Roodelyne Pierrelus Alireza Heidari Keisuke Okubo Shin Nakamura Umadevi Kandalam Mohamad Rawas-Qalaji Elizabeth Leon Maria Rita Pastore Patrick Hardigan Toshihisa Kawai 《International journal of molecular sciences》2022,23(6)
Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes. 相似文献
64.
Mustafa M. F. Al-Jarrah Numan A. Abdul-Latif Suham H. F. Al-Madfai Rita L. Apikian 《应用聚合物科学杂志》1989,38(3):477-482
The influence of the Al/Ti ratio of the heterogeneous Ziegler–Natta catalyst system AlEt3–TiCl4 on the isoprene polymerization in n-heptane at 30°C in a bench scale reactor was investigated. Each batch run consisted of 50 mL isoprene, 200 mL n-heptane with 0.45 and 0.5g catalyst. Conversion of isoprene and molecular weights of polyisoprene increased with increasing Al/Ti ratio, reaching their maxima values at 1.0 and 1.2, respectively. Conversion and molecular weights decreased remarkably at a higher ratio of Al/Ti. As this ratio decreases from the value of 1.2 to 0.4, the cis1,4 content in polyisoprene decreased from 97 to 25%. When the ratio of Al/Ti increased from 1.2 to 2.2 the cis-1,4 structure of polyisoprene decreased from 97 to 85%. 相似文献
65.
Nazanin Farahi Tamas Lazar Shoshana J. Wodak Peter Tompa Rita Pancsa 《International journal of molecular sciences》2021,22(6)
Liquid–liquid phase separation (LLPS) is a molecular process that leads to the formation of membraneless organelles, representing functionally specialized liquid-like cellular condensates formed by proteins and nucleic acids. Integrating the data on LLPS-associated proteins from dedicated databases revealed only modest agreement between them and yielded a high-confidence dataset of 89 human LLPS drivers. Analysis of the supporting evidence for our dataset uncovered a systematic and potentially concerning difference between protein concentrations used in a good fraction of the in vitro LLPS experiments, a key parameter that governs the phase behavior, and the proteomics-derived cellular abundance levels of the corresponding proteins. Closer scrutiny of the underlying experimental data enabled us to offer a sound rationale for this systematic difference, which draws on our current understanding of the cellular organization of the proteome and the LLPS process. In support of this rationale, we find that genes coding for our human LLPS drivers tend to be dosage-sensitive, suggesting that their cellular availability is tightly regulated to preserve their functional role in direct or indirect relation to condensate formation. Our analysis offers guideposts for increasing agreement between in vitro and in vivo studies, probing the roles of proteins in LLPS. 相似文献
66.
Storelli MM Normanno G Barone G Dambrosio A Errico L Garofalo R Giacominelli-Stuffler R 《Journal of food protection》2012,75(1):189-194
Mercury, cadmium, and lead concentrations were determined in various fishery products (fishes, cephalopod molluscs, and crustaceans) imported into Italy from many European and non-European coastal countries. Considerable differences were found in the concentrations of these metals among the products tested. The highest mean Hg concentration was found in fishes (0.21 μg g(-1) wet weight), whereas cephalopods had the highest mean Cd concentration (0.35 μg g(-1) wet weight). Swordfish (0.80 μg g(-1) wet weight), longtail tuna (0.53 μg g(-1) wet weight), and thornback ray (0.52 μg g(-1) wet weight) had the highest concentrations of Hg, whereas maximum Cd concentrations were found in samples of common cuttlefish (0.85 μg g(-1) wet weight) and common octopus (0.64 μg g(-1) wet weight). The majority of the samples analyzed were in compliance with European Union legislation, except for a few cases. The calculated mean weekly intakes of Hg, Cd, and Pb through consumption of the fishery products tested were all below the legislated respective provisional tolerable weekly intakes. In general, the samples analyzed were considered safe to eat with regard to the metal concentrations found and the allowable intakes based on legislation. Nevertheless, the consumption of some species may be of significant importance for consumer health. 相似文献
67.
Rita de Cassia P. Nunes Renata V. Pires Elizabete F. Lucas Angelo Vianna Rosana Lomba 《应用聚合物科学杂志》2014,131(16)
The drilling of petroleum wells requires the use of suitable drilling fluids to ensure efficient operation without causing rock damage. Specific polymers have been used to control infiltration during drilling, to reduce operational problems. In this study, spherical microparticles of poly(methyl methacrylate‐co‐vinyl acetate) were synthesized (by suspension polymerization), characterized, and evaluated in terms of their performance in controlling filtrate loss of aqueous fluids. A filter press test with ceramic disk, simulating the rock, was used. The performance of the synthesized materials was compared with commercial polymers. It was observed that the performance of the material is directly associated with the relation between particle size and pore size of the rock specimen. Furthermore, for a suitable particle size, the rubbery characteristic of the material produces a more efficient filter cake, for filtrate control. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40646. 相似文献
68.
Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation 下载免费PDF全文
Dr. Francesca Esposito Dr. Cristina Tintori Dr. Riccardo Martini Dr. Frauke Christ Prof. Zeger Debyser Roberto Ferrarese Dr. Gianluigi Cabiddu Dr. Angela Corona Dr. Elisa Rita Ceresola Dr. Andrea Calcaterra Dr. Valentina Iovine Prof. Bruno Botta Dr. Massimo Clementi Dr. Filippo Canducci Prof. Maurizio Botta Prof. Enzo Tramontano 《Chembiochem : a European journal of chemical biology》2015,16(17):2507-2512
HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents. 相似文献
69.
Ag nanoparticles were synthesized in the interlamellar space of a layered kaolinite. Disaggregation of the lamellae of the nonswelling kaolinite was achieved by the intercalation of dimethyl sulfoxide (DMSO). The kaolinite was suspended in aqueous AgNO3 solution and the adsorbed Ag+ ions were reduced on the surface of kaolinite lamellae with NaBH4 or UV light irradiation. The silver nanoparticles formed were characterized by X-ray diffraction (XRD), small angle X-ray scattering (SAXS), and transmission electron microscopy (TEM). We studied the effects of the two reduction methods on the size and the size distribution of Ag nanoparticles and how clay mineral structure is altered as a consequence of particle formation. It was established that the size of Ag nanoparticles depends on both silver content and the reduction method. Photoreduction of silver led to the formation of relatively large Ag nanoparticles (diameter 8–14 nm). 相似文献
70.
Rita Girão-Silva José Craveirinha João Clímaco 《International Transactions in Operational Research》2009,16(3):275-305
Modern multiservice network routing functionalities have to deal with multiple, heterogeneous and multifaceted Quality of Service (QoS) requirements. A heuristic approach devised to find "good" solutions to a hierarchical multiobjective alternative routing optimization problem in Multiprotocol Label Switching networks with two service classes (and different types of traffic flows in each class), namely QoS and Best Effort services, formulated within a hierarchical network-wide optimization framework, is presented. This heuristic solution is based on a bi-objective constrained shortest path model and is applied to a test network used in a benchmarking case study. An experimental study based on analytic and discrete event simulation results is presented, allowing for an assessment of the quality of results obtained with this new heuristic solution for various traffic matrices. A dynamic version of the routing method is formulated and its performance with the same case study network is analysed. 相似文献