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51.
Marina Paiva Abuafy Regina Celia Galvao Frem Giulia Polinario Fernando Rogerio Pavan Heng Zhao Angelika Mielcarek Cedric Boissiere Christian Serre Leila Aparecida Chiavacci 《International journal of molecular sciences》2022,23(14)
Nanoparticles of metal–organic frameworks (MOF NPs) are crystalline hybrid micro- or mesoporous nanomaterials that show great promise in biomedicine due to their significant drug loading ability and controlled release. Herein, we develop porous capsules from aggregate of nanoparticles of the iron carboxylate MIL-100(Fe) through a low-temperature spray-drying route. This enables the concomitant one-pot encapsulation of high loading of an antitumor drug, methotrexate, within the pores of the MOF NPs, and the collagenase enzyme (COL), inside the inter-particular mesoporous cavities, upon the formation of the capsule, enhancing tumor treatment. This association provides better control of the release of the active moieties, MTX and collagenase, in simulated body fluid conditions in comparison with the bare MOF NPs. In addition, the loaded MIL-100 capsules present, against the A-375 cancer cell line, selective toxicity nine times higher than for the normal HaCaT cells, suggesting that MTX@COL@MIL-100 capsules may have potential application in the selective treatment of cancer cells. We highlight that an appropriate level of collagenase activity remained after encapsulation using the spray dryer equipment. Therefore, this work describes a novel application of MOF-based capsules as a dual drug delivery system for cancer treatment. 相似文献
52.
Tnia Cemeli Marta Guasch-Valls Marina Ribes-Santolaria Eva Ibars Raúl Navaridas Xavier Dolcet Neus Pedraza Neus Colomina Jordi Torres-Rosell Francisco Ferrezuelo Judit Herreros Eloi Garí 《International journal of molecular sciences》2022,23(15)
Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence. 相似文献
53.
Luigi Borzacchiello Roberta Veglia Tranchese Roberta Grillo Roberta Arpino Laura Mosca Giovanna Cacciapuoti Marina Porcelli 《International journal of molecular sciences》2022,23(14)
Metastasis is a leading cause of mortality and poor prognosis in colorectal cancer (CRC). Thus, the identification of new compounds targeting cell migration represents a major clinical challenge. Recent findings evidenced a central role for dysregulated Notch in CRC and a correlation between Notch overexpression and tumor metastasis. MicroRNAs (miRNAs) have been reported to cross-talk with Notch for its regulation. Therefore, restoring underexpressed miRNAs targeting Notch could represent an encouraging therapeutic approach against CRC. In this context, S-adenosyl-L-methionine (AdoMet), the universal biological methyl donor, being able to modulate the expression of oncogenic miRNAs could act as a potential antimetastatic agent. Here, we showed that AdoMet upregulated the onco-suppressor miRNAs-34a/-34c/-449a and inhibited HCT-116 and Caco-2 CRC cell migration. This effect was associated with reduced expression of migration-/EMT-related protein markers. We also found that, in colorectal and triple-negative breast cancer cells, AdoMet inhibited the expression of Notch gene, which, by luciferase assay, resulted the direct target of miRNAs-34a/-34c/-449a. Gain- and loss-of-function experiments with miRNAs mimics and inhibitors demonstrated that AdoMet exerted its inhibitory effects by upregulating miRNAs-34a/-34c/-449a. Overall, these data highlighted AdoMet as a novel Notch inhibitor and suggested that the antimetastatic effects of AdoMet involve the miRNA-mediated targeting of Notch signaling pathway. 相似文献
54.
Bernette M. Oosterlaken Yifei Xu Mark M. J. van Rijt Marina Pilz da Cunha Gilles H. Timmermans Michael G. Debije Heiner Friedrich Albertus P. H. J. Schenning Nico A. J. M. Sommerdijk 《Advanced functional materials》2020,30(6)
In this work, a nanohybrid material based on a freestanding polymeric liquid crystal network capable of postmodification via cation exchange to tune birefringence is proposed. The smectic liquid crystal films can be infiltrated with a variety of cations, thereby changing the refractive indices (ne and no) and the effective birefringence (Δn) of the nanohybrid material, with reversible cation infiltration occurring within minutes. Birefringence could be tuned between values of 0.06 and 0.19, depending on the cation infiltrated into the network. Upon infiltration, a decrease in the smectic layer spacing is found with layer contraction independent of the induced change in birefringence. Potential applications are in the field of specialty optical devices, such as flexible, retunable reflective filters. 相似文献
55.
Giulia Poli Consuelo Fabi Chiara Sugoni Marina Maria Bellet Claudio Costantini Giovanni Luca Stefano Brancorsini 《International journal of molecular sciences》2022,23(9)
Varicocele (VC) is the most common abnormality identified in men evaluated for hypofertility. Increased levels of reactive oxygen species (ROS) and reduced antioxidants concentrations are key contributors in varicocele-mediated hypofertility. Moreover, inflammation and alterations in testicular immunity negatively impact male fertility. In particular, NLRP3 inflammasome activation was hypothesized to lead to seminal inflammation, in which the levels of specific cytokines, such as IL-1β and IL-18, are overexpressed. In this review, we described the role played by oxidative stress (OS), inflammation, and NLRP3 inflammasome activation in VC disease. The consequences of ROS overproduction in testis, including inflammation, lipid peroxidation, mitochondrial dysfunction, chromatin damage, and sperm DNA fragmentation, leading to abnormal testicular function and failed spermatogenesis, were highlighted. Finally, we described some therapeutic antioxidant strategies, with recognized beneficial effects in counteracting OS and inflammation in testes, as possible therapeutic drugs against varicocele-mediated hypofertility. 相似文献
56.
Marta Brambilla Maria Talmon Paola Canzano Luigia G. Fresu Sandra Brunelleschi Elena Tremoli Marina Camera 《International journal of molecular sciences》2022,23(9)
Several contributions of circulating microvesicles (MVs) to the endothelial dysfunction have been reported in the past; a head-to-head comparison of platelet- and monocyte–derived MVs has however never been performed. To this aim, we assessed the involvement of these MVs in vessel damage related processes, i.e., oxidative stress, inflammation, and leukocyte-endothelial adhesion. Platelets and monocytes isolated from healthy subjects (HS, n = 15) were stimulated with TRAP-6 and LPS to release MVs that were added to human vascular endothelial cell (hECV) culture to evaluate superoxide anion production, inflammatory markers (IL-6, TNFα, NF-κB mRNA expression), and hECV adhesiveness. The effects of the MVs-induced from HS were compared to those induced by MVs spontaneously released from cells of patients with ST-segment elevation myocardial infarction (STEMI, n = 7). MVs released by HS-activated cells triggered a threefold increase in oxidative burst in a concentration-dependent manner. Only MVs released from monocytes doubled IL-6, TNFα, and NF-κB mRNA expression and monocyte-endothelial adhesion. Interestingly, the effects of the MVs isolated from STEMI-monocytes were not superimposable to previous ones except for adhesion to hECV. Conversely, MVs released from STEMI-platelets sustained both redox state and inflammatory phenotype. These data provide evidence that MVs released from activated and/or pathologic platelets and monocytes differently affect endothelial behavior, highlighting platelet-MVs as causative factors of impaired endothelial function in the acute phase of STEMI. 相似文献
57.
Camilo Zúñiga Gerard Lligadas Juan Carlos Ronda Marina Galià Virginia Cádiz 《Polymer》2012,53(15):3089-3095
This work concerns the investigation of porous polybenzoxazines based on the non-toxic renewable diphenolic acid. The approach described relies on the in situ generation of foaming agent (CO2) during the thermal curing. For this purpose, the previously synthesized benzoxazine monomer from diphenolic acid was thermally polymerized at different temperatures. As the beginning of decarboxylation is about 200 °C, we selected five foaming temperatures (Tf) ranging from 190 to 230 °C. The influence of the foaming temperature on the cellular structure and its dependency on final properties is discussed. 相似文献
58.
Dr. Vladimir O. Talibov Dr. Edoardo Fabini Edward A. FitzGerald Dr. Daniele Tedesco Daniela Cederfeldt Martin J. Talu Moira M. Rachman Filip Mihalic Dr. Elisabetta Manoni Dr. Marina Naldi Dr. Paola Sanese Dr. Giovanna Forte Dr. Martina Lepore Signorile Prof. Xavier Barril Dr. Cristiano Simone Prof. Manuela Bartolini Dr. Doreen Dobritzsch Dr. Alberto Del Rio Prof. U. Helena Danielson 《Chembiochem : a European journal of chemical biology》2021,22(9):1597-1608
SMYD3 is a multifunctional epigenetic enzyme with lysine methyltransferase activity and various interaction partners. It is implicated in the pathophysiology of cancers but with an unclear mechanism. To discover tool compounds for clarifying its biochemistry and potential as a therapeutic target, a set of drug-like compounds was screened in a biosensor-based competition assay. Diperodon was identified as an allosteric ligand; its R and S enantiomers were isolated, and their affinities to SMYD3 were determined (KD=42 and 84 μM, respectively). Co-crystallization revealed that both enantiomers bind to a previously unidentified allosteric site in the C-terminal protein binding domain, consistent with its weak inhibitory effect. No competition between diperodon and HSP90 (a known SMYD3 interaction partner) was observed although SMYD3–HSP90 binding was confirmed (KD=13 μM). Diperodon clearly represents a novel starting point for the design of tool compounds interacting with a druggable allosteric site, suitable for the exploration of noncatalytic SMYD3 functions and therapeutics with new mechanisms of action. 相似文献
59.
Recently, feature grouping has been proposed as a method for improving retrieval results for logos and web images. This relies on the idea that a group of features matching over a local region in an image is more discriminative than a single feature match. In this paper, we evolve this concept further and apply it to the more challenging task of landmark recognition. We propose a novel combination of dense sampling of SIFT features with interest regions which represent the more salient parts of the image in greater detail. In place of conventional dense sampling used in category recognition that computes features on a regular grid at a number of fixed scales, we allow the sampling density and scale to vary based on the scale of the interest region. We develop new techniques for exploring stronger geometric constraints inside the feature groups and computing the match score. The spatial information is stored efficiently in an inverted index structure. The proposed approach considers part-based matching of interest regions instead of matching entire images using a histogram under bag-of-words. This helps reducing the influence of background clutter and works better under occlusion. Experiments reveal that directing more attention to the salient regions of the image and applying proposed geometric constraints helps in vastly improving recognition rates for reasonable vocabulary sizes. 相似文献
60.