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排序方式: 共有128条查询结果,搜索用时 15 毫秒
1.
Noemi Eiro Sandra Cid Nuria Aguado María Fraile Nagore de Pablo Berta Fernndez Francisco Domínguez Luis O. Gonzlez Francisco J. Vizoso 《International journal of molecular sciences》2021,22(1)
Tumor-infiltrating immune cells phenotype is associated with tumor progression. However, little is known about the phenotype of the peripheral blood mononuclear cells (PBMC) from breast cancer patients. We investigated MMP1 and MMP11 expression in PBMC from breast cancer patients and we analyzed gene expression changes upon their interaction with cancer cells and cancer-associated fibroblasts (CAF). We measured the impact of PBMC on proinflammatory gene expression in breast cancer cells, normal fibroblast (NF), and CAF and the impact on proliferation and invasiveness capacity of breast cancer cells. Gene expression of MMP1 and MMP11 in PBMC from breast cancer patients (n = 54) and control (n = 28); expression of IL1A, IL6, IL17, IFNβ, and NFĸB in breast cancer cell lines (MCF-7 and MDA-MB-231); and, additionally, IL10 and MMP11 in CAF and NF were analyzed by qRT-PCR before and after co-culture. Our results show the existence of a subpopulation of breast cancer patients (25.9%) with very high levels of MMP11 gene expression in PBMC. Also, gene expression of MMP1 and MMP11 increases in PBMC after co-culture with breast cancer cell lines, NF or CAF. PBMC from healthy or breast cancer patients induce an increased proliferation rate on MCF-7 and an increased invasiveness capacity of MDA-MB-231. Finally, we show a differential expression profile of inflammatory genes in NF and CAF when co-cultured with control or breast cancer PBMC. We have observed that MMPs’ expression in PBMC is regulated by the microenvironment, while the expression of inflammatory genes in NF or CAF is differentially regulated by PBMC. These findings confirm the importance of the crosstalk between stromal cells and suggest that PBMC would play a role in promoting aggressive tumor behavior. 相似文献
2.
Giuseppina Emanuela Grieco Noemi Brusco Giada Licata Daniela Fignani Caterina Formichi Laura Nigi Guido Sebastiani Francesco Dotta 《International journal of molecular sciences》2021,22(2)
Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules. 相似文献
3.
Magdalena Kotaska Anna Dziubina Magorzata Szafarz Kamil Mika Marek Bednarski Noemi Nicosia Ahmed Temirak Christa E. Müller Katarzyna Kie-Kononowicz 《International journal of molecular sciences》2022,23(21)
The adenosine A2A and A2B receptors are promising therapeutic targets in the treatment of obesity and diabetes since the agonists and antagonists of these receptors have the potential to positively affect metabolic disorders. The present study investigated the link between body weight reduction, glucose homeostasis, and anti-inflammatory activity induced by a highly potent and specific adenosine A2B receptor antagonist, compound PSB-603. Mice were fed a high-fat diet for 14 weeks, and after 12 weeks, they were treated for 14 days intraperitoneally with the test compound. The A1/A2A/A2B receptor antagonist theophylline was used as a reference. Following two weeks of treatment, different biochemical parameters were determined, including total cholesterol, triglycerides, glucose, TNF-α, and IL-6 blood levels, as well as glucose and insulin tolerance. To avoid false positive results, mouse locomotor and spontaneous activities were assessed. Both theophylline and PSB-603 significantly reduced body weight in obese mice. Both compounds had no effects on glucose levels in the obese state; however, PSB-603, contrary to theophylline, significantly reduced triglycerides and total cholesterol blood levels. Thus, our observations showed that selective A2B adenosine receptor blockade has a more favourable effect on the lipid profile than nonselective inhibition. 相似文献
4.
Aina Martín-Medina Noemi Cern-Pisa Esther Martinez-Font Hanaa Shafiek Antnia Obrador-Hevia Jaume Sauleda Amanda Iglesias 《International journal of molecular sciences》2022,23(12)
The most frequent cause of death by cancer worldwide is lung cancer, and the 5-year survival rate is still very poor for patients with advanced stage. Understanding the crosstalk between the signaling pathways that are involved in disease, especially in metastasis, is crucial to developing new targeted therapies. Toll-like receptors (TLRs) are master regulators of the immune responses, and their dysregulation in lung cancer is linked to immune escape and promotes tumor malignancy by facilitating angiogenesis and proliferation. On the other hand, over-activation of the WNT signaling pathway has been reported in lung cancer and is also associated with tumor metastasis via induction of Epithelial-to-mesenchymal-transition (EMT)-like processes. An interaction between both TLRs and the WNT pathway was discovered recently as it was found that the TLR pathway can be activated by WNT ligands in the tumor microenvironment; however, the implications of such interactions in the context of lung cancer have not been discussed yet. Here, we offer an overview of the interaction of TLR-WNT in the lung and its potential implications and role in the oncogenic process. 相似文献
5.
Alexandre Skyrme Noemi RodriguezAuthor VitaeRoberto IerusalimschyAuthor Vitae 《Journal of Parallel and Distributed Computing》2014
The two standard models used for communication in concurrent programs, shared memory and message passing, have been the focus of much debate for a long time. Still, we believe the main issue at stake should not be the choice between these models, but rather how to ensure that communication is structured, i.e., it occurs only in syntactically restricted code regions. In this survey, we explore concurrency control models and evaluate how their characteristics contribute positively or negatively to the support for structured communication. We focus the evaluation on three properties: reasonability, which is the main property we are interested in and determines how easily programmers can reason about a concurrent program’s execution; performance, which determines whether there are any distinct features which can prevent or facilitate efficient implementations; and composability, which determines whether a model offers constructs that can be used as building blocks for coarser-grained, or higher-level, concurrency abstractions. 相似文献
6.
Noga Gal Dr. Sofiya Kolusheva Dr. Noemi Kedei Dr. Andrea Telek Taiyabah A. Naeem Nancy E. Lewin Langston Lim Poonam Mannan Susan H. Garfield Dr. Saïd El Kazzouli Dr. Dina M. Sigano Dr. Victor E. Marquez Dr. Peter M. Blumberg Prof. Raz Jelinek 《Chembiochem : a European journal of chemical biology》2011,12(15):2331-2340
N‐methyl‐substituted diacylglycerol–indololactones (DAG–indololactones) are newly synthesized effectors of protein kinase C (PKC) isoforms and exhibit substantial selectivity between RasGRP3 and PKCα. We present a comprehensive analysis of membrane interactions and biological activities of several DAG–indololactones. Translocation and binding activity assays underline significant variations between the PKC translocation characteristics affected by the ligands as compared to their binding activities. In parallel, the fluorescent properties of the ligands were employed for analysis of their membrane association profiles. Specifically, we found that a slight change in the linkage to the indole ring resulted in significant differences in membrane binding and association of the DAG–indololactones with lipid bilayers. Our analysis shows that seemingly small structural modifications of the hydrophobic regions of these biomimetic PKC effectors contribute to pronounced modulation of membrane interactions of the ligands. 相似文献
7.
Elisa Mascolo Francesco Liguori Lorenzo Stufera Mecarelli Noemi Amoroso Chiara Merigliano Susanna Amadio Cinzia Volont Roberto Contestabile Angela Tramonti Fiammetta Vernì 《International journal of molecular sciences》2021,22(2)
Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity. 相似文献
8.
Valeria Fedeli Alessandra Cucina Simona Dinicola Gianmarco Fabrizi Angela Catizone Luisa Gesualdi Simona Ceccarelli Abdel Halim Harrath Saleh H. Alwasel Giulia Ricci Paola Pedata Mariano Bizzarri Noemi Monti 《International journal of molecular sciences》2022,23(4)
Microgravity impairs tissue organization and critical pathways involved in the cell–microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were analyzed and compared to control samples growing in a normal gravity field. Simulated microgravity impairs fibroblast conversion into myofibroblast and inhibits their migratory properties. Consequently, the normal interplay between fibroblasts and keratinocytes were remarkably altered in 3D co-culture experiments, giving rise to several ultra-structural abnormalities. Such phenotypic changes are associated with down-regulation of α-SMA that translocate in the nucleoplasm, altogether with the concomitant modification of the actin-vinculin apparatus. Noticeably, the stress associated with weightlessness induced oxidative damage, which seemed to concur with such modifications. These findings disclose new opportunities to establish antioxidant strategies that counteract the microgravity-induced disruptive effects on fibroblasts and tissue organization. 相似文献
9.
Dr. Jessica S. Kelsey Dr. Tamas Geczy Nancy E. Lewin Dr. Noemi Kedei Colin S. Hill Julia S. Selezneva Christopher J. Valle Wonhee Woo Dr. Inna Gorshkova Dr. Peter M. Blumberg 《Chembiochem : a European journal of chemical biology》2014,15(8):1131-1144
The C1 domain, which represents the recognition motif on protein kinase C for the lipophilic second messenger diacylglycerol and its ultrapotent analogues, the phorbol esters, has emerged as a promising therapeutic target for cancer and other indications. Potential target selectivity is markedly enhanced both because binding reflects ternary complex formation between the ligand, C1 domain, and phospholipid, and because binding drives membrane insertion of the C1 domain, permitting aspects of the C1 domain surface outside the binding site, per se, to influence binding energetics. Here, focusing on charged residues identified in atypical C1 domains which contribute to their loss of ligand binding activity, we showed that increasing charge along the rim of the binding cleft of the protein kinase C δ C1 b domain raises the requirement for anionic phospholipids. Correspondingly, it shifts the selectivity of C1 domain translocation to the plasma membrane, which is more negatively charged than internal membranes. This change in localization is most pronounced in the case of more hydrophilic ligands, which provide weaker membrane stabilization than do the more hydrophobic ligands and thus contributes an element to the structure–activity relations for C1 domain ligands. Coexpressing pairs of C1‐containing constructs with differing charges each expressing a distinct fluorescent tag provided a powerful tool to demonstrate the effect of increasing charge in the C1 domain. 相似文献
10.