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排序方式: 共有363条查询结果,搜索用时 15 毫秒
1.
Renata Gruszka Krzysztof Zakrzewski Pawe Piotr Liberski Magdalena Zakrzewska 《International journal of molecular sciences》2021,22(2)
Numerous molecular factors disrupt the correctness of the cell cycle process leading to the development of cancer due to increased cell proliferation. Among known causative factors of such process is abnormal gene expression. Nowadays in the light of current knowledge such alterations are frequently considered in the context of mRNA–miRNA correlation. One of the molecular factors with potential value in tumorigenesis is the feedback loop between MYC and E2F genes in which miR-17-5p and miR-20a from the miR-17-92 cluster are involved. The current literature shows that overexpression of the members of the OncomiR-1 are involved in the development of many solid tumors. In the present work, we investigated the expression of components of the MYC/E2F/miR-17-92 network and their closely related elements including members of MYC and E2F families and miRNAs from two paralogs of miR-17-92: miR-106b-25 and miR-106a-363, in the most common brain tumors of childhood, pilocytic astrocytoma (PA), WHO grade 1; ependymoma (EP), WHO grade 2; and medulloblastoma (MB), WHO grade 4. We showed that the highest gene expression was observed in the MYC family for MYCN and in the E2F family for E2F2. Positive correlation was observed between the gene expression and tumor grade and type, with the highest expression being noted for medulloblastomas, followed by ependymomas, and the lowest for pilocytic astrocytomas. Most members of miR-17-92, miR-106a-363 and miR-106b-25 clusters were upregulated and the highest expression was noted for miR-18a and miR-18b. The rest of the miRNAs, including miR-19a, miR-92a, miR-106a, miR-93, or miR-25 also showed high values. miR-17-5p, miR-20a obtained a high level of expression in medulloblastomas and ependymomas, while close to the control in the pilocytic astrocytoma samples. miRNA expression also depended on tumor grade and histology. 相似文献
2.
Margaret Ottaviano Emilio Francesco Giunta Marianna Tortora Marcello Curvietto Laura Attademo Davide Bosso Cinzia Cardalesi Mario Rosanova Pietro De Placido Erica Pietroluongo Vittorio Riccio Brigitta Mucci Sara Parola Maria Grazia Vitale Giovannella Palmieri Bruno Daniele Ester Simeone 《International journal of molecular sciences》2021,22(7)
As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients. 相似文献
3.
Serena Montalbano Francesca Degola Jennifer Bartoli Franco Bisceglie Annamaria Buschini Mauro Carcelli Donatella Feretti Serena Galati Laura Marchi Nicol Orsoni Giorgio Pelosi Marianna Pioli Francesco M. Restivo Dominga Rogolino Mirco Scaccaglia Olga Serra Giorgio Spadola Gaia C. V. Viola Ilaria Zerbini Claudia Zani 《International journal of molecular sciences》2021,22(9)
The control of the fungal contamination on crops is considered a priority by the sanitary authorities of an increasing number of countries, and this is also due to the fact that the geographic areas interested in mycotoxin outbreaks are widening. Among the different pre- and post-harvest strategies that may be applied to prevent fungal and/or aflatoxin contamination, fungicides still play a prominent role; however, despite of countless efforts, to date the problem of food and feed contamination remains unsolved, since the essential factors that affect aflatoxins production are various and hardly to handle as a whole. In this scenario, the exploitation of bioactive natural sources to obtain new agents presenting novel mechanisms of action may represent a successful strategy to minimize, at the same time, aflatoxin contamination and the use of toxic pesticides. The Aflatox® Project was aimed at the development of new-generation inhibitors of aflatoxigenic Aspergillus spp. proliferation and toxin production, through the modification of naturally occurring molecules: a panel of 177 compounds, belonging to the thiosemicarbazones class, have been synthesized and screened for their antifungal and anti-aflatoxigenic potential. The most effective compounds, selected as the best candidates as aflatoxin containment agents, were also evaluated in terms of cytotoxicity, genotoxicity and epi-genotoxicity to exclude potential harmful effect on the human health, the plants on which fungi grow and the whole ecosystem. 相似文献
4.
Marianna Sigala 《Computers in human behavior》2011,27(2):655-661
Although previous CRM studies treat eCRM as a synonymous with 1:1 communications and personalised service at an individual basis, web 2.0 further enables firms and users to generate customer value and build customer relations through social networking, co-learning, co-production and collaboration. The paper advocates the development of eCRM 2.0 strategies aiming at exploiting both the networking and social/customer intelligence of web 2.0 by integrating and engaging customers and communities along firms’ value chain operations. The usage and readiness of Greek tourism firms to embark on eCRM 2.0 strategies was examined by conducting an e-mail survey and focused groups with tourism professionals. Despite the low adoption rates of eCRM 2.0, respondents were aware and greatly concerned about the practical implications of this field, which in turn elucidated an agenda for future research studies. 相似文献
5.
Veronica Dimuccio Linda Bellucci Marianna Genta Cristina Grange Maria Felice Brizzi Maddalena Gili Sara Gallo Maria Laura Centomo Federica Collino Benedetta Bussolati 《International journal of molecular sciences》2022,23(20)
Simple SummaryDiabetic nephropathy is one of the most frequent complications of diabetes, resulting from diffuse damage to different kidney cells. The identification of subjects at risk is mandatory to prevent its development and provide appropriate therapies reducing the unmanageable evolution towards end-stage kidney disease. The aim of this work was to identify urinary-derived extracellular vesicles (EVs) miRNA cargo to be used as biomarker of kidney damage in diabetic patients. The miRNA profile was then correlated with the molecular mechanism associated with the glomerular and tubular damage using a diabetic-like model. In patients, miR145 and miR126 in urinary EVs increased together with albuminuria. MiR145 and miR126 increased in parallel in EVs from renal epithelial cells undergoing transition to a fibrotic mesenchymal phenotype. These data unveiled a role for miR126 and miR145 as the biomarkers of damage progression and proteinuria development in diabetic nephropathy. AbstractDiabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney’s physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition. 相似文献
6.
Franco Bisceglie Giorgio Pelosi Nicol Orsoni Marianna Pioli Mauro Carcelli Paolo Pelagatti Silvana Pinelli Peter J. Sadler 《International journal of molecular sciences》2022,23(14)
We report the synthesis and characterization of three half-sandwich Ru(II) arene complexes [(η6-arene)Ru(N,N′)L][PF6]2 containing arene = p-cymene, N,N′ = bipyridine, and L = pyridine meta- with methylenenaphthalimide (C1), methylene(nitro)naphthalimide (C2), or methylene(piperidinyl)naphthalimide (C3). The naphthalimide acts as an antenna for photoactivation. After 3 h of irradiation with blue light, the monodentate pyridyl ligand had almost completely dissociated from complex C3, which contains an electron donor on the naphthalimide ring, whereas only 50% dissociation was observed for C1 and C2. This correlates with the lower wavelength and strong absorption of C3 in this region of the spectrum (λmax = 418 nm) compared with C1 and C2 (λmax = 324 and 323 nm, respectively). All the complexes were relatively non-toxic towards A549 human lung cancer cells in the dark, but only complex C3 exhibited good photocytoxicity towards these cancer cells upon irradiation with blue light (IC50 = 10.55 ± 0.30 μM). Complex C3 has the potential for use in photoactivated chemotherapy (PACT). 相似文献
7.
Marianna A. Zolotovskaia Max A. Kovalenko Victor S. Tkachev Alexander M. Simonov Maxim I. Sorokin Ella Kim Denis V. Kuzmin Betul Karademir-Yilmaz Anton A. Buzdin 《International journal of molecular sciences》2022,23(13)
In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas. 相似文献
8.
Charlotte Szewczykowski Christian Mardin Marianna Lucio Gerd Wallukat Jakob Hoffmanns Thora Schrder Franziska Raith Lennart Rogge Felix Heltmann Michael Moritz Lorenz Beitlich Julia Schottenhamml Martin Herrmann Thomas Harrer Marion Ganslmayer Friedrich E. Kruse Martin Krter Jochen Guck Robert Lmmer Matthias Zenkel Andreas Gießl Bettina Hohberger 《International journal of molecular sciences》2022,23(13)
Long COVID (LC) describes the clinical phenotype of symptoms after infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Diagnostic and therapeutic options are limited, as the pathomechanism of LC is elusive. As the number of acute SARS-CoV-2 infections was and is large, LC will be a challenge for the healthcare system. Previous studies revealed an impaired blood flow, the formation of microclots, and autoimmune mechanisms as potential factors in this complex interplay. Since functionally active autoantibodies against G-protein-coupled receptors (GPCR-AAbs) were observed in patients after SARS-CoV-2 infection, this study aimed to correlate the appearance of GPCR-AAbs with capillary microcirculation. The seropositivity of GPCR-AAbs was measured by an established cardiomyocyte bioassay in 42 patients with LC and 6 controls. Retinal microcirculation was measured by OCT–angiography and quantified as macula and peripapillary vessel density (VD) by the Erlangen-Angio Tool. A statistical analysis yielded impaired VD in patients with LC compared to the controls, which was accentuated in female persons. A significant decrease in macula and peripapillary VD for AAbs targeting adrenergic β2-receptor, MAS-receptor angiotensin-II-type-1 receptor, and adrenergic α1-receptor were observed. The present study might suggest that a seropositivity of GPCR-AAbs can be linked to an impaired retinal capillary microcirculation, potentially mirroring the systemic microcirculation with consecutive clinical symptoms. 相似文献
9.
The stress-response Snf1 protein kinase of Saccharomyces cerevisiae serves as a powerful model for studies of the eukaryotic Snf1/AMP-activated protein kinase (AMPK) family. Central to studies of Snf1 are methods that determine its activation state under various physiological and genetic conditions. Here, we have developed a convenient and sensitive method for immunoblot analysis of endogenous yeast Snf1 and its activation-loop threonine (Thr210) phosphorylation. The method employs readily obtainable reagents and yields results that faithfully reflect the environmental and genetic conditions tested. Using our method, we have obtained evidence that Snf1 remains stress-regulated in reg1 Delta cells, revealing the existence of a Snf1 signalling mechanism(s) that is independent of Reg1-PP1 phosphatase. In addition to strains of common laboratory S. cerevisiae backgrounds, we have applied the method to two pathogenic Candida species, C. glabrata and C. albicans. We have detected proteins whose gel mobilities, immune properties and regulation patterns are consistent with those expected for the corresponding Snf1 homologues. Because Snf1 activation is a sensitive marker of several types of stress, including artifactual stresses associated with common cell harvesting and protein extraction procedures, the convenient and efficient protein extraction method described here should be advantageous for SDS-PAGE and immunoblot analyses of stress-regulated and other proteins from various yeast species. 相似文献
10.
Marianna Barbalinardo Marta Giannelli Ludovica Forcini Barbara Luppi Anna Donnadio Maria Luisa Navacchia Giampiero Ruani Giovanna Sotgiu Annalisa Aluigi Roberto Zamboni Tamara Posati 《International journal of molecular sciences》2022,23(12)
Skin disorders are widespread around the world, affecting people of all ages, and oxidative stress represents one of the main causes of alteration in the normal physiological parameters of skin cells. In this work, we combined a natural protein, fibroin, with antioxidant compounds extracted in water from pomegranate waste. We demonstrate the effective and facile fabrication of bioactive and eco-sustainable films of potential interest for skin repair. The blended films are visually transparent (around 90%); flexible; stable in physiological conditions and in the presence of trypsin for 12 days; able to release the bioactive compounds in a controlled manner; based on Fickian diffusion; and biocompatible towards the main skin cells, keratinocytes and fibroblasts. Furthermore, reactive oxygen species (ROS) production tests demonstrated the high capacity of our films to reduce the oxidative stress induced in cells, which is responsible for various skin diseases. 相似文献