Angelica Pace  Fabio Scirocchi  Chiara Napoletano  Ilaria Grazia Zizzari  Luca D&#x;Angelo  Antonio Santoro  Marianna Nuti  Hassan Rahimi  Aurelia Rughetti 《International journal of molecular sciences》2022,23(11)

Despite diagnostic and therapeutic improvements, glioblastoma (GB) remains one of the most threatening brain tumor in adults, underlining the urgent need of new therapeutic targets. Lectins are glycan-binding proteins that regulate several biological processes through the recognition of specific sugar motifs. Lectins and their ligands are found on immune cells, endothelial cells and, also, tumor cells, pointing out a strong correlation among immunity, tumor microenvironment and vascularization. In GB, altered glycans and lectins contribute to tumor progression and immune evasion, shaping the tumor-immune landscape promoting immunosuppressive cell subsets, such as myeloid-derived suppressor cells (MDSCs) and M2-macrophages, and affecting immunoeffector populations, such as CD8⁺ T cells and dendritic cells (DCs). Here, we discuss the latest knowledge on the immune cells, immune related lectin receptors (C-type lectins, Siglecs, galectins) and changes in glycosylation that are involved in immunosuppressive mechanisms in GB, highlighting their interest as possible novel therapeutical targets.  相似文献   

    

Marianna Abate  Lorena Scotti  Valeria Nele  Michele Caraglia  Marco Biondi  Giuseppe De Rosa  Carlo Leonetti  Virginia Campani  Silvia Zappavigna  Manuela Porru 《International journal of molecular sciences》2022,23(9)

Self-assembling nanoparticles (SANPs) promise an effective delivery of bisphosphonates or microRNAs in the treatment of glioblastoma (GBM) and are obtained through the sequential mixing of four components immediately before use. The self-assembling approach facilitates technology transfer, but the complexity of the SANP preparation protocol raises significant concerns in the clinical setting due to the high risk of human errors during the procedure. In this work, it was hypothesized that the SANP preparation protocol could be simplified by using freeze-dried formulations. An in-depth thermodynamic study was conducted on solutions of different cryoprotectants, namely sucrose, mannitol and trehalose, to test their ability to stabilize the produced SANPs. In addition, the ability of SANPs to deliver drugs after lyophilization was assessed on selected formulations encapsulating zoledronic acid in vitro in the T98G GBM cell line and in vivo in an orthotopic mouse model. Results showed that, after lyophilization optimization, freeze-dried SANPs encapsulating zoledronic acid could retain their delivery ability, showing a significant inhibition of T98G cell growth both in vitro and in vivo. Overall, these results suggest that freeze-drying may help boost the industrial development of SANPs for the delivery of drugs to the brain.  相似文献   

    

Lszl Ivanizs  Ilaria Marcotuli  Marianna Rakszegi  Balzs Kalapos  Kitti Sz&#x;ke-Pzsi  Andrs Farkas  Edina Türksi  Eszter Gal  Klaudia Kruppa  Pter Kovcs  va Dark  va Szakcs  Mahmoud Said  Petr Cpal  Jaroslav Doleel  Agata Gadaleta  Istvn Molnr 《International journal of molecular sciences》2022,23(7)

Grain dietary fiber content is an important health-promoting trait of bread wheat. A dominant dietary fiber component of wheat is the cell wall polysaccharide arabinoxylan and the goatgrass Aegilops biuncialis has high β-glucan content, which makes it an attractive gene source to develop wheat lines with modified fiber composition. In order to support introgression breeding, this work examined genetic variability in grain β-glucan, pentosan, and protein content in a collection of Ae. biuncialis. A large variation in grain protein and edible fiber content was revealed, reflecting the origin of Ae. biuncialis accessions from different eco-geographical habitats. Association analysis using DArTseq-derived SNPs identified 34 QTLs associated with β-glucan, pentosan, water-extractable pentosan, and protein content. Mapping the markers to draft chromosome assemblies of diploid progenitors of Ae. biuncialis underlined the role of genes on chromosomes 1M^b, 4M^b, and 5M^b in the formation of grain β-glucan content, while other QTLs on chromosome groups 3, 6, and 1 identified genes responsible for total- and water-extractable pentosan content. Functional annotation of the associated marker sequences identified fourteen genes, nine of which were identified in other monocots. The QTLs and genes identified in the present work are attractive targets for chromosome-mediated gene transfer to improve the health-promoting properties of wheat-derived foods.  相似文献   

    

Michela Cantiello  Monica Carletti  Mery Giantin  Giulia Gardini  Francesca Capolongo  Paolo Cascio  Marianna Pauletto  Flavia Girolami  Mauro Dacasto  Carlo Nebbia 《International journal of molecular sciences》2022,23(7)

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Marianna D&#x;Anca  Francesca R. Buccellato  Chiara Fenoglio  Daniela Galimberti 《International journal of molecular sciences》2022,23(8)

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Marianna Naki  Olga Gourdomichali  Katerina Zonke  Fedon-Giasin Kattan  Manousos Makridakis  Georgia Kontostathi  Antonia Vlahou  Epaminondas Doxakis 《International journal of molecular sciences》2022,23(9)

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Anna Birkov  Marcela Valko-Rokytovsk  Beta Hubkov  Marianna Zbavníkov  Mria Marekov 《International journal of molecular sciences》2021,22(4)

Urine autofluorescence at 295 nm is significantly higher in patients with malignant melanoma at each clinical stage compared to the healthy group. The largest difference is in the early-stages and without metastases. With increasing stage, the autofluorescence at 295 nm decreases. There is also a significant negative correlation between autofluorescence and Clark classification. Based on our results, it is assumed that the way malignant melanoma grows also affects urinary autofluorescence.  相似文献   

    

Michela Palleschi  Gianluca Tedaldi  Marianna Sirico  Alessandra Virga  Paola Ulivi  Ugo De Giorgi 《International journal of molecular sciences》2021,22(15)

Breast cancer is the most frequent and lethal tumor in women and finding the best therapeutic strategy for each patient is an important challenge. PARP inhibitors (PARPis) are the first, clinically approved drugs designed to exploit synthetic lethality in tumors harboring BRCA1/2 mutations. Recent evidence indicates that PARPis have the potential to be used both in monotherapy and combination strategies in breast cancer treatment. In this review, we show the mechanism of action of PARPis and discuss the latest clinical applications in different breast cancer treatment settings, including the use as neoadjuvant and adjuvant approaches. Furthermore, as a class, PARPis show many similarities but also certain critical differences which can have essential clinical implications. Finally, we report the current knowledge about the resistance mechanisms to PARPis. A systematic PubMed search, using the entry terms “PARP inhibitors” and “breast cancer”, was performed to identify all published clinical trials (Phase I-II-III) and ongoing trials (ClinicalTrials.gov), that have been reported and discussed in this review.  相似文献   

    

Virginia Brighenti  Ramona Iseppi  Luca Pinzi  Annamaria Mincuzzi  Antonio Ippolito  Patrizia Messi  Simona Marianna Sanzani  Giulio Rastelli  Federica Pellati 《International journal of molecular sciences》2021,22(8)

Punica granatum L. (pomegranate) fruit is known to be an important source of bioactive phenolic compounds belonging to hydrolysable tannins. Pomegranate extracts have shown antifungal activity, but the compounds responsible for this activity and their mechanism/s of action have not been completely elucidated up to now. The aim of the present study was the investigation of the inhibition ability of a selection of pomegranate phenolic compounds (i.e., punicalagin, punicalin, ellagic acid, gallic acid) on both plant and human fungal pathogens. In addition, the biological target of punicalagin was identified here for the first time. The antifungal activity of pomegranate phenolics was evaluated by means of Agar Disk Diffusion Assay and minimum inhibitory concentration (MIC) evaluation. A chemoinformatic analysis predicted for the first time topoisomerases I and II as potential biological targets of punicalagin, and this prediction was confirmed by in vitro inhibition assays. Concerning phytopathogens, all the tested compounds were effective, often similarly to the fungicide imazalil at the label dose. Particularly, punicalagin showed the lowest MIC for Alternaria alternata and Botrytis cinerea, whereas punicalin was the most active compound in terms of growth control extent. As for human pathogens, punicalagin was the most active compound among the tested ones against Candida albicans reference strains, as well as against the clinically isolates. UHPLC coupled with HRMS indicated that C. albicans, similarly to the phytopathogen Coniella granati, is able to hydrolyze both punicalagin and punicalin as a response to the fungal attack. Punicalagin showed a strong inhibitory activity, with IC₅₀ values of 9.0 and 4.6 µM against C. albicans topoisomerases I and II, respectively. Altogether, the results provide evidence that punicalagin is a valuable candidate to be further exploited as an antifungal agent in particular against human fungal infections.  相似文献   

    

Marianna Gabriella Rispoli  Silvia Valentinuzzi  Giovanna De Luca  Piero Del Boccio  Luca Federici  Maria Di Ioia  Anna Digiovanni  Eleonora Agata Grasso  Valeria Pozzilli  Alessandro Villani  Antonio Maria Chiarelli  Marco Onofrj  Richard G. Wise  Damiana Pieragostino  Valentina Tomassini 《International journal of molecular sciences》2021,22(20)

Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.  相似文献