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排序方式: 共有352条查询结果,搜索用时 15 毫秒
71.
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
72.
Eva Tvrd Daniel Lovíek Elika Glov Marianna Schwarzov Eva Kov
ikov Simona Kunov Jana
iarovsk Miroslava Ka
niov 《International journal of molecular sciences》2022,23(15)
This study focused on the identification of bacterial profiles of semen in normozoospermic men and their possible involvement in changes to the sperm structural integrity and functional activity. Furthermore, we studied possible fluctuations of selected cytokines, oxidative markers, and antibacterial proteins as a result of bacterial presence in the ejaculate. Sperm motility was assessed with computer-assisted sperm analysis, while sperm apoptosis, necrosis and acrosome integrity were examined with fluorescent methods. Reactive oxygen species (ROS) generation was quantified via luminometry, sperm DNA fragmentation was evaluated using the TUNEL protocol and chromatin-dispersion test, while the JC-1 assay was applied to evaluate the mitochondrial membrane potential. Cytokine levels were quantified with the biochip assay, whilst selected antibacterial proteins were quantified using the ELISA method. The predominant species identified by the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were Staphylococcus hominis, Staphylococcus capitis and Micrococcus luteus. The results revealed that the sperm quality decreased proportionally to the increasing bacterial load and occurrence of conditionally pathogenic bacteria, including Enterococcus faecalis, Staphylococcus aureus and Escherichia coli. Antimicrobial susceptibility tests revealed a substantial resistance of randomly selected bacterial strains to ampicillin, vancomycin, tobramycin, and tetracycline. Furthermore, an increased bacterial quantity in semen was accompanied by elevated levels of pro-inflammatory cytokines, including interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor alpha as well as ROS overproduction and lipid peroxidation of the sperm membranes. Our results suggest that semen quality may be notably affected by the bacterial quantity as well as quality. It seems that bacteriospermia may be associated with inflammatory processes, oxidative stress, sperm structural deterioration, and a subsequent risk for the development of subfertility, even in normozoospermic males. 相似文献
73.
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
74.
75.
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
76.
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
77.
78.
Edla Maria Bezerra Lima Antonieta Middea José Manoel Marconcini Ana Carolina Corrêa Jéssica Fernandes Pereira Alessandra Vieira Guimarães Josimar Firmino de Lima Marianna Ramos dos Anjos Izabela Miranda de Castro Renata Nunes Oliveira Carla Ramos Moreira Maurício Magalhães de Paiva Francisco Luiz Correa Rangel Reiner Neumann 《应用聚合物科学杂志》2021,138(36):50907
The effects of concentration and surface modification of two Brazilian bentonite clays on nanocomposites' properties based on polylactic acid – (PLA) were investigated. The samples were prepared by the extrusion/injection method to obtain biodegradable packaging plastics. The raw materials and their bionanocomposites were characterized by various techniques. Natural clay samples presented a size of around 2 μm while the modified ones' size was 5–6 μm, probably due to the presence of cetyltrimethylammonium bromide in the interlayer space. The particle size and the contact angle increased with the treatment and the clay's density decreased. The organoclays were homogeneously dispersed in PLA, which can be associated with the interactions between PLA chains' carbonyl groups and the organoclays. The bionanocomposites present modified clay particles axis aligned to the flow direction of the extruder/injector. Chocolate organoclay acts as a nucleating agent to PLA crystal growth, increasing the sample's crystallinity, while Bofe organoclay interferes with the amorphous chain's mobility and diminishes the sample's crystallization. The addition of both organoclays to PLA diminished the sample's elongation at break and strength, although the organoclays increased the sample's Young modulus, even though Bofe organoclay is more active in PLA amorphous phase and Chocolate organoclay on the crystalline one. 相似文献
79.
Nucleophilic Water Capture or Proton Loss: Single Amino Acid Switch Converts δ‐Cadinene Synthase into Germacradien‐4‐ol Synthase
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Marianna Loizzi Dr. Veronica González Dr. David J. Miller Prof. Dr. Rudolf K. Allemann 《Chembiochem : a European journal of chemical biology》2018,19(1):100-105
δ‐Cadinene synthase is a sesquiterpene cyclase that utilises the universal achiral precursor farnesyl diphosphate (FDP) to generate predominantly the bicyclic sesquiterpene δ‐cadinene and about 2 % germacradien‐4‐ol, which is also generated from FDP by the cyclase germacradien‐4‐ol synthase. Herein, the mechanism by which sesquiterpene synthases discriminate between deprotonation and reaction with a nucleophilic water molecule was investigated by site‐directed mutagenesis of δ‐cadinene synthase. If W279 in δ‐cadinene synthase was replaced with various smaller amino acids, the ratio of alcohol versus hydrocarbon product was directly proportional to the van der Waals volume of the amino acid side chain. DCS‐W279A is a catalytically highly efficient germacradien‐4‐ol synthase (kcat/KM=1.4×10?3 μm s?1) that produces predominantly germacradien‐4‐ol in addition to 11 % δ‐cadinene. Water capture is not achieved through strategic positioning of a water molecule in the active site, but through a coordinated series of loop movements that allow bulk water access to the final carbocation in the active site prior to product release. 相似文献
80.
Drug‐Loaded Multifunctional Nanoparticles Targeted to the Endocardial Layer of the Injured Heart Modulate Hypertrophic Signaling
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Mónica P. A. Ferreira Sanjeev Ranjan Sini Kinnunen Alexandra Correia Virpi Talman Ermei Mäkilä Brianda Barrios‐Lopez Marianna Kemell Vimalkumar Balasubramanian Jarno Salonen Jouni Hirvonen Heikki Ruskoaho Anu J. Airaksinen Hélder A. Santos 《Small (Weinheim an der Bergstrasse, Germany)》2017,13(33)
Ischemic heart disease is the leading cause of death globally. Severe myocardial ischemia results in a massive loss of myocytes and acute myocardial infarction, the endocardium being the most vulnerable region. At present, current therapeutic lines only ameliorate modestly the quality of life of these patients. Here, an engineered nanocarrier is reported for targeted drug delivery into the endocardial layer of the left ventricle for cardiac repair. Biodegradable porous silicon (PSi) nanoparticles are functionalized with atrial natriuretic peptide (ANP), which is known to be expressed predominantly in the endocardium of the failing heart. The ANP–PSi nanoparticles exhibit improved colloidal stability and enhanced cellular interactions with cardiomyocytes and non‐myocytes with minimal toxicity. After confirmation of good retention of the radioisotope 111‐Indium in relevant physiological buffers over 4 h, in vivo single‐photon emission computed tomography (SPECT/CT) imaging and autoradiography demonstrate increased accumulation of ANP–PSi nanoparticles in the ischemic heart, particularly in the endocardial layer of the left ventricle. Moreover, ANP–PSi nanoparticles loaded with a novel cardioprotective small molecule attenuate hypertrophic signaling in the endocardium, demonstrating cardioprotective potential. These results provide unique insights into the development of nanotherapies targeted to the injured region of the myocardium. 相似文献