1,720,980 research outputs found
Possible impact of CYP3A4 and CYP3A5 genotypes on carbamazepine metabolism and clinical outcome in epileptic patients
No full textMelanoma Cells Inhibit iNKT Cell Functions via PGE2 and IDO1
Full text linkSimple Summary The unique properties of invariant natural killer T (iNKT) cells make them an attractive candidate for cancer-adoptive immunotherapy. However, despite their potential, clinical studies have not consistently shown successful outcomes. This lack of efficacy is likely attributed to the immunosuppressive nature of the tumor microenvironment. In this study, we investigated the role of melanoma cell lines in suppressing iNKT cell functions, even in the presence of their specific antigen. Additionally, we aimed to identify the key factors responsible for this immunosuppressive effect. Understanding the primary contributors to the failure of iNKT cell-based therapy is crucial for developing new treatment strategies. Invariant natural killer T (iNKT) cells are a distinct group of immune cells known for their immunoregulatory and cytotoxic activities, which are crucial in immune surveillance against tumors. They have been extensively investigated as a potential target for adoptive cell immunotherapy. Despite the initial promise of iNKT cell-based immunotherapy as a treatment for melanoma patients, its effective utilization has unfortunately yielded inconsistent outcomes. The primary cause of this failure is the immunosuppressive tumor microenvironment (TME). In this study, we specifically directed our attention towards melanoma cells, as their roles within the TME remain partially understood and require further elucidation. Methods: We conducted co-culture experiments involving melanoma cell lines and iNKT cells. Results: We demonstrated that melanoma cell lines had a significant impact on the proliferation and functions of iNKT cells. Our findings revealed that co-culture with melanoma cell lines led to a significant impairment in the expression of the NKG2D receptor and cytolytic granules in iNKT cells. Moreover, we observed a strong impairment of their cytotoxic capability induced by the presence of melanoma cells. Furthermore, through the use of selective inhibitors targeting IDO1 and COX-2, we successfully demonstrated that the melanoma cell line's ability to impair iNKT cell activation and functions was attributed to the up-regulation of IDO1 expression and PGE2 production
8-prenylnaringenin: A natural compound with antioxidant and anti-inflammatory activities
No full textFlow cytometric detection of circulating invariant NKT cells in malignant pleural mesothelioma patients
No full textSynthesis, equilibrium, and biological study of a C-7 glucose boronic acid derivative as a potential candidate for boron neutron capture therapy
No full textThe synthesis of D-glucoheptose derivative containing a boronic moiety is described herein. Starting from benzyl 6,7-dideoxy-2,3,4-tri-O-benzyl-β-D-gluco-ept-6-enopyranoside, the introduction of the boronic acid was performed through a metathesis reaction by using MIDA vinyl boronic acid and the 2nd generation Grubbs catalyst. Hydrogenation led to the final product in only two reaction steps. This new sugar-containing boronic acid in the skeleton could mimic carbohydrate behavior and follow the glucose uptake in living cells. The in vitro toxicity tests performed in fibroblasts and glioma tumor cell lines showed minimal toxicity. Boron uptake measured using ICP-MS was minimal in fibroblasts, while in glioma cells showed a value of 6 ng of total boron accumulation per mg of cells, implying that compound 1a is able to accumulate selectively in the tumor tissues compared to normal
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Polyphenol Polymerization by an Alternative Oxidative Microbial Enzyme and Characterization of the Biological Activity of Oligomers
No full textThe recombinant catalase-peroxidase HPI from E. coli was used as an alternative enzyme in polymerization reactions for the production of (-) epicatechin oligomers and their biological activity was characterized. The enzyme was prepared in two forms: a purified and an immobilized form. Both were tested for their activity in oxidative polymerization reactions, and their stability and reusability were assessed. The polymerization reactions were followed by SEC-HPLC analyses, and the substrate was completely converted into one or more polymerization products depending on the reactions conditions. Results showed that the utilized conditions allowed for the isolation of some oligomers of different molecular weight: the oligomers containing 6 and 7 units of epicatechin substrate are the heaviest ones. Epicatechin was also used in reactions catalyzed by HRP in the same reaction conditions for comparison. In addition, one selected oligomer obtained by HPI enzyme catalysis was shown to act as in vitro inhibitor of tumor cell growth, like one oligomer deriving from epicatechin by HRP catalysis. These data confirm that epicatechin oligomeric form is more effective than its monomer in biological activity and suggest the use of HPI as an alternative enzyme in reactions for the production of epicatechin oligomers
Structural and functional features of Klebsiella pneumoniae capsular degradation by the phage depolymerase KP32gp38: Implications for vaccination against K. pneumoniae
No full textObjective: Klebsiella pneumoniae Przondovirus KP32 presents a complex capsular degradation machinery comprised of two serotype-specific depolymerases, KP32gp38 and KP32gp37. Methods: In this work, we performed capsular polysaccharide (CPS) degradation assays combined with mass spectrometry approaches to identify the reaction product of K21 serotype CPS degradation by KP32gp38. We determined the crystal structure of the KP32gp38 depolymerase in complex with the identified degradation product, a pyruvated pentasaccharide, called K21-pyr5. Results: The structure showed that K21-pyr5 binds to the inter-chain catalytic site, allowing the identification of important residues for CPS recognition. Importantly, we observed that the production of K21-pyr5 through CPS degradation by KP32gp38 is able to induce the maturation and differentiation of monocyte-derived dendritic cells, which, in turn, induce lymphocyte proliferation and Th polarization. By employing a T7 phage of Escherichia coli analogy, we were able to provide insights into the portal assembly of the Przondovirus K32. Our modeling studies suggest that the KP32 portal, attached to its icosahedral capsid shell, carries 12 depolymerase molecules on a single virion, arranged in 6 branches; in each branch, KP32gp38 depolymerase adheres to KP32gp37, which is directly connected to the phage portal. Conclusions: Overall, our results suggest that depolymerases act as anti-virulent agents, not only by depleting the bacteria of their CPS but also by producing immunostimulatory CPS degradation products. This indicates the use of CPS degradation products by depolymerases as potential antigens in K. pneumoniae vaccination strategies
Synthesis and characterisation of a boron-rich symmetric triazine bearing a hypoxia-targeting nitroimidazole moiety
Full text linkBoron Neutron Capture Therapy (BNCT) is a binary therapy that promises to be suitable in treating many non-curable cancers. To that, the discovery of new boron compounds able to accumulate selectively in the tumour tissue is still required. Hypoxia, a deficiency of oxygen in tumor tissue, is a great challenge in the conventional treatment of cancer, because hypoxic areas are resistant to conventional anticancer treatments. 2-Nitroimidazole derivatives are known to be hypoxia markers due to their enrichment by bioreduction in hypoxic cells. In the present work, 2-nitroimidazole was chosen as the starting point for the synthesis of a new boron-containing compound based on a 1,3,5-triazine skeleton. Two o-carborane moieties were inserted to achieve a high ratio of boron on the molecular weight, exploiting a short PEG spacer to enhance the polarity of the compound and outdistance the active part from the core. The compound showed no toxicity on normal human primary fibroblasts, while it showed noteworthy toxicity in multiple myeloma cells together with a consistent intracellular boron accumulation
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