Search results for "NR"
showing 10 items of 6911 documents
Induced arginine transport via cationic amino acid transporter-1 is necessary for human T-cell proliferation
2015
Availability of the semiessential amino acid arginine is fundamental for the efficient function of human T lymphocytes. Tumor-associated arginine deprivation, mainly induced by myeloid-derived suppressor cells, is a central mechanism of tumor immune escape from T-cell-mediated antitumor immune responses. We thus assumed that transmembranous transport of arginine must be crucial for T-cell function and studied which transporters are responsible for arginine influx into primary human T lymphocytes. Here, we show that activation via CD3 and CD28 induces arginine transport into primary human T cells. Both naive and memory CD4(+) T cells as well as CD8(+) T cells specifically upregulated the hum…
Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro
2021
Simple Summary Bleomycin (BLM) is a medication introduced used to treat various types of cancer, including testicular cancer, ovarian cancer, and Hodgkin’s disease. Its most serious side effect is pulmonary fibrosis and impaired lung function. Using A549 human lung cells it is shown that, in parallel to an increased cell toxicity and DNA damage, BLM causes a marked enlargement of the cell nucleus. This effect is abolished by inorganic polyphosphate (polyP), if this physiological polymer is administered together with BLM. The detoxification of BLM is–most likely–caused by the upregulation of the gene encoding the BLM hydrolase which inactivates BLM in vitro and in vivo. This study contribute…
Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism
2016
Abstract Aims: Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies, lack of correlation with the bioavailable concentrations is a critical issue. Some reports had suggested that these molecules downregulate the stress response, which may affect growth and the antioxidant protection of malignant cells. Initially, we studied this potential underlying mechanism using different human melanomas (with genetic backgrounds correlating with most melanomas), growing in nude mice as xenografts, and pterostilbene (Pter, a natural dimethoxylated analog of resveratrol). Results: Intravenous administration of Pter decreased human melanoma growth in vivo. However, Pter, …
Characterization of sulfhydryl oxidase from Aspergillus tubingensis
2017
Background Despite of the presence of sulfhydryl oxidases (SOXs) in the secretomes of industrially relevant organisms and their many potential applications, only few of these enzymes have been biochemically characterized. In addition, basic functions of most of the SOX enzymes reported so far are not fully understood. In particular, the physiological role of secreted fungal SOXs is unclear. Results The recently identified SOX from Aspergillus tubingensis (AtSOX) was produced, purified and characterized in the present work. AtSOX had a pH optimum of 6.5, and showed a good pH stability retaining more than 80% of the initial activity in a pH range 4-8.5 within 20 h. More than 70% of the initia…
How to deal with Haplotype data: An Extension to the Conceptual Schema of the Human Genome
2016
[EN] The goal of this work is to describe the advantages of the application of Conceptual Modeling (CM) in complex domains, such as genomics. Nowadays, the study and comprehension of the human genome is a major challenge due to its high level of complexity. The constant evolution in the genomic domain contributes to the generation of ever larger amounts of new data, which means that if we do not manage it correctly data quality could be compromised (i.e., problems related with heterogeneity and inconsistent data). In this paper, we propose the use of a Conceptual Schema of the Human Genome (CSHG), designed to understand and improve our ontological commitment to the domain and also extend (e…
Optimization of Bacillus cereus Fermentation Process for Selenium Enrichment as Organic Selenium Source
2020
Selenium is an essential trace element and micronutrient for human health. Application of organic selenium in plants and microorganisms as trace element supplement is attracting more and more attention. In this study, Bacillus cereus, an important probiotic, was used for selenium enrichment with sodium selenite as selenium source. The growth curve of B. cereus was investigated, and 150 μg/ml was selected as the concentration of selenium for B. cereus fermentation. With application of response surface methodology, the optimal fermentation conditions were obtained as follows: inoculation quantity of 7%, culture temperature of 33°C, and shaking speed of 170 rpm, leading to the maximal selenium…
Reconstitution of T Cell Proliferation under Arginine Limitation: Activated Human T Cells Take Up Citrulline via L-Type Amino Acid Transporter 1 and …
2017
In the tumor microenvironment, arginine is metabolized by arginase-expressing myeloid cells. This arginine depletion profoundly inhibits T cell functions and is crucially involved in tumor-induced immunosuppression. Reconstitution of adaptive immune functions in the context of arginase-mediated tumor immune escape is a promising therapeutic strategy to boost the immunological anti-tumor response. Arginine can be recycled in certain mammalian tissues from citrulline via argininosuccinate in a two-step enzymatic process involving the enzymes argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL). Here we demonstrate that anti-CD3/anti-CD28-activated human primary CD4+ and CD8+ T c…
Fluorouracil and bevacizumab plus anakinra for patients with metastatic colorectal cancer refractory to standard therapies (IRAFU): a single-arm phas…
2018
IF 5.503 (2017); International audience; In preclinical models, IL-1β inhibition could enhance the efficacy of fluorouracil (5-FU). In this phase 2 study, we assessed the activity and safety of 5-FU plus bevacizumab and anakinra (an IL-1β and α inhibitor) in patients with metastatic colorectal (mCRC) refractory to chemotherapy and anti-angiogenic therapy. Eligible patients had unresectable mCRC; were refractory or intolerant to fluoropyrimidine, irinotecan, oxaliplatin, anti-VEGF therapy, and anti-EGFR therapy (for tumors with wild-type KRAS). Patients were treated with a simplified acid folinic plus 5-FU regimen and bevacizumab (5 mg/kg) both administered by intravenous infusion for 30 min…
Methods for RNA Modification Mapping Using Deep Sequencing: Established and New Emerging Technologies
2019
New analytics of post-transcriptional RNA modifications have paved the way for a tremendous upswing of the biological and biomedical research in this field. This especially applies to methods that included RNA-Seq techniques, and which typically result in what is termed global scale modification mapping. In this process, positions inside a cell`s transcriptome are receiving a status of potential modification sites (so called modification calling), typically based on a score of some kind that issues from the particular method applied. The resulting data are thought to represent information that goes beyond what is contained in typical transcriptome data, and hence the field has taken to use …
Graphical Workflow System for Modification Calling by Machine Learning of Reverse Transcription Signatures
2019
Modification mapping from cDNA data has become a tremendously important approach in epitranscriptomics. So-called reverse transcription signatures in cDNA contain information on the position and nature of their causative RNA modifications. Data mining of, e.g. Illumina-based high-throughput sequencing data, is therefore fast growing in importance, and the field is still lacking effective tools. Here we present a versatile user-friendly graphical workflow system for modification calling based on machine learning. The workflow commences with a principal module for trimming, mapping, and postprocessing. The latter includes a quantification of mismatch and arrest rates with single-nucleotide re…