Search results for "Cog"
showing 10 items of 17676 documents
Cytotoxicity of sesquiterpene alkaloids from Nuphar plants toward sensitive and drug-resistant cell lines.
2018
Multi-drug resistance (MDR) is a critical problem in cancer chemotherapy. MDR causes the overexpression of ATP-binding cassette (ABC) transporters and mutations in tumor suppressor genes and oncogenes. To tackle this issue, in this study, we focused on Nuphar plants, which have been traditionally used as food. Sesquiterpene alkaloids (1–3) were isolated from N. japonicum and dimeric sesquiterpene thioalkaloids (4–10) were isolated from N. pumilum. P-glycoprotein-overexpressing CEM/ADR5000 cells were cross-resistant to 6,6′-dihydroxythiobinupharidine (10). Using in silico molecular docking, we calculated the binding energies and simulated the interactions of these compounds with the correspo…
Repurposing of Bromocriptine for Cancer Therapy
2018
Bromocriptine is an ergot alkaloid and dopamine D2 receptor agonist used to treat Parkinson’s disease, acromegaly, hyperprolactinemia, and galactorrhea, and more recently diabetes mellitus. The drug is also active against pituitary hormone-dependent tumors (prolactinomas and growth-hormone producing adenomas). We investigated, whether bromocriptine also inhibits hormone-independent and multidrug-resistant (MDR) tumors. We found that bromocriptine was cytotoxic towards drug-sensitive CCRF-CEM, multidrug-resistant CEM/ADR5000 leukemic cells as well as wild-type or multidrug-resistant ABCB5-transfected HEK293 cell lines, but not sensitive or BCRP-transfected multidrug-resistant MDA-MB-231 brea…
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine.
2018
For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study wer…
Multifactorial Modes of Action of Arsenic Trioxide in Cancer Cells as Analyzed by Classical and Network Pharmacology
2018
Arsenic trioxide is a traditional remedy in Chinese Medicine since ages. Nowadays, it is clinically used to treat acute promyelocytic leukemia (APL) by targeting PML/RARA. However, the drug’s activity is broader and the mechanisms of action in other tumor types remain unclear. In this study, we investigated molecular modes of action by classical and network pharmacological approaches. CEM/ADR5000 resistance leukemic cells were similar sensitive to As2O3 as their wild-type counterpart CCRF-CEM (resistance ratio: 1.88). Drug-resistant U87.MG ΔEGFR glioblastoma cells harboring mutated epidermal growth factor receptor were even more sensitive (collateral sensitive) than wild-type U87.MG cells (…
Engineering of a DNA Polymerase for Direct m6A Sequencing
2017
Methods for the detection of RNA modifications are of fundamental importance for advancing epitranscriptomics. N6-methyladenosine (m6A) is the most abundant RNA modification in mammalian mRNA and is involved in the regulation of gene expression. Current detection techniques are laborious and rely on antibody-based enrichment of m6A-containing RNA prior to sequencing, since m6A modifications are generally "erased" during reverse transcription (RT). To overcome the drawbacks associated with indirect detection, we aimed to generate novel DNA polymerase variants for direct m6A sequencing. Therefore, we developed a screen to evolve an RT-active KlenTaq DNA polymerase variant that sets a mark for…
Mutanome directed cancer immunotherapy
2015
Somatic mutations are important drivers of cancer development. Accumulating evidence suggests that a significant subset of mutations result in neo-epitopes recognized by autologous T cells and thus may constitute the Achilles' heel of tumor cells. T cells directed against mutations have been shown to have a key role in clinical efficacy of potent cancer immunotherapy modalities, such as adoptive transfer of autologous tumor infiltrating lymphocytes and immune checkpoint inhibitors. Whereas these findings strengthen the idea of a prominent role of neo-epitopes in tumor rejection, the systematic therapeutic exploitation of mutations was hampered until recently by the uniqueness of the reperto…
Positive Controls in Adults and Children Support That Very Few, If Any, New Neurons Are Born in the Adult Human Hippocampus.
2020
Adult hippocampal neurogenesis was originally discovered in rodents. Subsequent studies identified the adult neural stem cells and found important links between adult neurogenesis and plasticity, behavior, and disease. However, whether new neurons are produced in the human dentate gyrus (DG) during healthy aging is still debated. We and others readily observe proliferating neural progenitors in the infant hippocampus near immature cells expressing doublecortin (DCX), but the number of such cells decreases in children and few, if any, are present in adults. Recent investigations using dual antigen retrieval find many cells stained by DCX antibodies in adult human DG. This has been interprete…
Group analysis of ongoing EEG data based on fast double-coupled nonnegative tensor decomposition
2019
Abstract Background Ongoing EEG data are recorded as mixtures of stimulus-elicited EEG, spontaneous EEG and noises, which require advanced signal processing techniques for separation and analysis. Existing methods cannot simultaneously consider common and individual characteristics among/within subjects when extracting stimulus-elicited brain activities from ongoing EEG elicited by 512-s long modern tango music. New method Aiming to discover the commonly music-elicited brain activities among subjects, we provide a comprehensive framework based on fast double-coupled nonnegative tensor decomposition (FDC-NTD) algorithm. The proposed algorithm with a generalized model is capable of simultaneo…
Are the Motives for Food Choices Different in Orthorexia Nervosa and Healthy Orthorexia?
2019
Recent research points to the bidimensional nature of orthorexia, with one dimension related to interest in healthy eating (healthy orthorexia) and another dimension related to a pathological preoccupation with eating healthily (orthorexia nervosa). Research was needed to provide further support for this differentiation. We examined the food-choice motives related to both aspects of orthorexia. Participants were 460 students from a Spanish university who completed the Teruel Orthorexia Scale and the Food Choice Questionnaire. By means of structural equation modeling, we analyzed the relationship between orthorexia, food-choice motives, gender, body mass index, and age. The motives predictin…
Measuring Orthorexia Nervosa: Psychometric Limitations of the ORTO-15.
2017
AbstractOrthorexia nervosa has recently been defined as excessive preoccupation with healthy eating, causing significant nutritional deficiencies and social and personal impairments. The ORTO-15 is the most widely used instrument to evaluate orthorexia nervosa, although previous studies obtained inconsistent results about its psychometric properties, and there are no data on the Spanish version. Thus, the main objective of the present study was to analyze the psychometric properties of the Spanish adaptation of the ORTO-15. In order to cross-validate the results, two independent samples were used (Sample 1: n = 807, 74.1% women; Sample 2: n = 242, 63.2% women). The results did not support t…