Search results for "SSA"
showing 10 items of 6161 documents
Modification of DNA structure by reactive nitrogen species as a result of 2-methoxyestradiol–induced neuronal nitric oxide synthase uncoupling in met…
2020
Abstract 2-methoxyestradiol (2-ME) is a physiological anticancer compound, metabolite of 17β-estradiol. Previously, our group evidenced that from mechanistic point of view one of anticancer mechanisms of action of 2-ME is specific induction and nuclear hijacking of neuronal nitric oxide synthase (nNOS), resulting in local generation of nitro-oxidative stress and finally, cancer cell death. The current study aims to establish the substantial mechanism of generation of reactive nitrogen species by 2-ME. We further achieved to identify the specific reactive nitrogen species involved in DNA-damaging mechanism of 2-ME. The study was performed using metastatic osteosarcoma 143B cells. We detected…
Genotoxicity testing: Comparison of the γH2AX focus assay with the alkaline and neutral comet assays
2017
Genotoxicity testing relies on the quantitative measurement of adverse effects, such as chromosome aberrations, micronuclei, and mutations, resulting from primary DNA damage. Ideally, assays will detect DNA damage and cellular responses with high sensitivity, reliability, and throughput. Several novel genotoxicity assays may fulfill these requirements, including the comet assay and the more recently developed γH2AX assay. Although they are thought to be specific for genotoxicants, a systematic comparison of the assays has not yet been undertaken. In the present study, we compare the γH2AX focus assay with the alkaline and neutral versions of the comet assay, as to their sensitivities and li…
Inherent and toxicant-provoked reduction in DNA repair capacity: A key mechanism for personalized risk assessment, cancer prevention and intervention…
2018
Abstract Genomic investigations reveal novel evidence which indicates that genetic predisposition and inherent drug response are key factors for development of cancer and for poor response to therapy. However, mechanisms for these outcomes and interactions with environmental factors have not been well-characterized. Therefore, cancer risk, prevention, intervention and prognosis determinations have still mainly been based on population, rather than on individualized, evaluations. The objective of this review was to demonstrate that a key mechanism which contributes to the determination is inherent and/or toxicant-provoked reduction in DNA repair capacity. In addition, functional and quantita…
NMDA Receptors Regulate the Structural Plasticity of Spines and Axonal Boutons in Hippocampal Interneurons
2017
N-methyl-D-aspartate receptors (NMDARs) are present in both pyramidal neurons and interneurons of the hippocampus. These receptors play an important role in the adult structural plasticity of excitatory neurons, but their impact on the remodeling of interneurons is unknown. Among hippocampal interneurons, somatostatin-expressing cells located in the stratum oriens are of special interest because of their functional importance and structural characteristics: they display dendritic spines, which change density in response to different stimuli. In order to understand the role of NMDARs on the structural plasticity of these interneurons, we have injected acutely MK-801, an NMDAR antagonist, to …
Fishing anti-inflammatories from known drugs: In silico repurposing, design, synthesis and biological evaluation of bisacodyl analogues
2017
Herein is described in silico repositioning, design, synthesis, biological evaluation and structure-activity relationship (SAR) of an original class of anti-inflammatory agents based on a polyaromatic pharmacophore structurally related to bisacodyl (BSL) drug used in therapeutic as laxative. We describe the potential of TOMOCOMD-CARDD methods to find out new anti-inflammatory drug-like agents from a diverse series of compounds using the total and local atom based bilinear indices as molecular descriptors. The models obtained were validated by biological studies, identifying BSL as the first anti-inflammatory lead-like using in silico repurposing from commercially available drugs. Several bi…
Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury
2017
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…
Identification of NF-κB as Determinant of Posttraumatic Stress Disorder and Its Inhibition by the Chinese Herbal Remedy Free and Easy Wanderer
2017
Posttraumatic stress disorder (PTSD) is a mental disorder developing after exposure to traumatic events. Although psychotherapy reveals some therapeutic effectiveness, clinically sustainable cure is still uncertain. Some Chinese herbal formulae are reported to work well clinically against mental diseases in Asian countries, but the safety and their mode of action are still unclear. In this study, we investigated the mechanisms of Chinese remedy free and easy wanderer (FAEW) on PTSD. We used a reverse pharmacology approach combining clinical data to search for mechanisms of PTSD with subsequent in vitro verification and bioinformatics techniques as follows: (1) by analyzing microarray-based …
Are children more paternalistic than their mothers when choosing snacks?
2016
International audience; This paper focuses on an experiment in which mothers and their child separately chose between relatively healthy foods (flasks of stewed apples) and relatively unhealthy foods (candy bars). Each participant first filled up a first bag for her/himself, and then, a second one for the other person of the dyad. A simple nutritional message on vitamins and sugar contents of foods was then provided, and subsequently each participant filled up a third bag for her/himself and a fourth one for the other person of the dyad. The results show that before revealing the nutritional message, mothers are, on average, "indulgent", which means that they choose a lower number of relati…
The emergence of loss of efficacy during antidepressant drug treatment for major depressive disorder: An integrative review of evidence, mechanisms, …
2018
The re-emergence (i.e. ‘breakthrough’) of depressive symptoms despite maintenance treatment of depression with antidepressant drugs is a complex clinical phenomenon referred to as tolerance. Herein we critically appraise evidence from both pre-clinical and clinical studies, focusing on putative mechanisms as well as clinical correlates and implications of the emergence tolerance during antidepressant treatment for major depressive disorder (MDD). It is firstly unclear to what extent this phenotype reflects a pharmacological effect of an antidepressant, is driven by non-adherence, is a marker of latent bipolarity or another comorbidity, a marker of neuroprogression of the underlying disorder…
Melatonin Treatment Alters Biological and Immunomodulatory Properties of Human Dental Pulp Mesenchymal Stem Cells via Augmented Transforming Growth F…
2020
Melatonin is an endogenous neurohormone with well-reported anti-inflammatory and antioxidant properties, but the direct biological and immunomodulatory effects of melatonin on human dental pulp stem cells (hDPSCs) has not been fully elucidated. The aim of this study was to evaluate the influence of melatonin on the cytocompatibility, proliferation, cell migration, odontogenic differentiation, mineralized nodule formation, and immunomodulatory properties of hDPSCs.To address the melatonin biological effects on hDPSCs, the cytocompatibility, proliferation, cell migration, odontogenic differentiation, mineralized nodule formation, and immunomodulatory properties of hDPSCs after melatonin treat…