Evaluation of QSAR models for predicting mutagenicity: outcome of the Second Ames/QSAR international challenge project.

Quantitative structure-activity relationship (QSAR) models are powerful in silico tools for predicting the mutagenicity of unstable compounds, impurities and metabolites that are difficult to examine using the Ames test. Ideally, Ames/QSAR models for regulatory use should demonstrate high sensitivity, low false-negative rate and wide coverage of chemical space. To promote superior model development, the Division of Genetics and Mutagenesis, National Institute of Health Sciences, Japan (DGM/NIHS), conducted the Second Ames/QSAR International Challenge Project (2020-2022) as a successor to the First Project (2014-2017), with 21 teams from 11 countries participating. The DGM/NIHS provided a curated training dataset of approximately 12,000 chemicals and a trial dataset of approximately 1,600 chemicals, and each participating team predicted the Ames mutagenicity of each trial chemical using various Ames/QSAR models. The DGM/NIHS then provided the Ames test results for trial chemicals to assist in model improvement. Although overall model performance on the Second Project was not superior to that on the First, models from the eight teams participating in both projects achieved higher sensitivity than models from teams participating in only the Second Project. Thus, these evaluations have facilitated the development of QSAR models.

Behavioral effects of a low molecular weight peptide fraction from Phaseolus vulgaris in rats.

Seminal studies stated that bean proteins are efficient neuronal tracers with affinity for brain tissue. A low molecular weight peptide fraction (<3kDa) from Phaseolus vulgaris (PV3) was previously reported to be antioxidant, non-cytotoxic, and capable of reducing reactive oxygen species and increasing nitric oxide in cells. We evaluated the effects of PV3 (5, 50, 100, 500, and 5000 µg/kg) on behavior and the molecular routes potentially involved. Acute and chronic PV3 treatments were performed before testing Wistar rats: i) in the elevated plus-maze (EPM) to assess the anxiolytic-like effect; ii) in the open field (OF) to evaluate locomotion and exploration; and iii) for depression-like behavior in forced swimming (FS). Catecholaminergic involvement was tested using the tyrosine hydroxylases (TH) enzyme inhibitor, α-methyl-DL-tyrosine (AMPT). Brain areas of chronically treated groups were dissected to assess: i) lipid peroxidation (LPO); ii) carbonylated proteins (CP); iii) superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. Neuronal nitric oxide synthases (nNOS) and argininosuccinate synthase (ASS) protein expression was evaluated by western blotting. Acute treatment with PV3 increased the frequency and time spent in the EPM open arms, suggesting anxiolysis. PV3 increased crossing episodes in the OF. These PV3 effects on anxiety and locomotion were absent in the chronically treated group. Acute and chronic PV3 treatments reduced the immobility time in the FS test, suggesting an antidepressant effect. TH inhibition by AMPT reverted acute PV3 effects. PV3 decreased LPO and CP levels and SOD and CAT activities, whereas nNOS and ASS were reduced in few brain areas. In conclusion, PV3 displayed central antioxidant actions that are concomitant to catecholaminergic-dependent anxiolytic and antidepressant effects.

Behavioral effects of a low molecular weight peptide fraction from Phaseolus vulgaris in rats

Seminal studies stated that bean proteins are efficient neuronal tracers with affinity for brain tissue. A low molecular weight peptide fraction (<3kDa) from Phaseolus vulgaris (PV3) was previously reported to be antioxidant, non-cytotoxic, and capable of reducing reactive oxygen species and increasing nitric oxide in cells. We evaluated the effects of PV3 (5, 50, 100, 500, and 5000 µg/kg) on behavior and the molecular routes potentially involved. Acute and chronic PV3 treatments were performed before testing Wistar rats: i) in the elevated plus-maze (EPM) to assess the anxiolytic-like effect; ii) in the open field (OF) to evaluate locomotion and exploration; and iii) for depression-like behavior in forced swimming (FS). Catecholaminergic involvement was tested using the tyrosine hydroxylases (TH) enzyme inhibitor, α-methyl-DL-tyrosine (AMPT). Brain areas of chronically treated groups were dissected to assess: i) lipid peroxidation (LPO); ii) carbonylated proteins (CP); iii) superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. Neuronal nitric oxide synthases (nNOS) and argininosuccinate synthase (ASS) protein expression was evaluated by western blotting. Acute treatment with PV3 increased the frequency and time spent in the EPM open arms, suggesting anxiolysis. PV3 increased crossing episodes in the OF. These PV3 effects on anxiety and locomotion were absent in the chronically treated group. Acute and chronic PV3 treatments reduced the immobility time in the FS test, suggesting an antidepressant effect. TH inhibition by AMPT reverted acute PV3 effects. PV3 decreased LPO and CP levels and SOD and CAT activities, whereas nNOS and ASS were reduced in few brain areas. In conclusion, PV3 displayed central antioxidant actions that are concomitant to catecholaminergic-dependent anxiolytic and antidepressant effects.

COSMOS next generation - A public knowledge base leveraging chemical and biological data to support the regulatory assessment of chemicals.

The COSMOS Database (DB) was originally established to provide reliable data for cosmetics-related chemicals within the COSMOS Project funded as part of the SEURAT-1 Research Initiative. The database has subsequently been maintained and developed further into COSMOS Next Generation (NG), a combination of database and in silico tools, essential components of a knowledge base. COSMOS DB provided a cosmetics inventory as well as other regulatory inventories, accompanied by assessment results and in vitro and in vivo toxicity data. In addition to data content curation, much effort was dedicated to data governance - data authorisation, characterisation of quality, documentation of meta information, and control of data use. Through this effort, COSMOS DB was able to merge and fuse data of various types from different sources. Building on the previous effort, the COSMOS Minimum Inclusion (MINIS) criteria for a toxicity database were further expanded to quantify the reliability of studies. COSMOS NG features multiple fingerprints for analysing structure similarity, and new tools to calculate molecular properties and screen chemicals with endpoint-related public profilers, such as DNA and protein binders, liver alerts and genotoxic alerts. The publicly available COSMOS NG enables users to compile information and execute analyses such as category formation and read-across. This paper provides a step-by-step guided workflow for a simple read-across case, starting from a target structure and culminating in an estimation of a NOAEL confidence interval. Given its strong technical foundation, inclusion of quality-reviewed data, and provision of tools designed to facilitate communication between users, COSMOS NG is a first step towards building a toxicological knowledge hub leveraging many public data systems for chemical safety evaluation. We continue to monitor the feedback from the user community at support@mn-am.com.

Oxidonitrergic and antioxidant effects of a low molecular weight peptide fraction from hardened bean (Phaseolus vulgaris) on endothelium.

About 3000 tons of beans are not used in human food due to hardening. Several studies on bean-derived bioactive peptides have shown potential to treat some diseases, including those relying on oxidative dysfunctions. We assessed the effects of peptides extracted from hardened bean Phaseolus vulgaris (PV) on reactive oxygen species (ROS) and nitric oxide (NO) production, cytotoxic and cytoprotective effects in endothelial cells, and oxidonitrergic-dependent vasodilating effects. Extract was composed by peptide fraction <3 kDa (PV3) from hardened common bean residue. PV3 sequences were obtained and analyzed with bioinformatics. Human umbilical vein endothelial cells were treated with 10, 20, 30, and 250 µg/mL PV3. Oxidative stress was provoked by 3% H2O2. Cytotoxicity and cytoprotective effects were evaluated by MTT assay, whereas, ROS and NO were quantified using DHE and DAF-FM fluorescent probes by confocal microscopy. NO- and endothelium-dependent vasodilating effects of PV3 were assessed in isolated aortic rings. We found 35 peptides with an average mass of 1.14 kDa. There were no cell deaths with 10 and 20 µg/mL PV3. PV3 at 30 µg/mL increased cell viability, while cytotoxicity was observed only with 250 µg/mL PV3. PV3 at 10 µg/mL was able to protect cells from oxidative stress. PV3 also increased NO release without causing cell death. It also reduced relative ROS production induced by H2O2. PV3 vasodilating effects relied on endothelium-dependent NO release. PV3 obtained from low-commercial-value bean displays little cytotoxicity and exerts antioxidant effects, whereas it increases endothelial NO release.

Oxidonitrergic and antioxidant effects of a low molecular weight peptide fraction from hardened bean (Phaseolus vulgaris) on endothelium

About 3000 tons of beans are not used in human food due to hardening. Several studies on bean-derived bioactive peptides have shown potential to treat some diseases, including those relying on oxidative dysfunctions. We assessed the effects of peptides extracted from hardened bean Phaseolus vulgaris (PV) on reactive oxygen species (ROS) and nitric oxide (NO) production, cytotoxic and cytoprotective effects in endothelial cells, and oxidonitrergic-dependent vasodilating effects. Extract was composed by peptide fraction <3 kDa (PV3) from hardened common bean residue. PV3 sequences were obtained and analyzed with bioinformatics. Human umbilical vein endothelial cells were treated with 10, 20, 30, and 250 µg/mL PV3. Oxidative stress was provoked by 3% H2O2. Cytotoxicity and cytoprotective effects were evaluated by MTT assay, whereas, ROS and NO were quantified using DHE and DAF-FM fluorescent probes by confocal microscopy. NO- and endothelium-dependent vasodilating effects of PV3 were assessed in isolated aortic rings. We found 35 peptides with an average mass of 1.14 kDa. There were no cell deaths with 10 and 20 μg/mL PV3. PV3 at 30 μg/mL increased cell viability, while cytotoxicity was observed only with 250 μg/mL PV3. PV3 at 10 μg/mL was able to protect cells from oxidative stress. PV3 also increased NO release without causing cell death. It also reduced relative ROS production induced by H2O2. PV3 vasodilating effects relied on endothelium-dependent NO release. PV3 obtained from low-commercial-value bean displays little cytotoxicity and exerts antioxidant effects, whereas it increases endothelial NO release.

Nursing telematics education: a critical success factor to the "best practice".

This communication aims to help demonstrating that nurses education and training, in what information and telecommunications technologies are concerned, is a critical success factor in the achievement of a strategic goal: the "best practice" in nursing. This goal is seen from the formal perspective of the quality of the nursing care process. Simultaneously, one makes a methodological approach by employing a strategical planning technique in the nursing context.