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Water extracts from sea lavender (Limonium algarvense Erben) plants cultivated in greenhouse conditions and irrigated with freshwater and saline aquaculture effluents were evaluated for metabolomics by liquid chromatography-tandem high-resolution mass spectrometry (LC-HRMS/MS), and functional properties by in vitro and ex vivo methods. In vitro antioxidant methods included radical scavenging of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric-reducing antioxidant power (FRAP), and copper and iron chelating assets. Flowers’ extracts had the highest compounds’ diversity (flavonoids and its derivatives) and strongest in vitro antioxidant activity. These extracts were further tested for ex vivo antioxidant properties by oxidative haemolysis inhibition (OxHLIA), lipid peroxidation inhibition by thiobarbituric acid reactive substances (TBARS) formation, and anti-melanogenic, anti-tyrosinase, anti-inflammation, and cytotoxicity. Extract from plants irrigated with 300 mM NaCl was the most active towards TBARS (IC50 = 81 µg/mL) and tyrosinase (IC50 = 873 µg/mL). In OxHLIA, the activity was similar for fresh- and saltwater-irrigated plants (300 mM NaCl; IC50 = 136 and 140 µg/mL, respectively). Samples had no anti-inflammatory and anti-melanogenic abilities and were not toxic. Our results suggest that sea lavender cultivated under saline conditions could provide a flavonoid-rich water extract with antioxidant and anti-tyrosinase properties with potential use as a food preservative or as a functional ingredient in herbal supplements. [ABSTRACT FROM AUTHOR]

Consumers are very concerned with following a healthy diet, along with some precautions that may influence environmental impact. Solanum melongena L. is one of the most consumed vegetables due to its excellent nutritional value and antioxidant action. Associated with its high consumption, considerable amounts of agro-food wastes are produced. This work targets the valorization of this matrix, through the use of its bio-residues to study the obtention of coloring pigments, applying innovative technologies. Its nutritional value, chemical composition, and bioactive potential were evaluated, and the ultrasound-assisted extraction to obtain coloring pigments of high industrial interest was optimized. Considering the results, low contents of fat and carbohydrates and energy value were evident, as well as the presence of compounds of interest (free sugars, organic acids, unsaturated fatty acids, and phenolic acids). In addition, the antioxidant and antimicrobial potential was detected. Response surface methodology was performed to optimize the extraction of natural pigments, showing a concentration of 11.9 mg/g of anthocyanins/g of extract, applying optimal conditions of time, solvent, and solid/liquid ratio of 0.5 min, 68.2% (v/v) and 5 g/L, respectively. S. melongena proved to be a good source of bioactive compounds and natural pigments, which can generate great interest in the food industry. [ABSTRACT FROM AUTHOR]

In the present work, the knowledge on target proteins of standard antibiotics was extended to antimicrobial mushroom compounds. Docking studies were performed for 34 compounds in order to evaluate their affinity to bacterial proteins that are known targets for some antibiotics with different mechanism of action: inhibitors of cell wall synthesis, inhibitors of protein synthesis, inhibitors of nucleic acids synthesis and antimetabolites. After validation of the molecular docking approach, virtual screening of all the compounds was performed against penicillin binding protein 1a (PBP1a), alanine racemase (Alr), D-alanyl-D-alanine synthetase (Ddl), isoleucyl-tRNA sinthetase (IARS), DNA gyrase subunit B, topoisomerase IV (TopoIV), dihydropteroate synthetase (DHPS) and dihydrofolate reductase (DHFR) using AutoDock4. Overall, it seems that for the selected mushroom compounds (namely, enokipodins, ganomycins and austrocortiluteins) the main mechanism of the action is the inhibition of cell wall synthesis, being Alr and Ddl probable protein targets. [ABSTRACT FROM AUTHOR]

Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%–59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10–15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC. [ABSTRACT FROM AUTHOR]

Background: Virtual screening of small molecules using molecular docking has become an important tool in drug discovery. However, large scale virtual screening is time demanding and usually requires dedicated computer clusters. There are a number of software tools that perform virtual screening using AutoDock4 but they require access to dedicated Linux computer clusters. Also no software is available for performing virtual screening with Vina using computer clusters. In this paper we present MOLA, an easy-to-use graphical user interface tool that automates parallel virtual screening using AutoDock4 and/or Vina in bootable non-dedicated computer clusters. Implementation: MOLA automates several tasks including: ligand preparation, parallel AutoDock4/Vina jobs distribution and result analysis. When the virtual screening project finishes, an open-office spreadsheet file opens with the ligands ranked by binding energy and distance to the active site. All results files can automatically be recorded on an USB-flash drive or on the hard-disk drive using VirtualBox. MOLA works inside a customized Live CD GNU/Linux operating system, developed by us, that bypass the original operating system installed on the computers used in the cluster. This operating system boots from a CD on the master node and then clusters other computers as slave nodes via ethernet connections. Conclusion: MOLA is an ideal virtual screening tool for non-experienced users, with a limited number of multiplatform heterogeneous computers available and no access to dedicated Linux computer clusters. When a virtual screening project finishes, the computers can just be restarted to their original operating system. The originality of MOLA lies on the fact that, any platform-independent computer available can he added to the cluster, without ever using the computer hard-disk drive and without interfering with the installed operating system. With a cluster of 10 processors, and a potential maximum speed-up of 10x, the parallel algorithm of MOLA performed with a speed-up of 8,64x using AutoDock4 and 8,60x using Vina. [ABSTRACT FROM AUTHOR]

Juglans regia L. (walnut) green husks are an important fraction of waste resulting from the walnut production, thus representing an interesting natural matrix to explore as a source of bioactive compounds. In this work, the hydroethanolic extract of walnut green husks was studied considering the phytochemical composition and the biological activity using different cell model assays, most of them evaluated for the first time for this matrix. From the HPLC-DAD-ESI/MS n analysis, sixteen compounds were identified, being the extract mostly composed of naphthalene derivatives (including tetralone derivatives) and less abundant in phenolic compounds (hydroxycinnamic acids and flavonols). The cytotoxic potential of the extract was assessed against tumour (MCF-7, NCI-H460, HeLa and HepG2) and non-tumour (PLP2) cell lines. Moreover, the antioxidant activity of the extract was evaluated by inhibition of the oxidative haemolysis (OxHLIA) and the formation of thiobarbituric acid reactive substances (TBARS), and the anti-inflammatory potential by the inhibition of the NO production by the RAW264.7 cell culture. The antibacterial effects of the extract were also evaluated against Gram-negative and Gram-positive bacteria. The results obtained represent a stepping stone for the development of future applications using walnut green husks as a source of added value compounds with bioactive potential., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Pleurotus sajor-caju (PSC) is an edible mushroom used in food supplements, presenting antitumor properties through induction of cell death pathways. The PSC potential against colorectal cancer was analyzed by exposing HCT116 wt cells to different PSC extracts. The PSC n-hexane extract (PSC-hex) showed the highest cytotoxicity effect (IC 50 value 0.05 mg/mL). The observed cytotoxicity was then associated to apoptosis-promoting and cell cycle-arrest pathways. PSC-hex was able to induce apoptosis related to breakdown of mitochondrial membrane potential and ROS generation. The absence of cytotoxicity in HTC116 -p53 and HTC116 -Bax cells, alongside with an increase in p53, Bax and Caspase-3 expression, and decrease in Bcl-2 expression, supports that the pro-apoptotic effect is probably induced through a p53 associated pathway. PSC-hex induced cell cycle arrest at G2/M in HCT116 wt without cytotoxicity in HTC116 -p21  cells. These findings suggest that a p21/p53 cell cycle regulation pathway is probably disrupted by compounds present on PSC-hex. Identification of the major components was then performed with ergosta-5,7,22-trien-3β-ol representing 30.6% of total weight. In silico docking studies of ergosta-5,7,22-trien-3β against Bcl-2 were performed and results show a credible interaction with the Bcl-2 hydrophobic cleft. The results show that PSC-hex can be used as supplementary food for adjuvant therapy in colorectal carcinoma., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In some human cancer cases, the activity of p53 is inhibited by over-expressed Mdm2. The Mdm2 acts as an ubiquitin ligase, resulting in p53 ubiquitination and subsequent p53 proteasomal degradation. The disruption of the Mdm2-p53 interaction using small-molecule inhibitors is recognized as a promising strategy for anti-cancer drug design. Mushrooms are an important source of powerful compounds with anti-tumour properties. In this study, the first virtual screening of low molecular weight compounds present in mushroom is presented as potential Mdm2 inhibitors. A re-docking and cross-docking method was used to validate the virtual screening protocol. The steroids: ganoderic acids X (K(i) = 16nM), Y (K(i) = 22nM) and F (K(i) = 69nM); 5,6-epoxy-24(R)-methylcholesta-7,22-dien-3β-ol (K(i) = 74nM) and polyporenic acid C (K(i) = 59nM) stand out as the top ranked potential inhibitors of Mdm2. The docking pose of the most promising compounds were carefully analysed and the information provided shows several interesting starting points for further development of Mdm2 inhibitors.