From logical forms to SPARQL query with GETARUNS

We present a system for Question Answering which computes a prospective answer from Logical Forms produced by a full-fledged NLP for text understanding, and then maps the result onto schemata in SPARQL to be used for accessing the Semantic Web. As an intermediate step, and whenever there are complex concepts to be mapped, the system looks for a corresponding amalgam in YAGO classes. It is just by the internal structure of the Logical Form that we are able to produce a suitable and meaningful context for concept disambiguation. Logical Forms are the final output of a complex system for text understanding - GETARUNS - which can deal with different levels of syntactic and semantic ambiguity in the generation of a final structure, by accessing computational lexical equipped with sub-categorization frames and appropriate selectional restrictions applied to the attachment of complements and adjuncts. The system also produces pronominal binding and instantiates the implicit arguments, if needed, in order to complete the required Predicate Argument structure which is licensed by the semantic component

Traditional Ayurvedic medicines : pathway to develop anti-cancer drugs

Ayurveda, “life knowledge”, is an ancient Indian traditional medical system, which has been practiced for >5000 years and still in use with the same importance among many cultural tribes in Indian sub-continents. Ayurvedic medicine is a unique holistic approach to treatment where herbal medicines, special diets, yoga and relaxation methods, and lifestyle management are key strategies for curing various chronic diseases like diabetes, cancer, cardiovascular, neurological disorders and many other. Cancer is biologically complex disease, causing local damage and inflammation of cells due to lack of full response in a specific tissue that is responsible to maintain cellular differentiation, survival, proliferation and death. Studies have suggested that bioactive phytochemicals present in Ayurvedic plants (fruits, vegetables and herbs) mediate their effects by inhibiting some of the recently identified inflammatory pathways. Nevertheless, for successful implementation of Ayurvedic principles to drug discovery, major concerns relating to proportion, practicality, safety and drug interactions and possible side effects of newly developed Ayurvedic drugs and formulations need to be addressed. Systematic investigations of Ayurvedic drugs, employing contemporary scientific tools and methods, are expected to lead to the discoveries of major significance. Explorations involving studies of bioactive phytochemicals, their side effects, the specific potential targets and the mechanisms of action would transform this traditional therapeutic approach to standard Ayurvedic drug discovery which would be accepted and embraced by global populations. Current review focuses on the importance of anti-cancer drug discovery from Ayurvedic medicines in the modern context, ongoing improvements and major achievements in the field over the past decade or two

Antioxidant and anti-inflammatory activities of selected medicinal plants containing phenolic and flavonoid compounds

The antioxidant, anti-inflammatory, and cytotoxic activities of water and ethanol extracts of 14 Chinese medicinal plants were investigated and also their total phenolics and flavonoid contents measured. The antioxidant activity was evaluated in a biological assay using Saccharomyces cerevisiae, whereas the radical scavenging activity was measured using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Total phenolics and flavonoid contents were estimated by Folin–Ciocalteu and aluminum chloride methods, respectively. The anti-inflammatory activities of the plant extracts were determined by measuring the inhibition of production of nitric oxide (NO) and TNF-α in LPS and IFN-γ activated RAW 264.7 macrophages. Their cytotoxic activities against macrophages were determined by Alamar Blue assay. Four plants, namely, Scutellaria baicalensis, Taxillus chinensis, Rheum officinale, and Sophora japonica, showed significant antioxidant activity in both yeast model and also free radical scavenging methods. The ethanol extract of S. japonica showed highest levels of phenolics and flavonoids (91.33 GAE mg/g and 151.86 QE mg/g, respectively). A positive linear correlation between antioxidant activity and the total phenolics and flavonoid contents indicates that these compounds are likely to be the main antioxidants contributing to the observed activities. Five plant extracts (S. baicalensis, T. chinensis, S. japonica, Mahonia fortunei, and Sophora flavescens) exhibited significant anti-inflammatory activity by in vitro inhibition of the production of NO and TNF-α with low IC50 values. These findings suggest that some of the medicinal herbs studied in this paper are good sources of antioxidants

Discovery and mechanistic studies of cytotoxic cyclotides from the medicinal herb Hybanthus enneaspermus

Cyclotides are plant-derived peptides characterized by an ∼30-amino acid-long cyclic backbone and a cystine knot motif. Cyclotides have diverse bioactivities, and their cytotoxicity has attracted significant attention for its potential anticancer applications. Hybanthus enneaspermus (Linn) F. Muell is a medicinal herb widely used in India as a libido enhancer, and a previous study has reported that it may contain cyclotides. In the current study, we isolated 11 novel cyclotides and 1 known cyclotide (cycloviolacin O2) from H. enneaspermus and used tandem MS to determine their amino acid sequences. We found that among these cyclotides, hyen C comprises a unique sequence in loops 1, 2, 3, 4, and 6 compared with known cyclotides. The most abundant cyclotide in this plant, hyen D, had anticancer activity comparable to that of cycloviolacin O2, one of the most cytotoxic known cyclotides. We also provide mechanistic insights into how these novel cyclotides interact with and permeabilize cell membranes. Results from surface plasmon resonance experiments revealed that hyen D, E, L, and M and cycloviolacin O2 preferentially interact with model lipid membranes that contain phospholipids with phosphatidyl-ethanolamine headgroups. The results of a lactate dehydrogenase assay indicated that exposure to these cyclotides compromises cell membrane integrity. Using live-cell imaging, we show that hyen D induces rapid membrane blebbing and cell necrosis. Cyclotide-membrane interactions correlated with the observed cytotoxicity, suggesting that membrane permeabilization and disintegration underpin cyclotide cytotoxicity. These findings broaden our knowledge on the indigenous Indian herb H. enneaspermus and have uncovered cyclotides with potential anticancer activity.</p

Understanding the Diversity and Distribution of Cyclotides from Plants of Varied Genetic Origin

Cyclotides are a large family of naturally occurring plant-derived macrocyclic cystine-knot peptides, with more than 400 having been identified in species from the Violaceae, Rubiaceae, Cucurbitaceae, Fabaceae, and Solanaceae families. Nevertheless, their specialized distribution within the plant kingdom remains poorly understood. In this study, the diversity of cyclotides was explored through the screening of 197 plants belonging to 43 different families. In total, 28 cyclotides were sequenced from 15 plant species, one of which belonged to the Rubiaceae and 14 to the Violaceae. Every Violaceae species screened contained cyclotides, but they were only sparsely represented in Rubiaceae and nonexistent in other families. The study thus supports the hypothesis that cyclotides are ubiquitous in the Violaceae, and it adds to the list of plants found to express kalata S and cycloviolacin O12. Finally, previous studies suggested the existence of cyclotide isoforms with either an Asn or an Asp at the C-terminal processing site of the cyclotide domain within the precursor proteins. Here we found that despite the discovery of a few cyclotides genuinely containing an Asp in loop 6 as evidenced by gene sequencing, deamidation of Asn during enzymatic digestion resulted in the artifactual presence of Asp isoforms. This result is consistent with studies suggesting that peptides can undergo deamidation after being subjected to external factors, including pH, temperature, and enzymatic digestion

Screening for natural inhibitors in Chinese medicinal plants against Glycogen synthase kinase 3β (GSK-3β)

Background: The aim of this study is screening Chinese medicinal plants for inhibitors of Glycogen synthase kinase-3 (GSK-3). GSK-3 is a proline/serine protein kinase ubiquitously expressed and involved in many cellular signalling pathways. GSK-3 has emerged as one of the most attractive therapeutic targets for the development of selective inhibitors as promising new drugs for numerous pathologies, including neurodegenerative diseases and type II diabetes. Thus, the use of GSK-3 inhibitors is one of the most promising therapeutic strategies for the future treatment of these potentially life threatening diseases. Materials and Methods: In the aim of discovery of potential inhibitors, 42 traditional Chinese medicinal plants were screened against GSK-3β which were selected based on their folklore use. The selected plant materials were extracted with ethanol and water. In vitro assay was carried out to evaluate the inhibition of human GSK-3~. The Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was conducted with immortalized Hepatocyte cell line (Fa2N4) to evaluate the cytotoxicity of the plant material. Results: Many new ethanol and aqueous extracts showed significant inhibitory activity against GSK-3~ with moderate or no cytotoxicity. Water extracts of Prunella vulgaris, Rabdosia rubescens and Sarcandra glabre have exhibited highest inhibition against GSK-3β. This in turn was supported by the fact that a good correlation exists between GSK-3β inhibitory activity and antioxidant content of the extracts. Conclusion: Considering the potent activity of P. vulgaris, R. rubescens and S. glabre, further isolation and characterization of individual bioactive compounds is recommended for the discovery of potent natural inhibitors of GSK-3β

Redesigned spider peptide with improved antimicrobial and anticancer properties

Gomesin, a disulfide-rich antimicrobial peptide produced by the Brazilian spider Acanthoscurria gomesiana, has been shown to be potent against Gram-negative bacteria and to possess selective anticancer properties against melanoma cells. In a recent study, a backbone cyclized analogue of gomesin was shown to be as active but more stable than its native form. In the current study, we were interested in improving the antimicrobial properties of the cyclic gomesin, understanding its selectivity toward melanoma cells and elucidating its antimicrobial and anticancer mode of action. Rationally designed analogues of cyclic gomesin were examined for their antimicrobial potency, selectivity toward cancer cells, membrane-binding affinity, and ability to disrupt cell and model membranes. We improved the activity of cyclic gomesin by 10-fold against tested Gram-negative and Gram-positive bacteria without increasing toxicity to human red blood cells. In addition, we showed that gomesin and its analogues are more toxic toward melanoma and leukemia cells than toward red blood cells and act by selectively targeting and disrupting cancer cell membranes. Preference toward some cancer types is likely dependent on their different cell membrane properties. Our findings highlight the potential of peptides as antimicrobial and anticancer leads and the importance of selectively targeting cancer cell membranes for drug development

Effects of cyclotides against cutaneous infections caused by Staphylococcus aureus

The main bacterium associated with skin infection is Staphylococcus aureus, occurring especially in infections acquired via surgical wounds, commonly leading to lethal hospital-acquired infections, emphasizing the importance of identifying new antimicrobial compounds. Among them, cyclotides have gained interest due to their high stability and multifunctional properties. Here, cycloviolacin 2 (CyO2) and kalata B2 (KB2) were evaluated to determinate their anti-staphylococcal activities using a subcutaneous infection model. Anti-staphylococcal activities of 50 mM for KB2 and 25 mM for CyO2 were detected with no cytotoxic activities against RAW 264.7 monocytes. In the in vivo assays, both cyclotides reduced bacterial load and CyO2 demonstrated an increase in the phagocytosis index, suggesting that the CyO2 in vivo anti-staphylococcal activity may be associated with phagocytic activity, additionally to direct anti-pathogenicactivity. (C) 2014 Elsevier Inc. All rights reserved

Antiproliferative and apoptotic potential of Chinese medicinal plants against MCF-7 (luminal A), HCC1954 (HER2+) and Hs578t breast cancer cells

Breast cancer is a significant cause of death among women worldwide. Medicinal plant extracts with large amounts of polyphenolic compounds, which are antioxidants, can have an important role in cancer prevention. The purpose of this study is to test in vitro the antiproliferative activities of the ethanolic and aqueous extracts of selected Chinese medicinal plants against three human breast cancer cell lines [MCF-7 (luminal A); HCC1954 (HER2+); Hs578t (triple negative)] and one normal cell line [MCF-10A]. The ethanolic extracts of Polygonum cuspidatum, Rheum officinale, Eucomia ulmoides, Lysinachia christinae, Rhizoma Alpinae, Sarcandra glabre, Scutellaria baicalensis, Smilax glabra and Atractyloides macrocephala showed potent anti-cancer activity with little or no toxicity to normal cells. The apoptosis test was carried out for one of the active plant extract (S. baicalensis) and the results were found to be very significant. The plant extracts investigated in this study have significant anticancer activity against the breast cancer cell lines tested. Further investigation is required to isolate and elucidate the structure of the compounds responsible for the observed activity