101 research outputs found

    Antioxidant and DPPH-Scavenging Activities of Compounds and Ethanolic Extract of the Leaf and Twigs of Caesalpinia bonduc L. Roxb.

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    Antioxidant effects of ethanolic extract of Caesalpinia bonduc and its isolated bioactive compounds were evaluated in vitro. The compounds included two new cassanediterpenes, 1α,7α-diacetoxy-5α,6β-dihydroxyl-cass-14(15)-epoxy-16,12-olide (1)and 12α-ethoxyl-1α,14β-diacetoxy-2α,5α-dihydroxyl cass-13(15)-en-16,12-olide(2); and others, bonducellin (3), 7,4’-dihydroxy-3,11-dehydrohomoisoflavanone (4), daucosterol (5), luteolin (6), quercetin-3-methyl ether (7) and kaempferol-3-O-α-L-rhamnopyranosyl-(1Ç2)-β-D-xylopyranoside (8). The antioxidant properties of the extract and compounds were assessed by the measurement of the total phenolic content, ascorbic acid content, total antioxidant capacity and 1-1-diphenyl-2-picryl hydrazyl (DPPH) and hydrogen peroxide radicals scavenging activities.Compounds 3, 6, 7 and ethanolic extract had DPPH scavenging activities with IC50 values of 186, 75, 17 and 102 μg/ml respectively when compared to vitamin C with 15 μg/ml. On the other hand, no significant results were obtained for hydrogen peroxide radical. In addition, compound 7 has the highest phenolic content of 0.81±0.01 mg/ml of gallic acid equivalent while compound 8 showed the highest total antioxidant capacity with 254.31±3.54 and 199.82±2.78 μg/ml gallic and ascorbic acid equivalent respectively. Compound 4 and ethanolic extract showed a high ascorbic acid content of 2.26±0.01 and 6.78±0.03 mg/ml respectively.The results obtained showed the antioxidant activity of the ethanolic extract of C. bonduc and deduced that this activity was mediated by its isolated bioactive compounds

    Epilepsy

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    Epilepsy is the most common neurological disorder globally, affecting approximately 50 million people of all ages. It is one of the oldest diseases described in literature from remote ancient civilizations 2000-3000 years ago. Despite its long history and wide spread, epilepsy is still surrounded by myth and prejudice, which can only be overcome with great difficulty. The term epilepsy is derived from the Greek verb epilambanein, which by itself means to be seized and to be overwhelmed by surprise or attack. Therefore, epilepsy is a condition of getting over, seized, or attacked. The twelve very interesting chapters of this book cover various aspects of epileptology from the history and milestones of epilepsy as a disease entity, to the most recent advances in understanding and diagnosing epilepsy

    Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples

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    Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions

    MOLECULAR PROFILING IN BREAST CANCER AND TOXICOGENOMICS

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    Indiana University-Purdue University Indianapolis (IUPUI)This dissertation presents a body of research that attempts to tackle the ‘overfitting’ problem for gene signature and biomarker development in two different aspects (mechanistically and computationally). In achievement of a deeper understanding of cancer molecular mechanisms, this study presents new approaches to derive gene signatures for various biological phenotypes, including breast cancer, in the context of well-defined and mechanistically associated biological pathways. We identified the pattern of gene expression in the cell cycle pathway can indeed serve as a powerful biomarker for breast cancer prognosis. We further built a predictive model for prognosis based on the cell cycle gene signature, and found our model to be more accurate than the Amsterdam 70-gene signature when tested with multiple gene expression datasets generated from several patient populations. Aside from demonstrating the effectiveness of dimensionality reduction, phenotypic dissection, and prognostic or diagnostic prediction, this approach also provides an alternative to the current methodology of identifying gene expression markers that links to biological mechanism. This dissertation also presents the development of a novel feature selection algorithm called Predictive Power Estimate Analysis (PPEA) to computationally tackle on overfitting. The algorithm iteratively apply a two-way bootstrapping procedure to estimate predictive power of each individual gene, and make it possible to construct a predictive model from a much smaller set of genes with the highest predictive power. Using DrugMatrix™ rat liver data, we identified genomic biomarkers of hepatic specific injury for inflammation, cell death, and bile duct hyperplasia. We demonstrated that the signature genes were mechanistically related to the phenotype the signature intended to predict (e.g. 17 out of top 20 genes for inflammation selected by PPEA were members of NF-kB pathway, which is a key pre-inflammatory pathway for a xenobiotic response). The top 4 gene signature for BDH has been further validated by QPCR in a toxicology lab. This is important because our results suggest that the PPEA model not largely deters the over-fitting problem, but also has the capability to elucidate mechanism(s) of drug action and / or of toxicity

    Alternative methods for regulatory toxicology – a state-of-the-art review

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    This state-of-the art review is based on the final report of a project carried out by the European Commission’s Joint Research Centre (JRC) for the European Chemicals Agency (ECHA). The aim of the project was to review the state of the science of non-standard methods that are available for assessing the toxicological and ecotoxicological properties of chemicals. Non-standard methods refer to alternatives to animal experiments, such as in vitro tests and computational models, as well as animal methods that are not covered by current regulatory guidelines. This report therefore reviews the current scientific status of non-standard methods for a range of human health and ecotoxicological endpoints, and provides a commentary on the mechanistic basis and regulatory applicability of these methods. For completeness, and to provide context, currently accepted (standard) methods are also summarised. In particular, the following human health endpoints are covered: a) skin irritation and corrosion; b) serious eye damage and eye irritation; c) skin sensitisation; d) acute systemic toxicity; e) repeat dose toxicity; f) genotoxicity and mutagenicity; g) carcinogenicity; h) reproductive toxicity (including effects on development and fertility); i) endocrine disruption relevant to human health; and j) toxicokinetics. In relation to ecotoxicological endpoints, the report focuses on non-standard methods for acute and chronic fish toxicity. While specific reference is made to the information needs of REACH, the Biocidal Products Regulation and the Classification, Labelling and Packaging Regulation, this review is also expected to be informative in relation to the possible use of alternative and non-standard methods in other sectors, such as cosmetics and plant protection products.JRC.I.5-Systems Toxicolog

    Natural Medicinal Plants

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    This book, Natural Medicinal Plants is a comprehensive overview of drugs derived from medicinal plants and their use in treating human illnesses such as cancer. Chapters include scientific evidence on flora rich in active ingredients

    Molecular Science for Drug Development and Biomedicine

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    With the avalanche of biological sequences generated in the postgenomic age, molecular science is facing an unprecedented challenge, i.e., how to timely utilize the huge amount of data to benefit human beings. Stimulated by such a challenge, a rapid development has taken place in molecular science, particularly in the areas associated with drug development and biomedicine, both experimental and theoretical. The current thematic issue was launched with the focus on the topic of “Molecular Science for Drug Development and Biomedicine”, in hopes to further stimulate more useful techniques and findings from various approaches of molecular science for drug development and biomedicine

    Systems microscopy to unravel cellular stress response signalling in drug induced liver injury

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    Toxicological insults are met by cellular adaptive stress response pathway activation. We find that activation of adaptive stress responses occur well before the typical ultimate outcome of chemical cell injury. To increase our understanding of chemically-induced adaptive stress response pathway activation and its contribution to safety assessment we believe that a time-resolved, sensitive and multiplex readout of chemical-induced toxicological relevant cellular stress responses will be essential. For that purpose, we developed a platform containing a panel of distinct adaptive stress response reporter cell lines. These are used for automated high content live cell imaging and quantitative multi-parameter image analysis to elucidate critical adaptive stress response pathway activation that can contribute to human chemical safety assessment. To conserve the endogenous gene regulatory programs, we tag selected reporter target genes with GFP using BAC-transgenomics approaches. In this thesis we demonstrate the functionality of individual BAC-GFP pathway in toxicity reporter cell lines. The application of these reporters in chemical safety assessment in relation to drug-induced liver injury is discussed in detail. We anticipate that ultimately a phenotypic adaptive stress response profiling platform will allow a high throughput and time-resolved classification of chemical-induced stress responses assisting in the safety assessment of chemicals.UBL - phd migration 201

    Health-Promoting Components of Fruits and Vegetables in Human Health

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    Diet and lifestyle choices can substantially predispose an individual to, or protect against, many age- and obesity-related chronic diseases. According to the NIH Office of Dietary Supplements, dietary bioactives arecompounds in foodsnot needed for basic human nutrition but responsible for changes in health status.1 These compounds are safe at normal food consumption levels (e.g., anthocyanins in berries) and their biological activities may come from a single compound (e.g., lutein in spinach) or a class of compounds (e.g., avenanthramides in oats) even if the exact identity and composition are unknown. Bioactive compounds of plants; can vary significantly in their ratios and relative concentrations depending onfactors such as cultivation, soil, altitude, and weather conditions. Substantial scientific evidence is available for some health promoting phytochemicals, such as dose-response relations, for performance and/or reduction in the risk of chronic disease. However, several limitations relating to absorption, distribution, metabolism and excretion of many dietary bioactives still exist and must be better understood This Special Issue compiles recent discoveries that advance our understanding of how dietary bioactive, particularly from fruits and vegetables, influence long-term health maintenance and disease prevention
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