Drug Development: Molecular Targets for Gastrointestinal Disease provides a comprehensive review of today's molecular pharmacological approaches to the discovery and development of novel drugs for gastrointestinal and liver diseases. Help Centre. My Wishlist Sign In Join. Gaginella Editor , Antonio Guglietta Editor. Be the first to write a review. Add to Wishlist. Ships in 15 business days. Link Either by signing into your account or linking your membership details before your order is placed. Description Table of Contents Product Details Click on the cover image above to read some pages of this book!
Industry Reviews "The book focuses on specific molecules and the drugs that act on them, their receptors, metabolism or synthesis. Preface p. All Rights Reserved. Notably, SHD-middle 3.
Drug Development - Molecular Targets for GI Diseases | Timothy S. Gaginella | Springer
The results indicated that the myocardial damage was reduced by SHD from the morphological change. The myocardial pathological changes were analyzed by optical microscope analysis on the eighth day. These findings demonstrated that SHD treatment could effectively inhibit the production of free radicals of heart, and the results are consistent with those obtained by target protein function analysis. Compared with western medicine, TCM has been used in the synchronic treatment of heart and stomach for a long time in China.
- Im No Angel: From Victorias Secret Model to Role Model;
- Molecular Training in Gastroenterology – Chicago Medicine;
- Water Quality Assessments: A guide to the use of biota, sediments and water in environmental monitoring?
- Reward Yourself.
- Renal Medicine : a Colour Handbook;
- Fictions of Feminist Ethnography.
However, the complex action mechanisms of TCM have hindered the development of effective therapy for such kind of systematic diseases. How to understand the TCM as the whole and identification of the shared potential active compounds, targets and biological processes become the bottleneck restrictions for modern TCM study. Our main findings are as follows:. In summary, this study provided an integrative analysis of related complex diseases by the systems pharmacology approach to find potential active compounds and understand the action mechanisms of TCM.
Despite these potentially interesting findings above, further interpretation such as the drug-drug interaction and the herb dose-effect relationship is necessary to consider relied on experimental data analysis. Moreover, further experimental testing of these compound-target binding actions and molecular mechanism of active compounds in vivo will be required to support further assessments of potential clinical application. To understand the integrated treatment for co-occurring cardiovascular and gastrointestinal disorders, we firstly collected and analyzed the correlation of genes associated with CVDs and GIDs.
In addition, these herbs were mapped into Chinese Patent Medicine CPM to investigate their clinical application and explore the principles of drug combination of heart and stomach meridians. Based on these systematic analyses of Chinese medicine, we selected Sanhe Decoction as a typical example to elaborate the molecular mechanisms of the co-treatment for cardiovascular and gastrointestinal disorders.
Distance a i , b j represents the shortest path between gene a i and b j in the PPI network. To further compare the associations between genes of CVDs and GIDs with that in the random two genes, we randomly selected two genes from PPI network and calculate the association between them, the process was repeated times. To further investigate the clinical application of these HM and SM drugs, we restricted these drugs into a comprehensive encyclopedia of CPM, the National Chinese patent medicine CPM used in current clinical practice for CVDs including angina, cardiodynia and angina pectoris, and GIDs such as gastrointestinal ulcers, chronic atrophic gastritis and chronic gastritis were extracted for further study.
Considering the fact that herbs related to heart and stomach meridians occurred in CPM for the treatment of CVDs and GIDs, t -test was used to evaluate the combination of HM and SM in the integrated treatment for co-occurring disorders. To screen for potentpharmaceutical compounds from Sanhe Decoction, an in silico ADME-systems evaluation model, which integrated drug-likeness DL , oral bioavailability OB , aqueous solubility logS, the logarithm of aqueous solubility , lipophilicity logP, logarithm of octanol-water partition coefficient and Caco-2 permeability was proposed.
The value of log P less than 5 was selected for further analysis. Aqueous solubility: Log S, a measure of aqueous solubility, which has been considered as an important factor in drug absorption and distribution. Drug-likeness: To filter out the drug-like molecules, we have developed a database-dependent model to discriminate between drug-like and nondrug-like chemicals using the Tanimoto coefficient This model is constructed based on the molecular descriptors and Tanimoto coefficient as displayed in Equation2.
Oral bioavailability: OB, represents the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action Here the OB screening was performed by an in-house system OBioavail1. Caco-2 permeability: For an orally administered drug, the majority of drug absorption occurs in the small intestine where the presence of villi and microvilli greatly increases the surface available for absorption Here, we employed a robust in silico Caco-2 permeability prediction model PreCaco2 to predict the drug absorption.
The identification of drug targets is a critical step for both the pharmaceutical industry and academic biomedical research. In this work, a newly developed weighted ensemble similarity WES method based on over , drug-target relations was proposed to predict the direct targets of drugs. The proposed method consists of two steps: 1 evaluating the significance of ligand structure parameters for each target and 2 calculating the potential unity of a molecule for a specific target based on the top-important chemical features that are strongly related to pharmacological properties, then adopting a statistical model to control for random similarity.
What is Kobo Super Points?
The method integrates chemical, genomic and pharmacological data to build a high level model for acquiring higher prediction ability. More importantly, the reliability of the theoretical model is validated by a rat experiment. The WES model shows impressive performance for both internal and external validation data To characterize the interactions of drugs and target proteins, an in silico PreAM Prediction of the Action Mode model based on random forests RF algorithm was built.
- The Dancers Way: The New York City Ballet Guide to Mind, Body, and Nutrition.
- Targeted Cancer Therapies Fact Sheet - National Cancer Institute!
- Recommended for you.
- ENTEROME | olagynulehyb.gq?
- Molecular Targets for GI Diseases.
- The Epic of Gilgamesh.
- Drugs in Sport!
Firstly, drug structures and protein sequences were converted into numerical descriptors. Secondly, the multiple Compound-Target Interactions CTIs were represented by concatenating these chemical and protein descriptors, and minimal-redundancy—maximal-relevance mRMR was applied as a variable selected strategy to identify the best combination of descriptors to ensure the model with the highest predictive power. Thirdly, a random forests RF algorithm was trained to generate a nonlinear classifier tailored to CTIs with known action modes.
The PreAM model shows impressive performance of prediction for drug-target interactions, with an overall accuracy of The enriched KEGG pathways of targets with a false discovery rate less than 0. Finally, the pathways were divided into several modules after the enrichment analysis. In these networks, degree DD is used to characterize the connectedness of a node.
Drug Development: Molecular Targets for GI Diseases / Edition 1
The degree of a node is the number of edges associated with it. The topological properties of these networks were analyzed using the Network Analysis plugin and CentiScaPe 1. To further explore the underlying mechanisms of Sanhe Decoction that provides therapeutic effects in CVDs and GIDs, it is essential to validate the functional and tissue expression profile of the protein targets at the organ level.
We enriched the overrepresented gene ontology GO terms and checked the tissue distribution of the obtained targets. Shanghai, China. IMT is used as the positive control, which inhibits angiogenesis and mediates vasoconstriction to treat myocardial ischemia All these herbal drugs were identified and prepared in fluid extract for use. Pre-treatment was given daily for a period of 7 days. Following a procedure established in related reports , Sham group underwent a thoracotomy without infarct induction. Animal experiments were conducted in accordance with the Guiding Principles for the Care and Use of Laboratory Animals.
All efforts were made to minimize the number of the animals used and their suffering. Biochemical analysis: We collected blood samples and measured serum levels of superoxide dismutase SOD , creatine kinase CK , cyclic adenosine monophosphate cAMP , and cardiac troponin I cTnI using chemical colorimetry assay kits Nanjing Jiancheng Bioengineering Institute according to manufacturer instructions. P value less than 0. How to cite this article : Zhang, W. The effect of double dose of omeprazole on the course of angina pectoris and treadmill stress test in patients with coronary artery disease-a randomized, double-blind, placebo controlled, crossover trial.
International journal of cardiology , — Dobrzycki, S. Does gastro-esophageal reflux provoke the myocardial ischemia in patients with CAD? International journal of cardiology , 67—72 Xie, C. The common biological basis for common complex diseases: evidence from lipoprotein lipase gene. European Journal of Human Genetics 18 , 3—7 Pellicano, R.
Helicobacter pylori: from the stomach to the heart. Sana, A. Patients with chronic gastrointestinal ischemia have a higher cardiovascular disease risk and mortality. Atherosclerosis , — Shirzad, M. The relationship between heart and stomach in Iranian traditional medicine: a new concept in cardiovascular disease management.
Int J Cardiol , — Chen, K. Evidence-Based Complementary and Alternative Medicine , Roman, C. Atrial fibrillation in patients with gastroesophageal reflux disease: a comprehensive review. World J Gastroenterol 20 , — Velagapudi, P. Atrial fibrillation and acid reflux disease. Clinical cardiology 35 , — Unschuld, P.
Huang Di nei jing su wen. University of California Press I , 7—57 Li-Ling, J. Human phenome based on Traditional Chinese Medicine-a solution to congenital syndromology. The American journal of Chinese medicine 31 , — Qiu, J. When the East meets the West: the future of traditional Chinese medicine in the 21st century.
National Science Review 2 , — Steinmann, D. Patwardhan, B. Ayurveda and traditional Chinese medicine: a comparative overview. Evidence-Based Complementary and Alternative Medicine 2 , — Can, E. The Journal of Chinese Medicine and Acupuncture 20 , 2—6 Berger, S. Network analyses in systems pharmacology. Bioinformatics 25 , — Hopkins, A. Network pharmacology: the next paradigm in drug discovery. Janga, S. Structure and organization of drug-target networks: insights from genomic approaches for drug discovery. Hao, D. Network pharmacology: a Rosetta Stone for traditional Chinese medicine.
Join Kobo & start eReading today
Drug Dev. Li, P.
Systems pharmacology strategies for drug discovery and combination with applications to cardiovascular diseases. Huang, C. Systems pharmacology in drug discovery and therapeutic insight for herbal medicines. Briefings in bioinformatics bbt Tao, W. Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease.
Yu, H. A systematic prediction of multiple drug-target interactions from chemical, genomic, and pharmacological data. PLoS One 7 , e Li, X. A system-level investigation into the mechanisms of Chinese Traditional Medicine: Compound Danshen Formula for cardiovascular disease treatment. Liu, H. Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice. Practical internal medicine of traditional Chinese medicine 1 , 49—51 An, N.
Diarylheptanoids from Alpinia officinarum. Asian Nat. Tian, J. Xiangshaliujunzi Decoction for the treatment of diabetic gastroparesis: a systematic review. World journal of gastroenterology: WJG 20 , — DU, G. Herald of Medicine 6 , Zheng, C. Scientific reports 5 , Xu, X. A novel chemometric method for the prediction of human oral bioavailability. Park, J. The impact of cellular networks on disease comorbidity. Molecular systems biology 5 , 7 APR Clinical Cancer Research 11 , — Granger, C.
Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. The Lancet , — Schmieder, R. Renin-angiotensin system and cardiovascular risk. Lancet , — Nishijima, Y. Tetrahydrobiopterin depletion and NOS2 uncoupling contribute to heart failure-induced alterations in atrial electrophysiology.
Cardiovascular research 91 , 71—79 Jainu, M. Gastroprotective action of Cissus quadrangularis extract against NSAID induced gastric ulcer: role of proinflammatory cytokines and oxidative damage. Chemico-biological interactions , — Galea, E. Li, M. Towards the identification of protein complexes and functional modules by integrating PPI network and gene expression data.
BMC Bioinf. Committee, N. Fuhrman, B. Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: increased resistance of LDL to atherogenic modifications, reduced plasma lipid levels, and decreased systolic blood pressure. Nutrition 18 , — Xie, S. Antiarrhythmic effect of glycyrrhetinic acid. Herald Med 23 , — Zhan, C. Protective effects of isoliquiritigenin in transient middle cerebral artery occlusion-induced focal cerebral ischemia in rats. Zhang, M. Advances in studies on Glycyrrhizae Radix et Rhizoma and its active components in anti-inflammation and mechanism.
Revers, F. Licorice juice in therapy of ventricular and duodenal ulcers. Ned Tijdschr Geneeskd 92 , — Van Marle, J. Deglycyrrhizinised liquorice DGL and the renewal of rat stomach epithelium. Kassir, Z. Endoscopic controlled trial of four drug regimens in the treatment of chronic duodenal ulceration. Irish medical journal 78 , — Aly, A. Licorice: a possible anti-inflammatory and anti-ulcer drug. Jagetia, G. The evaluation of nitric oxide scavenging activity of certain Indian medicinal plants in vitro : a preliminary study.
Journal of Medicinal Food 7 , — Sivaramakrishnan, V. Investigation on the insecticidal properties of plant extractives-I testing of new medicinal oils, HESP from spent sandalwood powder on insects. Verma, S. Protective effect of ginger, Zingiber officinale Rose on experimental atherosclerosis in rabbits.
Indian journal of experimental biology 42 , — Ali, B. Some phytochemical, pharmacological and toxicological properties of ginger Zingiber officinale Roscoe : a review of recent research. Food and chemical Toxicology 46 , — Ginger: an ethnomedical, chemical and pharmacological review. Drug metabolism and drug interactions 18 , — Wang, Y. Pharmaceutical biotechnology-Beijing 12 , Cao, H.
Microbial biotransformation of bioactive flavonoids. Walle, T. Absorption and metabolism of flavonoids. The NIMML has identified novel naturally occurring compounds that modulate host immune responses during influenza virus infection. We characterized their molecular target and mechanism of action involving activation of the lanthionine synthetase C-like 2 pathway.
PPAR-gamma activation as an anti-inflammatory therapy for respiratory virus infections. We offer a diverse portfolio of patents and intellectual property and seek to establish key strategic alliances with pharma and biotech companies, which will help us to translate our new scientific discoveries from the laboratory bench to the global market.