| 1. |
- Mohammadi, Elyas, et al.
(författare)
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Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning
- 2020
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:9, s. 1-24
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Forskningsöversikt (refereegranskat)abstract
- Simple Summary Drug repurposing is an accelerated route for drug development and a promising approach for finding medications for orphan and common diseases. Here, we compiled databases that comprise both computationally- or experimentally-derived data, and categorized them based on quiddity and origin of data, further focusing on those that present high throughput omic data or drug screens. These databases were then contextualized with genome-wide screening methods such as CRISPR/Cas9 and RNA interference, as well as state of art systems biology approaches that enable systematic characterizations of multi-omic data to find new indications for approved drugs or those that reached the latest phases of clinical trials. Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug-target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches.
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| 2. |
- Turanli, Beste, et al.
(författare)
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A Network-Based Cancer Drug Discovery: From Integrated Multi-Omics Approaches to Precision Medicine
- 2018
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Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1873-4286 .- 1381-6128. ; 24:32, s. 3778-3790
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Forskningsöversikt (refereegranskat)abstract
- A complex framework of interacting partners including genetic, proteomic, and metabolic networks that cooperate to mediate specific functional phenotypes drives human biological processes. Recent technological and analytical advances in "omic" sciences allow the identification and elucidation of reprogramming biological functions in response to perturbations in cells and tissues. To understand such a complex system, biological networks are generated to reduce the complexity into relatively simple models, and the integration of these molecular networks from different perspectives is implemented for a holistic interpretation of the entire system. Ultimately, network-based methods will effectively facilitate the development and improvement of precision medicine by directing therapies based on the underlying biology of a given patient's disease. The goal of precision medicine is to identify novel therapeutic strategies that can be optimized for each disease type or each patient based on the underlying genetic, environmental, and lifestyle factors. Pharmaco-omics analyses based on an integration of pharmacology and various "omics" data types can be employed to develop effective treatment strategies using particular drugs and doses that are tailored to each individual. In the current review, we first present the core elements of network-based systems biology in the context of pharmaco-omics followed by integration of multi-omics data using various biological networks. Next, we provide an opening into precise medicine and drug targeting based on network approaches. Lastly, we review the current significant efforts as well as the accomplishments and limitations in precise drug targeting with the utility of network-based guided drug discovery methods for effective treatment of breast cancer.
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| 3. |
- Björnsson, Bergthor, et al.
(författare)
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Digital twins to personalize medicine
- 2020
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.
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| 4. |
- Marshall, Garland R, et al.
(författare)
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Limiting Assumptions in the Design of Peptidomimetics
- 2017
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Ingår i: Drug development research. - : Wiley. - 0272-4391 .- 1098-2299. ; 78:6, s. 245-267
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Forskningsöversikt (refereegranskat)abstract
- Limiting the flexibility of organic compounds to enhance their affinity and selectivity for targeting a macromolecule involved in molecular recognition has become a well-developed paradigm in medicinal chemistry. While the role of reverse-turn motifs as peptidomimetics has received the most attention, β-sheets and helices are also important motifs for protein/protein interactions. The more complicated problem of mimicking the interacting surface of noncontiguous epitopes will not be considered in this review. This limited overview focuses on efforts to use amino acid synthons as secondary-structure mimetics as well as providing examples of peptidomimetic design focused on nonpeptide synthetic chemistry in contrast. In particular, the rationale of optimal design criteria for mimicry and the many naïve violations of those criteria made in its pursuit are emphasized.
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| 5. |
- El-Seedi, Hesham R., et al.
(författare)
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Recent insights into the biosynthesis and biological activities of natural xanthones
- 2010
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 17:9, s. 854-901
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Forskningsöversikt (refereegranskat)abstract
- This review focuses on recent advances in our understanding of the complex biosynthetic pathways and diverse biological activities of naturally occurring xanthones. The biosynthesis section covers studies published from 1989 to 2008 on xanthone production in plants and fungi, while the bioactivity review presents tabulated activities of more than 250 xanthones described in studies published from 2001 to 2008, together with structural information and indications of their wide-ranging potential uses as pharmacological tools. A large number of relevant papers have been published on these subjects (128 cited here), illustrating the diversity of the xanthones and their possible uses.
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| 6. |
- Albofetileh, Mehdi, et al.
(författare)
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Seaweed Proteins as a Source of Bioactive Peptides
- 2021
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Ingår i: Current Pharmaceutical Design. - : Bentham Science Publishers Ltd.. - 1873-4286 .- 1381-6128. ; 27:11, s. 1342 -1352
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Forskningsöversikt (refereegranskat)abstract
- Seaweeds have gained great attention as a vegetarian and sustainable marine source of protein which do not need irrigation, arable land and fertilization. Besides, seaweeds are considered as an untapped resource for discovering bioactive compounds with health benefits where bioactive peptides have shown outstanding potential. This review provides a detailed overview of available scientific knowledge on production methods, bioactivity and application of peptides from seaweed proteins. The emphasize is on the effects form seaweed varieties and peptide production condition on the bioactivity of the peptides and their potential health benefits. Bioactive properties of seaweed peptides including antioxidant, antihypertensive, antidiabetic, anti-inflammatory, anticancer activities and other potential health benefits have been discussed. It also covers current challenges and required future research and innovations for the successful application of seaweeds proteins as a sustainable source of bioactive peptides. Effects from seasonal variation of seaweed composition on the bioactivity of their peptides, difficulties in the extraction of proteins from seaweed complex structure, scalability and reproducibility of the developed methods for the production of bioactive peptides, the safety of the peptides are examples of highlighted challenges. Further studies on the bioavailability of the seaweed bioactive peptides and validation of the results in animal models and human trials are needed before their application as functional foods or pharmaceutical ingredients.
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| 7. |
- Björklund, L., et al.
(författare)
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Aspirin in cardiology - benefits and risks
- 2009
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Ingår i: INTERNATIONAL JOURNAL OF CLINICAL PRACTICE. - : Hindawi Limited. - 1368-5031 .- 1742-1241. ; 63:3, s. 468-477
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Forskningsöversikt (refereegranskat)
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| 8. |
- Harris, J. Milton, et al.
(författare)
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Tuning drug release from polyoxazoline-drug conjugates
- 2019
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Ingår i: European Polymer Journal. - : Elsevier BV. - 0014-3057. ; 120
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Forskningsöversikt (refereegranskat)abstract
- Poly(2-oxazoline)-drug conjugates with drugs attached via releasable linkages are being developed for drug delivery. Such conjugates with pendent ester linkages that covalently bind drugs to the polymer backbone exhibit significantly slower hydrolytic release rates in plasma than the corresponding PEG- and dextran-drug conjugates. The slow drug release rates in-vitro of these POZ-drug conjugates contribute to extended in-vivo pharmacokinetic profiles. In some instances, the release kinetics may be relatively sustained and ideal for once-a-week subcutaneous injection, whereas the native drug by itself may only have an in-vivo half-life of a few hours. The origin of this unusual kinetic and pharmacokinetic behavior is proposed here to involve folding of the POZ conjugate such that the relatively hydrophobic drug forms a central core, and the relatively hydrophilic polymer wraps around the core and slows enzymatic attack on the drug-polymer chemical linkage. Here we present evidence supporting this hypothesis and demonstrate how the hypothesis can be used to tune hydrolytic release rates and pharmacokinetics. Evidence for the folding hypothesis is taken from hydrolysis kinetics of a range of drugs in plasma, pharmacokinetics of a range of drugs following subcutaneous injection in laboratory animals, and nuclear magnetic resonance (NMR) studies showing folding of the POZ-rotigotine molecule. The drugs included in this study to test the hypothesis are: rotigotine, buprenorphine, dexanabinol, cannabidiol (CBD), Delta(9)-tetrahydrocannabinol (THC) and cannabigerol (CBG).
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| 9. |
- Wu, Xiaofang, et al.
(författare)
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The effects of chondroitin and/or glucosamine on patients with Kashin-Beck disease
- 2016
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Ingår i: Science Insights Medicine. - : Insight Publisher. - 2378-8097. ; 2016
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Forskningsöversikt (refereegranskat)abstract
- Kashin-Beck disease (KBD), an endemic disease, is a special type of osteoarthritis (OA). Nowadays, due to prevention and treatment methods including selenium supplements, changing grains and water source as well as health education, the morbidity of KBD is reduced significantly as compared to that in the 1950s. However, many elderly adult KBD patients are still suffering from the degenerative changes of cartilage, pain, stiffness and deformation of joints, which are quite similar or even more serious than OA. Chondroitin sulfate and glucosamine have been widely used as symptomatic slow-acting drugs for the treatment of OA. Although their therapeutic effects, biochemical data, pharmacokinetics, preclinical studies, safety and economic evaluation have been well investigated in OA, they are not clearly studied in KBD. In this review, we will evaluate the clinical evidence (randomized controlled trials and non-randomized controlled trials), safeties and cost-effectiveness of chondroitin sulfate and glucosamine for the treatment of KBD. Moreover, the therapeutic mechanisms of chondroitin sulfate and glucosamine are also discussed in details.
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| 10. |
- Lindholm-Sethson, Britta, et al.
(författare)
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Electrochemical impedance spectroscopy in label-free biosensor applications : multivariate data analysis for an objective interpretation
- 2010
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 398:6, s. 2341-2349
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Forskningsöversikt (refereegranskat)abstract
- Electrochemical impedance spectroscopy plays an important role in biosensor science thanks to the possibility of finding specific information from processes with different kinetics at a chosen electrode potential in one experiment. In this paper we briefly discuss label-free impedimetric biosensors described in the literature. A novel method for neutral interpretation of impedance data is presented that includes complex number chemometrics. Three examples are given based on impedance measurements on synthetic biomembranes, in this case a lipid monolayer deposited on a mercury electrode. The interaction of various compounds with the monomolecular lipid layer is illustrated with the following: (1) different concentrations of magainin (Geladi et al. in Proc. Int. Fed. Med. Biomed. Eng. 9:219-220, 2005); (2) different derivatives of gramicidin A (Lindholm-Sethson et al. in Langmuir 24:5029-5032, 2007), and (3) an antimicrobial peptide (Ringstad et al. in Langmuir 24:208-216, 2008).
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