Search results for "M1"
showing 10 items of 837 documents
Artemisinin Derivatives Target Topoisomerase 1 and Cause DNA Damage in Silico and in Vitro
2017
DNA topoisomerases 1 and 2 are enzymes that maintain DNA topology and play important essential genome functions, including DNA replication and transcription. Aberrant topoisomerases cause genome instability and a wide range of diseases, cancer in particular. Both Topo 1 and 2 are the targets of valuable anticancer drugs, such as camptothecin. It has been previously shown that artemisinin, a sesquiterpene lactone from Artemisia annua L. also known as qinghaosu, possesses anti-cancer effects and one of its derivatives, artesunate inhibits Topo 2. In this study, we evaluated artemisinin and 40 derivatives as potential Topo 1 inhibitors at first by in silico molecular docking analyses. Five com…
Hepatoprotective Effect of Steroidal Glycosides From Dioscorea villosa on Hydrogen Peroxide-Induced Hepatotoxicity in HepG2 Cells
2018
Dioscorea villosa, commonly known as “Wild Yam” and native to North America, is well documented for its pharmacological properties due to the presence of steroidal glycosides. However, the hepatoprotective potential of these compounds has not been studied so far. The present investigation was aimed to study the hepatoprotective effect of the steroidal glycosides from D. villosa against H2O2, a known hepatotoxin, in human liver cell line (HepG2). Cytotoxicity assessment was carried out in cells exposed to various concentrations (10–50 μM) of compounds for 24 h using MTT assay and morphological changes. All tested compounds were known and among them, spirostans (zingiberensis saponin I, diosc…
Molecular docking-based virtual drug screening revealing an oxofluorenyl benzamide and a bromonaphthalene sulfonamido hydroxybenzoic acid as HDAC6 in…
2020
HDAC6 is a crucial epigenetic modifier that plays a vital role in tumor progression and carcinogenesis due to its multiple biological functions. It is a unique member of class-II HDAC enzymes. It possesses two catalytic domains, which function independently of the overall enzyme activity. Up to date, there are only a few selective HDAC6 inhibitors with anti-cancer activity. In this study, 175,204 ligands obtained from the ZINC15 and OTAVAchemical databases were used for virtual drug screening against HDAC6. Molecular docking studies were performed for 100 selected compounds. Furthermore, the top 10 compounds obtained from docking were tested for their efficacy to inhibit the function of HDA…
Considerations for an in vitro, cell-based testing platform for detection of adverse drug-induced inotropic effects in early drug development. Part 1…
2019
Drug-induced effects on cardiac contractility can be assessed through the measurement of the maximal rate of pressure increase in the left ventricle (LVdP/dtmax) in conscious animals, and such studies are often conducted at the late stage of preclinical drug development. Detection of such effects earlier in drug research using simpler, in vitro test systems would be a valuable addition to our strategies for identifying the best possible drug development candidates. Thus, testing platforms with reasonably high throughput, and affordable costs would be helpful for early screening purposes. There may also be utility for testing platforms that provide mechanistic information about how a given d…
Berberine Mediated Positive Inotropic Effects on Rat Hearts via a Ca2+-Dependent Mechanism
2020
Previous studies showed that berberine, an alkaloid from Coptis Chinensis Franch, might exert a positive inotropic effect on the heart. However, the underlying mechanisms were unclear. Here, we reported that berberine at 10-20 µM increased the left ventricular (LV) developed pressure and the maximal rate of the pressure rising, and it increased the maximal rate of the pressure descending at 20 µM in Langendorff-perfused isolated rat hearts. These effects diminished with the concentration of berberine increasing to 50 µM. In the concentration range of 50-300 µM, berberine increased the isometric tension of isolated left ventricular muscle (LVM) strips with or without electrical stimulations,…
Redox Status, Dose and Antioxidant Intake in Healthcare Workers Occupationally Exposed to Ionizing Radiation
2020
The purpose of this study was to evaluate the relationship between blood redox status, dose and antioxidant dietary intake of different hospital staff groups exposed to low doses of ionizing radiation (LDIR) (Interventional Radiology and Cardiology, Radiation Oncology, and Nuclear Medicine) and non-exposed. Personal dose equivalent (from last year and cumulative), plasma antioxidant markers (total antioxidant capacity, extracellular superoxide dismutase activity, and glutathione/oxidized glutathione ratio), oxidative stress markers (nitrites and nitrates, and lipid peroxidation) and dietary intake (antioxidant capacity using ORAC values) were collected and analyzed from 28 non-exposed healt…
Comparison of time and dose dependent gene expression and affected pathways in primary human fibroblasts after exposure to ionizing radiation
2020
Abstract Background Exposure to ionizing radiation induces complex stress responses in cells, which can lead to adverse health effects such as cancer. Although a variety of studies investigated gene expression and affected pathways in human fibroblasts after exposure to ionizing radiation, the understanding of underlying mechanisms and biological effects is still incomplete due to different experimental settings and small sample sizes. Therefore, this study aims to identify the time point with the highest number of differentially expressed genes and corresponding pathways in primary human fibroblasts after irradiation at two preselected time points. Methods Fibroblasts from skin biopsies of…
Opportunities and challenges for drug development: public-private partnerships, adaptive designs and big data
2016
Drug development faces the double challenge of increasing costs and increasing pressure on pricing. To avoid that lack of perceived commercial perspective will leave existing medical needs unmet, pharmaceutical companies and many other stakeholders are discussing ways to improve the efficiency of drug Research and Development. Based on an international symposium organized by the Medical School of the University of Duisburg-Essen (Germany) and held in January 2016, we discuss the opportunities and challenges of three specific areas, i.e., public-private partnerships, adaptive designs and big data. Public-private partnerships come in many different forms with regard to scope, duration and typ…
GLP-1 Analog Liraglutide Improves Vascular Function in Polymicrobial Sepsis by Reduction of Oxidative Stress and Inflammation
2021
Sepsis causes high mortality in the setting of septic shock. LEADER and other trials revealed cardioprotective and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) analogs like liraglutide (Lira). We previously demonstrated improved survival in lipopolysaccharide (LPS)-induced endotoxemia by inhibition of GLP-1 degradation. Here we investigate the effects of Lira in the polymicrobial sepsis model of cecal ligation and puncture (CLP). C57BL/6J mice were intraperitoneally injected with Lira (200 µg/kg/d
Amyloid β-peptide insertion in liposomes containing GM1-cholesterol domains.
2015
Neuronal membrane damage is related to the early impairments appearing in Alzheimer's disease due to the interaction of the amyloid β-peptide (Aβ) with the phospholipid bilayer. In particular, the ganglioside GM1, present with cholesterol in lipid rafts, seems to be able to initiate Aβ aggregation on membrane. We studied the thermodynamic and structural effects of the presence of GM1 on the interaction between Aβ and liposomes, a good membrane model system. Isothermal Titration Calorimetry highlighted the importance of the presence of GM1 in recruiting monomeric Aβ toward the lipid bilayer. Light and Small Angle X-ray Scattering revealed a different pattern for GM1 containing liposomes, bot…