Introduction. Wortmannin (WTN) is a steroid metabolite that inhibits phosphatidylinositol 3-kinase and other signaling pathways. Structurally, the WTN consists of a cyclopentanophenanthrene-like structure with several oxygen-rich moieties which have the potential to interact with deoxyribonucleic acid (DNA) molecules. Methods. We aim to evaluate the WTN and calf thymus DNA (ct-DNA) interaction with molecular docking using the AutoDock 4.2 software. UV and fluorescence spectroscopy and viscosity techniques were performed to confirm the in silico analysis. Results. Molecular docking showed that the WTN interacted with ct-DNA via hydrogen bonds at guanine-rich sequences. The number of hydrogen bonds between the WTN and DNA was 1-2 bonds (average 1.2) per WTN molecule. The in silico binding constant was 2 × 103 M−1. UV spectroscopy showed that the WTN induced a hyperchromic feature without wavelength shifting. The WTN and DNA interaction led to quenching of DNA-emitted fluorescence. The different concentrations of WTN had no effect on DNA viscosity. Taken together, our results demonstrated WTN interacts with DNA in the nonintercalating mode, which is considered as a new mechanism of action. Conclusion. These results suggest that the WTN may exert its biological effects, at least in part, via interaction with DNA.
Background: Over the last decades, the exposure to titanium dioxide nanoparticles (TiO 2 NPs) has increased due to the wide application in industry, food adduct, medicine, cosmetic products, etc. Literature review showed that the TiO 2 NPs exert toxic effects on several organs. Methods: We searched PubMed, MEDLINE and the other databases with the following keywords, "titanium dioxide nanoparticle", "TiO 2 NPs", "myocardial infarction", "endothelial", "blood pressure", "heart" and "cardiovascular", and reviewed the literature by focusing on the toxic effects of TiO 2 NPs on the cardiovascular system, and possible underlying mechanism. Results: The toxic effects of TiO 2 NPs on the cardiovascular system are controversial but some possible mechanisms were proposed. TiO 2 NPs and nanoparticle-derived titanium induce cardiac injury, endothelial dysfunction and increase blood pressure and heart rate. These effects are mediated via systemic or local oxidative stress and inflammation.
Conclusion:The TiO 2 NPs toxicity is dependent on cell type and particle characteristic, and the controversial results may be due to these variables. However, a growing body of evidence confirmed the possible TiO 2 NPs toxicity on the cardiovascular system.
Fever is a common feature in various pathological conditions that manifests a series of molecular events in the internal milieu. Much less attention has been paid to the clinical importance and the management of fever in breast cancer patients. However, several studies have reported an association between postoperative fever and poor treatment outcomes in breast cancer patients. The fever is a side effect of chemotherapy and a manifestation of cancer recurrence. The postmenopausal breast cancer patients experience another body temperature disturbance that is known as a hot flashes. Here, we reviewed the literature regarding postoperative fever and the possible underlying molecular and cellular mechanisms. Then the efficacy of non-steroidal anti-inflammatory drugs was discussed as a therapeutic option to control postoperative fever. Finally, we reviewed the chemotherapy-induced neutropenic fever and cancer vaccination-induced fever.
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