Cytochromes P450s (CYPs) constitute a superfamily of enzymes that catalyze the metabolism of drugs and othersubstances. Endogenous substrates of CYPs include eicosanoids, estradiol, arachidonic acids, cholesterol, vitamin Dand neurotransmitters. Exogenous substrates of CYPs include the polycyclic aromatic hydrocarbons and about 80% ofcurrently used drugs. Some isoforms can activate procarcinogens to ultimate carcinogens. Genetic polymorphisms ofCYPs may affect the enzyme catalytic activity and have been reported among different populations to be associatedwith various diseases and adverse drug reactions. With regard of drug metabolism, phenotypes for CYP polymorphismrange from ultrarapid to poor metabolizers. In this review, we discuss some of the most clinically important CYPsisoforms (CYP2D6, CYP2A6, CYP2C19, CYP2C9, CYP1B1 and CYP1A2) with respect to gene polymorphisms anddrug metabolism. Moreover, we review the role of CYPs in renal, lung, breast and prostate cancers and also discusstheir significance for atherosclerosis and type 2 diabetes mellitus.
Sedimentation equilibrium (analytical ultracentrifugation) is one of the most inherently suitable methods for the determination of average molecular weights and molecular weight distributions of polymers, because of its absolute basis (no conformation assumptions) and inherent fractionation ability (without the need for columns or membranes and associated assumptions over inertness). With modern instrumentation it is also possible to run up to 21 samples simultaneously in a single run. Its application has been severely hampered because of difficulties in terms of baseline determination (incorporating estimation of the concentration at the air/solution meniscus) and complexity of the analysis procedures. We describe a new method for baseline determination based on a smart-smoothing principle and built into the highly popular platform SEDFIT for the analysis of the sedimentation behavior of natural and synthetic polymer materials. The SEDFIT–MSTAR procedure – which takes only a few minutes to perform – is tested with four synthetic data sets (including a significantly non-ideal system), a naturally occurring protein (human IgG1) and two naturally occurring carbohydrate polymers (pullulan and λ-carrageenan) in terms of (i) weight average molecular weight for the whole distribution of species in the sample (ii) the variation in “point” average molecular weight with local concentration in the ultracentrifuge cell and (iii) molecular weight distribution.
1 December 2019 in International Journal of Biological Macromolecules
Chitosan and its nanoparticles (NPs) could be extracted from numerous fungal species and used as effectual carriers for bioactive compounds. The fungal chitosan (FC) was innovatively acquired from Fusarium oxysporum grown mycelia, characterized and used for NP synthesis and loading with bee venom (BV). The nano-FC (NFC) had 192.4 nm mean NP diameter, 38.22% loading capacity, and 92.42% entrapment efficiency. BV release from NFC was pH and time dependent; burst BV release was detected at the first 6 h, followed by gradual releases up to 30 h. The in vitro anticancer potentiality valuation, of NFC, BV, and NFC/BV nanoconjugates against HeLa cervix carcinoma, revealed that they all had potent dose-dependent anticancer activity; BV/NFC nanoconjugates were the most effective with . The fluorescent staining of treated HeLa cells with BV/NFC nanoconjugates, with DAPI and acridine orange/propidium iodide combination, indicated the appearance of early apoptosis, secondary apoptosis, and secondary necrosis markers and their increment with exposure prolongation. The production of NFC from F. oxysporum and their loading with BV are strongly counseled for production of potent natural antitumor agent with augmented activity against cervix carcinoma.