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.

Inhibitor of apoptosis (IAP) family comprises a group of endogenous proteins that function as main regulators of caspase activity and cell death. They are considered the main culprits in evasion of apoptosis, which is a fundamental hallmark of carcinogenesis. Overexpression of IAP proteins has been documented in various solid and hematological malignancies, rendering them resistant to standard chemotherapeutics and radiation therapy and conferring poor prognosis. This observation has urged their exploitation as therapeutic targets in cancer with promising pre-clinical outcomes. This review describes the structural and functional features of IAP proteins to elucidate the mechanism of their anti-apoptotic activity. We also provide an update on patterns of IAP expression in different tumors, their impact on treatment response and prognosis, as well as the emerging investigational drugs targeting them. This aims at shedding the light on the advances in IAP targeting achieved to date, and encourage further development of clinically applicable therapeutic approaches.

No abstract

Carbon tetrachloride (CCl 4 ) causes severe injury to the body particularly the liver and the kidney. The aim of the present study was testing the probable hepatonephro protective effect of Moringa oleifera seed methanolic extract against CCl 4 toxicity in male rat. 24 male rats were divided into 4 groups (n=6); the first group (G1) was the negative control group, rats of the other three groups were injected with CCl 4 twice a week. Rats of the second group (G2) were kept without treatment as positive CCl 4 group, the third group (G3) received a daily dose of M. oleifera methanolic extract and the fourth group (G4) received a silymarin dose as a positive treated group. The HPLC analysis of M. oleifera seed methanolic extract revealed that it is rich in ascorbic and oleic acids. Rats of the CCl 4 positive control group showed an increase in kidney and liver injury markers, interleukin-6, bilirubin and lipid peroxidation, and a decrease in antioxidants activity and total protein. In addition, liver and kidney tissues showed drastic histopathological changes. Treating the CCl 4 hepatonephrotoxicity in G3 and G4 with either M. oleifera seed methanolic extract or silymarin, respectively significantly alleviated all altered biochemical and histological changes approaching the normal values. M. oleifera methanolic extract revealed more protection to liver and kidney in G3 than silymarin in G4. This protecting activity of M. oleifera seed methanolic extract against CCl 4 hepatonephrotoxicity may be ascribed to its high content of phenols and flavonoids, in addition to ascorbic acid and oleic acid.

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 IC50=200 μg/mL. 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.

No abstract

No abstract

No abstract