Compare and contrast: pediatric cancer versus adult malignancies.

Cancer is a leading cause of death in both adults and children, but in terms of absolute numbers, pediatric cancer is a relatively rare disease. The rarity of pediatric cancer is consistent with our current understanding of how adult malignancies form, emphasizing the view of cancer as a genetic disease caused by the accumulation and selection of unrepaired mutations over time. However, considering those children who develop cancer merely as stochastically "unlucky" does not fully explain the underlying aetiology, which is distinct from that observed in adults. Here, we discuss the differences in cancer genetics, distribution, and microenvironment between adult and pediatric cancers and argue that pediatric tumours need to be seen as a distinct subset with their own distinct therapeutic challenges. While in adults, the benefit of any treatment should outweigh mostly short-term complications, potential long-term effects have a much stronger impact in children. In addition, clinical trials must cope with low participant numbers when evaluating novel treatment strategies, which need to address the specific requirements of children.

Medium-based optimization of an organic solvent-tolerant extracellular lipase from the isolated halophilic Alkalibacillus salilacus.

A haloalkaliphilic solvent-tolerant lipase was produced from Alkalibacillus salilacus within 48 h of growth in liquid medium. An overall 4.9-fold enhanced production was achieved over unoptimized media after medium optimization by statistical approaches. Plackett-Burman screening suggested lipase production maximally influenced by olive oil, KH2PO4, NaCl, and glucose; and response surface methodology predicted the appropriate levels of each parameter. Produced lipase was highly active and stable over broad ranges of temperature (15-65 °C), pH (4.0-11.0), and NaCl concentration (0-30 %) showing excellent thermostable, pH-stable, and halophilic properties. The enzyme was optimally active at pH 8.0 and 40 °C. Majority of cations, except some like Co(2+) and Al(3+) were positive signals for lipase activity. In addition, the presence of chemical agents and organic solvents with different log P ow was well tolerated by the enzyme. Finally, efficacy of lipase-mediated esterification of various alcohols with oleic acid in organic solvents was studied.

Synthesis and antibacterial activity of novel levofloxacin derivatives containing a substituted thienylethyl moiety.

BACKGROUND AND THE PURPOSE OF THE STUDY: Piperazinyl quinolones such as ciprofloxacin, ofloxacin and levofloxacin are an important group of quinolone antimicrobials which are widely used in the treatment of various infectious diseases. In the present study, we synthesized a new series of levofloxacin derivatives and evaluated their antibacterial activities. METHODS: The N-substituted analogs of levofloxacin 6a-j were prepared by nucleophilic reaction of N-desmethyl levofloxacin 11 with thienylethyl bromide derivatives 8 or 9. All target compounds were tested using conventional agar dilution method in comparison to levofloxacin and N-desmethyl levofloxacin and their MIC values were determined against a panel of Gram-positive and Gram-negative bacteria. RESULTS: All compounds showed significant antibacterial activities against Gram-positive bacteria (MIC = 0.04-6.25 µg/mL); however, the activity against Gram-negative bacteria was lower (MIC = 1.56-100 µg/mL). As is evident from the data, oxime derivatives 6e, 6h and 6i are superior in inhibiting the growth of Gram-positive bacteria (MIC = 0.04-0.19 µg/mL), and their activities were found to be 5-25 times better than N-desmethyl levofloxacin 11 and equal or better than levofloxacin 4. CONCLUSION: We have designed and synthesized novel quinolone derivatives bearing functionalized thienylethyl moiety on the piperazine ring of levofloxacin. The results of antibacterial screening against Gram-positive and Gram-negative bacteria revealed that the introduction of functionalized thienylethyl moiety on the piperazine ring of levofloxacin can improve the activity against Gram-positive bacteria. Gram-positive bacteria are responsible for a wide range of infectious diseases, and rising resistance in this group is causing increasing concern. Thus, this study introduces structural features of levofloxacin scaffold for development of new candidates in the field of anti-Gram positive chemotherapy.

Efficient Keratinolysis of Poultry Feather Waste by the Halotolerant Keratinase from Salicola Marasensis.

Sustainable development in the bio-treatment of large-scale biomass bulks requires high performance enzymes adapted to extreme conditions. An extracellular keratinolytic extract was obtained from the culture broth of a halotolerant strain of Salicola marasensis. Keratin hydrolyzing activity of the concentrated enzyme extract was observed on a 100 mg of pretreated feather waste. The concentrated enzyme was able to hydrolyze the poultry feathers by 25% after 12 h incubation. The bio-waste material was optimally hydrolyzed at pH 9 and temperature of 40 °C. Among reductants, 1,4-dithiothreitol, L-cysteine, 2-mercaptoethanol, glutathione, and sodium sulfate showed the most remarkable effect on the bio-waste keratinolysis, while the tested surfactants and urea had no significant effect on the keratinolytic activity. Hexane and hexadecane indicated strong effect on keratinase activity and bio-treatment in the presence of 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) as a hydrophobic ionic liquid resulted in a maximal of 80% extraction yield of soluble proteins from feathers. Considering the stability of the extracellular keratinolytic content in [BMIM][PF6], the observed keratinase activity was noteworthy suggesting that the secreted enzyme may contribute to the bioconversion of feather wastes.

Enhanced Production and Characterization of a Highly Stable Extracellular Protease from an Extreme Halophilic Isolate Salicola marasensis.

Owing to their superior catalytic activity in the extreme conditions, extremozymes have found the potential biotechnological applications for industrial purposes. A robust extracellular protease activity was detected in the culture broth of Salicola marasensis, an extreme halophilic bacterium, after a 48 h-incubation. The effect of different media ingredients in a liquid state fermentation was followed with the aim of improving the enzyme production yield. Fractional factorial and Box-Behnken designs were applied to get a 3.4 fold (from 6.0 to 20.3 U mL-1) improvement of protease production. The distinguishing features of this enzyme were stability at a wide range of pH (5.0-11.0) and temperature (25-60 °C), significant compatibility towards organic solvents, metal ions, chemicals, and surfactants, and hydrolysis of a variety of substrates. The properties of this enzyme can be of tremendous help in terms of the halophilic proteolytic extract's industrial applications.