Selecting dissimilar genes for multi-class classification,an application in cancer subtyping

Background  

Gene expression microarray is a powerful technology for genetic profiling diseases and their associated treatments. Such a process involves a key step of biomarker identification, which are expected to be closely related to the disease. A most important task of these identified genes is that they can be used to construct a classifier which can effectively diagnose disease and even recognize the disease subtypes. Binary classification, for example, diseased or healthy, in microarray data analysis has been successful, while multi-class classification, such as cancer subtyping, remains challenging.     

Modified AHP-based decision-making model toward accurate selection of eligible maintenance media for production of <Emphasis Type="Italic">taxanes</Emphasis> in <Emphasis Type="Italic">Taxus baccata</Emphasis> callus culture

Attempts were made here to apply a modified analytic hierarchy process (AHP) approach based on refinement assay of dominated alternatives in monitoring the most reliable callus maintenance media (supplemented with l-glutamine and Casamino acid) of Taxus baccata callus cultures in terms of five criteria. Generally, regarding stem-derived calli, 6 out of 18 maintenance media were nominated as non-dominated alternatives, and following AHP ranking test Casamino acid-based media (i.e., A12, A15 and A19) were overall nominated as the premiere. Taking leaf-derived calli into account, only l-glutamine-based media in an ascending order of A8, A4, A6, A5, A9 and A3 were introduced as non-dominated alternatives. Such results connote that l-glutamine-based feeding appears to generate more significant results either for continuous calli growth or taxanes production. In contrast, regarding the second explant, stem, both amino acid supplies had fairly equal worth. Our findings, overall, demonstrate promising applications of the proposed AHP method regarding accurate selection of the best callus maintenance cultures of T. baccata for production of different taxanes including paclitaxel, Baccatin III and 10-deacetylbaccatin III. Similarly, this statistical approach could be also applicable for other crops, for instance, for accurate selection of the best callus cultures/media and consequently production improvement of a given plant secondary metabolite/product.     

In Vitro Infectivity Assessment by Drug Susceptibility Comparison of Recombinant Leishmania major Expressing Enhanced Green Fluorescent Protein or EGFP-Luciferase Fused Genes with Wild-Type Parasite

Leishmaniasis is a worldwide uncontrolled parasitic disease due to the lack of effective drug and vaccine. To speed up effective drug development, we need powerful methods to rapidly assess drug effectiveness against the intracellular form of Leishmania in high throughput assays. Reporter gene technology has proven to be an excellent tool for drug screening in vitro. The effects of reporter proteins on parasite infectivity should be identified both in vitro and in vivo. In this research, we initially compared the infectivity rate of recombinant Leishmania major expressing stably enhanced green fluorescent protein (EGFP) alone or EGFP-luciferase (EGFP-LUC) with the wild-type strain. Next, we evaluated the sensitivity of these parasites to amphotericin B (AmB) as a standard drug in 2 parasitic phases, promastigote and amastigote. This comparison was made by MTT and nitric oxide (NO) assay and by quantifying the specific signals derived from reporter genes like EGFP intensity and luciferase activity. To study the amastigote form, both B10R and THP-1 macrophage cell lines were infected in the stationary phase and were exposed to AmB at different time points. Our results clearly revealed that the 3 parasite lines had similar in vitro infectivity rates with comparable parasite-induced levels of NO following interferon-γ/lipopolysaccharide induction. Based on our results we proposed the more reporter gene, the faster and more sensitive evaluation of the drug efficiency.     

Molecular docking analysis of known flavonoids as duel COX-2 inhibitors in the context of cancer

Cyclooxygenase-2 (COX-2) catalyzed synthesis of prostaglandin E2 and it associates with tumor growth, infiltration, and metastasis in preclinical experiments. Known inhibitors against COX-2 exhibit toxicity. Therefore, it is of interest to screen natural compounds like flavanoids against COX-2. Molecular docking using 12 known flavanoids against COX-2 by FlexX and of ArgusLab were performed. All compounds showed a favourable binding energy of >-10 KJ/mol in FlexX and > -8 kcal/mol in ArgusLab. However, this data requires in vitro and in vivo verification for further consideration.     

Toxicological Assessment of Arsenic-Induced Hematological Alterations and Chromosomal Aberrations in Tilapia Oreochromis mossambicus

Arsenic is an environmental contaminant and potential carcinogen. Toxicological assessment of As, which causes hematological alterations and chromosomal aberrations, was studied in freshwater fish Oreochromis mossambicus. Fish were exposed to 3 ppm, 28 ppm, and 56 ppm concentrations of sodium arsenite (NaAsO₂) and blood samples were collected after 48 h, 96 h, and 192 h of exposure. Hematological assay of exposed fish revealed abnormal mature and immature erythrocytes, deformed erythrocytes (spindle-shaped and triangular erythrocytes) and erythrocytes with segmented nuclei in all treatments. Arsenic exposure induced chromosomal aberration in a concentration-dependent manner, whereas, a decreasing trend was found after 192 h exposure. Observations on blood cells of exposed fish revealed chromosome breaks, chromatid breaks, and chromatid gaps. The alterations and aberrations of these parameters can be effectively used to assess toxicological effects of As on fish in the aquatic environment and at the same time this study elucidates the potential risks to humans who live in arsenic-contaminated areas.