ABSTRACT
Objective To make a systematic analysis of the interaction between osteoporosis and smoking to elucidate the molecular mechanisms underlying osteoporosis susceptibility affected by smoking.Methods First,a two-way ANOVA analysis was conducted using microarray data to search all potential genes associated with both smoking and osteoporosis.We further explored the potential biologically related metabolic pathways through gene pathway enrichment analysis.Then the interaction genes within enriched pathways were verified by genome-wide gene-environment interaction analysis.Finally,protein-protein interaction analysis was applied to identify the core regulatory network in which those verified genes involved.Results We identified 441 risk genes closely associated with both smoking and osteoporosis by microarray analysis.Through gene pathway analysis,we identified a vital metabolism pathway, gap junction, which is a potential mediator between smoking and osteoporosis process. Finally,we verified some critical genes by genome-wide gene-environment interaction analysis,and revealed a potential smoking-osteoporosis interaction core regulatory network that included 1 3 proteins by protein network analysis.Conclusion We have discovered a new regulatory framework connecting smoking and osteoporosis, which provides new clues about disease etiologies and novel promising drug targets.
ABSTRACT
A dissolution method with robust high performance liquid chromatographic (HPLC) analysis for im-mediate release tablet formulation was developed and validated to meet the requirement as per Inter-national Conference on Harmonization (ICH) and United States Food and Drug Administration (USFDA) guidelines. The method involved the use of Agilent ZORBAX Eclipse XDB C18 column, and temperature was maintained at 30 °C. After optimization, the mobile phase was selected as phosphate buffer (KH2PO4, 30 mM):ACN (60:40, v/v) with pH 3.0, and retention time Rt was found as 3.24, 4.16, and 2.55 min for paracetamol (PCM), chlorpheniramine maleate (CPM) and phenylephrine hydrochloride (PH) respec-tively at 265 nm and at a flow rate of 1 mL/min. The relative standard deviation (%RSD) for 6 replicate measurements was found to be less than 2%. Furthermore net analyte signal standard addition method (NASSAM) with spectrophotometer was performed for standard and liquid oral suspension. On the basis of selectivity, sensitivity and accuracy analysis, it was confirmed that this novel method could be useful for simultaneous estimation of the given drug combinations. Two-way analysis of variance (ANOVA) was applied for evaluating the statistical difference between the assay results obtained via both NASSAM and RP-HPLC methods and ultimately no significant difference was found between both the methods. All the methods and results were acceptable and confirmed that the method was suitable for intended use.