BackgroundRecQ helicases play an essential role in the maintenance of genome stability. In humans, loss of RecQ helicase function is linked with predisposition to cancer and/or premature ageing. Current data show that the specific depletion of the human RECQ1 helicase leads to mitotic catastrophe in cancer cells and inhibition of tumor growth in mice.ResultsHere, we show that RECQ1 is highly expressed in various types of solid tumors. However, only in the case of brain gliomas, the high expression of RECQ1 in glioblastoma tissues is paralleled by a lower expression in the control samples due to the poor expression of RECQ1 in non-dividing tissues. This conclusion is validated by immunohistochemical analysis of a tissue microarray containing 63 primary glioblastomas and 19 perilesional tissue samples, as control. We also show that acute depletion of RECQ1 by RNAi results in a significant reduction of cellular proliferation, perturbation of S-phase progression, and spontaneous γ-H2AX foci formation in T98G and U-87 glioblastoma cells. Moreover, RECQ1 depleted T98G and U-87 cells are hypersensitive to HU or temozolomide treatment.ConclusionsCollectively, these results indicate that RECQ1 has a unique and important role in the maintenance of genome integrity. Our results also suggest that RECQ1 might represent a new suitable target for anti cancer therapies aimed to arrest cell proliferation in brain gliomas.

The protein-protein interactions (PPIs) of the transmembrane glycoprotein E2 with the hydrophobic pocket on the surface of capsid protein (CP) plays a critical role in alphavirus life cycle. Dioxane based derivatives targeting PPIs have been reported to possess antiviral activity against Sindbis Virus (SINV), the prototype alphavirus. In this study, the binding of picolinic acid (PCA) to the conserved hydrophobic pocket of capsid protein was analyzed by molecular docking, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and fluorescence spectroscopy. The binding constant KD obtained for PCA was 2.1×10(-7)M. Additionally, PCA significantly inhibited CHIKV replication in infected Vero cells, decreasing viral mRNA and viral load as assessed by qRT-PCR and plaque reduction assay, respectively. This study is suggestive of the potential of pyridine ring compounds as antivirals against alphaviruses and may serve as the basis for the development of PCA based drugs against alphaviral diseases.

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Frail elderly is very common in Indian society and extremely difficult to manage in the clinical practice. Blood proteomic study may able to improve the specific diagnostic profiles and therapeutic templates for improving quality of life in elderly. The purpose of present study is to differentiate between frail and non-frail elderly on the basis of serum markers. The proteomic profile of 10 frail and 10 non-frail elderly diagnosed according to deficit accumulation model of Rockwood was identified by 2D-electrophoresis and analyzed using ImageMaster 2DPlatinum7.0 software. The proteins were identified by MALDI-TOF/TOF and performed gene ontology study by PANTHER 7.0 software. Overall 105 spots were identified in the study groups. In frail 22spots and in non-frail 12spots were found to be differentially expressed. Mass spectroscopy analysis of 13 spots showed up-regulated Haptoglobin, Serum amyloidA1, TRAK1, sp110, NLRC3, MMP12, Mortalin, NDK3 and downregulated PSRC1, NKG2A proteins in frail elderly. The differential expression of proteins in frailty are mostly associated with proinflammation and is well-known that frailty syndrome increases all inflammatory parameters. It can be summarized from the present proteomic study that these proteins can be used as potential biomarkers for early detection of frailty in the elderly.