Globalisation and health sector in India: some emerging issues

The paper explores challenges emerging out of the impact of the globalisation process and its dynamics on the healthcare sector in India. The paper highlights that a lot many changes are taking place in the health sector ranging from health seeking behaviour to access to public health services and their financing to actual health outcomes going hand in hand with the rise in dual disease burden. Challenges emerging from WTO agreements related to public health, health policies and their compliance, and also from globalisation induced shift in development models of production and consumption having far reaching impact on physical environment threatening the healthy human life. These issues and challenges require an immediate attention by the government, development economists and policy makers

Ethylene induced stay-green gene expression regulates drought stress in wheat

761-769Stay-green is an integrated drought adaptation trait characterized by a green leaf phenotype during grain filling under terminal drought. Ethylene is the key hormone for regulating the leaf senescence pathway under natural and stress conditions. The present study was conducted to assess the associative function of ethylene in regulating chlorophyll degrading enzymes viz., chlorophyllase (TaCHLase) and pheophorbide a oxygenase (TaPaO) in wheat (Triticum aestivum L.) under drought stress. Three wheat genotypes (HW 4059, HW 4022 and HW 2078) differing in drought tolerance efficiency were subjected to drought stress for ten days at the reproductive stage. A decline in stay-green traits was found in susceptible genotypes (HW 4059) with yield losses compared to tolerant ones (HW 4022 and HW 2078). The expression level of TaCHLase1 and TaPaO was higher in susceptible genotypes than tolerant ones under drought/osmotic stress. Ethylene upregulated, while ethylene inhibitors downregulated the gene expression. In this study, a novel gene annotated as TaCHLase1 was cloned. The complete cDNA sequence of TaCHLase1 is composed of 1054 bp nucleotides containing an open reading frame of 960 bp encoding 319 amino acids. The encoded protein contained conserved residues such as lipase motif GXSXGG at position 143-148 and putative active site Ser145. Sequence alignment showed TaCHLase1 shares a higher degree of identity with other species. The result suggested that ethylene upregulates the expression of TaCHLase1 gene, inducing chlorophyll degradation. The study further helps in understanding the mechanism of stay-green trait-induced drought tolerance mechanism in wheat

Coordinated Regulation of ATF2 by miR-26b in γ-Irradiated Lung Cancer Cells

MicroRNA regulates cellular responses to ionizing radiation (IR) through translational control of target genes. We analyzed time-series changes in microRNA expression following γ-irradiation in H1299 lung cancer cells using microarray analysis. Significantly changed IR-responsive microRNAs were selected based on analysis of variance analysis, and predicted target mRNAs were enriched in mitogen-activated protein kinase (MAPK) signaling. Concurrent analysis of time-series mRNA and microRNA profiles uncovered that expression of miR-26b was down regulated, and its target activating transcription factor 2 (ATF2) mRNA was up regulated in γ-irradiated H1299 cells. IR in miR-26b overexpressed H1299 cells could not induce expression of ATF2. When c-Jun N-terminal kinase activity was inhibited using SP600125, expression of miR-26b was induced following γ-irradiation in H1299 cells. From these results, we concluded that IR-induced up-regulation of ATF2 was coordinately enhanced by suppression of miR-26b in lung cancer cells, which may enhance the effect of IR in the MAPK signaling pathway

Acetyl-11-keto-β-boswellic acid (AKBA); targeting oral cavity pathogens

<p>Abstract</p> <p>Background</p> <p>Boswellic acids mixture of triterpenic acids obtained from the oleo gum resin of <it>Boswellia serrata </it>and known for its effectiveness in the treatment of chronic inflammatory disease including peritumor edema. Boswellic acids have been extensively studied for a number of activities including anti inflammatory, antitumor, immunomodulatory, and inflammatory bowel diseases. The present study describes the antimicrobial activities of boswellic acid molecules against oral cavity pathogens. Acetyl-11-keto-β-boswellic acid (AKBA), which exhibited the most potent antibacterial activity, was further evaluated in time kill studies, mutation prevention frequency, postantibiotic effect (PAE) and biofilm susceptibility assay against oral cavity pathogens.</p> <p>Findings</p> <p>AKBA exhibited an inhibitory effect on all the oral cavity pathogens tested (MIC of 2-4 μg/ml). It exhibited concentration dependent killing of S<it>treptococcus mutans </it>ATCC 25175 up to 8 × MIC and also prevented the emergence of mutants of <it>S.mutans </it>ATCC 25175 at 8× MIC. AKBA demonstrated postantibiotic effect (PAE) of 5.7 ± 0.1 h at 2 × MIC. Furthermore, AKBA inhibited the formation of biofilms generated by <it>S.mutans </it>and <it>Actinomyces viscosus </it>and also reduced the preformed biofilms by these bacteria.</p> <p>Conclusions</p> <p>AKBA can be useful compound for the development of antibacterial agent against oral pathogens and it has great potential for use in mouthwash for preventing and treating oral infections.</p

Dentin Sialophosphoprotein (DSPP) Gene-Silencing Inhibits Key Tumorigenic Activities in Human Oral Cancer Cell Line, OSC2

We determined recently that dentin sialophosphoprotein (DSPP), a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins, is highly upregulated in human oral squamous cell carcinomas (OSCCs) where upregulation is associated with tumor aggressiveness. To investigate the effects of DSPP-silencing on the tumorigenic profiles of the oral cancer cell line, OSC2, short-hairpin RNA (shRNA) interference was employed to silence DSPP in OSC2 cells.Multiple regions of DSPP transcript were targeted for shRNA interference using hDSP-shRNA lentiviral particles designed to silence DSPP gene expression. Control shRNA plasmid encoding a scrambled sequence incapable of degrading any known cellular mRNA was used for negative control. Following puromycin selection of stable lines of DSSP-silenced OSC2 cells, phenotypic hallmarks of oral carcinogenesis were assayed by western blot and RT-PCR analyses, MTT (cell-viability), colony-formation, modified Boyden-Chamber (migration and invasion), and flow cytometry (cell-cycle and apoptosis) analyses. DSPP-silenced OSC2 cells showed altered cell morphology, reduced viability, decreased colony-formation ability, decreased migration and invasion, G0/G1 cell-cycle arrest, and increased tumor cell sensitivity to cisplatin-induced apoptosis. Furthermore, MMP-2, MMP-3, MMP-9, VEGF, Ki-67, p53, and EGFR were down-regulated. There was a direct correlation between the degree of DSPP-silencing and MMP suppression, as indicated by least squares regression: MMP-2 {(y = 0.850x, p<0.001) (y = 1.156x, p<0.001)}, MMP-3 {(y = 0.994x, p<0.001) (y = 1.324x, p = 0.004)}, and MMP-9 {(y = 1.248x, p = 0.005, y = 0.809, p = 0.013)}.DSPP-silencing in OSC2 cell decreased salient hallmarks of oral tumorigenesis and provides the first functional evidence of a potential key role for DSPP in oral cancer biology. The down-regulation of MMP-2, MMP-3, MMP-9, p53 and VEGF in DSPP-silenced OSC2 cells provides a significant functional/molecular framework for deciphering the mechanisms of DSPP activities in oral cancer biology

Constructing the HBV-human protein interaction network to understand the relationship between HBV and hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies have clearly validated the association between hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). Patients with chronic HBV infection are at increased risk of HCC, in particular those with active liver disease and cirrhosis.</p> <p>Methods</p> <p>We catalogued all published interactions between HBV and human proteins, identifying 250 descriptions of HBV and human protein interactions and 146 unique human proteins that interact with HBV proteins by text mining.</p> <p>Results</p> <p>Integration of this data set into a reconstructed human interactome showed that cellular proteins interacting with HBV are made up of core proteins that are interconnected with many pathways. A global analysis based on functional annotation highlighted the enrichment of cellular pathways targeted by HBV.</p> <p>Conclusions</p> <p>By connecting the cellular proteins targeted by HBV, we have constructed a central network of proteins associated with hepatocellular carcinoma, which might be to regard as the basis of a detailed map for tracking new cellular interactions, and guiding future investigations.</p

Prediction and Testing of Biological Networks Underlying Intestinal Cancer

Colorectal cancer progresses through an accumulation of somatic mutations, some of which reside in so-called “driver” genes that provide a growth advantage to the tumor. To identify points of intersection between driver gene pathways, we implemented a network analysis framework using protein interactions to predict likely connections – both precedented and novel – between key driver genes in cancer. We applied the framework to find significant connections between two genes, Apc and Cdkn1a (p21), known to be synergistic in tumorigenesis in mouse models. We then assessed the functional coherence of the resulting Apc-Cdkn1a network by engineering in vivo single node perturbations of the network: mouse models mutated individually at Apc (Apc1638N+/−) or Cdkn1a (Cdkn1a−/−), followed by measurements of protein and gene expression changes in intestinal epithelial tissue. We hypothesized that if the predicted network is biologically coherent (functional), then the predicted nodes should associate more specifically with dysregulated genes and proteins than stochastically selected genes and proteins. The predicted Apc-Cdkn1a network was significantly perturbed at the mRNA-level by both single gene knockouts, and the predictions were also strongly supported based on physical proximity and mRNA coexpression of proteomic targets. These results support the functional coherence of the proposed Apc-Cdkn1a network and also demonstrate how network-based predictions can be statistically tested using high-throughput biological data