POTENTIAL ROLE OF ISORHAMNETIN TO SUPPRESS PROLIFERATION, INDUCE APOPTOSIS AND INHIBIT EMT THROUGH THE MODULATION OF PPAR¿/BMPR2 SIGNALING PATHWAYS

Ph.DDOCTOR OF PHILOSOPH

The role of Signal Processing in Meeting Privacy Challenges [an overview]

International audienceWith the increasing growth and sophistication of information technology, personal information is easily accessible electronically. This flood of released personal data raises important privacy concerns. However, electronic data sources exist to be used and have tremendous value (utility) to their users and collectors, leading to a tension between privacy and utility. This article aims to quantify that tension by means of an information-theoretic framework and motivate signal processing approaches to privacy problems. The framework is applied to a number of case studies to illustrate concretely how signal processing can be harnessed to provide data privacy

Gastro-intestinal absorption of isoniazid and rifampicin in patients with intestinal tuberculosis

The gastro-intestinal absorption of isoniazid and rifampicin was studied in 12 patients with intestinal tuberculosis (10 slow and 2 rapid acetylators of isoniazid) and compared with that in 18 patients with pulmonary tuberculosis (8 slow and 10 rapid acetylators). Exposure (area under the time-concentration curve), calculated on the basis of serum concentrations of the two drugs at 1, 2, 3, 6 and 8 hours, and the proportion of dose of isoniazid excreted in urine collected over the period (0-8½) hours as isoniccotinyl compounds after drug administration were similar in the 2 groups suggesting no impairment of gastro-intestinal absorption of the 2 drugs in patients with intestinal tuberculosis. It was also observed that there was no delay in the absorption of the 2 drugs in patients with intestinal tuberculosis as compared to that in patients with pulmonary tuberculosis. The absorption of D-xylose, used to assess the absorptive capacity of the proximal small intestine, was also similar and normal in both groups of patients

Impact of HIV Infection on the Recurrence of Tuberculosis in South India

Background. There is limited information on the relative proportion of reactivation and reinfection at the time of recurrence among human immunodeficiency virus (HIV)-infected and HIV-uninfected patients who are successfully treated for tuberculosis infection in India. Methods. HIV-infected and HIV-uninfected patients with sputum culture-positive pulmonary tuberculosis were treated with short-course regimens and followed up for 36 months at the Tuberculosis Research Centre, South India. Bacteriologic recurrences were documented, and typing of strains was performed using 3 different genotypic techniques: restriction fragment length polymorphism (RFLP) by IS6110, spoligotyping, and mycobacterial interspersed repeat unit (MIRU)-variable number tandem repeat (VNTR). DNA fingerprints of paired Mycobacterium tuberculosis isolates (baseline and recurrence) were compared. Results. Among 44 HIV-infected and 30 HIV-uninfected patients with recurrent tuberculosis during the period July 1999 to October 2005, 25 and 23 paired isolates, respectively, were typed using all 3 methods. Recurrence was due to exogenous reinfection in 88% of HIV-infected and 9% of HIV-uninfected patients (P < .05). Among recurrent isolates, the HIV-infected patients showed more clustering, as well as a higher proportion of drug resistance, including multidrug resistance. Conclusions. In India, a tuberculosis-endemic country, most recurrences after successful treatment of tuberculosis are due to exogenous reinfection in HIV-infected persons and endogenous reactivation in HIV-uninfected persons. Strategies for prevention and treatment of tuberculosis infection must take these findings into consideration

Plumbagin inhibits invasion and migration of breast and gastric cancer cells by downregulating the expression of chemokine receptor CXCR4

<p>Abstract</p> <p>Background</p> <p>Increasing evidence indicates that the interaction between the CXC chemokine receptor-4 (CXCR4) and its ligand CXCL12 is critical in the process of metastasis that accounts for more than 90% of cancer-related deaths. Thus, novel agents that can downregulate the CXCR4/CXCL12 axis have therapeutic potential in inhibiting cancer metastasis.</p> <p>Methods</p> <p>In this report, we investigated the potential of an agent, plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), for its ability to modulate CXCR4 expression and function in various tumor cells using Western blot analysis, DNA binding assay, transient transfection, real time PCR analysis, chromatin immunoprecipitation, and cellular migration and invasion assays.</p> <p>Results</p> <p>We found that plumbagin downregulated the expression of CXCR4 in breast cancer cells irrespective of their HER2 status. The decrease in CXCR4 expression induced by plumbagin was not cell type-specific as the inhibition also occurred in gastric, lung, renal, oral, and hepatocellular tumor cell lines. Neither proteasome inhibition nor lysosomal stabilization had any effect on plumbagin-induced decrease in CXCR4 expression. Detailed study of the underlying molecular mechanism(s) revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, inhibition of NF-κB activation, and suppression of chromatin immunoprecipitation activity. In addition, using a virtual, predictive, functional proteomics-based tumor pathway platform, we tested the hypothesis that NF-κB inhibition by plumbagin causes the decrease in CXCR4 and other metastatic genes. Suppression of CXCR4 expression by plumbagin was found to correlate with the inhibition of CXCL12-induced migration and invasion of both breast and gastric cancer cells.</p> <p>Conclusions</p> <p>Overall, our results indicate, for the first time, that plumbagin is a novel blocker of CXCR4 expression and thus has the potential to suppress metastasis of cancer.</p

The PE-PPE Domain in Mycobacterium Reveals a Serine α/β Hydrolase Fold and Function: An In-Silico Analysis

The PE and PPE proteins first reported in the genome sequence of Mycobacterium tuberculosis strain H37Rv are now identified in all mycobacterial species. The PE-PPE domain (Pfam ID: PF08237) is a 225 amino acid residue conserved region located towards the C-terminus of some PE and PPE proteins and hypothetical proteins. Our in-silico sequence analysis revealed that this domain is present in all Mycobacteria, some Rhodococcus and Nocardia farcinica genomes. This domain comprises a pentapeptide sequence motif GxSxG/S at the N-terminus and conserved amino acid residues Ser, Asp and His that constitute a catalytic triad characteristic of lipase, esterase and cutinase activity. The fold prediction and comparative modeling of the 3-D structure of the PE-PPE domain revealed a “serine α/β hydrolase” structure with a central β-sheet flanked by α-helices on either side. The structure comprises a lid insertion with a closed structure conformation and has a solvent inaccessible active site. The oxyanion hole that stabilizes the negative charge on the tetrahedral intermediate has been identified. Our findings add to the growing list of serine hydrolases in mycobacterium, which are essential for the maintenance of their impermeable cell wall and virulence. These results provide the directions for the design of experiments to establish the function of PE and PPE proteins

Multifaceted link between cancer and inflammation

10.1042/BSR20100136Bioscience Reports3211-15BRPT