196 research outputs found
Functional characterization of a competitive peptide antagonist of p65 in human macrophage-like cells suggests therapeutic potential for chronic inflammation
Mythily Srinivasan,1 Corinne Blackburn,1 Debomoy K Lahiri2,3 1Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry, 2Institute of Psychiatry Research, Department of Psychiatry, 3Department of Medical and Molecular Genetics, School of Medicine, Indiana University-Purdue University, Indianapolis, IN, USA Abstract: Glucocorticoid-induced leucine zipper (GILZ) is a glucocorticoid responsive protein that links the nuclear factor-kappa B (NFκB) and the glucocorticoid signaling pathways. Functional and binding studies suggest that the proline-rich region at the carboxy terminus of GILZ binds the p65 subunit of NFκB and suppresses the immunoinflammatory response. A widely-used strategy in the discovery of peptide drugs involves exploitation of the complementary surfaces of naturally occurring binding partners. Previously, we observed that a synthetic peptide (GILZ-P) derived from the proline-rich region of GILZ bound activated p65 and ameliorated experimental encephalomyelitis. Here we characterize the secondary structure of GILZ-P by circular dichroic analysis. GILZ-P adopts an extended polyproline type II helical conformation consistent with the structural conformation commonly observed in interfaces of transient intermolecular interactions. To determine the potential application of GILZ-P in humans, we evaluated the toxicity and efficacy of the peptide drug in mature human macrophage-like THP-1 cells. Treatment with GILZ-P at a wide range of concentrations commonly used for peptide drugs was nontoxic as determined by cell viability and apoptosis assays. Functionally, GILZ-P suppressed proliferation and glutamate secretion by activated macrophages by inhibiting nuclear translocation of p65. Collectively, our data suggest that the GILZ-P has therapeutic potential in chronic CNS diseases where persistent inflammation leads to neurodegeneration such as multiple sclerosis and Alzheimer’s disease. Keywords: glucocorticoid-induced leucine zipper, therapeutic potential, translational impact, chronic inflammatio
Study of risk of malignancy index scoring system in the preoperative evaluation of patients with ovarian tumor and its correlation with histopathological examination
BACKGROUND:
The discrimination between benign and malignant ovarian tumor is important in considering an optimal plan for an appropriate surgical treatment.
OBJECTIVE:
To evaluate the ability of risk of malignancy index based on menopausal status, ultrasonographic score and serum level of CA125 to discriminate between benign and malignant ovarian tumor.
MATERIAL AND METHODS:
This is a prospective observational study of 100 patients of all age group who admitted with a diagnosis of ovarian tumor at Govt. R.S.R.M Lying in hospital, Chennai during the period of 2015 to 2016 . The sensitivity, specificity, positive predictive value and negative predictive value of different cut off values of RMI were calculated. Finally it was correlated with histopathological examination.
RESULTS:
By comparing the RMI with different cut off values, the RMI with cut off value 200 gave sensitivity 82.6%, specificity 94.8%, positive predictive value 82.6% and negative predictive value 94.8%. It was significantly better in predicting malignancy.
CONCLUSION:
The RMI is able to discriminate between benign and malignant ovarian tumors. The RMI with a cut off value 200 was the most reliable in predicting malignancy. It is a simple method that can be incorporated into clinical practice easily to enable the selection of patients for proper referral to tertiary care centre
Impact of Job Satisfaction and Awareness towards Organisational Objectives and Policies on the Various Dimensions of Organisational Commitment:An Investigation among Employees of Public Sector Banks in Erode District
Comparing the Effects of Stretching and Cryotherapy in Treating Nocturnal Leg Cramps in Older Adults
A strong maximum principle for a class of non-positone singular elliptic problems
We prove that nonnegative solutions of quasilinear elliptic problems of the type (0.1) {-Δpu=f(u) in Ω, 1 < p ≤ 2 u = 0 on ∂Ω are actually positive in Ω , under the following assumptions: Ω is a regular bounded strictly convex domain in ,RN,N ≥ 2 symmetric with respect to a hyperplane, ƒ is a locally Lipschitz continuous function in [0,+ ∞) with ƒ(0) <0, and u is a weak solution in C1(Ω̅). The proof of this result uses the moving plane method as in [2] and can be adapted to more general geometric situations
Dynamic Modeling, Simulation and Multivariable Control Strategy Applied to Catalytic Cracking Unit
- …
