Institute of Life science

Bhubaneshwar, India

Institute of Life science

Bhubaneshwar, India

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Veiga-Parga T.,University of Tennessee at Knoxville | Sehrawat S.,Institute of Life science | Rouse B.T.,University of Tennessee at Knoxville
Immunological Reviews | Year: 2013

The host response to viruses includes multiple cell types that have regulatory function. Most information focuses on CD4+ regulatory T cells that express the transcription factor Foxp3+ (Tregs), which are the topic of this review. We explain how viruses through specific and non-specific means can trigger the response of thymus-derived natural Tregs as well as induce Tregs. The latter derive under appropriate stimulation conditions either from uncommitted precursors or from differentiated cells that convert to become Tregs. We describe instances where Tregs appear to limit the efficacy of antiviral protective immunity and other, perhaps more common, immune-mediated inflammatory conditions, where the Tregs function to limit the extent of tissue damage that occurs during a virus infection. We discuss the controversial roles that Tregs may play in the pathogenesis of human immunodeficiency and hepatitis C virus infections. The issue of plasticity is discussed, as this may result in Tregs losing their protective function when present in inflammatory environments. Finally, we mention approaches used to manipulate Treg numbers and function and assess their current value and likely future success to manage the outcome of virus infection, especially those that are responsible for chronic tissue damage. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Mohanty C.,Institute of Life science | Sahoo S.K.,Institute of Life science
Biomaterials | Year: 2010

Curcumin, the natural anticancer drug and its optimum potential is limited due to lack of solubility in aqueous solvent, degradation at alkaline pH and poor tissue absorption. In order to enhance its potency and improve bioavailability, we have synthesized curcumin loaded nanoparticulate delivery system. Unlike free curcumin, it is readily dispersed in aqueous medium, showing narrow size distribution "192 nm ranges (as observed by microscope) with biocompatibility (confocal studies and TNF-α assay). Furthermore, it displayed enhanced stability in phosphate buffer saline by protecting encapsulated curcumin against hydrolysis and biotransformation. Most importantly, nanoparticulate curcumin was comparatively more effective than native curcumin against different cancer cell lines under in vitro condition with time due to enhanced cellular uptake resulting in reduction of cell viability by inducing apoptosis. Molecular basis of apoptosis studied by western blotting revealed blockade of nuclear factor kappa B (NFκB) and its regulated gene expression through inhibition of IκB kinase and Akt activation. In mice, nanoparticulate curcumin was more bioavailable and had a longer half-life than native curcumin as revealed from pharmacokinetics study. Thus, the results demonstrated nanoparticulate curcumin may be useful as a potential anticancer drug for treatment of various malignant tumors. © 2010 Elsevier Ltd.


Bharati A.,Institute of Life science
PloS one | Year: 2012

Artemisinin, a secondary metabolite produced in Artemisia plant species, besides having antimalarial properties is also phytotoxic. Although, the phytotoxic activity of the compound has been long recognized, no information is available on the mechanism of action of the compound on photosynthetic activity of the plant. In this report, we have evaluated the effect of artemisinin on photoelectron transport activity of chloroplast thylakoid membrane. The inhibitory effect of the compound, under in vitro condition, was pronounced in loosely and fully coupled thylakoids; being strong in the former. The extent of inhibition was drastically reduced in the presence of uncouplers like ammonium chloride or gramicidin; a characteristic feature described for energy transfer inhibitors. The compound, on the other hand, when applied to plants (in vivo), behaved as a potent inhibitor of photosynthetic electron transport. The major site of its action was identified to be the Q(B); the secondary quinone moiety of photosystemII complex. Analysis of photoreduction kinetics of para-benzoquinone and duroquinone suggest that the inhibition leads to formation of low pool of plastoquinol, which becomes limiting for electron flow through photosystemI. Further it was ascertained that the in vivo inhibitory effect appeared as a consequence of the formation of an unidentified artemisinin-metabolite rather than by the interaction of the compound per se. The putative metabolite of artemisinin is highly reactive in instituting the inhibition of photosynthetic electron flow eventually reducing the plant growth.


Singh A.,Institute of Life science | Sahoo S.K.,Institute of Life science
Drug Discovery Today | Year: 2014

Multifunctional nanoplatforms represent a cutting edge tool in biomedical applications as a result of their applicability in the concurrent monitoring of medical treatment. Magnetic nanoparticles (MNPs) have generated great interest in the field of cancer nanotheranostics owing to their intrinsic magnetic property that enables them to be used as contrast agents in magnetic resonance imaging and as a therapeutic system in conjunction with hyperthermia. In addition, the physical properties and biocompatibility of MNPs help them to act as efficient drug carriers for targeted therapeutic regimes. In this review, we have discussed the different theranostic applications of MNPs. Further, we have raised the current challenges associated with the clinical translation of MNPs along with future opportunities in this field. © 2013 Elsevier Ltd.


Vandana M.,Institute of Life science | Sahoo S.K.,Institute of Life science
Biomaterials | Year: 2010

Gemcitabine [2′, 2′-difluoro-2′-deoxycytidine (dFdC)] is a low molecular weight, deoxycytidine analog inhibiting cellular DNA synthesis. Currently, it is the frontline drug approved by Food and Drug Administration (FDA) for the treatment of pancreatic cancer. However, efforts to use gemcitabine as an anti-cancer agent have been limited by its short circulation time and rapid metabolism that reflects in low tumor uptake and intracellular action. Polymer-drug conjugates, in this regard have spawned an approach to improve the cytotoxicity efficiency and bioavailability of gemcitabine by chemical modification. The present study describes the synthesis of a water soluble formulation of PEGylated gemcitabine characterized by FT IR, 1H NMR and RP-HPLC chromatography. The PEGylated gemcitabine has a prolonged circulation time in plasma as studied in an animal model. This eventually caused a marked improvement in the cytotoxicity and apoptosis-inducing activity in pancreatic cancer cell lines (MIA PaCa 2 and PANC 1). Hence, these findings demonstrate the PEGylated gemcitabine is a desirable approach for therapy by intravenous administration. Successful clinical application of this approach can significantly contribute to the treatment of pancreatic cancer. © 2010 Elsevier Ltd.


Misra R.,Institute of Life science | Sahoo S.K.,Institute of Life science
Molecular Pharmaceutics | Year: 2011

Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic used to treat a variety of cancers including leukemia. Chronic myeloid leukemia (CML) blasts like K562 cells are resistant to apoptosis induced by DOX due to several reasons, the primary being the sequestration of drug into cytoplasmic vesicles and induction of multidrug resistance (MDR) gene expression with DOX treatment resulting in intracellular resistance to this drug. Moreover, expression of antiapoptotic protein BCL-2 and the hybrid gene bcr/abl in K562 cells contributes resistance to DOX. Studies have shown that curcumin (CUR) has a pleiotropic therapeutic effect in cancer treatment, as it is an inhibitor of nuclear factor kappa B (NFκB) as well as a potent downregulator of MDR transporters. In this study, we investigated the potential benefit of using DOX and CUR in a single nanoparticle (NP) formulation to inhibit the development of drug resistance for the enhancement of antiproliferative activity of DOX in K562 cells. Results illustrate that the dual (DOX+CUR) drug loaded NPs were effectively delivered into K562 cells. CUR not only facilitates the retention of DOX in nucleus for a longer period of time but also inhibits the gradual expression of MDR1 and BCL-2 at the mRNA level in K562 cells. Moreover, Western blot results confirm that in combination both of the drugs were capable of inducing apoptosis even if in a lower concentration compared to either single drug in both solution or in formulation. Combinational therapy by using DOX and CUR, especially when administered in the NP formulation, has enhanced the cytotoxicity in K562 cells by promoting the apoptotic response. Overall, this combinational strategy has significant promise in the clinical management of intractable diseases, especially leukemia. © 2011 American Chemical Society.


Ofer D.,Institute of Life science | Linial M.,Institute of Life science
Bioinformatics | Year: 2014

Motivation: The evolution of multicellular organisms is associated with increasing variability of molecules governing behavioral and physiological states. This is often achieved by neuropeptides (NPs) that are produced in neurons from a longer protein, named neuropeptide precursor (NPP). The maturation of NPs occurs through a sequence of proteolytic cleavages. The difficulty in identifying NPPs is a consequence of their diversity and the lack of applicable sequence similarity among the short functionally related NPs.Results: Herein, we describe Neuropeptide Precursor Identifier (NeuroPID), a machine learning scheme that predicts metazoan NPPs. NeuroPID was trained on hundreds of identified NPPs from the UniProtKB database. Some 600 features were extracted from the primary sequences and processed using support vector machines (SVM) and ensemble decision tree classifiers. These features combined biophysical, chemical and informational-statistical properties of NPs and NPPs. Other features were guided by the defining characteristics of the dibasic cleavage sites motif. NeuroPID reached 89-94% accuracy and 90-93% precision in cross-validation blind tests against known NPPs (with an emphasis on Chordata and Arthropoda). NeuroPID also identified NPP-like proteins from extensively studied model organisms as well as from poorly annotated proteomes. We then focused on the most significant sets of features that contribute to the success of the classifiers. We propose that NPPs are attractive targets for investigating and modulating behavior, metabolism and homeostasis and that a rich repertoire of NPs remains to be identified. © 2013 The Author 2013. Published by Oxford University Press. All rights reserved.


Patent
Institute Of Life Science | Date: 2011-11-11

A novel method of isolation of TLR4 from cell lysates of mononuclear cells is provided. The method includes: collecting bovine adult filarial parasites (Setaria digitata); preparing aqueous extracts of setaria digitata (FAg) to produce affinity purified filarial glycoprotein (AgW); isolating human PBMCs from heparinised venous blood samples; subjecting the isolated human PBMCs to the step of incubation to produce PBMC lysates; coupling the said AgW with CNBR activated sepharose; and loading the AgW coupled with sepharose and PBMC lysates to an affinity purification column to isolate the receptor recognizing AgW and detecting the reactivity of anti-receptor antibodies and anti-human TLR4 antibodies to the affinity purified receptor using peroxidase conjugated anti-rabbit IgG (in solidphase assay).


Patent
Institute Of Life Science | Date: 2013-03-15

The present invention is an aqueous dispersible magnetic nanoparticle formulation with a high drug loading capacity used for sustained drug delivery. The formulated magnetic nanoparticles are composed of an iron oxide core coated with a long chain polymer, which provides aqueous dispersibility without the use of surfactant. A method is developed for the functionalization of magnetic nanoparticles for use in biomedical field.


Parveen S.,Institute of Life science | Misra R.,Institute of Life science | Sahoo S.K.,Institute of Life science
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2012

Drug delivery is an interdisciplinary and independent field of research and is gaining the attention of pharmaceutical researchers, medical doctors and industry. A safe and targeted drug delivery could improve the performance of some classic medicines already on the market, and moreover, will have implications for the development and success of new therapeutic strategies such as anticancer drug delivery, peptide and protein delivery and gene therapy. In the last decade, several drug-delivery technologies have emerged and a fascinating part of this field is the development of nanoscale drug delivery devices. Nanoparticles (NPs) have been developed as an important strategy to deliver conventional drugs, recombinant proteins, vaccines and more recently, nucleotides. NPs and other colloidal drug-delivery systems modify the kinetics, body distribution and drug release of an associated drug. This review article focuses on the potential of nanotechnology in medicine and discusses different nanoparticulate drug-delivery systems including polymeric NPs, ceramic NPs, magnetic NPs, polymeric micelles and dendrimers as well as their applications in therapeutics, diagnostics and imaging. From the Clinical Editor: This comprehensive review focuses on different nanoparticulate drug-delivery systems including polymeric NPs, ceramic NPs, magnetic NPs, polymeric micelles and dendrimers as well as their applications in therapeutics, diagnostics and imaging. © 2012 Elsevier Inc.

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