CSIR - Central Electrochemical Research Institute

Chennai, India

CSIR - Central Electrochemical Research Institute

Chennai, India
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Ganguly D.,CSIR - Central Electrochemical Research Institute
Trends in Immunology | Year: 2017

The central pathogenetic role of type I interferons (IFNs) in several systemic autoimmune diseases is well established. Recent studies have also discovered a similar crucial role of type I IFNs in different components of metabolic disorders. Self nucleic acid-driven Toll-like receptor (TLR) activation in plasmacytoid dendritic cells (pDCs) and type I IFN induction appear to be the key initiating events shared by most of these autoimmune and metabolic diseases. Further strengthening this link, many patients with systemic autoimmunities also present with metabolic disorders. This concurrence of autoimmunities and metabolic disorders may be explained by a single pathogenetic continuum, and suggests shared targets for potential new therapies. The roles of pDCs and type I IFNs are well established in several systemic autoimmunities, including systemic lupus erythematosus, psoriasis, type I diabetes, Sjögren's syndrome, and systemic sclerosis.Patients with these autoimmune diseases often develop insulin resistance and metabolic syndrome.Recent studies have discovered a central role of type I IFN induction in components of metabolic syndrome, including obesity-associated insulin resistance, hepatosteatosis, and atherosclerosis.Self nucleic acid-driven TLR activation in pDCs and type I IFN induction are key innate initiation events shared by several systemic autoimmune diseases as well as by metabolic syndrome components.Syndromic concurrences of autoimmunities and metabolic disorders result from shared pathogenetic events. They also share targets for potential new-generation therapies. © 2017 Elsevier Ltd.

Gupta A.,CSIR - Central Electrochemical Research Institute | Misra A.,CSIR - Central Electrochemical Research Institute | Deretic V.,University of New Mexico
Advanced Drug Delivery Reviews | Year: 2016

One of the promising host-directed chemotherapeutic interventions in tuberculosis (TB) is based on inducing autophagy as an immune effector. Here we consider the strengths and weaknesses of potential autophagy-based pharmacological intervention. Using the existing drugs that induce autophagy is an option, but it has limitations given the broad role of autophagy in most cells, tissues, and organs. Thus, it may be desirable that the agent being used to modulate autophagy is applied in a targeted manner, e.g. delivered to affected tissues, with infected macrophages being an obvious choice. This review addresses the advantages and disadvantages of delivering drugs to induce autophagy in M. tuberculosis-infected macrophages. One option, already being tested in models, is to design particles for inhalation delivery to lung macrophages. The choice of drugs, drug release kinetics and intracellular residence times, non-target cell exposure and feasibility of use by patients is discussed. We term here this (still experimental) approach, of compartment-targeting, autophagy-based, host-directed therapy as "Track-II antituberculosis chemotherapy.". © 2016.

Gopal V.,CSIR - Central Electrochemical Research Institute
Journal of Controlled Release | Year: 2013

Non-viral gene therapy approaches have strongly established the utility of peptides as integral constituents of delivery platforms devised for efficient transfer of therapeutic molecules into cells. Among these, cell-penetrating peptides (CPPs), encompassing a family of short peptide sequences and their chimeric derivatives, have gained versatility through the addition of de novo peptide ligands primarily to facilitate cell-specific nucleic acid delivery in vitro and in vivo. The review illustrates the structural requirements of a noteworthy peptide TAT-PTD and other derivatives chiefly to exemplify their implication in gene therapy. An overview of the emerging concept and recent explorations will be presented through unique examples which form a facet in nanotechnology-based cancer therapy. Finally the basis for the utility of CPPs in plants will be discussed in view of its biotechnological potential. © 2013 Elsevier B.V.

Kundu S.,CSIR - Central Electrochemical Research Institute
Journal of Materials Chemistry C | Year: 2013

A new route for the formation of shape-selective Au nanoparticles (NPs) has been demonstrated. The reduction of Au(iii) ions was done with alkaline 2,7-DHN in CTAB micellar media under 30 min of continuous UV-irradiation. The reaction results in uniform Au nanospheres and Au nanowires. With the change in Au(iii) ion to CTAB molar ratio, the particles' size and shape can be tuned. Au nanorods and nanoprisms are synthesized via seed mediated growth and microwave heating methods and the particles are characterized by several spectroscopic tools. The shape effects of the four different types of Au NPs were investigated using surface enhanced Raman scattering (SERS) studies. The results showed that the SERS intensity increases with the change in NPs' shape from nanospheres to nanorods to nanowires to nanoprisms. The highest enhancement observed for the nanoprisms is due to the presence of a maximum number of sharp edges or surface active rough surfaces compared to the smooth surfaces of the nanospheres. This high enhancement factor (EF) of these multiple shaped Au NPs might find potential application in detection of single molecules or in many other fields like detection of bio-molecules, bioassays, bio-diagnosis or even clinical diagnostics and in medical therapy. This journal is © 2013 The Royal Society of Chemistry.

Kundu S.,CSIR - Central Electrochemical Research Institute
Physical Chemistry Chemical Physics | Year: 2013

Self-assembled Ag NPs on DNA chains were synthesized using a simple photochemical technique. The size of the individual Ag NPs and their average diameter on the DNA chains can be tuned just by controlling the various reaction parameters. The average diameter of the self-assembled Ag NPs on DNA chains were varied in the 20-75 nm range, whereas the average diameters of the individual Ag NPs can be varied in the 5-15 nm range. The nominal length of the DNA chains self-assembled by Ag NPs can be extended to a few microns. The present process does not need any external reducing agent like sodium borohydride or hydrazine or others, and DNA itself can act in a dual role: a 'reducing agent' and a 'stabilizing agent' for the formation of DNA-Ag NPs colloidal dispersion. The synthesized DNA-Ag NPs were well characterized by UV-Vis, EDS, TEM, XRD, XPS, and FT-IR analyses. The self-assembled Ag NPs on DNA chains were found to have good catalytic activity towards the reduction of aromatic nitro compounds. The potentiality of the DNA-Ag NPs as catalyst was tested both in solution and after depositing over solid substrate as thin films. The synthesized Ag NPs on DNA were found to be extremely stable for a period of six months under ambient conditions while kept inside a refrigerator. This pronounced catalytic activity of the material might be useful for future applications in a variety of organic and inorganic catalysis reactions and in SERS-based detection of environmentally important bio-molecules and in sensors. © 2013 The Owner Societies.

Rayasam G.V.,CSIR - Central Electrochemical Research Institute
Expert Opinion on Therapeutic Targets | Year: 2014

Introduction: Tuberculosis (TB) is still a leading cause of mortality in the developing world and there is an unmet clinical need for new drugs with novel mechanism of action. Targeting the complex and unique cell wall of TB-causing pathogen Mycobacterium tuberculosis (Mtb) has been a mainstay of TB drug discovery. Though, the composition of the cell wall of Mtb is well understood, little is known about the assembly process of the cell wall such as the transport of mycolic acids across the cell wall. Areas covered: Recent research demonstrating MmpL3 protein as a transmembrane transporter of mycolic acids is discussed. In addition, MmpL3 has also been implicated in heme transport. Research describing several diverse chemical inhibitors that inhibit MmpL3 is reviewed. Expert opinion: Evidence so far suggests MmpL3 is a transporter of mycolic acids. It has emerged as a novel therapeutic target for Mtb that is essential and for which several small molecule inhibitors have been identified. Identifying the interacting partners, understanding the substrate specificity and the mechanism of transport by MmpL3 are some of the gaps in knowledge that need to be addressed. © 2014 Informa UK, Ltd.

Adlakha Y.K.,CSIR - Central Electrochemical Research Institute
Cell death & disease | Year: 2013

Aberrant regulation of cholesterol homeostasis is associated with obesity as well as multiple types of cancer. However, the mechanism behind these is largely missing. Here, we show that microRNA (miRNA)-128-2 is not only a pro-apoptotic microRNA but it also alters the expression of genes involved in cellular cholesterol homeostasis. Cholesterol efflux via ATP-binding cassette transporters (ABCA1 and ABCG1) is a mechanism for cells to eliminate excess cholesterol and prevent cellular cholesterol accumulation. The regulation of these pathways is complex with transcriptional regulation by sterol-regulatory element-binding protein (SREBP) and liver X receptor/retinoid X receptor (RXR) transcription factors but poorly understood at the post-transcriptional levels. MiR-128-2 increases the expression of SREBP2 and decreases the expression of SREBP1 in HepG2, MCF7 and HEK293T cells independent of sirtuin 1 (SIRT1) status. MiR-128-2 inhibits the expression of ABCA1, ABCG1 and RXRα directly through a miR-128-2-binding site within their respective 3'untranslated regions. The administration of miR-128-2 leads to decline in the protein and mRNA levels of ABCA1, ABCG1 and RXRα. Conversely, anti-miRNA treatment leads to increased ABCA1, ABCG1 and RXRα expression. The inverse correlation between miR-128-2 and its targets viz. ABCA1 and ABCG1 was also established during high-fat diet in different mice tissues. Our data show that cholesterol efflux is attenuated by miR-128-2 overexpression and, conversely, stimulated by miR-128-2 silencing. Further, we also observed the induction of ER stress response by miR-128-2. In this study, we provide the first evidence of miR-128-2 to be a new regulator of cholesterol homeostasis. Our study shows dual role of miR-128-2, as a pro-apoptotic molecule as well as a regulator of cholesterol homeostasis.

Sharma A.,CSIR - Central Electrochemical Research Institute
Trends in Molecular Medicine | Year: 2015

In his article, Szyf [1] has addressed the key challenges in and the controversies surrounding nongenetic inheritance. However, crucial findings that are important to counter two major criticisms held against transgenerational inheritance, especially in mammals - namely epigenetic memory survival across generations, and soma-to-germline transfer of heritable information - need additional discussion. Given the far-reaching implications of nongenetic inheritance on the one hand, and the skepticisms about its existence on the other, it is important that the advances concerned are examined deeply. The following discussion fills the gap left by Szyf [1] and provides an integrated perspective. © 2015 Elsevier Ltd.

Chaturvedi D.,CSIR - Central Electrochemical Research Institute
Tetrahedron | Year: 2012

In this review, various kinds of synthetic methodologies for the synthesis of organic carbamates employing diversity of reagents and catalytic systems have been reviewed, from the beginning to the recent reports (covering till December 2010). © 2011 Elsevier Ltd.

Goel A.,CSIR - Central Electrochemical Research Institute | Kumar A.,CSIR - Central Electrochemical Research Institute | Raghuvanshi A.,CSIR - Central Electrochemical Research Institute
Chemical Reviews | Year: 2013

Nature is a phenomenal source of biologically active simple and complex molecules having oxygen heterocyclic scaffolds such as flavonoids, isoflavonoids, pyranones, coumarins, and their benzannulated compounds. These oxygen heerocyclic compounds are originated from eclectic array of plants and marine sources through various de novo selective enzymatic reactions in a combinatorial fashion. To date, no review is available that deals with stereochemical aspects, chemical reactivity, or total syntheses of natural pterocarpans. To the surprise, many reports are published with ambiguous stereochemistry at positions 6a and 11a of pterocarpans. Considering the importance of the unique conformations of the pterocarpans and their biological activities, this review is concerned with conformational studies, assignment of absolute configurations, and state-of-the-art methodologies for their syntheses.

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