Sujay Singh

Oxidative stress induced by aluminum oxide nanomaterials after acute oral treatment in Wistar rats.

This study investigated the oxidative stress induced after acute oral treatment with 500, 1000 and 2000 mg kg−1 doses of Al2O3‐30 and −40 nm and bulk Al2O3 in Wistar rats. Both the nanomaterials induced significant oxidative stress in a dose‐dependent manner in comparison to the bulk. There was no significant difference between the two nanomaterials. However, the effect decreased with increase with time after treatment. The histopathological examination showed lesions only in liver with Al2O3 nanomaterials at 2000 mg kg−1. Copyright

Development and characterization of monoclonal antibody against non-structural protein-2 of Chikungunya virus and its application.

The recent epidemics of Chikungunya viruses (CHIKV) with unprecedented magnitude and unusual clinical severity have raised a great public health concern worldwide, especially due to unavailability of vaccine or specific therapy. This emphasizes the need to understand the biological processes of this virus in details. Although CHIKV associated research has been initiated, the availability of CHIKV specific reagents for in-depth investigation of viral infection and replication are scanty. For Alphavirus replication, non-structural protein 2 (nsP2) is known to play a key regulatory role among all other non-structural proteins. The current study describes the development and characterization of nsP2 specific monoclonal antibody (mAb) against a synthetic peptide of CHIKV. Reactivity and efficacy of this mAb have been demonstrated by ELISA, Western blot, Flow cytometry and Immunofluorescence assay. Time kinetic study confirms that this mAb is highly sensitive to CHIKV-nsP2 as this protein has been detected very early during viral replication in infected cells. Homology analysis of the selected epitope sequence reveals that it is conserved among all the CHIKV strains of different genotypes, while analysis with other Alphavirus sequences shows that none of them are 100% identical to the epitope sequence. Moreover, using the mAb, three isoforms of CHIKV-nsP2 have been detected in 2D blot analysis during infection in mammalian cells. Accordingly, it can be suggested that the mAb reported in this study can be a sensitive and specific tool for experimental investigations of CHIKV replication and infection.

PEGylation of an osteoclast inhibitory peptide: Suitable candidate for the treatment of osteoporosis

Osteoporosis is a condition of bone loss due to excessive osteoclastic activity. Several protein factors, such as receptor activator of nuclear factor kappa-B (RANK), receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG), have been identified that are important in the pathogenesis of osteoporosis. RANKL binds to RANK and activates the NF-κB pathway by interaction of its cytoplasmic domain with an intracellular adapter protein, TNF receptor associated factors 6 (TRAF 6). This interaction can be inhibited by cell-permeable peptides that prevent RANK-TRAF 6 interaction. However, similar to the peptides/proteins used in clinical setting, the effective application of this TRAF 6 Inhibitory peptide as a therapeutic agent is marred by several limitations for instance short half-life, rapid renal clearance and immunogenicity. In the present study, we have developed PEGylated TRAF 6 Inhibitory peptide by conjugating TRAF 6 Inhibitory peptide to linear PEG backbone that exhibits longer bioavailability in plasma in the animal model. Besides, it has an enhanced uptake at its site of action, i.e., bone marrow.

Induction of apoptosis by Fe(salen)Cl through caspase-dependent pathway specifically in tumor cells.

Iron‐based compounds possess the capability of inducing cell death due to their reactivity with oxidant molecules, but their specificity towards cancer cells and the mechanism of action are hitherto less investigated. A Fe(salen)Cl derivative has been synthesized that remains active in monomer form. The efficacy of this compound as an anti‐tumor agent has been investigated in mouse and human leukemia cell lines. Fe(salen)Cl induces cell death specifically in tumor cells and not in primary cells. Mouse and human T‐cell leukemia cell lines, EL4 and Jurkat cells are found to be susceptible to Fe(salen)Cl and undergo apoptosis, but normal mouse spleen cells and human peripheral blood mononuclear cells (PBMC) remain largely unaffected by Fe(salen)Cl. Fe(salen)Cl treated tumor cells show significantly higher expression level of cytochrome c that might have triggered the cascade of reactions leading to apoptosis in cancer cells. A significant loss of mitochondrial membrane potential upon Fe(salen)Cl treatment suggests that Fe(salen)Cl induces apoptosis by disrupting mitochondrial membrane potential and homeostasis, leading to cytotoxity. We also established that apoptosis in the Fe(salen)Cl‐treated tumor cells is mediated through caspase‐dependent pathway. This is the first report demonstrating that Fe(salen)Cl can specifically target the tumor cells, leaving the primary cells least affected, indicating an excellent potential for this compound to emerge as a next‐generation anti‐tumor drug.

“Toll” Extending Its Gate from Drosophila Development to T Cell Response: Implication in Innate Immunity, Adaptive Immunity and Immunotherapy

“Toll” protein was originally discovered as a developmental marker in fruit fly (Drosophila). Now Toll like receptor (TLR) is envisioned as one of the important innate immune group of receptors regulating mammalian immune system. Interestingly, TLR response has been translated in immuno-pathology of most of the diseases and its immune responses including tumor immunity, infection immunity and autoimmunity. Moreover, in very recent time, TLR response has been suggested to modulate cell mediated immunity (CMI). Accordingly, the new paradigm of TLR response in T cell proposes a challenging work of T cell biology, both in basic and in translational research. Here we have reviewed the structural and functional homology of “Toll” protein in Drosophila and mammalian TLR, role of TLR in innate immunity, adaptive immunity and immunotherapy, recent updates of TLR response in T cells and the yet unanswered questions on the role of TLR in T cells to explore the new paradigm of TLR as one of the important connecting bridges between innate and adaptive immunity.

Effect of electric field on reentrance transition in a binary mixture of liquid crystals

Employing a phenomenological mean field theory, we analyze the effect of an electric field on the N − SmA phase transition for pure liquid crystal and on the reentrant nematic phase in a binary mixture of liquid crystals exhibiting the phase sequence I − N − SmA − NR on cooling. The basic idea of the work is to explain the phase transition behavior of the system by assuming that certain Landau coefficients associated with the order parameters coupling terms of the free-energy density expansion are field dependent. These parameters play a crucial role and show a rapid variation at the SmA − NR transition as compared to the SmA − N transition.