TLR4 and NKT Cell Synergy in Immunotherapy against Visceral Leishmaniasis

NKT cells play an important role in autoimmune diseases, tumor surveillance, and infectious diseases, providing in most cases protection against infection. NKT cells are reactive to CD1d presented glycolipid antigens. They can modulate immune responses by promoting the secretion of type 1, type 2, or immune regulatory cytokines. Pathogen-derived signals to dendritic cells mediated via Toll like Receptors (TLR) can be modulated by activated invariant Natural Killer T (iNKT) cells. The terminal β-(1–4)-galactose residues of glycans can modulate host responsiveness in a T helper type-1 direction via IFN-γ and TLRs. We have attempted to develop a defined immunotherapeutic, based on the cooperative action of a TLR ligand and iNKT cell using a mouse model of visceral leishmaniasis. We evaluated the anti-Leishmania immune responses and the protective efficacy of the β-(1–4)-galactose terminal NKT cell ligand glycosphingophospholipid (GSPL) antigen of L. donovani parasites. Our results suggest that TLR4 can function as an upstream sensor for GSPL and provoke intracellular inflammatory signaling necessary for parasite killing. Treatment with GSPL was able to induce a strong effective T cell response that contributed to effective control of acute parasite burden and led to undetectable parasite persistence in the infected animals. These studies for the first time demonstrate the interactions between a TLR ligand and iNKT cell activation in visceral leishmaniasis immunotherapeutic.     

Design,synthesis and ex vivo evaluation of colon-specific azo based prodrugs of anticancer agents

Colon-specific azo based prodrugs of anticancer agents like methotrexate (6), gemcitabine (7) and analogue of oxaliplatin (RTB-4) (8) were synthesized and characterized by modern analytical techniques. The prepared prodrugs were stable in acidic (pH 1.2) and basic (pH 7.4) buffers which showed their stability in upper GIT environment. Further, an assay was performed which demonstrated the presence of azoreductase enzyme in the rat fecal material, rat cecum content and other parts of intestinal content which reduce specifically the azo bond and release the drug. The in vitro cytotoxicity assay was also performed which clearly indicated that these azo based prodrugs are active against human colorectal cancer cell lines (COLO 205, COLO 320 DM and HT-29). The release behavior of prodrugs (10, 11 and 15) was 60–70% after 24 h incubation at 37 °C. Therefore, the synthesized azo linked prodrugs of methotrexate, gemcitabine and RTB-4 are the potential candidates for colon targeted drug delivery system with minimal undesirable side effects.     

A Large Scale Preparation op Peanut Agglutinin on a New Affinity Matrix

A simple and rapid method for the purification of Peanut Agglutinin by affinity chromatography on cross-linked arabinogalactan is described. Cross-linked arabinogalactan shows a high capacity for PNA. The lectin has been obtained to electrophore-tic purity and has a high hemagglutinating specific activity.     

Effect of the presence of predatory cues and hunger on cannibalistic behaviour of ladybird beetle,Menochilus sexmaculatus Fabricius (Coleoptera: Coccinellidae)

1. Cannibalism and its role in population dynamics, along with various factors influencing the rate of cannibalism, have been widely studied across taxa.
2. The effects of predatory cue concentrations and starvation on cannibalistic tendencies and other life-history traits in cannibalistic and non-cannibalistic adults of Menochilus sexmaculatus were investigated.
3. Egg cannibalism increased with increasing predatory cue concentration and was maximum in high predatory cue treatment; increased with starvation irrespective of their diet history.
4. Latency to cannibalise eggs was shorter for cannibalistic adults as compared to non-cannibalistic adults irrespective of their hunger status and concentration of conspecific cues.
5. Non-cannibalistic females have higher fecundity than cannibalistic females.
6. In conclusion, both cannibalistic and non-cannibalistic individuals respond differently to intrinsic (hunger) and extrinsic cues (predatory cue concentrations). Cannibalistic individuals cannibalise more than non-cannibalistic ones at low levels of starvation and predatory cues.
7. Our finding suggests that cannibalistic individuals are better at assessing the risk and removing future competitors, which might favour these individuals over non-cannibalistic ones in adverse conditions and increased competition.