T cell costimulation, checkpoint inhibitors and anti-tumor therapy

The hallmarks of the adaptive immune response are specificity and memory. The cellular response is mediatedby T cells which express cell surface T cell receptors (TCRs) that recognize peptide antigens in complex withmajor histocompatibility complex (MHC) molecules on antigen presenting cells (APCs). However, binding ofcognate TCRs with MHC-peptide complexes alone (signal 1) does not trigger optimal T cell activation. Inaddition to signal 1, the binding of positive and negative costimulatory receptors to their ligands modulates Tcell activation. This complex signaling network prevents aberrant activation of T cells. CD28 is the mainpositive costimulatory receptor on naı¨ve T cells; upon activation, CTLA4 is induced but reduces T cellactivation. Further studies led to the identification of additional negative costimulatory receptors known ascheckpoints, e.g. PD1. This review chronicles the basic studies in T cell costimulation that led to the discoveryof checkpoint inhibitors, i.e. antibodies to negative costimulatory receptors (e.g. CTLA4 and PD1) whichreduce tumor growth. This discovery has been recognized with the award of the 2018 Nobel prize in Physiology/Medicine. This review highlights the structural and functional roles of costimulatory receptors, themechanisms by which checkpoint inhibitors work, the challenges encountered and future prospects.

Spectrophotometric Determination of Sun Protection Factor and Antioxidant Potential of an Herbal Mixture.

Objectives: Present research work deals with the determination of hydroxyl radical scavenging potential and Sun Protection Factor of herbal mixture which was prepared by the phytochemical composition of different herbal extracts. Materials and Methods: The herbal mixture was prepared by the composition of important herbal plant extracts such as; 50% ethanolic extract of Berberis aristata root, 30% ethanolic extract of Ficus benghalensis bark, ethanolic extract of Asparagus racemosus root, aqueous extract of Asparagus racemosus root, 30% methanolic extract of Butea monosperma flowers, gel extract of Aloe vera, 80% ethanolic extract of Terminalia arjuna bark, 80% ethanolic extract of Cyperus rotundus root, 80% ethanolic extract of Rubia cordifolia root and 50% methanolic extract of Hibiscus-rosa-sinensis flowers, which was further proceed for hydroxyl radical scavenging activity and Sun Protection Factor determination at different concentrations viz;0.5%, 1%, 5% and 10%. Results: IC50 values of Ascorbic acid was found to be 52.93±2.64% (Inhibition TBARS) at the concentration of 18.00 μg/ml and herbal mixture were 51.58±1.27% (Inhibition TBARS) observed at the concentration of 9.80 μg/ml respectively. The SPF values for different concentrations of herbal mixture were in between 2.14±0.15SPF to 12.97±0.07SPF. The results showed that 10% concentrated of herbal mixture has high SPF value of 12.97±0.07SPF which may be attributed due to the presence of active components. Conclusion: Herbs and herbal preparations have high potential due to their antioxidant activity, primarily. The bioactive compounds such as flavonoids, phenolic acids, saponins etc. of this prepared herbal mixture may able to reduce skin damages which are caused due to long time exposure of skin in sun rays specially UVA and UVB rays. The proposed spectrophotometric method is simple and rapid for the in vitro determination of SPF values of sunscreens emulsions.

Protective activity of picroliv on hepatic amoebiasis associated with carbon tetrachloride toxicity.

BACKGROUND AND OBJECTIVE: Picroliv, isolated from the root and rhizome of Picrorhiza kurroa, is known to have significant hepatoprotective activity. Its effects against Entamoeba histolytica induced liver damage are not studied. This study aims to evaluate the hepatoprotective action of picroliv against the hepatotoxic changes induced by carbon tetrachloride (CCl(4)) and E. histolytica infection in three animal models. METHODS: Mastomys, gerbils and albino Druckray rats were used in this study. A total of 30 animals were used for each model and divided into five groups of six animals each. Group I consisted of normal animals. The rest received six doses of CCl(4) intraperitoneally. Group II served as hepatotoxic control. The remaining animals were infected intraperitoneally with E. histolytica trophozoites, of which group III was the hepatotoxic plus amoeba infected control. The remaining animals were divided into two groups, one received hepatoprotective agent picroliv and the other silymarin. All animals were sacrificed seven days post amoeba infection. RESULTS: Increase in the enzyme levels induced by CCl(4) was further elevated after E. histolytica infection. Pinpoint abscesses were found to develop only in gerbils after E. histolytica infection. Picroliv was found to possess hepatoprotective activity against amoebic liver abscess. INTERPRETATION AND CONCLUSION: Significant recovery obtained in serum enzyme levels in all animal models and against amoebic liver abscess in gerbils on treatment with picroliv indicated that picroliv possesses therapeutic activity against E. histolytica induced hepatic damage.