Benzo(a)pyrene (BaP) is a well-known carcinogen and enhances oxidative stress and apoptosis and also alters several molecular pathways. Curcumin is an active ingredient of Curcuma longa, and it has potent anti-inflammatory, antioxidant activity that defends cells from oxidative stress and cell death. The objectives of the present study were to explore the protective effects of curcumin against long-term administration of BaP induced disturbances in lungs of rats. Male rats were randomly divided into four groups: saline control, BaP only, BaP + curcumin, and curcumin only. Lung histopathology, electron microscopy, inflammatory cytokine release, antioxidant levels, apoptosis, and cell cycle were examined. Instillation of BaP significantly increased infiltration of inflammatory cells in alveolar space and inflammatory cytokine in blood. BaP induced lung tissue alterations including mild bronchitis, scant chronic inflammatory cell infiltrate in the wall of the respiratory bronchiole, and mild intra-alveolar haemorrhage. However, these alterations were found to be significantly less as mild inflammatory cell infiltrate in curcumin plus BaP treated group. Furthermore, electron microscopy results also showed necrotic changes and broken cell membrane of Type-II epithelial cell of alveoli in BaP group, which was reduced after adding curcumin treatment. In addition, we found BaP plus curcumin treatment effectively reduced inflammatory cytokines Tumour Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6), and C-reactive protein (CRP) levels in blood serum. Moreover, the levels of tunnel staining and p53 expression were significantly increased by BaP, whereas these changes were noticeably modulated after curcumin treatment. BaP also interferes in normal cell cycle, which was significantly improved with curcumin treatment. Overall, our findings suggest that curcumin attenuates BaP -induced lung injury, probably through inhibiting inflammation, oxidative stress and apoptosis in lung epithelial cells, and improving cell proliferation and antioxidants level. Thus, curcumin may be an alternative therapy for improving the outcomes of Benzo(a)pyrene-induced lung injury.

Objective: Cancer chemotherapy at the recommended doses is largely associated with toxicity, and also it is noteffective enough to reduce the advancement of the disease at lower doses. Thymoquinone (TQ) is an active compoundderived from black seeds (Nigella sativa) which exhibits anticancer activities. The aim of the present study was toinvestigate the synergistic effect of TQ alone and in combination with cyclophosphamide (cyclo), and to unravel therole of TQ in fatty acid synthase (FASN) mediated molecular signaling in Her2 + and Her2- breast cancer cell lines.Methods: The effect of TQ on the growth of Her2+ SKBR-3 and Her2- MDA-231 breast cancer lines were evaluatedas percent cell viability by cytotoxicity-based MTT assay. The analysis of cell cycle arrest was done through flowcytometryfollowed by Western blot and RT-PCR to detect signaling events in the cells. Results: The data showedthat TQ-cyclo (0.5mM-10μM) combination significantly inhibited the proliferation through the 5.49% and 57.72%accumulation of cells in sub-G1 and G1 respectively as 12% cells were shifted from G2/M phase in Her2+ breast cancercells. Similarly, TQ-cyclo (0.5mM-20μM) combination exhibited that the 16.6% cells were arrested in Sub-G1 and only3.54% cells were remained in G2/M phase as it was 22.89% in DMSO control in Her-2- breast cancers cells. ThoughTQ alone or in combination with cyclo alleviated the PI3K/Akt signaling by downregulating the phosphorylation of Aktand upregulating the PTEN, no changes was observed in FASN and Her-2 as well in both type of cells. The significantdecreased expression of cyclin D1 was found in TQ-cyclo combinations. Conclusion: The current findings suggestedthat TQ can alter the cell cycle progression and induce cell death independent of FASN mediated signaling. In terms ofclinical perspective, the present study clearly showed that TQ can broadly augment the effect of cyclo in breast cancercases irrespective of Her-2+ or Her-.

Natural killer T (NKT) cells, a small population of T cells, are capable of influencing a wide range of the immune cells, including T cells, B cells, dendritic cells and macrophages. In the present review, the antiviral role of the NKT cells and the strategies of viruses to evade the functioning of NKT cell have been illustrated. The nanoparticle-based formulations have superior immunoadjuvant potential by facilitating the efficient antigen processing and presentation that favorably elicits the antigen-specific immune response. Finally, the immunoadjuvant potential of the NKT cell ligand was explored in the development of antiviral vaccines. The use of an NKT cell-activating nanoparticle-based vaccine delivery system was supported in order to avoid the NKT cell anergy. The results from the animal and preclinical studies demonstrated that nanoparticle-incorporated NKT cell ligands may have potential implications as an immunoadjuvant in the formulation of an effective antiviral vaccine that is capable of eliciting the antigen-specific activation of the cell-mediated and humoral immune responses.

Purpose: The overexpression of Her-2 in 25– 30% breast cancer cases and the crosstalk between Her-2 and fatty acid synthase (FASN) establishes Her-2 as a promising target for site-directed delivery. The present study aimed to develop the novel lipid base formulations to target and inhibit the cellular proliferation of Her-2-expressing breast cancer cells through the silencing of FASN. In order to achieve this goal, we prepared DSPC/Chol and DOPE/CHEMS immunoliposomes, conjugated with the anti-Her-2 fab’ and encapsulated FASN siRNA against breast cancer cells. Methods: We evaluated the size, stability, cellular uptake and internalization of various formulations of liposomes. The antiproliferative gene silencing potential was investigated by the cell cytotoxicity, crystal violet, wound healing and Western blot analyses in Her-2⁺ and Her-2^® breast cancer cells. Results: The data revealed that both nanosized FASN-siRNA-encapsulated liposomes showed significantly higher cellular uptake and internalization with enhanced stability. The cell viability of Her-2⁺ SK-BR3 cells treated with the targeted formulation of DSPC/Chol- and DOPE/CHEMS-encapsulating FASN-siRNA reduced to 30% and 20%, respectively, whereas it was found to be 45% and 36% in MCF-7 cells. The wounds were not only failed to close but they became broader in Her-2⁺ cells treated with targeted liposomes of siRNA. Consequently, the amount of FASN decreased by 80% in SK-BR3 cells treated with non-targeted liposomes and it was 30% and 60% in the MCF-7 cells treated with DSPC/Chol and DOPE/CHEMS liposomes, respectively. Conclusion: In this study, we developed the formulation that targeted Her-2 for the suppression of FASN and, therefore, inhibited the proliferation of breast cancer cells.

The present study aimed to evaluate the anti-cancer potential of methanolic FSE and its possible molecular mechanism of action in breast cancer cells.