Overall, our findings suggest that exosomal transfer of miR-100 may be a novel mechanism underlying the paracrine effects of MSC-derived exosomes and may provide a means by which these vesicles can modulate vascular responses within the microenvironment of breast cancer cells.

As one of the four major families of pattern recognition receptors (PRRs), toll like receptors (TLRs)are crucial and important components of the innate immune system. Peroxisome proliferatoractivatedreceptors (PPARs) with three isoforms are transcription factors classified as a subfamilyof nuclear receptor proteins, and are of significant regulatory activity in cellular differentiation,development, metabolism, and tumorigenesis. It is well established that PPARs agonists displayanti-inflammatory effects through inhibition of the nuclear factor-kappa B (NF-κB) pathway, akey regulator of immune and inflammatory responses, in a sense that TLRs signaling pathwaysare mainly toward activation of NF-κB. Through a systematic review of previous studies, weaimed to address and clarify the reciprocal interaction between TLRs and PPARs in hope to findalternative therapeutic approaches for inflammatory diseases. Among the available scientificdatabase, 31 articles were selected for this review. A comprehensive review of this databaseconfirms the presence of a cross-talk between PPARs and TLRs, indicating that not onlyPPARs stimulation may affect the expression level of TLRs via several mechanisms leading tomodulating TLRs activities, but also TLRs have the potential to moderate the expression of PPARs.We, therefore, conclude that, as a key regulator of the innate immune system, the interactionbetween PPARs and TLRs is a potential therapeutic target in disease treatment.

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Background:  Although previous studies demonstrated an anticancer effect for the ligands of peroxisome proliferator-activated receptor gamma (PPARγ) through activation of its anti-inflammatory responses, nevertheless the anti-tumor mechanism of PPARγ has not been intensively investigated. One of the molecules involved in cancer progression is toll-like receptor 4 (TLR4).Methods: B16F10 melanoma cells were cultured with or without LPS for 24 hr. The cells were subcutaneously injected to two groups of C57BL/6 mice. After the development of palpable tumors each group of animals were divide to four sub-groups and received pioglitazone in different dose ranges (0,10,50,100 mg/kg/day) for 10 days. At the end of the study, the expression of Tlr4, Myd-88, Nf-kb1 genes was evaluated by qRT-PCR in different groups in mice tumor. The TLR-4 protein expression was evaluated by IHC. TNF-α level in mice tumor and serum were measured by ELISA kits. Tumor volume was measured with Vernier calipers.Results: We observed that activation of PPARγ by its agonist, pioglitazone, reduces tumor volume, Tlr-4, Myd-88, Nf-kb1 mRNA expression, TLR4 protein expression and TNF-α production in melanoma tumor especially in groups that were injected with LPS –stimulated cells. Moreover, treatment of melanoma cells with pioglitazone showed that the inhibitory effects of pioglitazone on LPS-induced inflammatory responses were TLR4 dependent.Conclusions: The results indicate that pioglitazone, a PPARγ agonist, has a beneficial protective effect against melanoma via interfering with the TLR4-dependent signaling pathways.

Quinazolinone and benzimidazole are both fused heterocyclic compounds which have shown valuable biological properties including cytotoxic, antibacterial, and antifungal activities. In this study, a series of novel quinazolinone derivatives substituted with benzimidazole were synthesized in two parts. In the first part 2 - phenyl - 1 H - benzimidazol - 6 - amine ( 4 ) was synthesized from the reaction of 4-nitro-o-phenylenediamine and benzoic acid. In the second part, new 3-(2-phenyl-1 H benzoimidazol-5-yl)- 3H-quinazolin-4-one derivatives ( 8a-8f ) were also prepared. Finally compound 4 was reacted with the different benzoxazinone derivatives ( 8a-8f ) to give the target compounds. The structures of the synthesized compounds were confirmed by IR and 1 HNMR. Cytotoxic activities of the final compounds were assessed at 100, 200, 300, 400, and 500 μM against MCF-7 and HeLa cell lines using the MTT colorimetric assay. Almost all compounds exhibited good cytotoxic activity against both cell lines. Compound 9d demonstrated the highest cytotoxic activity against MCF7 and Hela cell lines with IC 50 70 μM and 50 μM, respectively.