A novel imidazo[1,2-a]pyridine derivative and its co-administration with curcumin exert anti-inflammatory effects by modulating the STAT3/NF-κB/iNOS/COX-2 signaling pathway in breast and ovarian cancer cell lines.

Introduction: Imidazo[1,2-a]pyridine derivatives with diverse pharmacological properties and curcumin, as a potential natural anti-inflammatory compound, are promising compounds for cancer treatment. This study aimed to synthesize a novel imidazo[1,2-a]pyridine derivative, (MIA), and evaluate its anti-inflammatory activity and effects on nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3) pathways, and their target genes, alone and in combination with curcumin, in MDA-MB-231 and SKOV3 cell lines. Methods: We evaluated the interaction between imidazo[1,2-a]pyridine ligand, curcumin, and NF-κB p50 protein, using molecular docking studies. MTT assay was used to investigate the impacts of compounds on cell viability. To evaluate the NF-κB DNA binding activity and the level of inflammatory cytokines in response to the compounds, ELISA-based methods were performed. In addition, quantitative polymerase chain reaction (qPCR) and western blotting were carried out to analyze the expression of genes and investigate NF-κB and STAT3 signaling pathways. Results: Molecular docking studies showed that MIA docked into the NF-κB p50 subunit, and curcumin augmented its binding. The MTT assay results indicated that MIA and its combination with curcumin reduced cell viability. According to the results of the ELISA-based methods, MIA lowered the levels of inflammatory cytokines and suppressed NF-κB activity. In addition, real-time PCR and Griess test results showed that the expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) genes, and nitrite production were reduced by MIA. Furthermore, the western blotting analysis demonstrated that MIA increased the expression of inhibitory κB (IκBα) and B-cell lymphoma 2 (Bcl-2)-associated X proteins (BAX), and suppressed the STAT3 phosphorylation, and Bcl-2 expression. Our findings revealed that curcumin had a potentiating role and enhanced all the anti-inflammatory effects of MIA. Conclusion: This study indicated that the anti-inflammatory activity of MIA is exerted by suppressing the NF-κB and STAT3 signaling pathways in MDA-MB-231 and SKOV3 cancer cell lines.

Production of human single-chain fragment antibody (ScFv) against human epidermal growth factor receptor-2 (HER-2) by phage display technology.

Breast cancer with more than 1.7 million diagnoses per year has been known as one of the most prevalent cancers among women worldwide. Despite the availability of advanced treatment options, cancer progression and metastasis is observed in 20% of patients. Human epidermal growth factor receptor-2 (HER-2) is considered as an important prognostic and diagnostic tumor marker for breast cancer. While HER-2 is expressed on the surface of normal cells, its overexpression occurs in 20-25% on breast cancer tumor cells. This type of tumor which is referred to as HER-2+ is the most aggressive type of breast cancer and shows more resistance to radiotherapy. Single-chain fragment antibodies (ScFvs) offer several advantages in comparison to conventional whole antibodies due to their small size. Particularly, ScFv fragments show improved diffusion and solid tumor penetration. In this study, a human ScFv antibody library was used to isolate anti-HER-2 ScFv antibodies through cell panning and mix antigen-cell panning strategies. Analysis of the binding activity and specificity of isolated ScFv antibodies against HER-2-expressing cell lines and recombinant HER-2 antigen indicated the higher efficiency of the cell panning strategy in isolation of ScFv antibody fragments.

Association of Warfarin Therapy with APOE and VKORC1 Genes Polymorphism in Iranian Population.

Warfarin is a vitamin K antagonist that genetic and non-genetic factors affected on its dose requirement in the patients with cardio vascular disease. The aim of this study was whether the APOE and VKORC1 polymorphisms influence on warfarin dose requirements in the part of Iranian patients. Blood samples were collected from 86 warfarin-treated patients. After extraction of genomic DNA, the VKORC1 (rs9923231) and the APOE (rs429358 and rs7412) polymorphisms were genotyped by PCR-RFLP technique. We found that the Iranian patients carrying genotypes GA or AA of VKORC1 polymorphism tended to receive lower dose of warfarin (p = 0.018). Furthermore, the E3/E3 genotype was observed with the frequency more than 60% in the patients with low dose of warfarin. The BMI and weight also showed a positive correlation with warfarin dose. However, it was not statistically significant (p > 0.05). The results of this study may be useful in defining of warfarin dose algorithms for Iranian patients.

Does green tea consumption improve the salivary antioxidant status of smokers?

OBJECTIVE: Considering the higher rate of oral cancer, and reduction in salivary antioxidants in smokers as indicated in previous studies, antioxidant- containing nutrients such as green tea, seem to be beneficial in counteracting against oxidative stress in this group. This study assessed the salivary total antioxidant alteration in smokers compared to nonsmokers, after short-tem (7days) and long-term (3 weeks), green tea drinking. DESIGN: In this experimental study, 20 volunteer moderate-to-heavy male smokers, and 20 matched healthy non-smokers were selected to participate, according to the inclusion criteria. Participants were instructed to drink two cups of green tea per day, by dissolving 2g of green tea in 150ml of hot water for each cup. After saliva collection, antioxidant capacity of saliva was measured at baseline, after 7days, and after 21days. Statistical evaluation was done by SPSS 21, using paired samplet tests, one-way ANOVA and Bonferroni tests. RESULTS: At day zero nonsmokers had a higher antioxidant capacity than smokers (686.6±62.22 vs. 338.8±59.9) mM/50µl, P<0.001. There was also a significant difference between two groups in salivary total antioxidant capacity after one week and three weeks of green tea consumption (P<0.001). However, there was an upward trend in both smokers and non-smokers over the study period (after tea drinking). In addition, a significant difference was found in total antioxidant capacity alteration in smokers compared to non-smokers from baseline to day 21. CONCLUSIONS: Results support the effectiveness of green tea consumption in salivary antioxidants enhancement in smokers, in both the short- and long term.