Ali Fallah; Esmaeil Samadian; Azadeh Mohammad-Hasani; Abasalt Hosseinzadeh Colagar
Abstract
In this study, putative interactions between all of the retinoic acid (RA) ligands (all-trans (At), 9-cis (9c), and 13-cis (13c)), and VEGF receptors (VEGFR-1, -2 and -3) were investigated. It was performed considering the glycosylation status of the receptors to achieve a more reliable ...
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In this study, putative interactions between all of the retinoic acid (RA) ligands (all-trans (At), 9-cis (9c), and 13-cis (13c)), and VEGF receptors (VEGFR-1, -2 and -3) were investigated. It was performed considering the glycosylation status of the receptors to achieve a more reliable mode of interactions based on glycomics. We found that RAs may have a higher affinity for ligand-binding domains in VEGFRs. Furthermore, all RA isomers can strongly attach to VEGFR-3 receptor in comparison to other ones. It was also demonstrated that receptor dimerization of RAs may be less targeted. Moreover, regarding post-translational modifications, glycosylated structures showed conflicting binding energies. RAs may target the human vasculature, specifically lymph vessels, through VEGFR-3. In addition, the ligand binding-mediated activation of VEGFRs may be affected by these agents. Also, the glycosylation status of the receptors can interfere with these manners. Furthermore, our results confirmed that the consideration of carbohydrates in crystal structures is essential for a better interpretation of ligand/receptor interactions during drug discovery studies. Even though these observations improved our understanding of the binding patterns of RAs to VEGFRs, validation of these results needs further analysis to introduce these biomolecules as anti-VEGF remedies.
Abasalt Hosseinzadeh Colagar; Masomeh Salehi-Doon
Abstract
Previous studies in human leptin receptor protein (LEPR) signaling are important in the establishment of fetal growth. Idiopathic recurrent miscarriage (IRM) may be the result of abnormal placental and fetal development. Thus single nucleotide polymorphisms (SNPs) of LEPR might be associated with IRM. ...
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Previous studies in human leptin receptor protein (LEPR) signaling are important in the establishment of fetal growth. Idiopathic recurrent miscarriage (IRM) may be the result of abnormal placental and fetal development. Thus single nucleotide polymorphisms (SNPs) of LEPR might be associated with IRM. In our case-control study, which conducted from 2017 to 2018 at the Milad Sari Genetic Detection Center and Razi Hospital (Ghaemshahr, Iran), 140 samples, including 70 cases with history of three or more IRM as before the 22nd week of gestation, and 70 controls with at least two live births and no history of pathologic pregnancies during reproductive period were studied. Polymorphisms of maternal LEPR 853A>G and 511A>G were assessed by PCR-RFLP and SSCP, respectively. Results showed that 853A>G SNP, contained frequent genotype AG (p= 0.002; OR= 0.391; 95% CI= 0.154-0.664) and G allele (p= 0.003; OR= 0.125; 95% CI= 0.032–0.489), revealed a significant protective association with IRM. Primary screening of 511A>G showed that 63 case-samples were AG genotype. PCR directed sequence showed this SNP contained frequent genotype for AG (p= 0.001; OR= 0.57; 95% CI= 0.22-0.147) and G allele (p= 0.006; OR= 0.34; 95% CI= 0.008–0.149), revealed a significant protective association with IRM. Based on our findings, LEPR (853A>G and 511A>G) gene transitions not only might enhance IRM but also could be useful genetic markers in susceptibility and severity of recurrent miscarriage.
Younes Aftabi; Habib Zarredar; Mohammadreza Sheikhi; Zahra Khoshkam; Abasalt Hosseinzadeh Colagar
Abstract
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and its induction may result in suppressing of cell proliferation in colorectal cancer (CRC). Cucurbitacin D (CucD), E (CucE) and I (CucI) are plant derived metabolites that inhibit cancer cells. This study ...
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Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor and its induction may result in suppressing of cell proliferation in colorectal cancer (CRC). Cucurbitacin D (CucD), E (CucE) and I (CucI) are plant derived metabolites that inhibit cancer cells. This study aimed to evaluate the possible potency of the cucurbitacins for activation of AHR expression in CRC cell lines SW-480 and HT-29. The MTT assay was used to find the LC50 value of the metabolites in the cell lines. Afterward, the cells incubated with the LC50 concentrations and AHR-mRNA expression assessed using RT-PCR. The LC50 values of CucD, CucE, and CucI were 4.5, 6.8, and 3.8 μM in HT-29 cell line and 35, 19, 17.5 μM in SW-480 cells respectively. The SW-480 cells were more resistant against Cucs in comparison with HT-29 cells and all three Cucs cause to more AHR-mRNA expression in HT-29 cells. CucE had the lowest effect on AHR-mRNA expression in the cell lines and CucI was a common metabolite for both HT-29 and SW-480 cells, which showed the lowest LC50 value (the highest toxicity) and the highest effect on AHR-mRNA expression. CucI may have a potential to be used as an activator of AHR expression in CRC studies.
