Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduct...Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduction: The GLP1R gene provides the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type-2 diabetes and stroke. Material and Methods: Different nsSNPs and protein-related sequences were obtained from NCBI and ExPASY database. Gene associations and interactions were predicted using GeneMANIA software. Deleterious and damaging effects of nsSNPs were analyzed using SIFT, Provean, and Polyphen-2. The association of the nsSNPs with the disease was predicted using SNPs & GO software. Protein stability was investigated using I-Mutant and MUpro software. The structural and functional impact of point mutations was predicted using Project Hope software. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Results: The GLP1R gene was found to have an association with 20 other different genes. Among the most important ones is the GCG (glucagon) gene which is also a trans membrane protein. Overall 7229 variants were seen, and the missense variants or nsSNPs (146) were selected for further analysis. The total number of nsSNPs obtained in this study was 146. After being subjected to SIFT software (27 Deleterious and 119 Tolerated) were predicted. Analysis with Provean showed that (20 deleterious and 7 neutral). Analysis using Polyphen-2 revealed 17 probably damaging, 2 possibly damaging and 1 benign nsSNPs. Using two additional software SNPs & GO and PHD-SNPs showed that 14 and 17 nsSNPs had a disease effect, respectively. Project Hope software predicts the effect of the 14 nsSNPs on the protein function due to differences in charge, size, hydrophobicity, and conservancy between the wild and mutant types. Conclusion: In this study, the 14 nsSNPs which were highly affected the protein function. This protein is providing the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes and also affect the treatment of diabetic patients due to the fact that the protein acts as an important drug target.展开更多
The genus Paeonia has gained great interest from the scientific community for exploration as a source of bioactive compounds.The current work focused on the chemical characterisation and biological properties of Paeon...The genus Paeonia has gained great interest from the scientific community for exploration as a source of bioactive compounds.The current work focused on the chemical characterisation and biological properties of Paeonia mascula L.from Turkey.The chemical characterisation of the extracts was analysed by LC-DAD-ESI and LC-APCI-MS.The antioxidant,enzyme inhibitory and anticancer properties were evaluated in vitro.The methanol extract was the most effective as antioxidant,metal chelator and was the most effective inhibitor of acetylcholinesterase(AChE)and tyrosinase.The chloroform extract showed highest inhibition of butrylcholinesterase(BChE)and amylase.Ethyl acetate extract displayed glucosidase inhibition.The most abundant compounds were hexagalloyl glucose,penta galloyl glucose,gallic acid,tetragalloyl glucose,paeoniflorin and the most abundant flavonoid was quercetin-3-O-glucoside.β-sitosterol was the most abundant phytosterol.The anticancer effect of P.mascula was evaluated by using HELA cells evaluating different pathways.The possible inhibition effect of P.mascula on the reactive oxygen species(ROS)pathway was controlled by performing the advanced glycation end product(AGE).To determine the effect of P.mascula on active molecular pathways in the HELA cancer cell line,the levels of Phospho-NF-Kβp65,AGE receptor RAGE protein,antiapoptotic BCL-2,proapoptotic BAX and P-53 proteins were checked,respectively.Phospho-NF-Kβp65,RAGE and BCL-2,which are both ROS inducers and play an active role in cancer prognosis,were found to have decreased levels after the application of P.mascula.Our findings provide a scientific basis for Paeonia mascula,which may serve as a source of naturally occurring bioactive compounds for healthpromoting applications.展开更多
文摘Aim: This study aimed to investigate the effect of non-synonymous SNPs (nsSNPs) of the Glucagon-like peptide-1 Receptor (GLP-1R) gene in protein function and structure using different computational software. Introduction: The GLP1R gene provides the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes. The protein is an important drug target for the treatment of type-2 diabetes and stroke. Material and Methods: Different nsSNPs and protein-related sequences were obtained from NCBI and ExPASY database. Gene associations and interactions were predicted using GeneMANIA software. Deleterious and damaging effects of nsSNPs were analyzed using SIFT, Provean, and Polyphen-2. The association of the nsSNPs with the disease was predicted using SNPs & GO software. Protein stability was investigated using I-Mutant and MUpro software. The structural and functional impact of point mutations was predicted using Project Hope software. Project Hope analyzes the mutations according to their size, charge, hydrophobicity, and conservancy. Results: The GLP1R gene was found to have an association with 20 other different genes. Among the most important ones is the GCG (glucagon) gene which is also a trans membrane protein. Overall 7229 variants were seen, and the missense variants or nsSNPs (146) were selected for further analysis. The total number of nsSNPs obtained in this study was 146. After being subjected to SIFT software (27 Deleterious and 119 Tolerated) were predicted. Analysis with Provean showed that (20 deleterious and 7 neutral). Analysis using Polyphen-2 revealed 17 probably damaging, 2 possibly damaging and 1 benign nsSNPs. Using two additional software SNPs & GO and PHD-SNPs showed that 14 and 17 nsSNPs had a disease effect, respectively. Project Hope software predicts the effect of the 14 nsSNPs on the protein function due to differences in charge, size, hydrophobicity, and conservancy between the wild and mutant types. Conclusion: In this study, the 14 nsSNPs which were highly affected the protein function. This protein is providing the necessary instruction for the synthesis of the insulin hormones which is needed for glucose catabolism. Polymorphisms in this gene are associated with diabetes and also affect the treatment of diabetic patients due to the fact that the protein acts as an important drug target.
文摘The genus Paeonia has gained great interest from the scientific community for exploration as a source of bioactive compounds.The current work focused on the chemical characterisation and biological properties of Paeonia mascula L.from Turkey.The chemical characterisation of the extracts was analysed by LC-DAD-ESI and LC-APCI-MS.The antioxidant,enzyme inhibitory and anticancer properties were evaluated in vitro.The methanol extract was the most effective as antioxidant,metal chelator and was the most effective inhibitor of acetylcholinesterase(AChE)and tyrosinase.The chloroform extract showed highest inhibition of butrylcholinesterase(BChE)and amylase.Ethyl acetate extract displayed glucosidase inhibition.The most abundant compounds were hexagalloyl glucose,penta galloyl glucose,gallic acid,tetragalloyl glucose,paeoniflorin and the most abundant flavonoid was quercetin-3-O-glucoside.β-sitosterol was the most abundant phytosterol.The anticancer effect of P.mascula was evaluated by using HELA cells evaluating different pathways.The possible inhibition effect of P.mascula on the reactive oxygen species(ROS)pathway was controlled by performing the advanced glycation end product(AGE).To determine the effect of P.mascula on active molecular pathways in the HELA cancer cell line,the levels of Phospho-NF-Kβp65,AGE receptor RAGE protein,antiapoptotic BCL-2,proapoptotic BAX and P-53 proteins were checked,respectively.Phospho-NF-Kβp65,RAGE and BCL-2,which are both ROS inducers and play an active role in cancer prognosis,were found to have decreased levels after the application of P.mascula.Our findings provide a scientific basis for Paeonia mascula,which may serve as a source of naturally occurring bioactive compounds for healthpromoting applications.
