Objective
Uncoupling protein 2 (UCP2) plays a crucial role in energy homeostasis via insulin secretion regulation, free fatty acid concentrations, and lipid metabolism. This study aimed to investigate the association of 45-bp ins/del polymorphism of UCP2 with susceptibility to NAFLD (Non-Alcoholic Fatty Liver Disease) and T2DM (Type 2 Diabetes Mellitus). DNA was extracted from the white blood cells of the subjects, and the gene polymorphism was determined using polymerase chain reaction (PCR). In this study, 72 patients with NAFLD, 71 healthy individuals as control, 80 patients with T2DM, and 77 healthy controls were enrolled in the study.
Results
A higher prevalence of insertion/insertion genotype was observed in T2DM patients compared to the controls (p- value˂ 0.05). There was no difference in genotype distribution between NAFLD patients and controls (p-value > 0.05). NAFLD patients with D/D, D/I genotype had higher triglyceride, ALT, and AST levels; however, their HDL levels were lower than healthy controls. Patients with T2DM with D/D or D/I genotype also had significantly higher fasting serum glucose (FSG). While we found an association between the 45 bp I/D polymorphism in 3ʹUTR of UCP2 and T2DM, no correlation between this polymorphism and NAFLD was identified.
Background
Epidermal growth factor receptor (EGFR) plays an important role in the progression and tumorigenesis of the various cancers. In this regards, anti-EGFR antibodies are valuable approved therapeutics for the EGFR over-expressing cancers. However, the occurrence of mutations in the
EGFR
and/or
KRAS
genes; a common phenomenon which is seen in many cancers, lead to the resistance to the EGFR-directed antibodies. EGFR based immunotoxins are capable of overcoming this limitation by directing the toxin moieties to the cancer cells resulting in cell death.
Objectives
In the present study, a novel immunotoxin consisting of the truncated Pseudomonas exotoxin A (PE-40) and anti-EGFR huscFv was developed and evaluated for the induction of cell death in EGFR positive A431tumoral cells.
Materials and Methods
PE-40 fragment of the exotoxin A was amplified by using PCR and ligated to pET22b-huscFv. The reaction was confirmed by PCR and restriction digestion. The immunotoxin was expressed in
E. coli
BL21 (plysS) and then was purified by Ni-NTA affinity column. Subsequently, the toxicity of the purified immunotoxin was evaluated on EGFR over-expressing epidermoid carcinoma of skin, A431 cell line.
Results
PCR and restriction digestion experiments have verified the integrity of the immunotoxin construct. Purification by affinity column resulted in a highly purified recombinant immunotoxin. MTT assay revealed the growth inhibitory effect of the huscFv-PE40 immunotoxin on EGFR-over-expressing A431 cells with an IC50 value of 250 ng.mL
-1
.
Conclusion
In conclusion, the results indicated that the immunotoxin developed in this study has a high toxicity on the EGFR-over-expressing tumor cells and could be considered as a promising candidate for the treatment of the EGFR positive cancers.
Objective: Uncoupling protein 2 (UCP2) plays a crucial role in energy homeostasis via regulation of insulin secretion, free fatty acid concentrations, and lipid metabolism. This study aimed to investigate the association of 45-bp ins/del polymorphism of UCP2 with susceptibility to NAFLD (Non Alcoholic Fatty Liver Disease) and T2DM (Type 2 Diabetes Mellitus). DNA was extracted from the white blood cells of the subjects, and the gene polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In this study, 72 patients with NAFLD, 71 healthy individuals as control, 80 patients with T2DM, and 77 healthy controls were enrolled in the study.Results: A higher prevalence of insertion/insertion genotype was observed in T2DM patients compared to the controls (p- value˂ 0.05). But, there was no difference in genotype distribution between NAFLD patients and controls (p-value> 0.05). NAFLD patients with D/D, D/I genotype had higher triglyceride, ALT, and AST levels; however, their HDL levels were lower than healthy controls. Patients with T2DM with D/D or D/I genotype also had significantly higher fasting serum glucose (FSG). While we found an association between the 45bp I/D polymorphism in 3ʹUTR of UCP2 and T2DM, no any correlation between this polymorphism and NAFLD was identified.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.