69 research outputs found

    Correlation of Serum Insulin-Like Growth Factor-1 and Hand Wrist Radiographs as Skeletal Maturity Indicators: An ex-vivo Study

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    Introduction: Conventional Hand and Wrist radiographs, have certain drawbacks of exposing orthodontic patients to unnecessary radiation hazards and subjectivity to errors. Serum insulin-like growth factor 1 (IGF-1) levels have been reported to increase until the pubertal peak in literature. The present study aims to assess the relationship between serum IGF-1 and skeletal maturity indicators Materials and Methods: Lateral cephalograms of 60 patients were assigned SMI stage according to Fishman’s classification system. The serum IGF-1 levels of the patients were also evaluated. Correlation between the serum IGF-1 levels, age of the patient, and their SMI stage was analyzed. Results: Pearson's coefficient of correlation revealed a non-significant weak positive correlation (p=0.69; >0.05) between age and IGF-1 levels, and a non-significant weak negative correlation (p =0.52; >0.05) between SMI stages and IGF-1 levels. Results of the ANOVA test indicated that there was no significant difference between mean IGF-1 levels across the different age groups and eleven SMI groups. However, there was a significant difference noted in the mean IGF-1 levels and the restructured SMI categories and groups. Conclusion: The moderate correlation between age and serum IGF-1 fluctuations during puberty underscores the hormone's pivotal role in adolescent growth. This positions serum IGF-1 as a potentially specific and reliable marker for assessing mandibular growth modifications, offering a radiation-free alternative to conventional radiographic methods

    Disulfide-Based Poly(amido amine)s for siRNA Delivery: Effects of Structure on siRNA Complexation, Cellular Uptake, Gene Silencing and Toxicity

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    Purpose\ud \ud RNA interference (RNAi) is a process by which small interfering RNAs (siRNA) induce sequence-specific gene silencing. Therefore, siRNA is an emerging promise as a novel therapeutic. In order to realize the high expectations for therapeutic applications, efficient delivery systems for siRNA are necessary.\ud \ud Methods\ud \ud In this study, a new series of biodegradable poly(amido amine)s with disulfide linkages in the backbone was synthesized out of N,Nâ€Č-cystaminebisacrylamide (CBA), 4-amino-1-butanol (ABOL) and ethylene diamine (EDA). Effects of different percentages of butanolic side chains and protonatable fragments in the main chain on siRNA complexation, cellular uptake, gene silencing and toxicity were investigated.\ud \ud Results\ud \ud Incorporation of EDA in the polymer resulted in increased siRNA condensation. Efficient siRNA condensation was shown to be necessary for cellular uptake; however, excess of polymer decreased siRNA uptake for polymers with high amounts of EDA. Silencing efficiency did not correlate with uptake, since silencing increased with increasing w/w ratio for all polymers. More than 80% knockdown was found for polyplexes formed with polymers containing 25% or 50% EDA, which was combined with low cytotoxicity.\ud \ud Conclusions\ud \ud Poly(amido amine)s with minor fractions of protonatable fragments in the main chain are promising carriers for delivery of siRNA\u

    Functional Promoter Polymorphisms Govern Differential Expression of HMG-CoA Reductase Gene in Mouse Models of Essential Hypertension

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    3-Hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase gene (Hmgcr) is a susceptibility gene for essential hypertension. Sequencing of the Hmgcr locus in genetically hypertensive BPH (blood pressure high), genetically hypotensive BPL (blood pressure low) and genetically normotensive BPN (blood pressure normal) mice yielded a number of single nucleotide polymorphisms (SNPs). BPH/BPL/BPN Hmgcr promoter-luciferase reporter constructs were generated and transfected into liver HepG2, ovarian CHO, kidney HEK-293 and neuronal N2A cells for functional characterization of the promoter SNPs. The BPH-Hmgcr promoter showed significantly less activity than the BPL-Hmgcr promoter under basal as well as nicotine/cholesterol-treated conditions. This finding was consistent with lower endogenous Hmgcr expression in liver and lower plasma cholesterol in BPH mice. Transfection experiments using 5â€Č-promoter deletion constructs (strategically made to assess the functional significance of each promoter SNP) and computational analysis predicted lower binding affinities of transcription factors c-Fos, n-Myc and Max with the BPH-promoter as compared to the BPL-promoter. Corroboratively, the BPH promoter-luciferase reporter construct co-transfected with expression plasmids of these transcription factors displayed less pronounced augmentation of luciferase activity than the BPL construct, particularly at lower amounts of transcription factor plasmids. Electrophoretic mobility shift assays also showed diminished interactions of the BPH promoter with HepG2 nuclear proteins. Taken together, this study provides mechanistic basis for the differential Hmgcr expression in these mouse models of human essential hypertension and have implications for better understanding the role of this gene in regulation of blood pressure
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