Determination of IL-6 Gene Promoter Polymorphism in Patients with Hepatitis C and Its Impact on RNA Secondary Structure.

Background and Objectives: A polymorphism in the promoter region of the IL-6 gene would influence the level of IL-6 expression in patients with HCV, resulting in a pro-inflammatory response. Few studies have shown the association between -174G>C (rs1800795) and -1363G>T (rs2069827) polymorphisms and HCV infection, and their results have been contradictory. There are no data published in our population to study such an IL-6 stimulus against HCV infection and its impact on RNA secondary structure. Therefore, we isolated human subjects from the province of Punjab, Pakistan. The objective was to screen for IL-6 gene promoter polymorphisms -174G/C and -1363G/T and those correlated with serum concentrations of IL-6 in patients with HCV and compared with a control. Materials and Methods: In conventional PCR, measurement of serum IL-6 by CLIA and statistical analysis were performed to observe the genotype association studies. By integrating bioinformatics and computational tools, our study aimed to provide a comprehensive understanding of how variations in the promoter region of IL-6 may have functional implications on gene expression. Results: The -174G>C and -1363G>T genotypes in the promoter region of patients with HCV were in strong allelic association (Δ = 0.97, p < 0.001). Interestingly, the bioinformatics analysis was well aligned with our experimental data. Conclusions: Based on the data, it can be inferred that IL-6 gene promoter polymorphisms are important in the dysregulation of IL-6 levels in patients with HCV.

Immunohistochemical Expression of Cyclin D1 and Ki-67 in Primary and Metastatic Oral Squamous Cell Carcinoma.

OBJECTIVE: The aim of current study was to investigate the expression of Cyclin D1 and Ki-67 in primary and metastatic oral squamous cell carcinoma (OSCC) and their different histological grades. METHODS: Paraffin embedded 30 oral squamous cell carcinoma (15 each of primary and cervical lymph node metastatic OSCC) were included in the study. Cyclin D1 and Ki 67 expressions were evaluated by immunohistochemistry and compared in primary and lymph node metastasis of OSCC and their histological grades. The data was analyzed using SPSS software. RESULTS: The mean age of patients with primary OSCC was 53.47 ±16.67 years and 61.47 ±11.94 years in patients with metastasis. Males were comparatively affected more than females with tongue as the most common site involved in both primary and metastatic tumours. The mean size of primary and metastatic tumour biopsies were 1.16 mm and 3.93 mm respectively. Comparison of the expression of Cyclin D1 in these primary and metastatic OSCC revealed a statistically significant difference (p = 0.003) whereas it was insignificant for Ki-67 (p = 0.715). CONCLUSION: Cyclin D1 can be a useful marker in predicting aggressive or metastatic behaviour of OSCC on premier biopsies.

Effect of Metformin on Adult Hippocampal Neurogenesis: Comparison with Donepezil and Links to Cognition.

Recent studies have uncovered evidence suggesting that interference with hippocampal adult neurogenesis contributes to neurodegeneration in Alzheimer's disease (AD). Evidence supporting that AD is a metabolic disease with derangements in brain glucose utilization implies the use of anti-diabetics as an alternate therapeutic strategy. The present study drew comparison between the pro-neurogenic potential of metformin and donepezil in AlCl3-induced mouse model of neurodegeneration. Morris water maze task and subsequent immunohistochemical evaluation for NeuN was conducted. Expression of neurogenesis markers and hippocampal proteome analysis was determined by qRT-PCR and SDS-PAGE, respectively, followed by ESI-QTOFF MS/MS identification. The results demonstrated impaired spatial memory and differential expression of eight proteins in the AlCl3 group as compared to the controls. Interestingly, treatment with metformin normalized the proteome profile and expression levels of neurogenesis markers along with improvement in the spatial memory. Moreover, as compared to donepezil, metformin-treated mice exhibited an enhanced number of post-mitotic NeuN-positive neurons. It is suggested that underlying molecular mechanisms of metformin-mediated adult hippocampal neurogenesis may have implications in treatment of neurodegenerative disorders.