tRNA structural and functional changes induced by oxidative stress

Oxidatively damaged biomolecules impair cellular functions and contribute to the pathology of a variety of diseases. RNA is also attacked by reactive oxygen species, and oxidized RNA is increasingly recognized as an important contributor to neurodegenerative complications in humans. Recently, evidence has accumulated supporting the notion that tRNA is involved in cellular responses to various stress conditions. This review focuses on the intriguing consequences of oxidative modification of tRNA at the structural and functional level

Association of CARD10 rs6000782 and TNF rs1799724 variants with paediatric-onset autoimmune hepatitis

Although the pathogenesis of paediatric-onset autoimmune hepatitis (pAIH) remains incompletely understood, genetic variants and environmental factors are known to be involved. Caspase recruitment domain family member 10 (CARD10) is a scaffold protein that participates in a complex pathway activating nuclear factor kappa-B (NFκB) and tumour necrosis factor alpha (TNF-α). This study aimed to investigate the association of CARD10 rs6000782 (g.37928186A > C) and TNF gene promoter rs1799724 (c.-1037C > T) variants with pAIH susceptibility in a cohort of Egyptian children. The research was also extended to assess the relationship of these variants with levels of NFκB-p65 and TNF-α. Fifty-six pAIH patients and 44 age- and sex-matched healthy controls were included. Variant genotyping was performed by polymerase chain reaction (PCR). Serum NFκB-p65 and TNF-α levels were measured using enzyme-linked immunosorbent assays (ELISAs). rs6000782 C and rs1799724 T alleles, separate or in combination, were significantly increased in pAIH patients compared to controls. Serum levels of NFκB-p65 and TNF-α were higher in pAIH differentiating both groups. Moreover, the recessive model of rs6000782 revealed a significant association with the levels of both NFκB-p65 and TNF-α. In conclusion, rs6000782 and rs1799724 variants are potential genetic risk factors for pAIH predisposition, with the former affecting NFκB-p65 and TNF-α levels. Overall, the inflammatory cascade was associated with the degree of liver cell destruction. Clinically, screening and genetic counselling are recommended for relatives of pAIH patients. Keywords: Hepatitis, Autoimmune, Variants, Paediatrics, Cytokines, Tumour necrosis facto

EFFECTIVENESS OF MULTIMODAL PREEMPTIVE ANALGESIC THERAPY IN MAXILLOFACIAL SURGERY

This study was an attempt to find out the efficacy of pre-emptive analgesia in reducing post-operative pain. Multiple pre-emptive therapies were used in an attempt to see its superiority over single preemption. Pain scores showed significant differences between the pre-emptive and non pre-emptive groups. Pethidine consumed by the pre-emptive non-recipient group was much higher. Patient’s satisfaction was higher and post operative complications were less in the pre-emptive recipient group. Thus pre-emptive multimodal therapy would be better, in reducing post-operative pain, and the amount of post-operative analgesic requirement. It might be concluded that multimodal preemptive therapy by using I/V Ketorolac & Bupivacaine infiltration is an effective method for post operative pain management in maxillofacial surgery. (Bangladesh J Physiol Pharmacol 2008; 24(1&2) : 17-23

Serum MicroRNAs as Potential Biomarkers for Early Diagnosis of Hepatitis C Virus-Related Hepatocellular Carcinoma in Egyptian Patients

<div><p>Circulating microRNAs are deregulated in liver fibrosis and hepatocellular carcinoma (HCC) and are candidate biomarkers. This study investigated the potential of serum microRNAs; miR-19a, miR-296, miR-130a, miR-195, miR-192, miR-34a, and miR-146a as early diagnostic biomarkers for hepatitis C virus (HCV)-related HCC. As how these microRNAs change during liver fibrosis progression is not clear, we explored their serum levels during fibrosis progression in HCV-associated chronic liver disease (CLD) and if they could serve as non-invasive biomarkers for fibrosis progression to HCC. 112 Egyptian HCV-HCC patients, 125 non-malignant HCV-CLD patients, and 42 healthy controls were included. CLD patients were subdivided according to Metavir fibrosis-scoring. Serum microRNAs were measured by qRT-PCR custom array. Serum microRNAs were deregulated in HCC versus controls, and except miR-130a, they were differentially expressed between HCC and CLD or late fibrosis (F3-F4) subgroup. Serum microRNAs were not significantly different between individual fibrosis-stages or between F1-F2 (early/moderate fibrosis) and F3-F4. Only miR-19a was significantly downregulated from liver fibrosis (F1-F3) to cirrhosis (F4) to HCC. Individual microRNAs discriminated HCC from controls, and except miR-130a, they distinguished HCC from CLD or F3-F4 patients by receiver-operating-characteristic analysis. Multivariate logistic analysis revealed a panel of four microRNAs (miR-19a, miR-195, miR-192, and miR-146a) with high diagnostic accuracy for HCC (AUC = 0.946). The microRNA panel also discriminated HCC from controls (AUC = 0.949), CLD (AUC = 0.945), and F3-F4 (AUC = 0.955). Studied microRNAs were positively correlated in HCC group. miR-19a and miR-34a were correlated with portal vein thrombosis and HCC staging scores, respectively. In conclusion, studied microRNAs, but not miR-130a, could serve as potential early biomarkers for HCC in high-risk groups, with miR-19a as a biomarker for liver fibrosis progression to cirrhosis to HCC. We identified a panel of four serum microRNAs with high accuracy in HCC diagnosis. Additional studies are required to confirm this panel and test its prognostic significance.</p></div

Clinicopathological characteristics of HCC patients.

<p>BCLC: Barcelona Clinic Liver Cancer staging, CT: computed tomography.</p><p>Clinicopathological characteristics of HCC patients.</p

Comparison of AUC of the miRNA panel with that of AFP.

<p>AUCs of the miRNA panel and AFP in differentiating HCC from healthy controls (A), CLD (B), and F3-F4 patients (C).</p

Correlations between serum miRNAs levels in HCC group.

<p>A correlation map with a blue-red (cold-hot) scale. The blue color corresponds to a correlation close to -1 and the red color corresponds to a correlation close to 1. Green corresponds to a correlation close to 0. Correlations are made by spearman correlation.</p

Differential expression of serum miRNA levels in HCC and CLD patients.

<p>The box represents the 25%-75% percentiles; the line inside the box represents the median and the upper and lower lines representing the 10%-90% percentiles of fold change in expression levels of studied miRNAs in serum of CLD (n = 125) and HCC patients (n = 112). Data were analyzed by Mann-Whitney <i>U</i>-test.</p