Adenosine Improves Mitochondrial Function and Biogenesis in Friedreich's Ataxia Fibroblasts Following L-Buthionine Sulfoximine-Induced Oxidative Stress.

Adenosine is a nucleoside that is widely distributed in the central nervous system and acts as a central excitatory and inhibitory neurotransmitter in the brain. The protective role of adenosine in different pathological conditions and neurodegenerative diseases is mainly mediated by adenosine receptors. However, its potential role in mitigating the deleterious effects of oxidative stress in Friedreich's ataxia (FRDA) remains poorly understood. We aimed to investigate the protective effects of adenosine against mitochondrial dysfunction and impaired mitochondrial biogenesis in L-buthionine sulfoximine (BSO)-induced oxidative stress in dermal fibroblasts derived from an FRDA patient. The FRDA fibroblasts were pre-treated with adenosine for 2 h, followed by 12.50 mM BSO to induce oxidative stress. Cells in medium without any treatments or pre-treated with 5 µM idebenone served as the negative and positive controls, respectively. Cell viability, mitochondrial membrane potential (MMP), aconitase activity, adenosine triphosphate (ATP) level, mitochondrial biogenesis, and associated gene expressions were assessed. We observed disruption of mitochondrial function and biogenesis and alteration in gene expression patterns in BSO-treated FRDA fibroblasts. Pre-treatment with adenosine ranging from 0-600 µM restored MMP, promoted ATP production and mitochondrial biogenesis, and modulated the expression of key metabolic genes, namely nuclear respiratory factor 1 (NRF1), transcription factor A, mitochondrial (TFAM), and NFE2-like bZIP transcription factor 2 (NFE2L2). Our study demonstrated that adenosine targeted mitochondrial defects in FRDA, contributing to improved mitochondrial function and biogenesis, leading to cellular iron homeostasis. Therefore, we suggest a possible therapeutic role for adenosine in FRDA.

Dental age estimation of Malaysian Indian children and adolescents: applicability of Chaillet and Demirjian's modified method using artificial neural network.

BACKGROUND: Recognising the importance of dental age (DA) estimation in forensic investigations, a variety of methods abound in the literature due to population-specific attributes. A reference eight-tooth method developed by Chaillet and Demirjian estimated the DA of children and adolescents. AIM: This study aims to investigate the applicability of Chaillet and Demirjian's method among Malaysian Indians aged 5.00-17.99 years. SUBJECTS AND METHODS: Dental panoramic tomographs of Malaysian Indians aged 5.00-17.99 years were statistically analysed using paired t-test and artificial neural networks multilayer perceptron (ANN-MLP). RESULTS: A total of 1015 dental panoramic tomographs were analysed. Paired t-test analysis against the reference dental maturity scores revealed underestimation of DA in boys of 1.68 years and girls of 2.56 years indicating inaccurate age estimation. A population-specific prediction model with a new set of dental maturity scores was established on Chaillet and Demirjian's scores using ANN-MLP. The new dental maturity scores showed accurate estimation of DA with differences between CA and DA being 12 and 25 days for boys and girls, respectively. Furthermore, a new DA prediction formula was developed using regression analysis following the establishment of new dental scores based on ANN-MLP. CONCLUSION: A novel Malaysian Indian-specific prediction model that demonstrated accurate DA estimation was established.