A review of Rett syndrome (RTT) with induced pluripotent stem cells.

Human induced pluripotent stem cells (hiPSCs) are pluripotent stem cells generated from somatic cells by the introduction of a combination of pluripotency-associated genes such as OCT4, SOX2, along with either KLF4 and c-MYC or NANOG and LIN28 via retroviral or lentiviral vectors. Most importantly, hiPSCs are similar to human embryonic stem cells (hESCs) functionally as they are pluripotent and can potentially differentiate into any desired cell type when provided with the appropriate cues, but do not have the ethical issues surrounding hESCs. For these reasons, hiPSCs have huge potential in translational medicine such as disease modeling, drug screening, and cellular therapy. Indeed, patient-specific hiPSCs have been generated for a multitude of diseases, including many with a neurological basis, in which disease phenotypes have been recapitulated in vitro and proof-of-principle drug screening has been performed. As the techniques for generating hiPSCs are refined and these cells become a more widely used tool for understanding brain development, the insights they produce must be understood in the context of the greater complexity of the human genome and the human brain. Disease models using iPS from Rett syndrome (RTT) patient's fibroblasts have opened up a new avenue of drug discovery for therapeutic treatment of RTT. The analysis of X chromosome inactivation (XCI) upon differentiation of RTT-hiPSCs into neurons will be critical to conclusively demonstrate the isolation of pre-XCI RTT-hiPSCs in comparison to post-XCI RTT-hiPSCs. The current review projects on iPSC studies in RTT as well as XCI in hiPSC were it suggests for screening new potential therapeutic targets for RTT in future for the benefit of RTT patients. In conclusion, patient-specific drug screening might be feasible and would be particularly helpful in disorders where patients frequently have to try multiple drugs before finding a regimen that works.

Cytogenetic damage in khaini users of Tamilnadu, Southern India

Aim: The smokeless tobacco (ST) has a strong association with the risk of oral leukoplakia (OL), oral submucous fibrosis (OSF) and oral cancer (OC). ST components exhibit genotoxicity and may alter the structure of DNA, proteins and lipids, resulting in the production of antigenicity. In this study, an attempt was made to estimate the cytogenetic damage [chromosomal aberrations (CA) and micronucleus (MN)] in people habituated to consume khaini (ST), which is one of the major forms of tobacco consumption in Tamilnadu, India, and believed to be a major risk factor for OC. Methods: After signing a consent form, volunteers provided blood samples (108 samples from including experimental and control subjects) to establish cell cultures at 52 h. For CA analysis, 100 complete metaphase cells per subject were evaluated. Chromatid- and chromosomal- type aberrations were identified in experimental and control subjects, where the latter showed a very minimal number of CA in age wise manner. Results: Statistically significant results were obtained in experimental subjects when compared to controls as confirmed by chi-square test. Exfoliated cells from the buccal mucosaof Khaini users were examined by using the micronucleus assay. The difference in mean micronucleated cell count for buccal mucosa between cases and controls were significant (p<0.01). Hence, specific biomarkers on cytogenetic endpoints might help in establishing preventive measures to reduce cancer risks. Conclusion: the genotoxic effect of smokeless tobacco should be considered in addition to other known hazards for assessing health risks.