1.A Glimpse into the Genome-wide DNA Methylation Changes in 6-hydroxydopamine-induced In Vitro Model of Parkinson’s Disease
Kasthuri Bai MAGALINGAM ; Sushela Devi SOMANATH ; Ammu Kutty RADHAKRISHNAN
Experimental Neurobiology 2023;32(3):119-132
A cell-based model of Parkinson’s disease (PD) is a well-established in vitro experimental prototype to investigate the disease mechanism and therapeutic approach for a potential anti-PD drug. The SH-SY5Y human neuroblastoma cells and 6-OHDA combo is one of the many neurotoxininduced neuronal cell models employed in numerous neuroscience-related research for discovering neuroprotective drug compounds. Emerging studies have reported a significant correlation between PD and epigenetic alterations, particularly DNA methylation. However, the DNA methylation changes of PD-related CpG sites on the 6-OHDA-induced toxicity on human neuronal cells have not yet been reported. We performed a genome-wide association study (GWAS) using Infinium Epic beadchip array surveying 850000 CpG sites in differentiated human neuroblastoma cells exposed to 6-OHDA. We identified 236 differentially methylated probes (DMPs) or 163 differentially methylated regions (DMRs) in 6-OHDA treated differentiated neuroblastoma cells than the untreated reference group with p<0.01, Δbeta cut-off of 0.1. Among 236 DMPs, hypermethylated DMPs are 110 (47%), whereas 126 (53%) are hypomethylated. Our bioinformatic analysis revealed 3 DMRs that are significantly hypermethylated and associated with neurological disorders, namely AKT1, ITPR1 and GNG7. This preliminary study demonstrates the methylation status of PD-related CpGs in the 6-OHDA-induced toxicity in the differentiated neuroblastoma cells model.
2.Navigating the horizon of mRNA vaccines: Tracing their evolution, ensuring safety, and unveiling therapeutic potential
Eunice Chieu Teng Yap ; Sushela Devi Somanath ; Saatheeyavaane Bhuvanendran ; Ammu Kutty Radhakrishnan
International e-Journal of Science, Medicine and Education 2023;17(3):13-25
Vaccines are vital tools in public health as they play critical roles in preventing and controlling infectious diseases. Vaccine technology has advanced from virus-infected lesions to live attenuated, inactivated or killed pathogens, toxoids, and subunits that consist of only specific pathogen parts needed to elicit an immune response. The progression of virus-like particle vaccines, recombinant viral-vectored vaccines, toxoids, protein or polysaccharide-based vaccines designed to conjugate with a distinct carrier protein to enhance immune reaction is a significant milestone. However, some infectious pathogens can avoid the adaptive immune system, while traditional methods may be unsuitable against non-infectious diseases like cancer. Recent studies have demonstrated the potential of messenger RNA (mRNA) vaccines as an alternative to traditional vaccine approaches. mRNA vaccines contain mRNA that encodes the specific antigen and triggers a directed immune response. The two main forms of mRNA used in the study of mRNA vaccines are conventional non-amplifying mRNA and self-amplifying mRNA (saRNA). This article discusses the mRNA vaccine structure, delivery strategies, and protective functions, focusing on mRNA vaccines’ safety and therapeutic potential. Pre-clinical research has demonstrated the broad utility of mRNA vaccines in animal models. Human clinical trials, however, are still under validation. Hence, further studies will need to focus on adapting reliable results of preclinical trials to human applications. The evidence to date suggests that mRNA vaccines are promising next-generation vaccines and, in the future, clinical trials would transform basic research into mRNA therapeutics in medical practices.
COVID-19
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mRNA Vaccines
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Safety
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Vaccination