Biology subjects

Ng, G. Y.-Q.

Publications and source records attributed to Ng, G. Y.-Q..

4 recordsLinked to original sources

bioRxiv2025

Role of Cockayne Syndrome B (CSB) Protein in Genome Maintenance in Human Cells under Oxidative Stress

Cockayne Syndrome (CS), a disorder marked by premature ageing and neurodevelopmental abnormalities, is primarily caused by mutations in the CSB protein, a critical component of the transcription-coupled repair pathway of nucleotide excision repair. This study explores the role of CSB in managing oxidative DNA damage and maintaining telomere integrity under oxidative stress conditions. We subjected CSB-deficient human fibroblasts (CS-B) and control fibroblasts to acute and chronic oxidative stress through hydrogen peroxide (H2O2) treatment and elevated oxygen levels. Our findings reveal that CS-B fibroblasts exhibit a distinct resistance to acute oxidative stress, as evidenced by their sustained viability and minimal cell cycle arrest compared to control fibroblasts. However, chronic oxidative conditions led to accelerated senescence in CS-B fibroblasts, demonstrated by increased telomere attrition rates, senescent morphology, and upregulated senescence-associated {beta}-galactosidase activity. Further, gene expression analysis post-H2O2 exposure identified the downregulation of key DNA repair and cell cycle genes in CS-B fibroblasts, suggesting a compromised ability to respond to oxidative DNA damage. These observations underscore the multifaceted role of CSB in genomic maintenance and highlight its potential involvement in the pathology of CS through impaired response to oxidative stress and telomere instability. The study contributes to a deeper understanding of the cellular mechanisms that underlie CS symptoms and may inform potential therapeutic strategies targeting oxidative damage repair systems.

cell biology↗

bioRxiv2023

Telomerase inhibition by MST-312 sensitises breast cancer cells to anti-cancer properties of Plumbagin

Breast cancer is the most common cause of malignancy and the second most common cause of cancer death in women. This heterogeneous disease is currently broadly classified as ER, PG positive luminal tumours, HER2 amplified tumours and triple-negative breast cancers (TNBC). Natural plant derived compounds are proven to be promising anti-cancer chemotherapeutics agents with minimal cytotoxic effects on healthy cells. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone) is a phytochemical derived from the roots of Plumbago zeylanica and it is known to possess anti-cancer properties similar to other compounds of naphthoquinones. In about 90 % of cancer cells, the telomerase enzyme activity is revived to add telomeric repeats to evade apoptosis. In this study, a combinatorial approach of combining anti-cancer compound Plumbagin to induce genotoxicity and a potent telomerase inhibitor, MST-312 (synthetic derivative of tea-catechins) was used to determine the synthetic lethality in breast cancer cells such as MDA-MB-231 (TNBC) and MCF-7 (lumina) cells. MDA-MB-231 cells were responsive to combination treatment to both short-term (48 hours) and long-term treatment (14 days) in a synergistic manner, whereas in MCF-7, the combination treatment was more effective in the long-term regimen. Furthermore, the cytotoxic effects of the Plumbagin and MST-312 combination treatment were not recoverable after the short-term treatment. In conclusion, combination treatment of MST-312 and Plumbagin is proven to be more effective than single Plumbagin compound treatment, in inducing DNA damage and telomere dysfunction leading to greater genome instability, cell cycle arrest and eventually cell death in cancer cells.

cancer biology↗

bioRxiv2021

Multiomics Analyses Reveal Dynamic Bioenergetic Pathways and Functional Remodeling of the Heart During Intermittent Fasting

AimsIntermittent fasting (IF) reduces cardiovascular risk factors in animals and humans, and can protect the heart against ischemic injury in models of myocardial infarction, but the underlying molecular mechanisms are unknown. To delineate molecular and cellular adaptations of the heart to IF, we carried out system-wide comprehensive analyses of proteome and phosphoproteome, complemented with transcriptome profiling, followed by functional analysis. Methods and resultsIn order to understand molecular and cellular remodeling of the heart during IF, we employed advanced mass spectrometry for system-wide profiling of the proteome and phosphoproteome of heart tissues obtained from mice maintained for 6 months on either daily 12- or 16-hour fasting, every-other-day fasting or ad libitum control feeding regimens. We also performed transcriptome analyses using RNA sequencing to evaluate whether the observed molecular responses to IF occur at the transcriptional or post-transcriptional levels. IF regimens significantly affected pathways that regulate cyclic GMP signaling, lipid and amino acid metabolism, cell adhesion, cell death, and inflammation. Comparison of differentially expressed proteome and transcriptome upon IF showed the higher correlation of pathway alternation in short IF regimen but the inverse correlation of metabolic processes such as fatty acid oxidation and immune processes in longer IF regimens. In addition, functional echocardiographic analyses demonstrated that IF enhances stress-induced cardiac performance. ConclusionOur systematic multi-omics study elucidates a molecular framework for understanding how IF impacts the hearts function and its vulnerability to injury and disease. Translational perspectiveIntermittent fasting is emerging as a desirable lifestyle adaptation to impact cardiovascular health through the modulation of molecular and cellular mechanisms, and by acting on disease risk factors. Evidence from numerous studies indicates that the fasting cycles are highly and consistently effective in protecting against cardiovascular diseases and improving cardiac health in animals and human. Using multi-omics, here we dissect distinct molecular adaptations of the heart to different intermittent fasting regimens. Our results unveil novel cardioprotective mechanisms and open up new avenues for innovative pharmacological approaches to prevent and treat cardiovascular diseases.

systems biology↗

bioRxiv2020

Integrative Epigenomic and Transcriptomic Analysis Reveals Robust Metabolic Switching in the Brain During Intermittent Fasting

Intermittent fasting (IF) is a lifestyle intervention comprising a dietary regimen in which energy intake is restricted via alternating periods of fasting and ad libitum food consumption, without compromising nutritional composition. While epigenetic modifications can mediate effects of environmental factors on gene expression, no information is yet available on potential effects of IF on the epigenome. In this study, we found that IF causes modulation of histone H3 lysine 9 trimethylation (H3K9me3) epigenetic mark in the cerebellum of male C57/BL6 mice, which in turn orchestrates a plethora of transcriptomic changes involved in the robust metabolic switching processes commonly observed during IF. Interestingly, both epigenomic and transcriptomic modulation continued to be observed after refeeding, suggesting that memory of the IF-induced epigenetic change is maintained at the locus. Notably though, we found that termination of IF results in a loss of H3K9me3 regulation of the transcriptome. Collectively, our study characterizes a novel mechanism of IF in the epigenetic-transcriptomic axis, which controls myriad metabolic process changes. In addition to providing a valuable and innovative resource, our systemic analyses reveal molecular framework for understanding how IF impacts the metaboloepigenetics axis of the brain. Highlights{circ} Intermittent fasting (IF) and refeeding modifies epigenome in the cerebellum {circ}Integrative epigenomic and transcriptomic analyses revealed metabolic switching {circ}IF affects the metaboloepigenetics axis in regulating metabolic processes {circ}Integrative analyses revealed a loss of epigenetic reprogramme following refeeding

neuroscience↗