Biology subjects

Hande, P.

Publications and source records attributed to Hande, P..

3 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↗

bioRxiv2023

FUNCTIONAL AGEING: A Science-Technology-Society Approach to teach Ageing and Age-related Diseases

PurposeAgeing is a complex biological process that involves numerous genes and pathways. Experimental studies have identified several of these genes and pathways that that can extend or shorten an individuals lifespan. Understanding these genes and pathways can help develop interventions that improve health and quality of life of older people. Nonetheless, as the global population continues to age, it is essential to comprehend the ageing processs impact on society. Functional age is defined as a combination of chronological, biological, and psychological ages. An educational course called "Functional Ageing" was created for life science students at the National University of Singapore (NUS) during the academic year 2016-2017. The module adopted an interdisciplinary approach based on science-technology-society (STS) methodology and aimed to equip students with the analytical tools needed to assess the ageing process at both the molecular and physiological/functional levels. Ultimately, the module aimed to promote the understanding of ageing processes, particularly functional ageing in a population and its societal impacts. MethodsThis "Functional Ageing" course spanned over 13 weeks, consisting of weekly four-hour sessions that aimed to integrate both biology of ageing and societal perceptions of an ageing population. The first half of the semester covered the molecular processes that govern ageing, while the second half focussed on societal perception, burden of disease, healthy ageing interventions and creating an ageless society. Experimental and epidemiological studies were used to explain the ageing process. Expert guest lecturers were invited throughout the module to share their experiences on the demanding research areas of ageing today, as well as clinical aspects of age-related diseases. In addition, a field visit to a geriatric ward at the mental health organisation was arranged to showcase the countrys approach to dealing with the rising demands of ageing, and to provide experiential learning that can help inculcate a clearer public perception of ageing. ResultsThis 13-week module helped to improve students perception about functional ageing in todays society. After the module, a reflection analysis was conducted to evaluate students perceptions of ageing society. Overall findings garnered have demonstrated that while students generally have a brief understanding of the biological processes of ageing, their perception on how ageing is being manifested in a public health and societal setting is in paucity. However, the routine university-directed feedback survey indicated that the module had a positive impact on students appreciation and comprehension of the interplay between biological and sociological aspects of ageing, thus achieving the learning objectives of the module. ConclusionThe aim of the "Functional ageing" module was to integrate the biology and sociology of ageing to provide a better interdisciplinary understanding of ageing in society. After completing the module, students demonstrated a change in their mindset and attitude towards how their scientific understanding of ageing can be coupled to their public perception of ageing. As ageing populations become more prevalent in many societies, it is crucial that we prepare for an ageing population and develop a positive perception of ageing. Through educational efforts like this course/module, students will exhibit greater awareness of ageing issues, leading to more informed and balanced perceptions.

scientific communication and education↗