Pusat Pengajian Sains Perubatan - Tesis
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- PublicationDysregulation of transcriptomic profiles of mm1.s and u266 multiple myeloma cell lines treated with epigenetic inhibitors(2024-09)Ismail, Nor HayatiMultiple myeloma (MM) is a hematological malignancy characterized by the uncontrolled proliferation of plasma cells in the bone marrow. Epigenetic dysregulation plays a pivotal role in MM pathogenesis, making epigenetic inhibitors promising therapeutic targets. This study examines the effects of three epigenetic inhibitors—Trichostatin A (TSA), Panobinostat (PAN), and 5-azacytidine (5-AZA) on MM1.S and U266 cell lines, focusing on transcriptomic dysregulation and the identification of core genes associated with survival outcomes. Dose-response curves revealed that all three inhibitors inhibited cell proliferation in a dose-dependent manner, with PAN showing the most potent anti-proliferative effect at the half maximal inhibitory concentration (IC50) dose. Flow cytometry analysis indicated significant changes in cell cycle distribution upon treatment. TSA, PAN, and 5-AZA induced G0/G1 phase arrest, suppression in S phase and no changes observed in G2/M phase in MM1.S cells and U266 cells. Apoptosis assays demonstrated that MM1.S cell lines experienced late apoptosis with the highest impact induced by PAN. Meanwhile, U266 cell lines demonstrated early apoptosis event after treatment with epigenetic inhibitors and the most profound impact induced by 5-AZA. KEGG enrichment analysis of both MM cell lines treated with these epigenetic inhibitors identified significant pathways involving cell adhesion molecules, microRNAs in cancer, and viral protein interactions with cytokines and receptors. Notably, this study also demonstrated that PAN and 5-AZA treatments upregulated certain core histone genes (H2A, H2B, H3, H4), co-impacting chromatin structure and gene regulation, thus influencing cellular processes and therapeutic responses. Furthermore, Kaplan-Meier plot analysis revealed that core genes linked to transcriptomic dysregulation were significantly associated with improved overall survival (OS) outcomes. The highest number of survival-associated core genes was found in 5-AZA-treated cell lines. Specifically, 5-AZA treatment increased the expression of similar core genes in both MM1.S and U266 cells, downregulating KIF20A, KIF4A, and PLK1, which correlated significantly with improved OS rate (log-rank P: 1.4e-16). In PAN-treated MM cell lines, ORC1, MCM2, MCM5, and CXCL1 were identified as core genes with therapeutic potential. TSA-treated U266 cell lines revealed more significant core genes than MM1.S cell lines, with APOE emerging as a key gene linked to improved survival outcomes (log-rank P < 1e-16). Overall, this study provides comprehensive insights into the transcriptomic alterations induced by epigenetic inhibitors in MM cell lines. These findings enhance the understanding of MM pathogenesis and offer potential therapeutic targets for treating this challenging disease.
- PublicationExploring mental toughness and perceived stress of nursing students of Universiti Sains Malaysia(2023-06)Celina, TanPossessing mental toughness (MT) enables one to bounce back from adversities, feel confident in completing tasks and be assertive in social situations while remaining committed in the face of stress. Stress can serve as a driving force, but too much stress can cause poor performance and stress-related disorders. Nursing students are vulnerable groups with higher risk of burning out, with anxiety and self-efficacy being among the strongest intrinsic predictors of stress. MT has not been explicitly studied in the context of nursing students hence this research was carried out to contribute to the gap in research. This study aimed to explore the suitability of MT in the nursing context and identify stressors pertaining to the current study’s population of interest and pin-pointing visual themes useful for developing exploratory stress-coping neuroimaging paradigm suited for healthcare education context. The current research was broken down and carried out in three phases with nursing students from Universiti Sains Malaysia (USM) exploring: 1) the suitability of the 4/6Cs MT model via reliability testing of MTQ-48 and its correlation with the Nursing Anxiety and Self-Confidence with Clinical Decision Making (NASC-CDM) scale; 2) the visual themes nursing students perceive as stressful by validating images showing scenarios from daily life, academic and clinical situations; lastly, 3) the relationship between Perceived Stress and MT with images/ visual cues perceived as stressful using Perceived Stress Scale (PSS-10) and MTQ-10. Findings from this research show MT have fair to moderate significant correlations with Anxiety (r=-0.293, p<0.001) and Self-Confidence (r=0.429, p<0.001). The initial 48-item MTQ-48 has good reliability with Cronbach’s coefficient alpha of 0.851 but reported unsatisfactory fit across indices after running confirmatory factor analysis (CFA). After refining the items, a modified 10-item Mental Toughness Questionnaire (MTQ-10) presented decent reliability (α=0.789) achieving all recommended minimum values for CFA fit indices. Image validation via Self-Assessment Manikin (SAM) yielded 36 images with low valence and low arousal reflecting stressful emotions when viewing the images. Finally, concurrent stress rating of images with assessment of MT and Perceived Stress reported 31 images have significant correlation with both MT and Perceived Stress, with strong significant negative correlation between total MT scores and Perceived Stress scores (r=-0.768, p<0.001). The goal of this research to explore the suitability of MT in nursing student context and produce relevant visual themes for perceived stress-coping as surrogate of MT for future neuroimaging research is achieved.
- PublicationThe role of probiotics with lactic acid-producing bacteria in modulating the behaviour of rodent model following contusive spinal cord injury: preliminary study(2023-06)Manickam, Danniya LakshmiThe disruption of gut dysbiosis after spinal cord injury (SCI) is a crucial but poorly understood phenomenon that might affect SCI healing. This study addresses the need to examine locomotor recovery after SCI and presents an animal model that may help restore a healthy gut flora and improve SCI therapies. The primary objective is to create a reliable animal model of SCI with gut dysbiosis to test probiotic treatments. With a 10% dropout rate (1 additional rat), this study included 13 rats. Adult female Wistar rats were carefully weighed and randomly allocated to one of four groups: Group 1 (control, n = 3), Group 2 (control with antibiotic intake, n = 4), Group 3 (SCI with antibiotic intake, n = 3), and Group 4 (SCI with antibiotic intake and probiotic therapy, n = 3). A rod was dropped from 25 mm to cause a moderate contusion injury in the T9/T10 thoracic area after a laminectomy. Successful surgery was established by the rats' hindlimb paralysis. Five days before SCI, rats received antibiotic mixtures to produce intestinal dysbiosis. Their drinking water included 2 g/L streptomycin, 0.17 g/L gentamicin, 0.125 mg/L ciprofloxacin, and 1 g/L bacitracin. After surgery, the rats returned to their usual drinking water. Multi-strain probiotic therapy began on the thirteenth day post-SCI and lasted until the eighteenth. Oral forced feeding of 3g of 30 x 109 CFU/kg probiotics in sterile water was performed. Post-injury faeces were tested for gut dysbiosis on days 4, 11, 18, and 25. In addition to faecal sample analysis, the Basso Beattie Bresnahan Locomotor Rating Scale was used to evaluate the rats' behavioural and locomotor recovery on the 4th, 11th, 18th, and 25th dpi for 4 minutes per rat. After six days of probiotic therapy, faecal sample morphology and BBB locomotor assessments showed a mild effect. Overall, this study sheds light on the significant connection between SCI, intestinal dysbiosis, and probiotics. The study found that probiotics may help SCI patients recover locomotion and gut eubiosis. More study is needed to determine the full range of probiotic benefits. This research reveals new ways to improve SCI patients' results and quality of life.
- PublicationValidity and reliability of the malay translated version of the diabetes health literacy scale among malaysian adults with type 2 diabetes mellitus(2024-08)Ling, Ng PeiIntroduction: The instrument for measuring health literacy among Malaysian adults with type 2 diabetes mellitus (T2DM) is limited. A valid and reliable diabetes-specific health literacy instrument in Malay is required before it can be used in measuring diabetes health literacy and determining its relationship with other variables. Objective: The aim of this study was to determine the validity and reliability of the Malay version of the Diabetes Health Literacy Scale (DHLS-M) among Malaysian adults with T2DM. Method: The Diabetes Health Literacy Scale (DHLS) was translated and culturally adapted into Malay, followed by a cross-sectional study which was conducted using a self-administered questionnaire among the adults with T2DM in Hospital Universiti Sains Malaysia (USM). The participants were recruited by convenience sampling. Confirmatory factor analysis (CFA), reliability testing and correlation analysis were performed. Results: A total of 250 adults with T2DM were participated in this study. The median age of the participants was 63.0 years old (interquartile range, IQR = 12.3) and most of the participants were male (51.2%). The final measurement model of DHLS-M with removal of one problematic item, fit the data well based on several fit indices: Relative chi-square (χ2/df) = 3.858, comparative fit index (CFI) = 0.981, Tucker–Lewis index (TLI) = 0.976. The composite reliability of the three subscales based on Raykov's rho were 0.962, 0.836 and 0.828 respectively. The subscales of DHLS-M were significantly correlated with the Malay version of the Michigan Diabetes Knowledge Test (MDKT) (r = 0.26 – 0.31) and the Malay version of the short form Health Literacy Survey Questionnaire (HLS-SF12) (r = 0.43 – 0.66). Conclusion: DHLS-M which consisted of three subscales and 13 items is valid and reliable. DHLS-M can be used to measure diabetes health literacy among Malaysian adults with T2DM.