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Microarray-based analysis of differential gene expression profile in rotenone-induced Parkinson's disease zebrafish model

Nies YH, Yahaya MF, Lim WL, Teoh SL

CNS Neurol Disord Drug Targets, 2023 Jun 08.
PMID: 37291778 DOI: 10.2174/1871527322666230608122552

BACKGROUND & OBJECTIVES: Despite much clinical and laboratory research that has been performed to explore the mechanisms of Parkinson's disease (PD), its pathogenesis remains elusive to date. Therefore, this study aimed to identify possible regulators of neurodegeneration by performing microarray analysis of the zebrafish PD model's brain following rotenone exposure.
METHODS: A total of 36 adult zebrafish were divided into two groups: control (n = 17) and rotenone-treated (n = 19). Fish were treated with rotenone water (5 µg/L water) for 28 days and subjected to locomotor behavior analysis. Total RNA was extracted from the brain tissue after rotenone treatment. The cDNA synthesized was subjected to microarray analysis and subsequently validated by qPCR.
RESULTS: Administration of rotenone has significantly reduced locomotor activity in zebrafish (p < 0.05), dysregulated dopamine-related gene expression (dat, th1, and th2, p < 0.001), and reduced dopamine level in the brain (p < 0.001). In the rotenone-treated group, genes involved in cytotoxic T lymphocytes (gzm3, cd8a, p < 0.001) and T cell receptor signaling (themis, lck, p < 0.001) were upregulated significantly. Additionally, gene expression involved in microgliosis regulation (tyrobp, p < 0.001), cellular response to IL-1 (ccl34b4, il2rb, p < 0.05), and regulation of apoptotic process (dedd1, p < 0.001) were also upregulated significantly.
CONCLUSION: The mechanisms of T cell receptor signaling, microgliosis regulation, cellular response to IL-1, and apoptotic signaling pathways have potentially contributed to PD development in rotenone-treated zebrafish.
Fulltext MicroRNA Dysregulation in Parkinson's Disease: A Narrative Review

Nies YH, Mohamad Najib NH, Lim WL, Kamaruzzaman MA, Yahaya MF, Teoh SL

Front Neurosci, 2021;15:660379.
PMID: 33994934 DOI: 10.3389/fnins.2021.660379

Parkinson's disease (PD) is a severely debilitating neurodegenerative disease, affecting the motor system, leading to resting tremor, cogwheel rigidity, bradykinesia, walking and gait difficulties, and postural instability. The severe loss of dopaminergic neurons in the substantia nigra pars compacta causes striatal dopamine deficiency and the presence of Lewy bodies indicates a pathological hallmark of PD. Although the current treatment of PD aims to preserve dopaminergic neurons or to replace dopamine depletion in the brain, it is notable that complete recovery from the disease is yet to be achieved. Given the complexity and multisystem effects of PD, the underlying mechanisms of PD pathogenesis are yet to be elucidated. The advancement of medical technologies has given some insights in understanding the mechanism and potential treatment of PD with a special interest in the role of microRNAs (miRNAs) to unravel the pathophysiology of PD. In PD patients, it was found that striatal brain tissue and dopaminergic neurons from the substantia nigra demonstrated dysregulated miRNAs expression profiles. Hence, dysregulation of miRNAs may contribute to the pathogenesis of PD through modulation of PD-associated gene and protein expression. This review will discuss recent findings on PD-associated miRNAs dysregulation, from the regulation of PD-associated genes, dopaminergic neuron survival, α-synuclein-induced inflammation and circulating miRNAs. The next section of this review also provides an update on the potential uses of miRNAs as diagnostic biomarkers and therapeutic tools for PD.
Fulltext A qualitative study among breast cancer patients on chemotherapy: experiences and side-effects

Nies YH, Ali AM, Abdullah N, Islahudin F, Shah NM

Patient Prefer Adherence, 2018;12:1955-1964.
PMID: 30319245 DOI: 10.2147/PPA.S168638

Purpose: The objective of this study was to explore the experiences and side-effects of breast cancer patients on chemotherapy in Malaysia.
Participants and methods: Purposive sampling of 36 breast cancer patients who have completed chemotherapy and agreed to participate in semi-structured in-depth interviews. A constant comparative method and thematic analysis were used to analyze the interviews.
Results: Data were categorized into six main themes: know nothing of chemotherapy; fear of chemotherapy; patients' beliefs in alternative treatments; symptom management; staying healthy after chemotherapy; and concerns of patients after chemotherapy.
Conclusion: Despite complaints about the bad experiences of their chemotherapy-induced side-effects, these patients still managed to complete the entire course of chemotherapy. Moreover, there is a need for a clinical pharmacy service in the oncology clinic setting in Malaysia in order to provide relevant information to help patients understand the chemotherapy received.

Study site: two tertiary care hospitals in Malaysia as well as the National Cancer Society Malaysia.
Fulltext Enhanced Directed Random Walk for the Identification of Breast Cancer Prognostic Markers from Multiclass Expression Data

Nies HW, Mohamad MS, Zakaria Z, Chan WH, Remli MA, Nies YH

Entropy (Basel), 2021 Sep 20;23(9).
PMID: 34573857 DOI: 10.3390/e23091232

Artificial intelligence in healthcare can potentially identify the probability of contracting a particular disease more accurately. There are five common molecular subtypes of breast cancer: luminal A, luminal B, basal, ERBB2, and normal-like. Previous investigations showed that pathway-based microarray analysis could help in the identification of prognostic markers from gene expressions. For example, directed random walk (DRW) can infer a greater reproducibility power of the pathway activity between two classes of samples with a higher classification accuracy. However, most of the existing methods (including DRW) ignored the characteristics of different cancer subtypes and considered all of the pathways to contribute equally to the analysis. Therefore, an enhanced DRW (eDRW+) is proposed to identify breast cancer prognostic markers from multiclass expression data. An improved weight strategy using one-way ANOVA (F-test) and pathway selection based on the greatest reproducibility power is proposed in eDRW+. The experimental results show that the eDRW+ exceeds other methods in terms of AUC. Besides this, the eDRW+ identifies 294 gene markers and 45 pathway markers from the breast cancer datasets with better AUC. Therefore, the prognostic markers (pathway markers and gene markers) can identify drug targets and look for cancer subtypes with clinically distinct outcomes.
Modeling Parkinson's Disease in Zebrafish

Najib NHM, Nies YH, Abd Halim SAS, Yahaya MF, Das S, Lim WL, et al.

CNS Neurol Disord Drug Targets, 2020;19(5):386-399.
PMID: 32640968 DOI: 10.2174/1871527319666200708124117

Parkinson's Disease (PD) is one of the most common neurodegenerative disorders that affects the motor system, and includes cardinal motor symptoms such as resting tremor, cogwheel rigidity, bradykinesia and postural instability. Its prevalence is increasing worldwide due to the increase in life span. Although, two centuries since the first description of the disease, no proper cure with regard to treatment strategies and control of symptoms could be reached. One of the major challenges faced by the researchers is to have a suitable research model. Rodents are the most common PD models used, but no single model can replicate the true nature of PD. In this review, we aim to discuss another animal model, the zebrafish (Danio rerio), which is gaining popularity. Zebrafish brain has all the major structures found in the mammalian brain, with neurotransmitter systems, and it also possesses a functional blood-brain barrier similar to humans. From the perspective of PD research, the zebrafish possesses the ventral diencephalon, which is thought to be homologous to the mammalian substantia nigra. We summarize the various zebrafish models available to study PD, namely chemical-induced and genetic models. The zebrafish can complement the use of other animal models for the mechanistic study of PD and help in the screening of new potential therapeutic compounds.
Fulltext Treatment decision-making among breast cancer patients in Malaysia

Nies YH, Islahudin F, Chong WW, Abdullah N, Ismail F, Ahmad Bustamam RS, et al.

Patient Prefer Adherence, 2017;11:1767-1777.
PMID: 29081652 DOI: 10.2147/PPA.S143611

PURPOSE: This study investigated breast cancer patients' involvement level in the treatment decision-making process and the concordance between patients' and physician's perspectives in decision-making.
PARTICIPANTS AND METHODS: A cross-sectional study was conducted involving physicians and newly diagnosed breast cancer patients from three public/teaching hospitals in Malaysia. The Control Preference Scale (CPS) was administered to patients and physicians, and the Krantz Health Opinion Survey (KHOS) was completed by the patients alone. Binary logistic regression was used to determine the association between sociodemographic characteristics, the patients' involvement in treatment decision-making, and patients' preference for behavioral involvement and information related to their disease.
RESULTS: The majority of patients preferred to share decision-making with their physicians (47.5%), while the second largest group preferred being passive (42.6%) and a small number preferred being active (9.8%). However, the physicians perceived that the majority of patients preferred active decision-making (56.9%), followed by those who desired shared decision-making (32.8%), and those who preferred passive decision-making (10.3%). The overall concordance was 26.5% (54 of 204 patient-physician dyads). The median of preference for information score and behavioral involvement score was 4 (interquartile range [IQR] =3-5) and 2 (IQR =2-3), respectively. In univariate analysis, the ethnicity and educational qualification of patients were significantly associated with the patients' preferred role in the process of treatment decision-making and the patients' preference for information seeking (p>0.05). However, only educational qualification (p=0.004) was significantly associated with patients' preference for information seeking in multivariate analysis.
CONCLUSION: Physicians failed to understand patients' perspectives and preferences in treatment decision-making. The concordance between physicians' perception and patients' perception was quite low as the physicians perceived that more than half of the patients were active in treatment decision-making. In actuality, more than half of patients perceived that they shared decision-making with their physicians.