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  1. Ridzuan N, Al Abbar A, Yip WK, Maqbool M, Ramasamy R
    Stem Cells Int, 2016;2016:8487264.
    PMID: 27579045 DOI: 10.1155/2016/8487264
    The present study is aimed at optimizing the in vitro culture protocol for generation of rat bone marrow- (BM-) derived mesenchymal stem cells (MSCs) and characterizing the culture-mediated cellular senescence. The initial phase of generation and characterization was conducted using the adherent cells from Sprague Dawley (SD) rat's BM via morphological analysis, growth kinetics, colony forming unit capacity, immunophenotyping, and mesodermal lineage differentiation. Mesenchymal stem cells were successfully generated and characterized as delineated by the expressions of CD90.1, CD44H, CD29, and CD71 and lack of CD11b/c and CD45 markers. Upon induction, rBM-MSCs differentiated into osteocytes and adipocytes and expressed osteocytes and adipocytes genes. However, a decline in cell growth was observed at passage 4 onwards and it was further deciphered through apoptosis, cell cycle, and senescence assays. Despite the enhanced cell viability at later passages (P4-5), the expression of senescence marker, β-galactosidase, was significantly increased at passage 5. Furthermore, the cell cycle analysis has confirmed the in vitro culture-mediated cellular senescence where cells were arrested at the G0/G1 phase of cell cycle. Although the currently optimized protocols had successfully yielded rBM-MSCs, the culture-mediated cellular senescence limits the growth of rBM-MSCs and its potential use in rat-based MSC research.
  2. Ridzuan N, John CM, Sandrasaigaran P, Maqbool M, Liew LC, Lim J, et al.
    World J Diabetes, 2016 Jul 10;7(13):271-8.
    PMID: 27433296 DOI: 10.4239/wjd.v7.i13.271
    To assess the amount and pattern of reactive oxygen species (ROS) production in diabetic patient-derived neutrophils.
  3. Shakhih MFM, Ridzuan N, Wahab AA, Zainuddin NF, Delestri LFU, Rosslan AS, et al.
    Med Biol Eng Comput, 2021 Aug;59(7-8):1447-1459.
    PMID: 34156602 DOI: 10.1007/s11517-021-02387-x
    Surface electromyography (sEMG) has been widely used in evaluating muscle fatigue among athletes where electrodes are attached on the skin during the activity. Recently, infrared thermography technique (IRT) has gain popularity and shown to be another preferred method in monitoring and predicting muscle fatigue non-obstructively. This paper investigates the correlation between surface temperature and muscle activation parameters obtained using both IRT and sEMG methods simultaneously. Twenty healthy subjects were required to perform a repetitive calf raise exercise with various loads attached around their ankle for 3 min to induce fatigue on the targeted gastrocnemius muscles. Average temperature and temperature difference information were extracted from thermal images, while root mean square (RMS) and median frequency (MF) were extracted from sEMG signals. Spearman statistical analysis performed shows that there is a significant correlation between average temperature with RMS and between temperature difference with MF values at p<0.05. While ANOVA test conducted shows that there is significant impact of loads on RMS and MF where F=12.61 and 3.59, respectively, at p< 0.05. This study suggested that skin surface temperature can be utilized in monitoring and predicting muscle fatigue in low intensity dynamic exercise and can be extended to other dynamic exercises.
  4. Mun-Fun H, Ferdaos N, Hamzah SN, Ridzuan N, Hisham NA, Abdullah S, et al.
    Res Vet Sci, 2015 Oct;102:89-99.
    PMID: 26412526 DOI: 10.1016/j.rvsc.2015.07.010
    Amniotic fluid stem cells (AFSCs) are commonly isolated from mid-term amniotic fluid (AF) of animals and human collected via an invasive technique, amniocentesis. Alternatively, AFSCs could be collected at full-term. However, it is unclear whether AFSCs are present in the AF at full term. Here, we aimed to isolate and characterize stem cells isolated from AF of full term pregnant rats. Three stem cell lines have been established following immuno-selection against the stem cell marker, c-kit. Two of the new lines expressed multiple markers of pluripotency until more than passage 90. Further, they spontaneously differentiated into derivatives of the three primary germ layers through the formation of good quality embryoid bodies (EBs), and can be directly differentiated into neural lineage. Their strong stemness and potent neurogenic properties highlight the presence of highly potent stem cells in AF of full-term pregnancies, which could serve as a potential source of stem cells for regenerative medicine.
  5. Ridzuan N, Zakaria N, Widera D, Sheard J, Morimoto M, Kiyokawa H, et al.
    Stem Cell Res Ther, 2021 01 12;12(1):54.
    PMID: 33436065 DOI: 10.1186/s13287-020-02088-6
    BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin.

    METHODS: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student's t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD).

    RESULTS: Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD.

    CONCLUSIONS: In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

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