Displaying publications 1 - 20 of 32 in total

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  1. Interferon-gamma (IFN-γ): Reviewing its mechanisms and signaling pathways on the regulation of endothelial barrier function
    Ng CT, Fong LY, Abdullah MNH
    Cytokine, 2023 Jun;166:156208.
    PMID: 37088004 DOI: 10.1016/j.cyto.2023.156208
    Interferon-gamma (IFN-γ) is a pleiotropic cytokine that plays a critical role in mediating an array of immune responses including promotes antiviral activity, facilitates macrophage activation, controls Th1/Th2 balance, and regulates cellular apoptosis and proliferation. A few articles have previously reviewed the effects of IFN-γ in the regulation of barrier permeability, but none of these articles focuses on barrier function of endothelial cells. This review aims to discuss the regulatory mechanisms of IFN-γ on endothelial barrier function and its underlying signaling pathways. Articles were retrieved from electronic databases such as PubMed and Google Scholar using keywords "Interferon-gamma", "endothelial cells", "barrier function", and "signaling pathway". The articles published between 2000 and 2022 that are related to the aforementioned topics were selected. A few journals published beyond this period were also included due to limited information available. The results showed that IFN-γ modulates endothelial barrier function, mainly involves small GTPases, STAT1-dependent pathway, p38 MAPK and nitric oxide. In conclusion, more in depth cellular and molecular studies are needed to elucidate the pathways of IFN-γ in the regulation of endothelial barrier function.
  2. Barrier protective effect of asiatic acid in TNF-α-induced activation of human aortic endothelial cells
    Fong LY, Ng CT, Cheok ZL, Mohd Moklas MA, Hakim MN, Ahmad Z
    Phytomedicine, 2016 Feb 15;23(2):191-9.
    PMID: 26926181 DOI: 10.1016/j.phymed.2015.11.019
    Endothelial cell activation is characterized by increased endothelial permeability and increased expression of cell adhesion molecules (CAMs). This allows monocyte adherence and migration across the endothelium to occur and thereby initiates atherogenesis process. Asiatic acid is a major triterpene isolated from Centella asiatica (L.) Urban and has been shown to possess anti-oxidant, anti-hyperlipidemia and anti-inflammatory activities.
  3. Nitric oxide participates in IFN-gamma-induced HUVECs hyperpermeability
    Ng CT, Fong LY, Low YY, Ban J, Hakim MN, Ahmad Z
    Physiol Res, 2016 12 13;65(6):1053-1058.
    PMID: 27539106
    The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability. The flux of fluorescein isothiocyanate-labeled dextran across cell monolayers was used to study the permeability of endothelial cells. Here, we found that IFN-gamma significantly attenuated basal NO concentration and the increased NO levels supplied by a NO donor, sodium nitroprusside (SNP). Besides, application of IFN-gamma also significantly attenuated both the basal cGMP concentration and the increased cGMP production donated by a cell permeable cGMP analogue, 8-bromo-cyclic GMP (8-Br-cGMP). In addition, exposure of the cell monolayer to IFN-gamma significantly increased HUVECs basal permeability. However, L-NAME pretreatment did not suppress IFN-gamma-induced HUVECs hyperpermeability. L-NAME pretreatment followed by SNP or SNP pretreatment partially reduced IFN-gamma-induced HUVECs hyperpermeability. Pretreatment with a guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), led to a further increase in IFN-gamma-induced HUVECs hyperpermeability. The findings suggest that the mechanism underlying IFN-gamma-induced increased HUVECs permeability is partly related to the inhibition of NO production.
  4. Interferon-γ induces biphasic changes in caldesmon localization as well as adherens junction organization and expression in HUVECs
    Ng CT, Fong LY, Yong YK, Hakim MN, Ahmad Z
    Cytokine, 2018 11;111:541-550.
    PMID: 29909980 DOI: 10.1016/j.cyto.2018.06.010
    Endothelial barrier dysfunction leads to increased endothelial permeability and is an early step in the development of vascular inflammatory diseases such as atherosclerosis. Interferon-γ (IFN-γ), a proinflammatory cytokine, is known to cause increased endothelial permeability. However, the mechanisms by which IFN-γ disrupts the endothelial barrier have not been clarified. This study aimed to investigate how IFN-γ impairs the endothelial barrier integrity by specifically examining the roles of caldesmon, adherens junctions (AJs) and p38 mitogen-activated protein (MAP) kinase in IFN-γ-induced endothelial barrier dysfunction. IFN-γ exhibited a biphasic effect on caldesmon localization and both the structural organization and protein expression of AJs. In the early phase (4-8 h), IFN-γ induced the formation of peripheral caldesmon bands and discontinuous AJs, while AJ protein expression was unchanged. Interestingly, IFN-γ also stimulated caldesmon phosphorylation, resulting in actin dissociation from caldesmon at 8 h. Conversely, changes seen in the late phase (16-24 h) included cytoplasmic caldesmon dispersal, AJ linearization and junctional area reduction, which were associated with reduced membrane, cytoskeletal and total AJ protein expression. In addition, IFN-γ enhanced myosin binding to caldesmon at 12 h and persisted up to 24 h. Furthermore, inhibition of p38 MAP kinase by SB203580 did not reverse either the early or late phase changes observed. These data suggest that IFN-γ may activate signaling molecules other than p38 MAP kinase. In conclusion, our findings enhance the current understanding of how IFN-γ disrupts endothelial barrier function and reveal potential therapeutic targets, such as caldesmon and AJs, for the treatment of IFN-γ-associated vascular inflammatory diseases.
  5. Asiatic acid stabilizes cytoskeletal proteins and prevents TNF-α-induced disorganization of cell-cell junctions in human aortic endothelial cells
    Fong LY, Ng CT, Yong YK, Hakim MN, Ahmad Z
    Vascul. Pharmacol., 2019 06;117:15-26.
    PMID: 30114509 DOI: 10.1016/j.vph.2018.08.005
    Endothelial hyperpermeability represents an initiating step in early atherosclerosis and it often occurs as a result of endothelial barrier dysfunction. Asiatic acid, a major triterpene isolated from Centella asiatica (L.) Urban, has previously been demonstrated to protect against tumor necrosis factor (TNF)-α-induced endothelial barrier dysfunction. The present study aimed to investigate the mechanisms underlying the barrier protective effect of asiatic acid in human aortic endothelial cells (HAECs). The localization of F-actin, diphosphorylated myosin light chain (diphospho-MLC), adherens junctions (AJs) and tight junctions (TJs) was studied using immunocytochemistry techniques and confocal microscopy. Their total protein expressions were examined using western blot analysis. The endothelial permeability was assessed using In Vitro Vascular Permeability Assay kits. In addition, intracellular redistribution of the junctional proteins was evaluated using subcellular fractionation kits. We show that asiatic acid stabilized F-actin and diphospho-MLC at the cell periphery and prevented their rearrangement stimulated by TNF-α. However, asiatic acid failed to attenuate cytochalasin D-induced increased permeability. Besides, asiatic acid abrogated TNF-α-induced structural reorganization of vascular endothelial (VE)-cadherin and β-catenin by preserving their reticulum structures at cell-cell contact areas. In addition, asiatic acid also inhibited TNF-α-induced redistribution of occludin and zona occludens (ZO)-1 in different subcellular fractions. In conclusion, the barrier-stabilizing effect of asiatic acid might be associated with preservation of AJs and prevention of TJ redistribution caused by TNF-α. This study provides evidence to support the potential use of asiatic acid in the prevention of early atherosclerosis, which is initiated by endothelial barrier dysfunction.
  6. Interferon-Gamma Increases Endothelial Permeability by Causing Activation of p38 MAP Kinase and Actin Cytoskeleton Alteration
    Ng CT, Fong LY, Sulaiman MR, Moklas MA, Yong YK, Hakim MN, et al.
    J Interferon Cytokine Res, 2015 Jul;35(7):513-22.
    PMID: 25830506 DOI: 10.1089/jir.2014.0188
    Interferon-gamma (IFN-γ) is known to potentiate the progression of inflammatory diseases, such as inflammatory bowel disease and atherosclerosis. IFN-γ has been found to disrupt the barrier integrity of epithelial and endothelial cell both in vivo and in vitro. However, the mechanisms of IFN-γ underlying increased endothelial cell permeability have not been extensively elucidated. We reported that IFN-γ exhibits a biphasic nature in increasing endothelial permeability. The changes observed in the first phase (4-8 h) involve cell retraction and rounding in addition to condensed peripheral F-actin without a significant change in the F-/G-actin ratio. However, cell elongation, stress fiber formation, and an increased F-/G-actin ratio were noticed in the second phase (16-24 h). Consistent with our finding from the permeability assay, IFN-γ induced the formation of intercellular gaps in both phases. A delayed phase of increased permeability was observed at 12 h, which paralleled the onset of cell elongation, stress fiber formation, and increased F-/G-actin ratio. In addition, IFN-γ stimulated p38 mitogen-activated protein (MAP) kinase phosphorylation over a 24 h period. Inhibition of p38 MAP kinase by SB203580 prevented increases in paracellular permeability, actin rearrangement, and increases in the F-/G-actin ratio caused by IFN-γ. Our results suggest that p38 MAP kinase is activated in response to IFN-γ and causes actin rearrangement and altered cell morphology, which in turn mediates endothelial cell hyperpermeability. The F-/G-actin ratio might be involved in the regulation of actin distribution and cell morphology rather than the increased permeability induced by IFN-γ.
  7. APLAR rheumatoid arthritis treatment recommendations
    Lau CS, Chia F, Harrison A, Hsieh TY, Jain R, Jung SM, et al.
    Int J Rheum Dis, 2015 Sep;18(7):685-713.
    PMID: 26334449 DOI: 10.1111/1756-185X.12754
    Rheumatoid arthritis is a chronic inflammatory condition that affects approximately 1% of the world's population. There are a wide number of guidelines and recommendations available to support the treatment of rheumatoid arthritis; however, the evidence used for these guidelines is predominantly based on studies in Caucasian subjects and may not be relevant for rheumatoid arthritis patients in the Asia-Pacific region. Therefore, the Asia Pacific League of Associations for Rheumatology established a Steering Committee in 2013 to address this issue.
  8. Cardiovascular Protective Effects of Centella asiatica and Its Triterpenes: A Review
    Razali NNM, Ng CT, Fong LY
    Planta Med, 2019 Nov;85(16):1203-1215.
    PMID: 31539918 DOI: 10.1055/a-1008-6138
    Centella asiatica, a triterpene-rich medicinal herb, is traditionally used to treat various types of diseases including neurological, dermatological, and metabolic diseases. A few articles have previously reviewed a broad range of pharmacological activities of C. asiatica, but none of these reviews focuses on the use of C. asiatica in cardiovascular diseases. This review aims to summarize recent findings on protective effects of C. asiatica and its active constituents (asiatic acid, asiaticoside, madecassic acid, and madecassoside) in cardiovascular diseases. In addition, their beneficial effects on conditions associated with cardiovascular diseases were also reviewed. Articles were retrieved from electronic databases such as PubMed and Google Scholar using keywords "Centella asiatica," "asiatic acid," "asiaticoside," "madecassic acid," and "madecassoside." The articles published between 2004 and 2018 that are related to the aforementioned topics were selected. A few clinical studies published beyond this period were also included. The results showed that C. asiatica and its active compounds possess potential therapeutic effects in cardiovascular diseases and cardiovascular disease-related conditions, as evidenced by numerous in silico, in vitro, in vivo, and clinical studies. C. asiatica and its triterpenes have been reported to exhibit cardioprotective, anti-atherosclerotic, antihypertensive, antihyperlipidemic, antidiabetic, antioxidant, and anti-inflammatory activities. In conclusion, more clinical and pharmacokinetic studies are needed to support the use of C. asiatica and its triterpenes as therapeutic agents for cardiovascular diseases. Besides, elucidation of the molecular pathways modulated by C. asiatica and its active constituents will help to understand the mechanisms underlying the cardioprotective action of C. asiatica.
  9. Cryptotanshinone inhibits TNF-α-induced early atherogenic events in vitro
    Ahmad Z, Ng CT, Fong LY, Bakar NA, Hussain NH, Ang KP, et al.
    J Physiol Sci, 2016 May;66(3):213-20.
    PMID: 26732386 DOI: 10.1007/s12576-015-0410-7
    Endothelial dysfunction has been implicated in the pathogenesis of atherosclerosis. Salvia miltiorrhiza (danshen) is a traditional Chinese medicine that has been effectively used to treat cardiovascular disease. Cryptotanshinone (CTS), a major lipophilic compound isolated from S. miltiorrhiza, has been reported to possess cardioprotective effects. However, the anti-atherogenic effects of CTS, particularly on tumor necrosis factor-α (TNF-α)-induced endothelial cell activation, are still unclear. This study aimed to determine the effect of CTS on TNF-α-induced increased endothelial permeability, monocyte adhesion, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), monocyte chemoattractant protein 1 (MCP-1) and impaired nitric oxide production in human umbilical vein endothelial cells (HUVECs), all of which are early events occurring in atherogenesis. We showed that CTS significantly suppressed TNF-α-induced increased endothelial permeability, monocyte adhesion, sICAM-1, sVCAM-1 and MCP-1, and restored nitric oxide production. These observations suggest that CTS possesses anti-inflammatory properties and could be a promising treatment for the prevention of cytokine-induced early atherogenesis.
  10. Clinical and autoantibody profile in systemic sclerosis: baseline characteristics from a West Malaysian cohort
    Sujau I, Ng CT, Sthaneshwar P, Sockalingam S, Cheah TE, Yahya F, et al.
    Int J Rheum Dis, 2015 May;18(4):459-65.
    PMID: 24618222 DOI: 10.1111/1756-185X.12322
    AIM: To evaluate the clinical and antibody profile of systemic sclerosis (SSc) in a Malaysian cohort.
    METHODS: Consecutive patients with SSc in University Malaya Medical Centre from March to November 2012 were included in this study. In addition to clinical characterization, all subjects underwent autoantibody testing using Euroline immunoblot assay. The association between clinical features and autoantibody profile was evaluated.
    RESULTS: There were 31, predominantly Chinese (45.2%), subjects. Limited cutaneous disease was the most common subtype (71%). Raynaud's phenomenon was the most commonly observed feature (83.9%). Nine (29%) had esophageal dysmotility symptoms and 23 (74.2%), including all patients with diffuse SSc, had symptoms of gastro-esophageal reflux disease (GERD). Restrictive pattern on pulmonary function test and evidence of lung fibrosis were seen in more than 70% of patients. Echocardiographic evidence of pulmonary arterial hypertension was seen in 58.1%. Telangiectasia, calcinosis, digital ulcers, digital pulp loss or pitting were seen more commonly in the diffuse subtype. The two most prevalent autoantibodies were anti-Scl-70 and anti-Ro-52. The presence of anti-Scl-70 was significantly associated with restrictive lung disease (P = 0.05). Anti-Ro-52 was associated with control subjects with other autoimmune diseases (P = 0.043). The presence of anti-PM-Scl-75 was associated with overlap syndrome (P = 0.032). Patients with anticentromere antibodies were more likely to have vasculitic rash (P = 0.012).
    CONCLUSION: In Malaysia, SSc most commonly affects the Chinese. Limited cutaneous is more common than diffuse subtype. Features of CREST (calcinosis, Reynaud disease, esophageal dysmotility, sclerodactyly, telangiectasia) are more commonly observed in the diffuse cutaneous subgroup. Anti-Scl-70 and anti-Ro-52 antibodies are promising biomarkers for pulmonary involvement in SSc.
    KEYWORDS: Malaysia; autoantibodies; clinical profile; systemic sclerosis
  11. Clinical and economic implications of upper gastrointestinal adverse events in Asian rheumatological patients on long-term non-steroidal anti-inflammatory drugs
    Pok LSL, Shabaruddin FH, Dahlui M, Sockalingam S, Mohamed Said MS, Rosman A, et al.
    Int J Rheum Dis, 2018 May;21(5):943-951.
    PMID: 29314744 DOI: 10.1111/1756-185X.13256
    AIM: To determine the incidence and direct costs of NSAID-induced upper GI adverse events in Malaysian rheumatology patients.
    METHODS: A retrospective, multi-centre, cohort study of rheumatology patients on long-term NSAIDs was conducted. Clinical data of patients treated between 2010 and 2013 were collected for a 24-month follow-up period. The costs of managing upper GI adverse events were based on patient level resource use data.
    RESULTS: Six hundred and thirty-four patients met the inclusion criteria: mean age 53.4 years, 89.9% female, diagnosis of rheumatoid arthritis (RA; 59.3%), osteoarthritis (OA; 10.3%) and both RA and OA (30.3%). Three hundred and seventy-one (58.5%) patients were prescribed non-selective NSAIDs and 263 (41.5%) had cyclo-oxygenase-2 inhibitors. Eighty-four upper GI adverse events occurred, translating into a risk of 13.2% and an incidence rate of 66.2 per 1000 person-years. GI adverse events comprised: dyspepsia n = 78 (12.3%), peptic ulcer disease (PUD) n = 5 (0.79%) and upper GI bleeding (UGIB) n = 1 (0.16%). The total direct healthcare cost of managing adverse events was Malaysian Ringgit (MR) 37 352 (US dollars [USD] 11 419) with a mean cost of MR 446.81 ± 534.56 (USD 136.60 ± 163.42) per patient, consisting mainly of GI pharmacotherapy (33.8%), oesophagoduodenoscopies (23.1%) and outpatient clinic visits (18.2%). Mean cost per patient by GI events were: dyspepsia, MR 408.98 ± 513.29 (USD125.03 ± 156.92); PUD, MR 805.93 ± 578.80 (USD 246.39 ± 176.95); UGIB, MR 1601.94 (USD 489.74, n = 1).
    CONCLUSION: The economic burden of GI adverse events due to long-term NSAIDs use in Malaysian patients with chronic rheumatic diseases is modest.
    Study site: Rheumatology clinics, Hospital Putrajaya, Hospital Selayang, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  12. Fulltext Physical therapies for improving balance and reducing falls risk in osteoarthritis of the knee: a systematic review
    Mat S, Tan MP, Kamaruzzaman SB, Ng CT
    Age Ageing, 2015 Jan;44(1):16-24.
    PMID: 25149678 DOI: 10.1093/ageing/afu112
    INTRODUCTION: osteoarthritis (OA) of knee has been reported as a risk factor for falls and reduced balance in the elderly. This systematic review evaluated the effectiveness of physical therapies in improving balance and reducing falls risk among patients with knee OA.
    METHODS: a computerised search was performed to identify relevant studies up to November 2013. Two investigators identified eligible studies and extracted data independently. The quality of the included studies was assessed by the PeDro score.
    RESULTS: a total of 15 randomised controlled trials involving 1482 patients were identified. The mean PeDro score was 7. The pooled standardised mean difference in balance outcome for strength training = 0.3346 (95% CI: 0.3207-0.60, P = 0.01 < 0.00001, P for heterogeneity = 0.85, I(2) = 0%). Tai Chi = 0.7597 (95% CI: 0.5130-1.2043, P<=0.0014, P for heterogeneity = 0.26, I(2) = 0%) and aerobic exercises = 0.6880 (95% CI: 0.5704-1.302, P < 0.00001, P for heterogeneity = 0.71, I(2) = 0%). While pooled results for falls risk outcomes in, strength training, Tai chi and aerobics also showed a significant reduction in reduced risk of falls significantly with pooled result 0.55 (95% CI: 0.41-0.68, P < 0.00001, P for heterogeneity = 0.39, I(2) = 6%).
    CONCLUSION: strength training, Tai Chi and aerobics exercises improved balance and falls risk in older individuals with knee OA, while water-based exercises and light treatment did not significantly improve balance outcomes. Strength training, Tai Chi and aerobics exercises can therefore be recommended as falls prevention strategies for individuals with OA. However, a large randomised controlled study using actual falls outcomes is recommended to determine the appropriate dosage and to measure the potential benefits in falls reduction.
    KEYWORDS: Tai Chi; elderly; exercises; falls; older people; osteoarthritis
  13. Painless ascites and elevated CA125: initial presentation of lupus-associated protein-losing enteropathy
    Ong CS, Cheah TE, Jasmin R, Yahya F, Sockalingam S, Ng CT
    Lupus, 2013 Oct;22(11):1174-7.
    PMID: 23886639 DOI: 10.1177/0961203313498792
    Lupus associated protein loosing enteropathy (LUPLE) is a rare gastrointestinal manifestation of SLE. We presented a case of painless ascites from serve hypoalbuminaemia secondary to LUPLE. The patient responded to a course of intravenous cyclophosphamide. The remission was maintained by azathioprine and low dose prednisolone.
  14. Monophasic synovial sarcoma of the pyriform fossa
    Ng CT, Wong EHC, Prepageran N
    BMJ Case Rep, 2020 Nov 30;13(11).
    PMID: 33257363 DOI: 10.1136/bcr-2020-236204
    Head and neck synovial sarcoma is rare. We report the case of a 71-year-old man who presented with progressive dysphagia, odynophagia, shortness of breath on exertion and hoarseness of voice. Nasendoscopy revealed a smooth, non-fungating, non-ulcerative mass arising from the left lateral pharyngeal wall. CT showed a well-defined, heterogenous enhancing lesion arising from the left pyriform fossa. Initial biopsy taken was inconclusive and patient underwent a transcervical complete excision of the tumour, where histopathological analysis confirmed the diagnosis of monophasic synovial sarcoma of the left pyriform fossa. This patient also received adjuvant radiotherapy postoperatively and remained disease free 1 year after completion of treatment.
  15. Myocardial infarction with normal coronaries: an unexpected finding in a 13-year-old girl with systemic lupus erythematosus
    Jasmin R, Ng CT, Sockalingam S, Yahya F, Cheah TE, Sadiq MA
    Lupus, 2013 Dec;22(14):1518-22.
    PMID: 24004952 DOI: 10.1177/0961203313503913
    We report a 13-year-old girl diagnosed with systemic lupus erythematosus (SLE) who presented with left-sided chest pain, with ECG changes and elevation troponins that were suggestive of an acute inferior wall myocardial infarction (MI). Her multi-slice computed tomography coronary angiogram and standard angiogram were normal. The cardiac magnetic resonance imaging revealed an area of infarcted myocardium that was in the right coronary artery territory. We believe her MI was most likely secondary to coronary vasospasm. MI is rare and coronary vasospasm is an uncommon cause of MI in children and adolescents with SLE.
  16. Fulltext Comparison of invasion by human microvascular endothelial cell lines in response to vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in a threedimensional (3D) cell culture system
    Ng CT, Yip WK, Mohtarrudin N, Seow HF
    Malays J Pathol, 2015 Dec;37(3):219-25.
    PMID: 26712666 MyJurnal
    Immortalized human endothelial cells are widely used as in vitro models for debilitating conditions such as cancer, cardiovascular and ocular diseases. Human microvascular endothelial cell (HMEC-1) is immortalized via stable transfection with a gene encoding SV40 large antigen whilst telomerase-immortalized human microvascular endothelial (TIME) cells is immortalized by engineering the human telomerase catalytic protein (hTERT) into primary microvascular endothelial cells. Here, we established a three-dimensional (3D) spheroid invasion assay with HMEC-1 and TIME and compared the difference in their ability to invade through the collagen matrix in response to exogenous growth factors, namely vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).
  17. Fulltext Circulating miRNAs in Type 2 Diabetic Patients with and without Albuminuria in Malaysia
    Zahari Sham SY, Ng CT, Azwar S, Yip WK, Abdullah M, Thevandran K, et al.
    Kidney Blood Press Res, 2022;47(2):81-93.
    PMID: 35158353 DOI: 10.1159/000518866
    INTRODUCTION: Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease. Dysregulation of circulating miRNAs has been reported, suggesting their pathological roles in DKD. This study aimed to investigate differentially expressed miRNAs in the sera of type 2 diabetes mellitus (T2DM) patients with and without albuminuria in a selected Malaysian population.

    METHOD: Forty-one T2DM patients on follow-up at a community clinic were divided into normo-(NA), micro-(MIC), and macroalbuminuria (MAC) groups. Differential levels of miRNAs in 12 samples were determined using the pathway-focused (human fibrosis) miScript miRNA qPCR array and was validated in 33 samples, using the miScript custom qPCR array (CMIHS02742) (Qiagen GmbH, Hilden, Germany).

    RESULTS: Trends of upregulation of 3 miRNAs in the serum, namely, miR-874-3p, miR-101-3p, and miR-145-5p of T2DM patients with MAC compared to those with NA. Statistically significant upregulation of miR-874-3p (p = 0.04) and miR-101-3p (p = 0.01) was seen in validation cohort. Significant negative correlations between the estimated glomerular filtration rate (eGFR) and miR-874-3p (p = 0.05), miR-101-3p (p = 0.03), and miR-145-5p (p = 0.05) as well as positive correlation between miR-874-3p and age (p = 0.03) were shown by Pearson's correlation coefficient analysis.

    CONCLUSION: Upregulation of previously known miRNA, namely, miR-145-5p, and possibly novel ones, namely, miR-874-3p and miR-101-3p in the serum of T2DM patients, was found in this study. There was a significant correlation between the eGFR and these miRNAs. The findings of this study have provided encouraging evidence to further investigate the putative roles of these differentially expressed miRNAs in DKD.

  18. Increased tube formation and up-regulation of FGFR3 mRNA expression in microvascular endothelial cell by exosomes derived from SW480-7
    Ng CT, Yip WK, Mohtarrudin N, Jabar MF, Seow HF
    Malays J Pathol, 2023 Aug;45(2):195-204.
    PMID: 37658529
    INTRODUCTION: Extracellular vesicles (exosome-like vesicles) are small membrane vesicles ranging from 20-200nm in size that are released by various cells into the extracellular space. These extracellular vesicles play a major role in cell-to-cell communication and contain materials, such as proteins, mRNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). The effect of exosomes derived from an invasive colon cancer cell line on angiogenesis is unclear. Hence, the aim of this study is to investigate the effect of exosomes derived from an invasive colon cancer cell line on angiogenesis of endothelial cells.

    MATERIALS AND METHODS: In the present study, the exosomes from the cell culture supernatants of an invasive colon cancer cell line SW480-7 were characterised. The effect on tube formation and expression of angiogenic genes in a microvascular endothelial cell, telomerase-immortalised microvascular endothelial cell (TIME) was examined after co-cultured with exosomes secreted from SW480-7.

    RESULTS: Zetasizer result showed average diameter of exosomes derived from SW480-7 was 246.2 nm and morphological analysis showed the size of majority of exosomes were less than 200 nm. Results showed that exosomes derived from SW480-7 increased tube formation and up-regulated FGFR3 mRNA expression in TIME.

    CONCLUSION: Our findings suggest that exosomes derived from SW480-7 increased tube formation and up-regulated expression of FGFR3 mRNA in TIME.

  19. Open label randomized controlled trial assessing the efficacy of mycophenolate sodium against other conventional immunosuppressive agents in active systemic lupus erythematosus patients without renal involvement
    Yahya F, Jasmin R, Ng CT, Cheah TE, Sockalingam S
    Int J Rheum Dis, 2013 Dec;16(6):724-30.
    PMID: 24119227 DOI: 10.1111/1756-185X.12179
    Mycophenolate is an immunosuppressive agent which has been used in systemic lupus erythematosus (SLE) patients who have failed conventional therapy. However, the use of mycophenolate sodium in extra-renal SLE involvement has yet to be established. This study aimed to assess the efficacy of mycophenolate sodium in extra-renal SLE.
  20. Chronic intestinal pseudo-obstruction: a rare first manifestation of systemic lupus erythematosus
    Khairullah S, Jasmin R, Yahya F, Cheah TE, Ng CT, Sockalingam S
    Lupus, 2013 Aug;22(9):957-60.
    PMID: 23761180 DOI: 10.1177/0961203313492873
    Chronic intestinal pseudo-obstruction (CIPO) is a rare clinical syndrome of ineffective intestinal motility characterised by clinical and radiological evidence of intestinal obstruction with no identifiable mechanical lesion. CIPO can either be idiopathic or secondary to a systemic disease, like systemic lupus erythematosus (SLE). Fewer than 30 cases of CIPO secondary to SLE have been reported so far. Here we describe a case of SLE with the initial presentation of CIPO. In SLE-related CIPO, treatment includes a combination of high-dose intravenous corticosteroids, immunosuppressants and supportive care. With awareness of this condition, unnecessary surgical intervention and repeated invasive procedures could be avoided. Early initiation of treatment would avoid complications and bring about resolution of symptoms.
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