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  1. Nik Ramli NN, Omar N, Husin A, Ismail Z, Siran R
    Neurosci Lett, 2015 Feb 19;588:137-41.
    PMID: 25562631 DOI: 10.1016/j.neulet.2014.12.062
    Glutamate receptors are the integral cellular components associated with excitotoxicity mechanism induced by the ischemic cascade events. Therefore the glutamate receptors have become the major molecular targets of neuroprotective agents in stroke researches. Recent studies have demonstrated that a Group I metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) preconditioning elicits neuroprotection in the hippocampal slice cultures exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated the preconditioning effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10 or 100μM of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult male rats, 2h prior to induction of acute ischemic stroke by middle cerebral artery occlusion (MCAO). After 24h, neurological deficits were evaluated by modified stroke severity scores and grid-walking test. All rats were sacrificed and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. The serum level of neuron-specific enolase (NSE) of each rat was analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10μM of (S)-3,5-DHPG preconditioning in the stroke rats showed significant improvements in motor impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in the NSE serum level (P<0.01) compared to the control stroke rats. We conclude that 1 and 10μM (S)-3,5-DHPG preconditioning induced protective effects against acute ischemic insult in vivo.
  2. Nik Ramli NN, Asokan A, Mayakrishnan D, Annamalai H
    Malays J Med Sci, 2021 Aug;28(4):14-23.
    PMID: 34512127 DOI: 10.21315/mjms2021.28.4.3
    Ranked as the second leading cause of death and the primary factor to adult disability worldwide, stroke has become a global epidemic problem and burden. As a developing country, Malaysia still faces challenges in providing ideal rehabilitation services to individuals with physical disabilities including stroke survivors. Conventional post-stroke care is often delivered in a team-based approach and involves several disciplines, such as physical therapy, occupational therapy, speech and language therapy, depending on the nature and severity of the deficits. Robots are potential tools for stroke rehabilitation as they can enhance existing conventional therapy by delivering a precise and consistent therapy of highly repetitive movements. In addition, robot-assisted physiotherapy could facilitate the effectiveness of unsupervised rehabilitation and thus, may reduce the cost and duration of therapist-assisted rehabilitation. Research on robot-assisted physiotherapy for stroke in Malaysia is slowly coming into the limelight in the past two decades. This review explores the effectiveness of robot-assisted physiotherapy particularly in improving motor functions of stroke survivors in Malaysia.
  3. Abd Aziz SN, Pung SY, Ramli NN, Lockman Z
    ScientificWorldJournal, 2014;2014:252851.
    PMID: 24587716 DOI: 10.1155/2014/252851
    The photodegradation efficiency of ZnO nanoparticles in removal of organic pollutants deteriorates over time as a high percentage of the nanoparticles can be drained away by water during the wastewater treatment. This problem can be solved by growing the ZnO nanorods on stainless steel wire. In this work, ZnO nanorods were successfully grown on stainless steel wire by chemical vapour deposition. The SAED analysis indicates that ZnO nanorod is a single crystal and is preferentially grown in [0001] direction. The deconvoluted O 1s peak at 531.5 eV in XPS analysis is associated with oxygen deficient, revealing that the ZnO nanorods contain many oxygen vacancies. This observation is further supported by the finding of the small I(uv)/I(vis) ratio, that is, ~1 in the photoluminescence analysis. The growth of ZnO nanorods on stainless steel wire was governed by vapour-solid mechanism as there were no Fe particles observed at the tips of the nanorods. The photodegradation of Rhodamine B solution by ZnO nanorods followed the first-order kinetics.
  4. Ramli NN, Othman AR, Kurniawan SB, Abdullah SRS, Hasan HA
    Microbiol Res, 2023 Mar;268:127288.
    PMID: 36571921 DOI: 10.1016/j.micres.2022.127288
    Heavy metal wastes, particularly hexavalent chromium [Cr(VI)], are generated from anthropogenic activities, and their increasing abundance has been a research concern due to their toxicity, genotoxicity, carcinogenicity and mutagenicity. Exposure to these dangerous pollutants could lead to chronic infections and even mortality in humans and animals. Bioremediation using microorganisms, particularly bacteria, has gained considerable interest because it can remove contaminants naturally and is safe to the surrounding environment. Bacteria, such as Pseudomonas putida and Bacillus subtilis, can reduce the toxic Cr(VI) to the less toxic trivalent chromium Cr(III) through mechanisms including biotransformation, biosorption and bioaccumulation. These mechanisms are mostly linked to chromium reductase and nitroreductase enzymes, which are involved in the Cr(VI) reduction pathway. However, relevant data on the nitroreductase route remain insufficient. Thus, this work proposes an alternative metabolic pathway of nitroreductase, wherein nitrate activates the reaction and indirectly reduces toxic chromium. This nitroreductase pathway occurs concurrently with the chromium reduction pathway.
  5. Ahamad Tarmizi AA, Nik Ramli NN, Adam SH, Abdul Mutalib M, Mokhtar MH, Tang SGH
    Molecules, 2023 Jul 10;28(14).
    PMID: 37513196 DOI: 10.3390/molecules28145322
    The advancement in nanotechnology is the trigger for exploring the synthesis of selenium nanoparticles and their use in biomedicine. Therefore, this study aims to synthesize selenium nanoparticles using M. oleifera as a reducing agent and evaluate their antioxidant and antidiabetic potential. Our result demonstrated a change in the color of the mixture from yellow to red, and UV-Vis spectrometry of the suspension solution confirmed the formation of MO-SeNPs with a single absorbance peak in the range of 240-560 nm wavelength. FTIR analysis revealed several bioactive compounds, such as phenols and amines, that could possibly be responsible for the reduction and stabilization of the MO-SeNPs. FESEM + EDX analysis revealed that the amorphous MO-SeNPs are of high purity, have a spherical shape, and have a size of 20-250 nm in diameter, as determined by HRTEM. MO-SeNPs also exhibit the highest DPPH scavenging activity of 84% at 1000 μg/mL with an IC50 of 454.1 μg/mL and noteworthy reducing ability by reducing power assay. Furthermore, MO-SeNPs showed promising antidiabetic properties with dose-dependent inhibition of α-amylase (26.7% to 44.53%) and α-glucosidase enzyme (4.73% to 19.26%). Hence, these results demonstrated that M. oleifera plant extract possesses the potential to reduce selenium ions to SeNPs under optimized conditions with notable antioxidant and antidiabetic activities.
  6. Ramli NN, Iberahim S, Mohd Noor NH, Zulkafli Z, Tengku Shihabuddin TM, Din MH, et al.
    Cureus, 2024 Jan;16(1):e51552.
    PMID: 38313946 DOI: 10.7759/cureus.51552
    Background Venous thromboembolism (VTE) is a common and potentially life-threatening complication in patients with lower limb traumatic fractures. Orthopaedic patients who experience trauma in the lower limbs with prolonged immobilization may experience a hypercoagulable state, which could eventually lead to the development of VTE. Therefore, this study aims to evaluate the changes in hypercoagulable markers, including haemostatic, inflammatory, and haematological biomarkers in orthopaedic trauma patients with prolonged immobilization. Materials/method This prospective cohort study was conducted at Hospital Universiti Sains Malaysia from August 2020 to March 2022. Every patient with fractures in the lower limbs was screened for eligibility, and patients who required immobilization for more than five days without receiving anticoagulant prophylaxis were recruited for this study. The laboratory tests, including D-dimer, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), erythrocyte sedimentation rate (ESR), and platelet count, were serially measured on day one and day five of hospitalization. The biomarkers were analyzed using a paired t-test, with a p-value <0.05 as a significant result. Results A total of 54 patients with fractures in the lower limbs, ages ranging from 12 to 50 years old, were involved in this study. The paired t-test analysis demonstrated that several biomarkers showed a significant increase in mean difference between day one and day five of immobilization, which included fibrinogen, ESR, and platelet count. The mean differences for each biomarker with fibrinogen were 0.66 g/L (p<0.001, 95% CI of mean difference: -1.04, -0.27), ESR increased by 17.98mm/hr (p<0.001, 95% CI of mean difference: -24.69, -11.27), and platelet count increased by 128.59×109/L (p<0.001, 95% CI of mean difference: -166.55, -90.64) on day five of immobilization. D-dimer was elevated in all patients on both post-trauma days; however, no significant difference was observed in this biomarker between day one and day five of immobilization. Conclusion In conclusion, our study found that fibrinogen, ESR, and platelet count levels were significantly increased in orthopaedic trauma patients with prolonged immobilization. The increase in these biomarkers indicates the body's reaction to tissue injury after trauma, which may contribute to the hypercoagulable states. Further research with a larger sample size is warranted to assess the viability of these biomarkers as potential diagnostic indicators for the development of VTE related to hypercoagulability.
  7. Iberahim S, Muhamat Yusoff R, Mohd Noor NH, Hassan R, Ramli NN, Bahar R, et al.
    Cureus, 2024 Jan;16(1):e51483.
    PMID: 38304638 DOI: 10.7759/cureus.51483
    Background Prolonged immobilization is widely recognized as a risk factor for thromboembolism. In this prospective study, we investigated the changes in clot waveform analysis (CWA) parameters in prolonged immobilized patients following lower limb trauma. CWA is an advanced method for assessing global coagulation that involves continuously monitoring changes in light transmittance, absorbance, or light scattering during routine clotting tests. Additionally, we also aim to determine the CWA parameters between day one and after day three of immobilization. Methods A total of 30 patients with prolonged immobilization were enrolled in this study. The plasma of these patients was collected on the first day of their admission and subsequently obtained again after day three of immobilization. Prothrombin time (PT)-based CWA and activated partial thromboplastin time (aPTT)-based CWA were performed using the ACL TOP 300 CTS (Werfen: Bedford, USA) coagulation analyzer, which utilizes the optical method for clot detection. Plasma samples for 20 normal controls were recruited from a healthy blood donor. The CWA parameters generated during clot formation were analyzed. For the comparison of CWA parameters between patients with prolonged immobilization and healthy controls, the Mann-Whitney test was used. A paired t-test was used for the comparison of clot wave parameters between day one and after day three of immobilization. This study was approved by the Universiti Sains Malaysia Research Ethics Committee. Result The mean values of PT and aPTT in healthy controls were 11.66 seconds and 33.98 seconds, respectively. There was no statistically significant difference between the patients and the healthy controls in the median values of aPTT (P=0.935). However, patients with prolonged immobilization exhibited significantly higher median PT CWA parameter values than controls (P=0.007). These parameters included the delta change (P<0.001), peak time velocity (P=0.008), and height velocity (P<0.001). On the other hand, the delta change (P<0.001) and height velocity (P<0.001) of the aPTT CWA parameters were significantly higher in patients with prolonged immobilization than in controls. In patients with prolonged immobilization, there was no significant difference in PT CWA parameters between day one and after day three of immobilization, while for aPTT CWA, all parameters were higher on day three, except for the endpoint time. Conclusion Patients with prolonged immobilization exhibit increased PT and aPTT CWA parameters compared to normal controls. CWA parameters could aid in identifying patients at risk of developing thrombosis through changes in the clot waveform. However, further study is needed to fully utilize additional information from routine coagulation testing.
  8. Ismail NH, Mussa A, Zakaria NA, Al-Khreisat MJ, Zahidin MA, Ramli NN, et al.
    Biomedicines, 2022 Oct 31;10(11).
    PMID: 36359286 DOI: 10.3390/biomedicines10112767
    Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology.
  9. Ramli NN, Kurniawan SB, Ighalo JO, Mohd Said NS, Marsidi N, Buhari J, et al.
    Biometals, 2023 May 20.
    PMID: 37209220 DOI: 10.1007/s10534-023-00512-x
    The toxicity of hexavalent chromium (Cr(VI)) present in the environment has exceeded the current limits or standards and thus may lead to biotic and abiotic catastrophes. Accordingly, several treatments, including chemical, biological, and physical approaches, are being used to reduce Cr(VI) waste in the surrounding environment. This study compares the Cr(VI) treatment approaches from several areas of science and their competence in Cr(VI) removal. As an effective combination of physical and chemical approaches, the coagulation-flocculation technique removes more than 98% of Cr(VI) in less than 30 min. Most membrane filtering approaches can remove up to 90% of Cr(VI). Biological approaches that involve the use of plants, fungi, and bacteria also successfully eliminate Cr(VI) but are difficult to scale up. Each of these approaches has its benefits and drawbacks, and their applicability is determined by the research aims. These approaches are also sustainable and environmentally benign, thus limiting their effects on the ecosystem.
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