Displaying publications 1 - 20 of 36 in total

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  1. Fulltext Perioperative death in Malaysia: the transition phase from a developing nation to a developed one
    Kandasami P, Inbasegaran K, Lim WL
    Med J Malaysia, 2003 Aug;58(3):413-9.
    PMID: 14750382
    This paper examines the surgical pathology associated with perioperative deaths in a country that is undergoing the transition from a developing to a developed nation status. The data from an ongoing nation-wide perioperative mortality study was prospectively collected for the period July 1996 to December 1997 and analyzed. The surgical pathology related to perioperative deaths in Malaysia is different from other developing and developed countries. While death from trauma and the late presentation of surgical conditions are similar to developing countries, infective gastrointestinal conditions were rarely encountered. Diseases associated with advanced age such as colorectal cancer, peptic ulcer, urological diseases and vascular conditions are beginning to emerge. As the country races towards a developed nation status, increasing life expectancy and changing life-styles are expected to influence the disease pattern. The planning of surgical facilities and manpower development must recognize the changes taking place.
  2. Fulltext Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring
    Lim WL, Soga T, Parhar IS
    Cell Tissue Res, 2014 Feb;355(2):409-23.
    PMID: 24374911 DOI: 10.1007/s00441-013-1765-9
    The migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the preoptic area (POA) from embryonic day 13 is important for successful reproduction during adulthood. Whether maternal glucocorticoid exposure alters GnRH neuronal morphology and number in the offspring is unknown. This study determines the effect of maternal dexamethasone (DEX) exposure on enhanced green fluorescent protein (EGFP) driven by GnRH promoter neurons (TG-GnRH) in transgenic rats dual-labelled with GnRH immunofluorescence (IF-GnRH). The TG-GnRH neurons were examined in intact male and female rats at different postnatal ages, as a marker for GnRH promoter activity. Pregnant females were subcutaneously injected with DEX (0.1 mg/kg) or vehicle daily during gestation days 13-20 to examine the number of GnRH neurons in P0 male offspring. The total number of TG-GnRH neurons and TG-GnRH/IF-GnRH neuronal ratio increased from P0 and P5 stages to P47-52 stages, suggesting temporal regulation of GnRH promoter activity during postnatal development in intact rats. In DEX-treated P0 males, the number of IF-GnRH neurons decreased within the medial septum, organum vasculosom of the lamina terminalis (OVLT) and anterior hypothalamus. The percentage of TG-GnRH neurons with branched dendritic structures decreased in the OVLT of DEX-P0 males. These results suggest that maternal DEX exposure affects the number and dendritic development of early postnatal GnRH neurons in the OVLT/POA, which may lead to altered reproductive functions in adults.
  3. Fulltext Audit of perioperative blood transfusion
    Choy YC, Lim WL, Ng SH
    Med J Malaysia, 2007 Oct;62(4):299-302.
    PMID: 18551933 MyJurnal
    The main goal of perioperative transfusion is to reduce the morbidity and mortality associated with inadequate delivery of oxygen to the tissues during surgery. In this audit, the primary trigger for transfusion was clinical anaemia assessed by examination of a patient's conjunctiva [40.7%] followed by estimation of blood loss of greater 20% of total blood volume [29.3%]. Haemoglobin estimation in the operation theater was not done in 45.9% of studied patients and only 7.8% patients had transfusion based on this criteria. A common practice is to transfuse blood for hypovolaemia. This was the indication for blood transfusion in 96 patients (7.8%). Inappropriate use of blood in this way has led to wastage of a valuable resource and exposed patients to potential risks of unwanted side effects. Analysis of haemoglobin estimation at recovery room showed 32% of patient with co-morbidities had Hb > 10 gm% while 65% and 29.5% of patients without co-morbidities had Hb > 8 gm% and 10 gm% respectively. This reflects the practice of anaesthetists in maintaining a target of Hb of 10 gm% for both groups of patients while a target of 8 gm% is still relatively safe for patients with good cardiovascular reserves. This has resulted in signifant use of homologous blood which will certainly burden the blood bank and increase the cost of healthcare.
  4. Fulltext The effectiveness of surfactant replacement therapy for preterm infants with respiratory distress syndrome
    Lim WL, Lim CT, Chye JK
    Med J Malaysia, 1998 Dec;53(4):376-84.
    PMID: 10971981
    Thirty preterm infants weighing > or = 800 g with clinical and radiological evidence of respiratory distress syndrome (RDS) requiring mechanical ventilation with FiO2 of > or = 40% were given modified bovine surfactant (Survanta). They were compared with equal number of historical controls. Infants who received surfactant showed prompt and highly significant improvement in FiO2, mean airway pressure, arterial/alveolar oxygen tension ratio and ventilatory index. There was significant improvement in mortality rate (10% vs 33%; p = 0.03). Among the survivors, surfactant-treated infants required shorter duration of continuous positive airway pressure (CPAP) (3.4 vs 9.6 days; p = 0.04). For survivors with birthweight of > 1000 g, surfactant-treated infants required shorter duration of ventilatory support (intermittent positive pressure ventilation + CPAP) (7.5 vs 18.9 days, p = 0.02). Overall, surfactant-treated infants achieved full enteral feeds sooner (15.7 days vs 24.6 days; p = 0.03) and required shorter duration of total parenteral nutrition (13.9 days vs 25.6 days; p = 0.02). We concluded that surfactant replacement therapy was effective in the treatment of preterm infants with RDS.
  5. Comparison of propofol and methohexitone as an induction agent in anaesthesia for electroconvulsive therapy
    Lim SK, Lim WL, Elegbe EO
    West Afr J Med, 1996 Oct-Dec;15(4):186-9.
    PMID: 9020593
    30 patients who received electroconvulsive therapy were anaesthetized with either Propofol or Methohexitone in a randomized cross-over study. Recovery times were shorter in those who received Propofol. The decrease in diastolic pressure after induction was greater with Propofol than with Methohexitone. There was a greater increase in the blood pressure after the electroconvulsive therapy in those who received Methohexitone. The duration of convulsion was similar for both agents.
  6. Maternal dexamethasone exposure inhibits the gonadotropin-releasing hormone neuronal movement in the preoptic area of rat offspring
    Lim WL, Soga T, Parhar IS
    Dev Neurosci, 2014;36(2):95-107.
    PMID: 24713635 DOI: 10.1159/000360416
    Migration and final positioning of gonadotropin-releasing hormone (GnRH) neurons in the preoptic area (POA) is critical for reproduction. It is known that maternal dexamethasone (DEX) exposure impairs reproductive function and behaviour in the offspring. However, it is still not known whether maternal DEX exposure affects the postnatal GnRH neurons in the offspring. This study determined the neuronal movement of enhanced green fluorescent protein (EGFP)-tagged GnRH neurons in slice culture of postnatal day 0 (P0), P5 and P50-60 transgenic male rats. Effect of maternal DEX treatment on EGFP-GnRH neuronal movement and F-actin distribution on GnRH neurons at P0 stage were studied. Time-lapse analysis of P0 and P5 EGFP-GnRH neurons displayed active cellular movement within the POA compared to young adult P50-60 stages, suggesting possible fine-tuning movement for positioning of early postnatal GnRH neurons. The DEX-treated EGFP-GnRH neurons demonstrated decreased motility in the POA and reduced F-actin distribution in the GnRH neurons at 60 h culture compared to the vehicle-treated. These results suggest that the P0 GnRH neuronal movement in the POA is altered by maternal DEX exposure, which possibly disrupts the fine-tuning process for positioning and development of early postnatal GnRH neurons in the brain, potentially linked to reproductive dysfunction in adulthood.
  7. Plant Polyphenols as Neuroprotective Agents in Parkinson's Disease Targeting Oxidative Stress
    Hor SL, Teoh SL, Lim WL
    Curr Drug Targets, 2020;21(5):458-476.
    PMID: 31625473 DOI: 10.2174/1389450120666191017120505
    Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.
  8. Fulltext Kisspeptin Activates Ankrd 26 Gene Expression in Migrating Embryonic GnRH Neurons
    Soga T, Lim WL, Khoo AS, Parhar IS
    Front Endocrinol (Lausanne), 2016;7:15.
    PMID: 26973595 DOI: 10.3389/fendo.2016.00015
    Kisspeptin, a newly discovered neuropeptide, regulates gonadotropin-releasing hormone (GnRH). Kisspeptins are a large RF-amide family of peptides. The kisspeptin coded by KiSS-1 gene is a 145-amino acid protein that is cleaved to C-terminal peptide kisspeptin-10. G-protein-coupled receptor 54 (GPR54) has been identified as a kisspeptin receptor, and it is expressed in GnRH neurons and in a variety of cancer cells. In this study, enhanced green fluorescent protein (EGFP) labeled GnRH cells with migratory properties, which express GPR54, served as a model to study the effects of kisspeptin on cell migration. We monitored EGFP-GnRH neuronal migration in brain slide culture of embryonic day 14 transgenic rat by live cell imaging system and studied the effects of kisspeptin-10 (1 nM) treatment for 36 h on GnRH migration. Furthermore, to determine kisspeptin-induced molecular pathways related with apoptosis and cytoskeletal changes during neuronal migration, we studied the expression levels of candidate genes in laser-captured EGFP-GnRH neurons by real-time PCR. We found that there was no change in the expression level of genes related to cell proliferation and apoptosis. The expression of ankyrin repeat domain-containing protein (ankrd) 26 in EGFP-GnRH neurons was upregulated by the exposure to kisspeptin. These studies suggest that ankrd 26 gene plays an unidentified role in regulating neuronal movement mediated by kisspeptin-GPR54 signaling, which could be a potential pathway to suppress cell migration.
  9. Fulltext A Biogeography-Based Optimization Algorithm Hybridized with Tabu Search for the Quadratic Assignment Problem
    Lim WL, Wibowo A, Desa MI, Haron H
    Comput Intell Neurosci, 2016;2016:5803893.
    PMID: 26819585 DOI: 10.1155/2016/5803893
    The quadratic assignment problem (QAP) is an NP-hard combinatorial optimization problem with a wide variety of applications. Biogeography-based optimization (BBO), a relatively new optimization technique based on the biogeography concept, uses the idea of migration strategy of species to derive algorithm for solving optimization problems. It has been shown that BBO provides performance on a par with other optimization methods. A classical BBO algorithm employs the mutation operator as its diversification strategy. However, this process will often ruin the quality of solutions in QAP. In this paper, we propose a hybrid technique to overcome the weakness of classical BBO algorithm to solve QAP, by replacing the mutation operator with a tabu search procedure. Our experiments using the benchmark instances from QAPLIB show that the proposed hybrid method is able to find good solutions for them within reasonable computational times. Out of 61 benchmark instances tested, the proposed method is able to obtain the best known solutions for 57 of them.
  10. Breastfeeding at 6 weeks and predictive factors
    Chye JK, Zain Z, Lim WL, Lim CT
    J Trop Pediatr, 1997 10;43(5):287-92.
    PMID: 9364127 DOI: 10.1093/tropej/43.5.287
    Despite the numerous changes made in accordance with the Baby Friendly Hospital Initiative at the University Hospital, Kuala Lumpur, the low rates of breastfeeding have persisted. This study aims to examine the current trend in infant feeding, and the influences of some perinatal and sociodemographic factors on breastfeeding. Five-hundred mothers with singleton pregnancies and healthy infants were interviewed at 6 weeks post-partum. Only 124 (25 per cent) mothers were practising exclusive breastfeeding (EBF), and 132 (26 per cent) mothers were using exclusive infant formula feeding (EIF). On logistic regression analyses, mothers who followed EBF were more likely to have had antenatal plans to breastfeed (Odds ratio 2.44, 95 per cent confidence interval 1.75-3.45), not in paid employment post-natally (OR 1.76, 95 per cent CI 1.31-2.36), of older age group (> 27 years) (OR 1.48, 95 per cent CI 1.13-1.93), had female infants (OR 1.38, 95 per cent CI 1.05-1.80) and of Indian ethnicity (compared to Chinese) (OR 3.87, 95 per cent CI 2.16-6.89). Breastfeeding difficulties were associated with decreased odds of EBF (OR 0.21, 95 per cent CI 0.13-0.34). Parental education, fathers' ages and incomes, primigravida status, Caesarean section, present of episiotomy, late first breastfeed, phototherapy, and length of hospital stay were not significant predictors of failure of EBF. In comparison, predictive factors for increased use of EIF were mothers who have had breastfeeding difficulties, < or = 9 years of schooling, and of Chinese descent. In conclusions, the overall rate of EBF by 6 weeks of age in infants born in this urban hospital had remained poor. The adverse factors for EBF identified in this study warrant further in-depth studies to determine effective ways of improving EBF rates.
  11. Pyogenic meningitis in hospitalized children in Kelantan, Malaysia
    Choo KE, Ariffin WA, Ahmad T, Lim WL, Gururaj AK
    Ann Trop Paediatr, 1990 Mar;10(1):89-98.
    PMID: 1694651
    A 2.5-year retrospective study of pyogenic meningitis in hospitalized children in Kelantan was carried out with regard to aetiology, clinical features, investigation, treatment and outcome. There were 58 children with 43 cases (74.1%) occurring below the age of 1 year. Frequent presenting symptoms included fever (98.3%), fits (77.6%), anorexia (39.7%), vomiting (34.5%) and drowsiness (12.1%). On admission, 37 (63.7%) had neck stiffness, 10 (17.2%) had Kernig's sign and 32 (55.2%) had coma. CSF cultures were positive for Haemophilus influenzae in 29 (50%), Streptococcus pneumonia in 13 (22.4%) and Neisseria meningitidis in 3 (5.2%). The antibiotic sensitivity profiles showed that the three main organisms were 100% sensitive to Chloramphenicol, Streptococcus pneumoniae was 100% sensitive to penicillin, Neisseria meningitidis was 100% sensitive to penicillin and ampicillin, and Haemophilus influenzae was 90% sensitive to penicillin and ampicillin. The total hospital mortality was 18.9%. All but two of the eleven deaths occurred in children younger than 1 year. Nineteen of the 35 (54.3%) survivors attended for at least one follow-up after discharge from hospital. Of these 19 children, 47.4% had neurological sequelae.
  12. Ultrasound-guided combined supraclavicular brachial plexus and PECS II blocks for brachiobasilic fistula transposition surgery
    Beh ZY, Lim SM, Lim WL, Ramli ARH
    Indian J Anaesth, 2020 Dec;64(12):1079-1080.
    PMID: 33542576 DOI: 10.4103/ija.IJA_535_20
  13. Erector spinae plane block as analgesic adjunct for traumatic rib fractures in intensive care unit
    Beh ZY, Lim SM, Lim WL, Sitaram PN
    Indian J Anaesth, 2020 Dec;64(12):1086-1089.
    PMID: 33542581 DOI: 10.4103/ija.IJA_1110_20
  14. Fulltext Physicochemical Properties and Biocompatibility of Electrospun Polycaprolactone/Gelatin Nanofibers
    Lim WL, Chowdhury SR, Ng MH, Law JX
    Int J Environ Res Public Health, 2021 04 29;18(9).
    PMID: 33947053 DOI: 10.3390/ijerph18094764
    Tissue-engineered substitutes have shown great promise as a potential replacement for current tissue grafts to treat tendon/ligament injury. Herein, we have fabricated aligned polycaprolactone (PCL) and gelatin (GT) nanofibers and further evaluated their physicochemical properties and biocompatibility. PCL and GT were mixed at a ratio of 100:0, 70:30, 50:50, 30:70, 0:100, and electrospun to generate aligned nanofibers. The PCL/GT nanofibers were assessed to determine the diameter, alignment, water contact angle, degradation, and surface chemical analysis. The effects on cells were evaluated through Wharton's jelly-derived mesenchymal stem cell (WJ-MSC) viability, alignment and tenogenic differentiation. The PCL/GT nanofibers were aligned and had a mean fiber diameter within 200-800 nm. Increasing the GT concentration reduced the water contact angle of the nanofibers. GT nanofibers alone degraded fastest, observed only within 2 days. Chemical composition analysis confirmed the presence of PCL and GT in the nanofibers. The WJ-MSCs were aligned and remained viable after 7 days with the PCL/GT nanofibers. Additionally, the PCL/GT nanofibers supported tenogenic differentiation of WJ-MSCs. The fabricated PCL/GT nanofibers have a diameter that closely resembles the native tissue's collagen fibrils and have good biocompatibility. Thus, our study demonstrated the suitability of PCL/GT nanofibers for tendon/ligament tissue engineering applications.
  15. Flavonoids and its Neuroprotective Effects on Brain Ischemia and Neurodegenerative Diseases
    Putteeraj M, Lim WL, Teoh SL, Yahaya MF
    Curr Drug Targets, 2018;19(14):1710-1720.
    PMID: 29577854 DOI: 10.2174/1389450119666180326125252
    Brain ischemia is among the leading cause of death with majority of the cases are associated with ischemic strokes. It can occur in two forms of either focal or global ischemia. Neurodegenerative disorder such as Alzheimer and Parkinson diseases is also on the rise worldwide. These disorders have common similarities; i.e. they all affecting the central nervous system with debilitating effect to the patient. In this review, we look into the promising role of flavonoids, a natural bioactive compound found abundant in vegetables, fruits and traditional herbs. Treatment with flavonoids such as curcumin, lycopene, ginsenoside, vitexin and baicalin have shown promising neuroprotective effects against ischemic-induced injury. Besides anticancer, antioxidant and immunomodulation properties, flavonoid also exerts neuroprotective effects by increases neuronal viability, increases tissue perfusion and cerebral blood flow and reduce ischemic-related apoptosis. In addition, flavonoid also exerts anti-amyloidogenic effect and reduces loss of dopaminergic neurons in the brain. These results suggesting flavonoids might be able to serve as a potential therapeutic agent in brain disorders.
  16. Fulltext Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential
    Yong SJ, Tong T, Chew J, Lim WL
    Front Neurosci, 2019;13:1361.
    PMID: 32009871 DOI: 10.3389/fnins.2019.01361
    The accumulating knowledge of the host-microbiota interplay gives rise to the microbiota-gut-brain (MGB) axis. The MGB axis depicts the interkingdom communication between the gut microbiota and the brain. This communication process involves the endocrine, immune and neurotransmitters systems. Dysfunction of these systems, along with the presence of gut dysbiosis, have been detected among clinically depressed patients. This implicates the involvement of a maladaptive MGB axis in the pathophysiology of depression. Depression refers to symptoms that characterize major depressive disorder (MDD), a mood disorder with a disease burden that rivals that of heart diseases. The use of probiotics to treat depression has gained attention in recent years, as evidenced by increasing numbers of animal and human studies that have supported the antidepressive efficacy of probiotics. Physiological changes observed in these studies allow for the elucidation of probiotics antidepressive mechanisms, which ultimately aim to restore proper functioning of the MGB axis. However, the understanding of mechanisms does not yet complete the endeavor in applying probiotics to treat MDD. Other challenges remain which include the heterogeneous nature of both the gut microbiota composition and depressive symptoms in the clinical setting. Nevertheless, probiotics offer some advantages over standard pharmaceutical antidepressants, in terms of residual symptoms, side effects and stigma involved. This review outlines antidepressive mechanisms of probiotics based on the currently available literature and discusses therapeutic potentials of probiotics for depression.
  17. Neuroprotective Effects of Lactoferrin in Alzheimer's and Parkinson's Diseases: A Narrative Review
    Yong SJ, Veerakumarasivam A, Lim WL, Chew J
    ACS Chem Neurosci, 2023 Mar 30.
    PMID: 36995304 DOI: 10.1021/acschemneuro.2c00679
    Recent advancements in lactoferrin research have uncovered that lactoferrin does function not only as an antimicrobial protein but also as an immunomodulatory, anticancer, and neuroprotective agent. Focusing on neuroprotection, this literature review delineates how lactoferrin interacts in the brain, specifically its neuroprotective effects and mechanisms against Alzheimer's and Parkinson's diseases (AD and PD), the two most common neurodegenerative diseases. The neuroprotective pathways involving surface receptors (heparan sulfate proteoglycan (HSPG) and lactoferrin receptor (LfR)), signaling pathways (extracellular regulated protein kinase-cAMP response element-binding protein (ERK-CREB) and phosphoinositide 3-kinase/Akt (PI3K/Akt)), and effector proteins (A disintegrin and metalloprotease10 (ADAM10) and hypoxia-inducible factor 1α (HIF-1α)) in cortical/hippocampal and dopaminergic neurons are described. These cellular effects of lactoferrin are likely responsible for attenuating cognitive and motor deficits, amyloid-β and α-synuclein accumulation, and neurodegeneration in animal and cellular models of AD and PD. This review also discusses the inconsistent findings related to the neuroprotective effects of lactoferrin against AD. Overall, this review contributes to the existing literature by clarifying the potential neuroprotective effects and mechanisms of lactoferrin in the context of AD and PD neuropathology.
  18. 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.

  19. Fulltext Human Embryonic Stem Cell-Derived Neural Lineages as In Vitro Models for Screening the Neuroprotective Properties of Lignosus rhinocerus (Cooke) Ryvarden
    Yeo Y, Tan JBL, Lim LW, Tan KO, Heng BC, Lim WL
    Biomed Res Int, 2019;2019:3126376.
    PMID: 33204680 DOI: 10.1155/2019/3126376
    In the biomedical field, there is growing interest in using human stem cell-derived neurons as in vitro models for pharmacological and toxicological screening of bioactive compounds extracted from natural products. Lignosus rhinocerus (Tiger Milk Mushroom) is used by indigenous communities in Malaysia as a traditional medicine to treat various diseases. The sclerotium of L. rhinocerus has been reported to have medicinal properties, including various bioactivities such as neuritogenic, anti-inflammatory, and anticancer effects. This study aims to investigate the neuroprotective activities of L. rhinocerus sclerotial extracts. Human embryonic stem cell (hESC)-derived neural lineages exposed to the synthetic glucocorticoid, dexamethasone (DEX), were used as the in vitro models. Excess glucocorticoids have been shown to adversely affect fetal brain development and impair differentiation of neural progenitor cells. Screening of different L. rhinocerus sclerotial extracts and DEX on the hESC-derived neural lineages was conducted using cell viability and neurite outgrowth assays. The neuroprotective effects of L. rhinocerus sclerotial extracts against DEX were further evaluated using apoptosis assays and Western blot analysis. Hot aqueous and methanol extracts of L. rhinocerus sclerotium promoted neurite outgrowth of hESC-derived neural stem cells (NSCs) with negligible cytotoxicity. Treatment with DEX decreased viability of NSCs by inducing apoptosis. Coincubation of L. rhinocerus methanol extract with DEX attenuated the DEX-induced apoptosis and reduction in phospho-Akt (pAkt) level in NSCs. These results suggest the involvement of Akt signaling in the neuroprotection of L. rhinocerus methanol extract against DEX-induced apoptosis in NSCs. Methanol extract of L. rhinocerus sclerotium exhibited potential neuroprotective activities against DEX-induced toxicity in hESC-derived NSCs. This study thus validates the use of human stem cell-derived neural lineages as potential in vitro models for screening of natural products with neuroprotective properties.
  20. Behavioural responses of anxiety in aversive and non-aversive conditions between young and aged Sprague-Dawley rats
    Hiew LF, Khairuddin S, Aquili L, Koh J, Fung ML, Lim WL, et al.
    Behav Brain Res, 2020 05 15;385:112559.
    PMID: 32097707 DOI: 10.1016/j.bbr.2020.112559
    Measures of anxiety in behavioural tests remain largely unclear even decades after their establishment. Differences in the severity of anxiety measured by anxiety tests is an important issue that must be addressed. To test the hypothesis that the addition of light as an aversive stimulus will elicit a difference in behaviour between aged and young animals, we compared the responses of aged and young animals in the home cage emergence test (HCET) and elevated plus maze (EPM), in high aversive bright light and low aversive dim light conditions. In the HCET, our results demonstrated that young animals escaped with shorter latency and greater frequency than aged animals in both bright and dim light conditions, indicating that young animals display greater exploratory tendencies than aged animals. In the EPM, bright light conditions induced anxiogenic effects in both age groups. Interestingly, two-way ANOVA showed a significant interaction effect of age and light on the number of entries into the open arms of the EPM as well as frequency of escape in the HCET. These results show that the addition of light as an aversive stimulus in the EPM and HCET produced different responses in aged versus young animals in each test. In conclusion, significant interactions between age and light affected aged and young animals differently in the HCET and EPM, indicating that the two tests measure different aspects of anxiety.
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