Displaying publications 81 - 100 of 105 in total

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  1. Vijayanathan Y, Lim FT, Lim SM, Long CM, Tan MP, Majeed ABA, et al.
    Neurotox Res, 2017 Oct;32(3):496-508.
    PMID: 28707266 DOI: 10.1007/s12640-017-9778-x
    Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6.25, 12.5, 18.75, 25, 37.5, 50 and 100 mg/kg) into the ventral diencephalon (Dn). This was facilitated by an optimised protocol that utilised 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate (DiI) dye to precisely identify the injection site. Immunostaining was utilised to identify the number of tyrosine hydroxylase immunoreactive (TH-ir) DpN in brain regions of interest (i.e. olfactory bulb, telencephalon, preoptic area, posterior tuberculum and hypothalamus). Open tank video recordings were performed for locomotor studies. The Dn was accessed by setting the injection angle of the microinjection capillary to 60° and injection depth to 1200 μm (from the exposed brain surface). 6-OHDA (25 mg/kg) successfully ablated >85% of the Dn DpN (preoptic area, posterior tuberculum and hypothalamus) whilst maintaining a 100% survival. Locomotor analysis of 5-min recordings revealed that 6-OHDA-lesioned adult zebrafish were significantly (p 
  2. Vijayanathan Y, Lim SM, Tan MP, Lim FT, Majeed ABA, Ramasamy K
    Neurotox Res, 2021 Apr;39(2):504-532.
    PMID: 33141428 DOI: 10.1007/s12640-020-00298-7
    Parkinson's disease (PD) is the second most common neurodegenerative disease. The etiology of PD remains an enigma with no available disease modifying treatment or cure. Pharmacological compensation is the only quality of life improving treatments available. Endogenous dopaminergic neuroregeneration has recently been considered a plausible therapeutic strategy for PD. However, researchers have to first decipher the complexity of adult endogenous neuroregeneration. This raises the need of animal models to understand the underlying molecular basis. Mammalian models with highly conserved genetic homology might aid researchers to identify specific molecular mechanisms. However, the scarcity of adult neuroregeneration potential in mammals obfuscates such investigations. Nowadays, non-mammalian models are gaining popularity due to their explicit ability to neuroregenerate naturally without the need of external enhancements, yet these non-mammals have a much diverse gene homology that critical molecular signals might not be conserved across species. The present review highlights the advantages and disadvantages of both mammalian and non-mammalian animal models that can be essentially used to study the potential of endogenous DpN regeneration against PD.
  3. Harun A, James RM, Lim SM, Abdul Majeed AB, Cole AL, Ramasamy K
    BMC Complement Altern Med, 2011 Sep 24;11:79.
    PMID: 21943123 DOI: 10.1186/1472-6882-11-79
    BACKGROUND: BACE1 was found to be the major β-secretase in neurons and its appearance and activity were found to be elevated in the brains of AD patients. Fungal endophytic extracts for BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated.

    METHODS: Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang and the extracts were tested for BACE1 inhibition. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate.

    RESULTS: Of 212 endophytic extracts (1000 μg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC(50(BACE1)) values of less than 3.0 μg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with K(i) value of 10.0 μg/ml. HAB16R13 was considered non-potent against PC-12 and WRL68 (IC(50(CT))) of 60.0 and 40.0 μg/ml, respectively).

    CONCLUSIONS: This first report on endophytic fungal extract with good BACE1 inhibitory activity demonstrates that more extensive study is required to uncover the potential of endophytes.

  4. Zaki RM, Ramasamy K, Ahmad Alwi NA, Mohd Yusoff R, Lim SM
    Probiotics Antimicrob Proteins, 2024 Feb;16(1):62-75.
    PMID: 36443559 DOI: 10.1007/s12602-022-10009-7
    Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) plaque. RhoA may serve as a potential target for prevention against AD given its role in the amyloidogenic pathway. The recent emergence of the gut-brain axis has linked lactic acid bacteria (LAB) to neuroprotection against AD. This study assessed the importance of RhoA inhibition in mediating the neuroprotective potential of LAB. To this end, de Man, Rogosa and Sharpe (MRS) broth fermented by lactobacilli or pediococci were tested against SK-N-SH (a human neuroblastoma cell line) in the presence of RhoA activator II for 24 h after which the RhoA activity was measured using the G-LISA Kit. Fluorescence staining of f-actin stress fibres was performed to validate RhoA inhibition. SK-N-SH was transfected with plasmid expressing amyloid precursor protein (APP) gene. The Aβ concentration in transfected cells exposed to LAB-derived cell free supernatant (CFS) in the presence of RhoA activator II was measured using the ELISA kit. Furthermore, this study measured organic acids in LAB-derived CFS using the gas chromatography. It was found that LAB-derived CFS yielded strain-dependent inhibition of RhoA, with LAB6- and LAB12-derived CFS being the most potent Pediococcal- and Lactiplantibacillus-based RhoA inhibitor, respectively. Lesser stress fibres were formed under treatment with LAB-derived CFS. The LAB-derived CFS also significantly inhibited Aβ in SK-N-SH transfected with APP gene in the presence of RhoA activator II. The LAB-derived CFS was presented with increased lactic acid, acetic acid, butyric acid and propionic acid. The present findings warrant in-depth study using animal models.
  5. Ibrahim NA, Wong YY, Lean QY, Ramasamy K, Lim SM, Tan MP, et al.
    Res Social Adm Pharm, 2024 Feb;20(2):172-181.
    PMID: 37980238 DOI: 10.1016/j.sapharm.2023.11.001
    BACKGROUND: Independent and safe medication self-management is essential for successful aging. Nevertheless, how older adults with cognitive frailty (CF) self-manage medications at their own homes remain elusive.

    OBJECTIVE: This study aimed at assessing the medication self-management capability of home-dwelling older adults with CF and exploring the ways, perceived challenges and barriers in medication self-management.

    METHODS: A convergent mixed-method study design was used. The medication management capability of 16 CF individuals aged ≥ 60 years on ≥ 1 long-term prescription drugs were assessed using the Drug Regimen Unassisted Grading Scale (DRUGS). Virtual in-depth interviews were also performed between July-August 2022 using a semi-structured interview guide. All interviews were audio-recorded and transcribed verbatim. Qualitative data were analysed using a thematic analysis approach guided by Bailey and colleagues' model of medication self-management.

    RESULTS: The mean DRUGS summary score was 96.86 [standard deviation (SD) 3.74] with highest performance scores observed in medication access (100 %) and lowest performance score in medication identification (91.46 %). Informants were able to independently take their medications and they tended to organise their medication intakes according to mealtime even though some admitted missing medication doses due to forgetfulness. Informants had difficulties with recalling drug names, with little awareness of self-monitoring their own health conditions and the effects of medications. Misconceptions towards medications, difficulties in accessing medications, reduced mobility and worsening health conditions could potentially deter informants from safe and independent medication self-management. In contrast, trust in doctors and a desire to achieve treatment goal could motivate medication self-management.

    CONCLUSION: The findings revealed knowledge gaps among older adults with CF in identifying their medications and self-monitoring which warrant reinforcement by healthcare professionals to ensure chronic safe medication use. Future studies should evaluate strategies to enhance medication safety in terms of self-monitoring in individuals with CF.

  6. Kumar S, Lim SM, Ramasamy K, Vasudevan M, Shah SAA, Narasimhan B
    Chem Cent J, 2017 Aug 08;11(1):80.
    PMID: 29086907 DOI: 10.1186/s13065-017-0312-2
    BACKGROUND: In the past few years, increased resistance of microorganisms towards antimicrobial agents become a serious health problem, so there is a need for the discovery of new antimicrobial agents. On the other hand, bis-pyrimidines possess various types of biological activity. In view of this, in the present study we have designed and synthesized a new series of bis-pyrimidine acetamides by Claisen-Schmidt condensation and screened for its in vitro antimicrobial and anticancer activities.

    RESULTS: The synthesized bis-pyrimidine acetamide derivatives were confirmed by IR, (1)H/(13)C-NMR, Mass spectral studies as well C, H, N analyses. The synthesized compounds were evaluated for their in vitro antimicrobial potential against Gram positive (Staphylococcus aureus and Bacillus subtilis); Gram negative (Escherichia coli, Pseudomonas aeruginosa and Salmonella enterica) bacterial and fungal (Candida albicans and Aspergillus niger) strains by tube dilution technique and the minimum inhibitory concentration (MIC) recorded in µmol/mL was comparable to reference drugs, cefadroxil (antibacterial) and fluconazole (antifungal). The in vitro anticancer activity (IC50 value) determined against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B (SRB) technique and 5-fluorouracil used as reference drug.

    CONCLUSIONS: The biological study demonstrated that compounds 3, 13, 16, 17 and 18 were found to be most active antimicrobial agents with best MIC values than the cefadroxil (antibacterial) and fluconazole (antifungal) and compounds 12, 16 and 18 found to have better anticancer activity against human colorectal carcinoma (HCT116) cancer cell line with best IC50 value than the 5-fluorouracil (anticancer). Graphical abstract SAR of bis-pyrimidine acetamides.

  7. Shokryazdan P, Faseleh Jahromi M, Liang JB, Ramasamy K, Sieo CC, Ho YW
    PLoS One, 2017;12(5):e0175959.
    PMID: 28459856 DOI: 10.1371/journal.pone.0175959
    The ban or severe restriction on the use of antibiotics in poultry feeds to promote growth has led to considerable interest to find alternative approaches. Probiotics have been considered as such alternatives. In the present study, the effects of a Lactobacillus mixture composed from three previously isolated Lactobacillus salivarius strains (CI1, CI2 and CI3) from chicken intestines on performance, intestinal health status and serum lipids of broiler chickens has been evaluated. Supplementation of the mixture at a concentration of 0.5 or 1 g kg-1 of diet to broilers for 42 days improved body weight, body weight gain and FCR, reduced total cholesterol, LDL-cholesterol and triglycerides, increased populations of beneficial bacteria such as lactobacilli and bifidobacteria, decreased harmful bacteria such as E. coli and total aerobes, reduced harmful cecal bacterial enzymes such as β-glucosidase and β-glucuronidase, and improved intestinal histomorphology of broilers. Because of its remarkable efficacy on broiler chickens, the L. salivarius mixture could be considered as a good potential probiotic for chickens, and its benefits should be further evaluated on a commercial scale.
  8. Kumar S, Lim SM, Ramasamy K, Vasudevan M, Shah SAA, Selvaraj M, et al.
    Chem Cent J, 2017 Sep 18;11(1):89.
    PMID: 29086867 DOI: 10.1186/s13065-017-0322-0
    BACKGROUND: Heterocyclic pyrimidine nucleus, which is an essential base component of the genetic material of deoxyribonucleic acid, demonstrated various biological activities. A series of bis-pyrimidine Schiff bases were synthesized and screened for its antimicrobial and anticancer potentials. The molecular docking study was carried to find the interaction between active molecules with receptor.

    RESULTS: The structures of synthesized bis-pyrimidine Schiff bases were confirmed by spectral studies. The synthesized bis-pyrimidine derivatives were evaluated for their antimicrobial activity (MIC = µmol/mL) against selected Gram positive; Gram negative bacterial and fungal strains by tube dilution method. The anticancer activity (IC50 = µmol/mL) of the synthesized compounds was determined against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B (SRB) assay. Molecular docking studies provided information regarding the binding mode of active bis-pyrimidine Schiff bases with the cyclin-dependent kinase 8 (CDK8) receptor.

    CONCLUSIONS: The antimicrobial screening results indicated that compounds, q1 (MICbs = 0.83 µmol/mL), q16 (MICan = 1.54 µmol/mL and MICec = 0.77 µmol/mL), q1 and q19 (MICca = 0.41 µmol/mL) and q20 (MIC = 0.36 µmol/mL) are the most active ones. Compounds q1 (IC50 = 0.18 µmol/mL) have emerged as potent anticancer molecule against human colorectal carcinoma cancer cell line than the reference drug, 5-fluorouracil. Molecular docking studies indicated that compound q1 (the most active molecule) has the maximum hydrogen bond interaction (four) and π-π stacking (three) network among the bis-pyrimidine Schiff bases. Graphical abstract Graphical illustration of predicted binding mode of bis-pyrimidine Schiff bases in the active site of CDK8. a. Compound 1 (magenta color), b. Compound 5 (green color), c. Compound 8 (red color), d. Compound 13 (split pea color).

  9. Mani V, Ramasamy K, Ahmad A, Wahab SN, Jaafar SM, Kek TL, et al.
    Phytother Res, 2013 Jan;27(1):46-53.
    PMID: 22447662 DOI: 10.1002/ptr.4676
    Alzheimer's disease (AD) is characterized by signs of major oxidative stress and the loss of cholinergic cells. The present study was designed to investigate the role of the total alkaloidal extract from Murraya koenigii (MKA) leaves on age related oxidative stress and the cholinergic pathway in aged mice. Ascorbic acid (100 mg/kg, p.o.) was used as a standard drug. The MKA improved the level of protective antioxidants such as glutathione peroxidase (GPx), reduced glutathione (GSH), glutathione reductase (GRD), superoxide dismutase (SOD) and catalase (CAT) in brain homogenate at higher doses (20 and 40 mg/kg, p.o.). Moreover, a dose dependent decline was noted in lipid peroxidation (LPO) and the nitric oxide assay (NO) at all doses of MKA (10, 20 and 40 mg/kg, p.o.). Interestingly, significant progress was noted with the supplementation of MKA by an improvement of the acetylcholine (ACh) levels and a reduction in the acetylcholinesterase (AChE) activity in aged mouse brain. In addition, a significant elevation of serum albumin (ALBU), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST) and total protein as well as a decline in creatinine, total cholesterol, urea nitrogen and glucose levels with MKA also ameliorated the hepatic and renal functions in normal ageing process. The results showed the possible utility of Murraya koenigii leaves in neuroprotection against neurodegenerative disorders such as Alzheimer's disease.
  10. Ramasamy K, Lim SM, Abu Bakar H, Ismail N, Ismail MS, Ali MF, et al.
    Phytother Res, 2010 May;24(5):640-3.
    PMID: 19468989 DOI: 10.1002/ptr.2891
    Endophytes, which are receiving increasing attention, have been found to be potential sources of bioactive metabolites following the discovery of paclitaxel producing endophytic fungi. In the present study, a total of 348 endophytes were isolated from different parts of 24 Malaysian medicinal plants. Three selected endophytes (HAB10R12, HAB11R3 and HAB21F25) were investigated for their antimicrobial and cytotoxic activities. For antimicrobial activity, HAB10R12 and HAB11R3 were found to be most active against bacteria and fungi, respectively. Their antimicrobial effects were comparable to, if not better than, a number of current commercial antibacterial and antifungal agents. Both HAB10R12 and HAB21F25 were found to be potential anticancer drug candidates, having potent activity against MCF-7 and HCT116 cell lines and warrant further investigation.
  11. Appukutty M, Radhakrishnan AK, Ramasamy K, Ramasamy R, Abdul Majeed AB, Noor MI, et al.
    BMC Res Notes, 2012;5:649.
    PMID: 23173926 DOI: 10.1186/1756-0500-5-649
    This study examined the effects of bovine colostrum on exercise -induced modulation of antioxidant parameters in skeletal muscle in mice. Adult male BALB/c mice were randomly divided into four groups (control, colostrum alone, exercise and exercise with colostrum) and each group had three subgroups (day 0, 21 and 42). Colostrum groups of mice were given a daily oral supplement of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were made to exercise on the treadmill for 30 minutes per day. Total antioxidants, lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was assayed from the homogenate of hind limb skeletal muscle.
  12. Mohd Hasni DS, Lim SM, Chin AV, Tan MP, Poi PJH, Kamaruzzaman SB, et al.
    Geriatr Gerontol Int, 2017 May;17(5):839-846.
    PMID: 27215446 DOI: 10.1111/ggi.12783
    AIM: Cytokines released from chronically-activated microglia could result in neuroinflammation. An accurate profile of the relationship between cytokines and Alzheimer's disease (AD) pathogenesis, as well as the patterns of these inflammatory mediators in AD patients could lead to the identification of peripheral markers for the disease. The present study was undertaken to identify pro- and anti-inflammatory cytokines associated with AD in the Malaysian population.

    METHODS: Further to informed consent from 39 healthy subjects and 39 probable AD patients, 8.5 mL of peripheral blood was collected and serum was extracted. The differential levels of 12 serum cytokines extracted from peripheral blood samples were measured using Procarta Multiplex Cytokine and enzyme-linked immunoassay kits. Concentrations of cytokines were measured at 615 nm using a fluorometer.

    RESULTS: Except for tumor necrosis factor-α, all classical pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-12 and interferon-γ) were found to be significantly upregulated (P 53.65 ρg/mL and <9.315 ρg/mL, respectively).

    CONCLUSIONS: Both the non-classical pro-inflammatory CXCL-10 and anti-inflammatory IL-13 cytokines showed promising potential as blood-based cytokine biomarkers for AD. This is the first study of non-classical cytokine profiles of Malaysian AD patients. Geriatr Gerontol Int 2017; 17: 839-846.

  13. Ismail NFF, Neoh CF, Lim SM, Abdullah AH, Mastuki MF, Ramasamy K, et al.
    Medicine (Baltimore), 2017 Jul;96(30):e7511.
    PMID: 28746195 DOI: 10.1097/MD.0000000000007511
    INTRODUCTION: Asian countries have a variety of ethnic groups and culture that provide their own traditional treatment in health care. Facial candling appears to be one of the popular traditional treatments in Southeast Asian. The complementary medicine practitioners promote that the facial candling treatment would help in reducing the symptoms of allergic rhinitis and other problems related to sinus. Due to the lack of evidence available, the effectiveness of this treatment method and its mechanism, however, remains unknown. The objective of this research is therefore to study impact of facial candling on inflammatory mediators, substance P (SP), symptoms severity, and quality of life (QoL) in allergic rhinitis patients.

    METHOD AND ANALYSIS: A randomized, nonblinded, controlled trial will be carried out by recruiting a total of 66 eligible allergic rhinitis patients who fulfill the inclusion criteria from a university health center. The subjects will be randomly assigned into 2 groups: intervention group receiving facial candling treatment and control group (no treatment given). Samples of blood and nasal mucus will be collected right before and after intervention. Samples collected will be analyzed. The primary outcomes are the changes in the level of SP in both blood and mucus samples between both groups. The secondary outcomes include the levels of inflammatory mediators (ie, tumor necrosis factor alpha, interleukin (IL)-3, IL-5, IL-6, IL-10, and IL-13) and the severity of allergic rhinitis symptoms as measured by a visual analogous scale and QoL using the Rhinitis Quality of Life Questionnaire (RQLQ).

    ETHICAL AND TRIAL REGISTRATION: The study protocols are approved from the Ethical and Research Committee of the Universiti Teknologi MARA (REC/113/15). The trial is registered under the Australia New Zealand Clinical Trial Registry (ACTRN12616000299404). The trial was registered on 03/07/2016 and the first patient was enrolled on 10/12/2016.

    CONCLUSION: Facial candling is one of the unique treatments using candles to reduce the severity of symptoms and inflammation. This is the first ever study conducted on facial candling that will give rise to new knowledge underlying the effects of facial candling on severity of symptoms and inflammation relief mechanism mediated by substance P and inflammatory mediators.

  14. Ismail NFF, Neoh CF, Lean QY, Abdullah AH, Lim SM, Ramasamy K, et al.
    J Pharm Bioallied Sci, 2018 12 21;10(4):199-207.
    PMID: 30568377 DOI: 10.4103/JPBS.JPBS_33_18
    Aims: Facial candling is one of the traditional treatments that is claimed to be able to help in curing or reducing various allergy and inflammation conditions such as allergic rhinitis. We aimed to explore the perceptions of participants with allergic rhinitis toward their disease conditions and facial candling treatment.

    Materials and Methods: The study used a qualitative exploratory design, comprising 12 in-depth interviews. A semi-structured topic guide was used to explore all relevant aspects of the topic, which were audio recorded, transcribed verbatim. All the interviews were conducted in a few beauty salons in purposively selected city areas in the state of Kedah, Malaysia.

    Results: Of the 12 patients, seven (58%) reported a positive experience of facial candling treatment, with improvement in the condition of their allergic rhinitis. Specific themes about the experience of facial candling treatment that were identified within the transcript data included knowledge about facial candling, options for disease treatment, effectiveness of facial candling, sources of information, comparison, application of treatment, treatment budget, and safety. The major strength lies in the fact that reasons for using facial candling were uncovered from the perspectives of people with allergic rhinitis through the in-depth interviews.

    Conclusions: The motives of these participants for using facial candling are mainly due to cultural influence and its low cost of treatment. There were mixed responses from the participants about the usefulness of facial candling. Most of the respondents had not assessed the safety of prolonged use of facial candling and regarded it as a safe procedure as this has been practiced for generations.

  15. Rehiman SH, Lim SM, Lim FT, Chin AV, Tan MP, Kamaruzzaman SB, et al.
    Int J Neurosci, 2020 Dec 15.
    PMID: 33280461 DOI: 10.1080/00207454.2020.1860038
    Objective: Alzheimer's disease (AD), the commonest form of dementia which is characterized by progressive decline in cognitive function, can only be definitively diagnosed after death. Although biomarkers may aid diagnosis, currently available AD biomarkers, which are predominantly based on cerebrospinal fluid and neuroimaging facilities, are either invasive or costly. Blood-based biomarkers for AD diagnosis are highly sought after due to its practicality at the clinic. This study was undertaken to determine the differential protein expression in plasma amongst Malaysian AD, mild cognitive impairment (MCI) and non-AD individuals. Methods: A proteomic approach which utilized two-dimensional differential in gel electrophoresis (2 D DIGE) was performed for blood samples from 15 AD, 14 MCI and 15 non-AD individuals. Results: Mass spectrometry (MS)-based protein identification via MALDI ToF/ToF showed that fibrinogen-β-chain (spot 64) and fibrinogen-γ-chain (spot 91) with differential expression ratio >1.5 were significantly upregulated (p 
  16. Aravindhan K, Mat S, Hamid TA, Shahar S, Abdul Majeed AB, Teh PL, et al.
    Gerontology, 2021 Aug 17.
    PMID: 34515120 DOI: 10.1159/000517946
    BACKGROUND: Rapid population aging occurring in developing nations necessitates innovation to ensure we continue to gain ground on aging research despite pandemic threats. While developed nations have resorted to virtual communications, this is challenging in developing nations due to poor internet connectivity and digital literacy.

    OBJECTIVES: The aim of this study was to determine the feasibility of virtual data collection for a longitudinal study of aging assessing cognitive frailty in a middle-income Southeast Asian country.

    METHODS: The Transforming Cognitive Frailty into Later-Life Self-Sufficiency (AGELESS) longitudinal study of aging involved community-dwelling participants aged 60 years and above. A semi-structured focus group discussion was conducted via videoconferencing with selected representatives from existing participants. The survey instrument was compiled during a hybrid meeting and refined using a virtual Delphi process involving 51 AGELESS investigators. The final draft survey and recruitment strategy were then piloted among selected participants.

    RESULTS: Twelve individuals participated in the virtual focus group interview. Smartphone, tablet computer, laptops, and desktop personal computers were used for information gathering, communication, banking, shopping, leisure, religion, and education, within this group. The survey instrument was redacted from 362 items in 18 sections to 141 items in 12 sections through 3 virtual Delphi rounds facilitated by email, social media messaging, and videoconferencing which attracted 213 comments. Of 45 participants selected for the pilot survey, 30 were successfully contacted after one attempt and 18 completed the survey. Cognitive frailty was present in 13%, cognitive impairment in 20%, frailty in 20%, and 47% were robust.

    CONCLUSION: A virtual survey instrument was developed for the AGELESS longitudinal survey of aging which was vital for determining the effects of the COVID-19 pandemic on our older population as well as sustaining research into aging despite barriers posed by the pandemic.

  17. Zakaria N, Ramli MZ, Ramasamy K, Meng LS, Yean CY, Banga Singh KK, et al.
    Anal Biochem, 2018 08 15;555:12-21.
    PMID: 29879415 DOI: 10.1016/j.ab.2018.05.031
    A miniaturized biosensing platform, based on monoclonal amyloid-beta antibodies (mAβab) that were immobilized on a disc-shaped platinum/iridium (Pt/Ir) microelectrode surface coupled with an impedimetric signal transducer, was developed for the label-free and sensitive detection of amyloid-beta peptide fragment 1-40 (Aβ40); a reliable biomarker for early diagnosis of Alzheimer's disease (AD). A Pt/Ir microelectrode was electropolymerized with poly (ortho-phenylenediamine), a conducting free amine-containing aromatic polymer; followed by crosslinking with glutaraldehyde for subsequent coupling of mAβab on the microelectrode surface. This modification strategy efficiently improved the impedimetric detection performance of Aβ40 in terms of charge transfer resistance (∼400-fold difference) and normalized impedance magnitude percentage change (∼40% increase) compared with a passive adsorption-based immobilization method. The sensitivity of the micro-immunosensing assay was found to be 1056 kΩ/(pg/mL)/cm2 and the limit of detection was found to be 4.81 pg/mL with a dynamic range of 1-104 pg/mL (R2 = 0.9932). The overall precision of the assay, as measured by relative standard deviation, ranged from 0.84 to 5.15%, demonstrating its reliability and accuracy; while in respect to assay durability and stability, the immobilized mAβab were able to maintain 80% of their binding activity to Aβ40 after incubation for 48 h at ambient temperature (25 °C). To validate the practical applicability, the assay was tested using brain tissue lysates prepared from AD-induced rats. Results indicate that the proposed impedimetric micro-immunosensing platform is highly versatile and adaptable for the quantitative detection of other disease-related biomarkers.
  18. Rehiman SH, Lim SM, Neoh CF, Majeed ABA, Chin AV, Tan MP, et al.
    Ageing Res Rev, 2020 07;60:101066.
    PMID: 32294542 DOI: 10.1016/j.arr.2020.101066
    In order to gauge the impact of proteomics in discovery of Alzheimer's disease (AD) blood-based biomarkers, this study had systematically reviewed articles published between 1984-2019. Articles that fulfilled the inclusion criteria were assessed for risk of bias. A meta-analysis was performed for replicable candidate biomarkers (CB). Of the 1651 articles that were identified, 17 case-control and two cohort studies, as well as three combined case-control and longitudinal designs were shortlisted. A total of 207 AD and mild cognitive impairment (MCI) CB were discovered, with 48 reported in >2 studies. This review highlights six CB, namely alpha-2-macroglobulin (α2M)ps, pancreatic polypeptide (PP)ps, apolipoprotein A-1 (ApoA-1)ps, afaminp, insulin growth factor binding protein-2 (IGFBP-2)ps and fibrinogen-γ-chainp, all of which exhibited consistent pattern of regulation in >three independent cohorts. They are involved in AD pathogenesis via amyloid-beta (Aβ), neurofibrillary tangles, diabetes and cardiovascular diseases (CVD). Meta-analysis indicated that ApoA-1ps was significantly downregulated in AD (SMD = -1.52, 95% CI: -1.89, -1.16, p 
  19. Rashidah NH, Lim SM, Neoh CF, Majeed ABA, Tan MP, Khor HM, et al.
    Ageing Res Rev, 2022 Dec;82:101744.
    PMID: 36202312 DOI: 10.1016/j.arr.2022.101744
    This systematic review appraised previous findings on differential gut microbiota composition and intestinal permeability markers between frail and healthy older adults. A literature search was performed using PubMed, Scopus, ScienceDirect and the Cochrane Library. Relevant studies were shortlisted based on inclusion and exclusion criteria as well as assessed for risk of bias. The primary outcome was the differential composition of gut microbiota and/ or intestinal permeability markers between frail and healthy older adults. A total of 10 case-control studies and one cohort study were shortlisted. Based on consistent findings reported by more than one shortlisted study, the microbiota of frail older adults was characterised by decreased phylum Firmicutes, with Dialister, Lactobacillus and Ruminococcus being the prominent genera. Healthy controls, on the other hand, exhibited higher Eubacterium at the genera level. In terms of intestinal permeability, frail older adults were presented with increased serum zonulin, pro-inflammatory cytokines (TNF-α, HMGB-1, IL-6, IL1-ra, MIP-1β) and amino acids (aspartic acid and phosphoethanolamine) when compared to healthy controls. Altogether, frail elderlies had lower gut microbiota diversity and lower abundance of SCFA producers, which may have led to leaky guts, upregulated pro-inflammatory cytokines, frailty and sarcopenia.
  20. Darawi MN, Ai-Vyrn C, Ramasamy K, Hua PP, Pin TM, Kamaruzzaman SB, et al.
    BMC Med Genet, 2013;14:27.
    PMID: 23419238 DOI: 10.1186/1471-2350-14-27
    The incidence of Alzheimer's disease, particularly in developing countries, is expected to increase exponentially as the population ages. Continuing research in this area is essential in order to better understand this disease and develop strategies for treatment and prevention. Genome-wide association studies have identified several loci as genetic risk factors of AD aside from apolipoprotein E such as bridging integrator (BIN1), clusterin (CLU), ATP-binding cassette sub-family A member 7 (ABCA7), complement receptor 1 (CR1) and phosphatidylinositol binding clathrin assembly protein (PICALM). However genetic research in developing countries is often limited by lack of funding and expertise. This study therefore developed and validated a simple, cost effective polymerase chain reaction based technique to determine these single nucleotide polymorphisms.
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