Displaying publications 1 - 20 of 106 in total

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  1. Fareez IM, Lim SM, Ramasamy K
    Probiotics Antimicrob Proteins, 2024 Feb;16(1):99-112.
    PMID: 36508139 DOI: 10.1007/s12602-022-10020-y
    The pathogenesis of colorectal cancer (CRC) is associated with gut dysbiosis that is attributed to unhealthy lifestyles and dietary habits. Consumption of microencapsulated probiotics may potentially restore the gut microbiota in favour of prevention against CRC. This study determined the fate of microencapsulated Lactiplantibacillus plantarum (formerly known as Lactobacillus plantarum) LAB12 in the gastrointestinal tract (GIT) and assessed the chemopreventive effect of microencapsulated L. plantarum LAB12 in vivo. The targeted release of L. plantarum LAB12 from Alg-based microcapsules at the stomach, ileum, caecum and colon of Sprague-Dawley rats was examined by confocal microscopy and qPCR. Microcapsules loaded with L. plantarum LAB12 remained intact in the stomach. Free L. plantarum LAB12 were present in abundance (> 7 log CFU) only in the intestines. Subsequently, the chemopreventive properties of microencapsulated L. plantarum LAB12 were validated against NU/NU nude mice bearing orthotopic transplanted CT-26 CRC (12 female mice; 4-6 weeks old; 20-22 g; n = 6/group). Orthotopic mice pre-supplemented with microencapsulated L. plantarum LAB12 (10 log CFU kg-1 BW for 11 weeks) were presented with significantly (p 
  2. 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.
  3. 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.

  4. Ismail MF, Lim SM, Lim FT, Ramasamy K
    PMID: 37816988 DOI: 10.1007/s12602-023-10171-6
    The susceptibility of probiotics to high temperature and low pH remains a major challenge in food industries. Numerous commercially available probiotic products were reportedly presented with lower probiotic viability than claimed. To confer health benefits to the host, it is essential that probiotic strain remains viable at optimal amount during food processing procedures, storage and passage through the gastrointestinal tract. This study addressed these issues by immobilising Lactiplantibacillus plantarum LAB12 isolated from tempeh (fermented soybean) in a polymeric matrix made up of alginate (Alg, 0.5% w/v) and denatured pea protein isolate (PPi, 1-10% w/v) using the emulsion/acidification technique. Alg supplemented with 10% PPi (Alg-PPi10) appeared to be optimally small ( 9 log CFU g-1) in simulated intestinal fluid (at pH 6.8 for 240 min). Whilst retaining their intrinsic cholesterol lowering effect, microencapsulation conferred additional advantages to L. plantarum LAB12 in terms of lowering serum triglyceride and increasing HDL cholesterol in zebrafish fed with high-cholesterol diet (HCD). Overall, our findings strongly imply the potential use of Alg-PPi10 as an effective medium that confers thermal protection and facilitates pH-sensitive release of cholesterol-reducing L. plantarum LAB12. This will allow the diverse applications L. plantarum LAB12 across health, food and agro-feed industries amongst others.
  5. Ahmad Alwi NA, Lim SM, Mani V, Ramasamy K
    J Diet Suppl, 2023;20(5):717-734.
    PMID: 35876040 DOI: 10.1080/19390211.2022.2103608
    This study explored mechanisms underpinning enhanced memory in amyloid precursor protein (APP) transgenic mice (male; 10-12 months; n = 6/group) supplemented with Lactobacillus plantarum LAB12 (LAB12)/Lactobacillus casei Shirota (LcS). Morris Water Maze test was performed before brains were harvested for gene expression and biochemical studies. LAB-supplemented mice exhibited reduced escape latency and distance but significant increased time spent in platform zone. This was associated with downregulated beta-site APP cleaving enzyme-1 (BACE1) mRNA and significant reduced nitric oxide in brains. LAB12 also significantly increased glutathione. The LAB-enhanced memory is strain-dependent and could be mediated, in part, through amyloidogenic pathway and anti-oxidant/oxidative stress interplay.
  6. Sheshala R, Wai NZ, Said ID, Ashraf K, Lim SM, Ramasamy K, et al.
    Turk J Pharm Sci, 2022 Dec 21;19(6):671-680.
    PMID: 36544377 DOI: 10.4274/tjps.galenos.2021.40121
    OBJECTIVES: Orthosiphon stamineus Benth. (OS) is a commonly used medicinal plant for curbing bacterial infections globally. This work aimed to fabricate poloxamer and chitosan-based in situ gels loaded with standardized aqueous-ethanolic OS leaf extracts and investigate their antimicrobial efficacy as a potential remedy against ocular infections.

    MATERIALS AND METHODS: In situ gels containing 0.5% w/v OS extract prepared using cold dispersion method were subjected to physicochemical characterization, including in vitro-release studies. Antimicrobial efficacy was tested against Staphylococcus aureus, Micrococcus luteus, Escherichia coli, and Pseudomonas aeruginosa using agar diffusion method.

    RESULTS: Thin layer chromatography and high performance liquid chromatography chromatograms confirmed the presence of rosmarinic acid (RA) and sinensitin in OS extracts with same retention factor (0.26 and 0.49) and retention times (12.2 and 20.7 min) against reference standards. A homogenous brown coloured in situ gel exhibited low viscosity as a solution and increased viscosity in gel form at ocular temperature. The optimized formulations, P7 (21% P407/4% P188), P8 (21% P407/5% P188) and F5 (1.5% chitosan and 45% β-glycerophosphate) exhibited ideal ocular pH (7.27-7.46), phase transition at ocular temperature (33-37°C) and prolonged RA release up to 12 h. Formulation F5 showed an inhibition zone of 4.3 mm against M. luteus.

    CONCLUSION: Among all, formulation F5 alone exhibited modest antimicrobial activity against M. luteus. OS extracts at 5% and 10% were most active against tested bacteria however, loading them into in situ gels resulted in sedimentation. Hence, isolation of RA from OS extract is suggested before loading into formulations for a better antimicrobial activity.

  7. 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.
  8. Vijayanathan Y, Hamzah NM, Lim SM, Lim FT, Tan MP, Majeed ABA, et al.
    Brain Res Bull, 2022 Nov;190:218-233.
    PMID: 36228872 DOI: 10.1016/j.brainresbull.2022.10.001
    In order to understand the biological processes underlying dopaminergic neurons (DpN) regeneration in a 6-hydroxydopamine(6-OHDA)-induced adult zebrafish-based Parkinson's disease model, this study investigated the specific phases of neuroregeneration in a time-based manner. Bromodeoxyuridine (BrdU) was administered 24 h before the harvest of brain tissues at day three, five, seven, nine, 12 and 14 postlesion. Potential migration of proliferative cells was tracked over 14 days postlesion through double-pulse tracking [BrdU and 5-ethynyl-2'-deoxyuridine (EdU)] of cells and immunohistostaining of astrocytes [glial fibrillary acidic protein (GFAP)]. Gene expression of foxa2 and nurr1 (nr4a2a) at day three, nine, 14, 18, 22 and 30 postlesion was quantified using qPCR. Protein expression of foxa2 at day three, seven, 14 and 22 postlesion was validated using the western blot technique. Double labelling [EdU and tyrosine hydroxylase (TH)] of proliferative cells was performed to ascertain their fate after the neuroregeneration processes. It was found that whilst cell proliferation remained unchanged in the area of substantial DpN loss, the ventral diencephalon (vDn), there was a transient increase of cell proliferation in the olfactory bulb (OB) and telencephalon (Tel) seven days postlesion. BrdU-immunoreactive (ir)/ EdU-ir cells and activated astrocytes were later found to be significantly increased in the vDn and its nearby area (Tel) 14 days postlesion. There was a significant but transient downregulation of foxa2 at day three and nine postlesion, and nr4a2a at day three, nine and 14 postlesion. The expression of both genes remained unchanged in the OB and Tel. There was a transient downregulation of foxa2 protein expression at day three and seven postlesion. The significant increase of EdU-ir/ TH-ir cells in the vDn 30 days postlesion indicates maturation of proliferative cells (formed between day five-seven postlesion) into DpN. The present findings warrant future investigation of critical factors that govern the distinctive phases of DpN regeneration.
  9. Mohd-Zubri NS, Ramasamy K, Abdul-Rahman NZ
    Arch Oral Biol, 2022 Nov;143:105515.
    PMID: 36084351 DOI: 10.1016/j.archoralbio.2022.105515
    OBJECTIVE: This study aims to characterise the lactic acid bacteria (LAB) isolated from local Malaysian fermented foods with oral probiotics properties.

    DESIGN: The LAB strains isolated from Malaysian fermented foods, Lactobacillus brevis FT 6 and Lactobacillus plantarum FT 12, were assessed for their antimicrobial properties against Porphyromonas gingivalis ATCC 33277 via disc diffusion assay. Anti-biofilm properties were determined by treating the overnight P. gingivalis ATCC 33277 biofilm with different concentrations of LAB cell-free supernatant (LAB CFS). Quantification of biofilm was carried out by measuring the optical density of stained biofilm. The ability of L. brevis FT 6 and L. plantarum FT 12 to tolerate salivary amylase was also investigated. Acid production with different sugars was carried out by pH measurement and screening for potential antimicrobial organic acid by disc diffusion assay of neutralised probiotics CFS samples. In this study, L. rhamnosus ATCC 7469, a commercial strain was used to compare the efficacy of the isolated strain with the commercial strain.

    RESULTS: Lactobacillus brevis FT 6 and L. plantarum FT 12 possess antimicrobial activity against P. gingivalis with inhibition diameters of more than 10 mm, and the results were comparable with L. rhamnosus ATCC 7469. The MIC and MBC assay results for all tested strains were recorded to be 25 µl/µl concentration. All LAB CFS reduced biofilm formation proportionally to the CFS concentration and tolerated salivary amylase with more than 50% viability. Overnight cultures of all lactic acid bacteria strains showed a pH reduction and neutralised CFS of all lactic acid bacteria strains did not show any inhibition towards P. gingivalis.

    CONCLUSIONS: These results indicate that the isolated probiotics have the potential as probiotics to be used as a supportive oral health treatment, especially against a periodontal pathogen, P. gingivalis.

  10. Md Hamzah N, Lim SM, Vijayanathan Y, Lim FT, Abdul Majeed AB, Tan MP, et al.
    J Vis Exp, 2021 Dec 28.
    PMID: 35037659 DOI: 10.3791/63355
    The limitations of current treatments in delaying dopaminergic neuronal loss in Parkinson's disease (PD) raise the need for alternative therapies that can restore these neurons. Much effort is currently directed toward a better understanding of neuroregeneration using preclinical in vivo models. This regenerative capability for self-repair is, however, inefficient in mammals. Non-mammalian animals like zebrafish have thus emerged as an excellent neuroregenerative model due to its capability to continuously self-renew and have a close brain homology to humans. As part of the effort in elucidating cellular events involved in neuroregeneration in vivo, we have established the 6-hydroxydopamine (6-OHDA)-induced adult zebrafish-based PD model. This was achieved through the optimized intracerebroventricular (ICV) microinjection of 99.96 mM 6-OHDA to specifically ablate dopaminergic neurons (DpN) in the ventral diencephalon (Dn) of zebrafish brain. Immunofluorescence indicated more than 85% of DpN ablation at day three postlesion and full restoration of DpN at lesioned site 30 days postlesion. The present study determined the impairment and subsequent recovery of zebrafish swimming behavior following lesion by using the open field test through which two parameters, distance traveled (cm) and mean speed (cm/s), were quantified. The locomotion was assessed by analyzing the recordings of individual fish of each group (n = 6) using video tracking software. The findings showed a significant (p < 0.0001) reduction in speed (cm/s) and distance traveled (cm) of lesioned zebrafish 3 days postlesion when compared to sham. The lesioned zebrafish exhibited full recovery of swimming behavior 30 days postlesion. The present findings suggest that 6-OHDA lesioned adult zebrafish is an excellent model with reproducible quality to facilitate the study of neuroregeneration in PD. Future studies on the mechanisms underlying neuroregeneration as well as intrinsic and extrinsic factors that modulate the process may provide important insight into new cell replacement treatment strategies against PD.
  11. Mani V, Mohd Azahan NS, Ramasamy K, Lim SM, Abdul Majeed AB
    Brain Sci, 2021 Dec 23;12(1).
    PMID: 35053756 DOI: 10.3390/brainsci12010012
    Murraya koenigii leaves contain mahanimbine, a carbazole alkaloid, reported with improving cholinergic neuronal transmission and reducing neuroinflammation in the CNS. The current research investigated the effects of mahanimbine on age-related memory deficits, oxidative stress, cholinergic dysfunction, amyloid formation, and neuroinflammation in aged mice (16 months old). Mahanimbine was administered (1 and 2 mg/kg, p.o.) daily to groups of aged mice for 30 days. The Morris water maze (MWM) task was performed to study spatial learning (escape latency (EL) and swimming distance (SD)) and memory (probe test). The levels of malondialdehyde (MDA), glutathione (GSH), acetylcholine (ACh), acetylcholinesterase (AChE), β-amyloid (Aβ1-40 and Aβ1-42), β-secretase (BACE-1), as well as neuroinflammation markers (total cyclooxygenase (COX) and COX-2 expression), were measured from the isolated brain. Mahanimbine reduced the EL time and SD in the MWM test. From the probe trial, the mahanimbine-treated group spent more time in the targeted quadrant related to the age-matched control, which indicated the enhancement of memory retention. From the biochemical tests, the treatment decreased MDA, AChE, Aβ1-40, and Aβ1-42, BACE-1, total COX activity, and COX-2 expression. It also raised the brain GSH and ACh levels in aged mice compared to age-matched control. These results have supported the reversal of memory dysfunctions by mahanimbine in aged mice and hypothesized that it could be a potential target to treat age-related neurodegenerative disease.
  12. 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.

  13. Ramasamy K, Saniasiaya J
    Iran J Otorhinolaryngol, 2021 Jul;33(117):249-251.
    PMID: 34395326 DOI: 10.22038/ijorl.2021.51303.2752
    Introduction: Clicking larynx syndrome is a rare condition that may be intriguing to the attending clinician. Patients typically present with clicking sensations in the neck, often obvious during head movement or swallowing. Due to the scarce presentation of such cases, clicking larynx syndrome harbors a high propensity to be an overlooked diagnosis, resulting in a clinical stalemate.

    Case Report: Herein, we present a case of clicking larynx in a young girl followed by an overview of the latest literature on the aetiology and treatment options. This case aims to reinforce the presence of this entity further and subsequently increase its awareness among clinicians.

    Conclusion: Expeditious diagnosis is imperative not just for the eventual treatment but also for timely relief to the anxious patients who would have been perplexed by the strange clicking in the throat.

  14. Ramasamy K, Saniasiaya J, Abdul Gani N
    Ann Otol Rhinol Laryngol, 2021 May;130(5):513-519.
    PMID: 33025798 DOI: 10.1177/0003489420963165
    OBJECTIVE: To investigate the prevalence of olfactory and gustatory dysfunction among patients with COVID-19 infection and the recovery rate.

    METHODS: Adult patients (≥18 years) tested positive for COVID-19 via reverse transcription-polymerase chain reaction (RT-PCR) and admitted in Hospital Tuanku Ja'afar Seremban, Malaysia, were recruited in this study. Patients completed a questionnaire via telephone interview comprising the following details: age, sex, ethnicity, comorbidities, general and otorhinolaryngological symptoms, onset and duration of olfactory and gustatory dysfunction. Patients with persistent olfactory and gustatory dysfunction at the time of the initial interview were followed-up every 3 to 5 days till resolution.

    RESULTS: A total of 145 patients were included in our study. The mean age of patients was 43.0 ± 17.7 (range: 18-86). Fever (44.1%) and cough (39.3%) were the most prevalent general symptoms. Thirty-one patients (21.4%) reported olfactory dysfunction and 34 (23.4%) reported dysgeusia. There was a significant association between both olfactory and gustatory dysfunction (P 

  15. Ramasamy K, Saniasiaya J, Abdul Gani N
    Eur Ann Otorhinolaryngol Head Neck Dis, 2021 May;138(3):213-214.
    PMID: 33032966 DOI: 10.1016/j.anorl.2020.05.018
  16. 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.
  17. Umirah F, Neoh CF, Ramasamy K, Lim SM
    Diabetes Res Clin Pract, 2021 Mar;173:108689.
    PMID: 33549678 DOI: 10.1016/j.diabres.2021.108689
    AIMS: This systematic review summarised the latest findings on differential composition of gut microbiota in T2DM.

    METHODS: Literature search was performed using electronic databases. Relevant studies were identified, extracted and assessed for risk of bias. The primary outcome of this systematic review was the composition of gut microbiota in healthy controls and T2DM while the secondary outcomes included the correlation of gut microbiota with metabolic parameters.

    RESULTS: Thirteen case-control studies involving 575 T2DM and 840 healthy controls were included. T2DM patients exhibited a marked increase in lactobacilli. Six studies found lactobacilli to predominate the gut of T2DM patients; however, this could be confounded by the types of antihyperglyacemic medications. Conversely, butyrate producers dominate the gut of healthy controls. In T2DM patients, butyrate producers were surprisingly higher in those taking metformin intake than those not taking the drug. Whilst lactobacilli were found to be higher with increased plasma glucose, conflicting correlations were observed between various genera and anthropometric measurements, dietary intake, lipid profiles and inflammatory markers. There were moderate to strong significant positive correlations between the class Clostridia and phylum Firmicutes with pro-inflammatory IFN-γ as well as between Negativicutes and IL-6.

    CONCLUSIONS: Altogether, butyrate-producing bacteria are negatively correlated to glycaemic parameters. Lactobacilli are higher in T2DM patients and Firmicutes is correlated with inflammation.

  18. Lim SM, Agatonovic-Kustrin S, Lim FT, Ramasamy K
    J Pharm Biomed Anal, 2021 Jan 30;193:113702.
    PMID: 33160220 DOI: 10.1016/j.jpba.2020.113702
    Bioactive compounds from endophytic fungi exhibit diverse biological activities which include anticancer effect. Capitalising on the abundance of unexplored endophytes that reside within marine plants, this study assessed the anticancer potential of ethyl acetate endophytic fungal extracts (i.e. MBFT Tip 2.1, MBL 1.2, MBS 3.2, MKS 3 and MKS 3.1) derived from leaves, stem and fruits of marine plants that grow along Morib Beach, Malaysia. For identification of endophytic fungi, EF 4/ EF 3 and ITS 1/ ITS 4 PCR primer pairs were used to amplify the fungal 18S rDNA sequence and ITS region sequence, respectively. The resultant sequences were subjected to similarity search via the NCBI GenBank database. High-performance thin layer chromatography (HPTLC) hyphenated with bioassays was used to characterise the extracts in terms of their phytochemical profiles and bioactivity. Microchemical derivatisation was used to assess polyphenolic and phytosterol/ terpenoid content whereas biochemical derivatisation was used to establish antioxidant activities and α-amylase enzyme inhibition. The sulforhodamine B (SRB) assay was used to assess the anticancer effect of the extracts against HCT116 (a human colorectal cancer cell line). The present results indicated MBS 3.2 (Penicillium decumbens) as the most potent extract against HCT116 (IC50 = 0.16 μg/mL), approximately 3-times more potent than 5-flurouracil (IC50 = 0.46 μg/mL). Stepwise multiple regression method suggests that the anticancer effect of MBS 3.2 could be associated with high polyphenolic content and antioxidant potential. Nonlinear regression analysis confirmed that low to moderate α-amylase inhibition exhibits maximum anticancer activity. Current findings warrant further in-depth mechanistic studies.
  19. Kumari M, Tahlan S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2021 Jan 21;15(1):5.
    PMID: 33478538 DOI: 10.1186/s13065-020-00717-y
    BACKGROUND: Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents.

    METHODS: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards.

    RESULTS, DISCUSSION AND CONCLUSION: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 μM) and T7 (IC50 = 3.25 μM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 μM).

  20. Ponvel P, Shahar S, Singh DKA, Ludin AFM, Rajikan R, Rajab NF, et al.
    J Alzheimers Dis, 2021;82(2):673-687.
    PMID: 34092633 DOI: 10.3233/JAD-201607
    BACKGROUND: Cognitive frailty (CF) is identified as one of the main precursors of dementia. Multidomain intervention has been found to delay or prevent the onset of CF.

    OBJECTIVE: The aim of our present study is to determine the effectiveness of a comprehensive, multidomain intervention on CF; to evaluate its cost effectiveness and the factors influencing adherence toward this intensive intervention.

    METHODS: A total of 1,000 community dwelling older adults, aged 60 years and above will be screened for CF. This randomized controlled trial involves recruitment of 330 older adults with CF from urban, semi-urban, and rural areas in Malaysia. Multidomain intervention comprised of physical, nutritional, cognitive, and psychosocial aspects will be provided to participants in the experimental group (n = 165). The control group (n = 165) will continue their usual care with their physician. Primary outcomes include CF status, physical function, psychosocial and nutritional status as well as cognitive performance. Vascular health and gut microbiome will be assessed using blood and stool samples. A 24-month intensive intervention will be prescribed to the participants and its sustainability will be assessed for the following 12 months. The effective intervention strategies will be integrated as a personalized telerehabilitation package for the reversal of CF for future use.

    RESULTS: The multidomain intervention developed from this trial is expected to be cost effective compared to usual care as well as able is to reverse CF.

    CONCLUSION: This project will be part of the World-Wide FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) Network, of which common identifiable data will be shared and harmonized among the consortia.

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