Displaying publications 61 - 74 of 74 in total

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  1. Mohd Taha MD, Mohd Jaini MF, Saidi NB, Abdul Rahim R, Md Shah UK, Mohd Hashim A
    PLoS One, 2019;14(12):e0224431.
    PMID: 31841519 DOI: 10.1371/journal.pone.0224431
    Dieback disease caused by Erwinia mallotivora is a major threat to papaya plantation in Malaysia. The current study was conducted to evaluate the potential of endophytic lactic acid bacteria (LAB) isolated from papaya seeds for disease suppression of papaya dieback. Two hundred and thirty isolates were screened against E. mallotivora BT-MARDI, and the inhibitory activity of the isolates against the pathogen was ranging from 11.7-23.7 mm inhibition zones. The synergistic experiments revealed that combination of W. cibaria PPKSD19 and Lactococcus lactis subsp. lactis PPSSD39 increased antibacterial activity against the pathogen. The antibacterial activity was partially due to the production of bacteriocin-like inhibitory substances (BLIS). The nursery experiment confirmed that the application of bacterial consortium W. cibaria PPKSD19 and L. lactis subsp. lactis PPSSD39 significantly reduced disease severity to 19% and increased biocontrol efficacy to 69% of infected papaya plants after 18 days of treatment. This study showed that W. cibaria PPKSD19 and L. lactis subsp. lactis PPSSD39 are potential candidate as biocontrol agents against papaya dieback disease.
  2. Omar AA, Khai Leng L, Apana AN, Ibrahim A, Abdul Rahim R, Yaacob NM, et al.
    Cureus, 2022 Oct;14(10):e30395.
    PMID: 36407144 DOI: 10.7759/cureus.30395
    Background Ectopic pregnancy was recorded as the fourth principal cause of maternal death in Malaysia in 2019. Early diagnosis and use of methotrexate treatment proved to be safe and effective alternatives to surgical treatment. This study investigates the success rate of methotrexate treatment for ectopic pregnancy in a tertiary hospital in Malaysia. Methods This was a retrospective review of 73 patients with ectopic pregnancies treated with methotrexate according to a single-dose protocol from January 2009 until November 2019. The diagnosis of ectopic pregnancy was made using a combination of transvaginal scan and serial serum β-hCG levels. Their clinical and demographic data were reviewed. Serum β-hCG levels were measured at pre- and post-treatment to determine the rate of successful resolution. Results The overall success rate was 87.7% (64/73 patients) with methotrexate treatment. Fifty-six patients (76.7%) were successfully treated with a single dose of methotrexate, and eight patients (11.0%) required a second dose of methotrexate. There was no relation between socio-demographic, pre-treatment β-hCG levels, ectopic mass size, and treatment efficacy. Smaller size of ectopic pregnancy (adjusted OR=29.23; 95% CI: 2.69, 317.90; P=0.006) and absence of free fluid at the pouch of Douglas (POD) (adjusted OR=27.31; 95% CI: 2.84, 262.32; P=0.004) was found to increase the likelihood of overall treatment success. Absence of fetal cardiac activities was found to increase the likelihood of first-dose methotrexate treatment success (OR=10.20; 95% CI: 1.93, 53.79; P=0.006). Conclusions Early diagnosis of ectopic pregnancy may reduce morbidity and mortality. In carefully selected cases, methotrexate treatment has been proven to be cost-effective and avoided risks associated with surgery and anaesthesia.
  3. Dakheel KH, Abdul Rahim R, Al-Obaidi JR, Neela VK, Hun TG, Mat Isa MN, et al.
    Biotechnol Lett, 2022 Feb 05.
    PMID: 35122191 DOI: 10.1007/s10529-022-03229-y
    OBJECTIVE: The degradation activity of two bacteriophages UPMK_1 and UPMK_2 against methicillin-resistant Staphylococcus aureus phages were examined using gel zymography.

    METHODS: The analysis was done using BLASTP to detect peptides catalytic domains. Many peptides that are related to several phage proteins were revealed.

    RESULTS: UPMK_1 and UPMK_2 custom sequence database were used for peptide identification. The biofilm-degrading proteins in the bacteriophage UPMK_2 revealed the same lytic activity towards polysaccharide intercellular adhesin-dependent and independent of Methicillin-resistant Staphylococcus aureus (MRSA) biofilm producers in comparison to UPMK_1, which had lytic activity restricted solely to its host.

    CONCLUSION: Both bacteriophage enzymes were involved in MRSA biofilm degradation during phage infection and they have promising enzybiotics properties against MRSA biofilm formation.

  4. Jee PF, Tiong V, Shu MH, Khoo JJ, Wong WF, Abdul Rahim R, et al.
    PLoS One, 2017;12(11):e0187718.
    PMID: 29108012 DOI: 10.1371/journal.pone.0187718
    Mucosal immunization of influenza vaccine is potentially an effective approach for the prevention and control of influenza. The objective of the present study was to evaluate the ability of oral immunization with a non-recombinant Lactococcus lactis displaying HA1/L/AcmA recombinant protein, LL-HA1/L/AcmA, to induce mucosal immune responses and to accord protection against influenza virus infection in mice. The LL-HA1/L/AcmA was orally administered into mice and the immune response was evaluated. Mice immunized with LL-HA1/L/AcmA developed detectable specific sIgA in faecal extract, small intestine wash, BAL fluid and nasal fluid. The results obtained demonstrated that oral immunization of mice with LL-HA1/L/AcmA elicited mucosal immunity in both the gastrointestinal tract and the respiratory tract. The protective efficacy of LL-HA1/L/AcmA in immunized mice against a lethal dose challenge with influenza virus was also assessed. Upon challenge, the non-immunized group of mice showed high susceptibility to influenza virus infection. In contrast, 7/8 of mice orally immunized with LL-HA1/L/AcmA survived. In conclusion, oral administration of LL-HA1/L/AcmA in mice induced mucosal immunity and most importantly, provided protection against lethal influenza virus challenge. These results highlight the potential application of L. lactis as a platform for delivery of influenza virus vaccine.
  5. Ashaari NS, Ab Rahim MH, Sabri S, Lai KS, Song AA, Abdul Rahim R, et al.
    Sci Rep, 2021 Aug 24;11(1):17094.
    PMID: 34429465 DOI: 10.1038/s41598-021-96524-z
    Linalool and nerolidol are terpene alcohols that occur naturally in many aromatic plants and are commonly used in food and cosmetic industries as flavors and fragrances. In plants, linalool and nerolidol are biosynthesized as a result of respective linalool synthase and nerolidol synthase, or a single linalool/nerolidol synthase. In our previous work, we have isolated a linalool/nerolidol synthase (designated as PamTps1) from a local herbal plant, Plectranthus amboinicus, and successfully demonstrated the production of linalool and nerolidol in an Escherichia coli system. In this work, the biochemical properties of PamTps1 were analyzed, and its 3D homology model with the docking positions of its substrates, geranyl pyrophosphate (C10) and farnesyl pyrophosphate (C15) in the active site were constructed. PamTps1 exhibited the highest enzymatic activity at an optimal pH and temperature of 6.5 and 30 °C, respectively, and in the presence of 20 mM magnesium as a cofactor. The Michaelis-Menten constant (Km) and catalytic efficiency (kcat/Km) values of 16.72 ± 1.32 µM and 9.57 × 10-3 µM-1 s-1, respectively, showed that PamTps1 had a higher binding affinity and specificity for GPP instead of FPP as expected for a monoterpene synthase. The PamTps1 exhibits feature of a class I terpene synthase fold that made up of α-helices architecture with N-terminal domain and catalytic C-terminal domain. Nine aromatic residues (W268, Y272, Y299, F371, Y378, Y379, F447, Y517 and Y523) outlined the hydrophobic walls of the active site cavity, whilst residues from the RRx8W motif, RxR motif, H-α1 and J-K loops formed the active site lid that shielded the highly reactive carbocationic intermediates from the solvents. The dual substrates use by PamTps1 was hypothesized to be possible due to the architecture and residues lining the catalytic site that can accommodate larger substrate (FPP) as demonstrated by the protein modelling and docking analysis. This model serves as a first glimpse into the structural insights of the PamTps1 catalytic active site as a multi-substrate linalool/nerolidol synthase.
  6. Zamhuri SA, Soon CF, Nordin AN, Ab Rahim R, Sultana N, Khan MA, et al.
    Sens Biosensing Res, 2022 Jun;36:100482.
    PMID: 35251937 DOI: 10.1016/j.sbsr.2022.100482
    The discovery of SARS-CoV-2 virus in the water bodies has been reported, and the risk of virus transmission to human via the water route due to poor wastewater management cannot be disregarded. The main source of the virus in water bodies is the sewage network systems which connects to the surface water. Wastewater-based epidemiology has been applied as an early surveillance tool to sense SARS-CoV-2 virus in the sewage network. This review discussed possible transmission routes of the SARS-CoV-2 virus and the challenges of the existing method in detecting the virus in wastewater. One significant challenge for the detection of the virus is that the high virus loading is diluted by the sheer volume of the wastewater. Hence, virus preconcentration from water samples prior to the application of virus assay is essential to accurately detect traceable virus loading. The preparation time, materials and conditions, virus type, recovery percentage, and various virus recovery techniques are comprehensively discussed in this review. The practicability of molecular methods such as Polymer-Chain-Reaction (PCR) for the detection of SARS-CoV-2 in wastewater will be revealed. The conventional virus detection techniques have several shortcomings and the potential of biosensors as an alternative is also considered. Biosensing techniques have also been proposed as an alternative to PCR and have reported detection limits of 10 pg/μl. This review serves to guide the reader on the future designs and development of highly sensitive, robust and, cost effective SARS-CoV-2 lab-on-a-chip biosensors for use in complex wastewater.
  7. Chan XY, Anthonysamy J, Sivaganabalan R, Tan CH, Safferi RSB, Abdul Rahim R, et al.
    Toxicon, 2024 Sep 02.
    PMID: 39233130 DOI: 10.1016/j.toxicon.2024.108086
    (256 words) OBJECTIVE: There is very limited published experience on mangrove pit viper envenomation in the medical literature. This study aims to analyze the clinical characteristics, treatment modalities and outcomes of patients presenting to Selangor middle zone cluster Hospitals in Malaysia with confirmed mangrove pit viper bites.

    METHODS: We conducted a retrospective observational study, reviewing medical records of patients treated for mangrove pit viper bites between 1st July 2020 to 30th June 2023. Data on patient demographics, clinical characteristic, laboratory findings, treatment modalities and clinical outcomes were collected and analyzed.

    RESULTS: A total of 25 patients were included in this study. The majority of the patients were male (n=23, 92%) with the mean age of 38.7±17.6 years. Most frequent anatomical region involved is foot (n=12, 48%). Common clinical presentation included localized pain (n=xx, 96%), swelling (n=22, 88%) and fang mark (n=22, 88%). Systemic symptoms were less common, with 1 patient exhibit coagulopathy with clinical bleeding at 28 hours post bite. Antivenom was administered to 68% (n=17) of the patients. The majority of the patients (n=23, 92%) recovered without significant morbidity while 8% (n=2) of the patients developed skin infection that required antibiotic therapy. No fatalities were reported.

    CONCLUSION: Mangrove pit viper envenomation encounter in these regions predominantly causes local symptoms while systemic symptoms were less common. This study provides a glimpse to the clinical characteristics and management of mangrove pit viper envenomation, coagulopathy may be delayed due to characteristic of the snake venom and patient's preexisting illness. Further research is needed to enhance our understanding of this snakebite envenomation.

  8. Ashaari NS, Ab Rahim MH, Sabri S, Lai KS, Song AA, Abdul Rahim R, et al.
    PLoS One, 2020;15(7):e0235416.
    PMID: 32614884 DOI: 10.1371/journal.pone.0235416
    Plectranthus amboinicus (Lour.) Spreng is an aromatic medicinal herb known for its therapeutic and nutritional properties attributed by the presence of monoterpene and sesquiterpene compounds. Up until now, research on terpenoid biosynthesis has focused on a few mint species with economic importance such as thyme and oregano, yet the terpene synthases responsible for monoterpene production in P. amboinicus have not been described. Here we report the isolation, heterologous expression and functional characterization of a terpene synthase involved in P. amboinicus terpenoid biosynthesis. A putative monoterpene synthase gene (PamTps1) from P. amboinicus was isolated with an open reading frame of 1797 bp encoding a predicted protein of 598 amino acids with molecular weight of 69.6 kDa. PamTps1 shares 60-70% amino acid sequence similarity with other known terpene synthases of Lamiaceae. The in vitro enzymatic activity of PamTps1 demonstrated the conversion of geranyl pyrophosphate and farnesyl pyrophosphate exclusively into linalool and nerolidol, respectively, and thus PamTps1 was classified as a linalool/nerolidol synthase. In vivo activity of PamTps1 in a recombinant Escherichia coli strain revealed production of linalool and nerolidol which correlated with its in vitro activity. This outcome validated the multi-substrate usage of this enzyme in producing linalool and nerolidol both in in vivo and in vitro systems. The transcript level of PamTps1 was prominent in the leaf during daytime as compared to the stem. Gas chromatography-mass spectrometry (GC-MS) and quantitative real-time PCR analyses showed that maximal linalool level was released during the daytime and lower at night following a diurnal circadian pattern which correlated with the PamTps1 expression pattern. The PamTps1 cloned herein provides a molecular basis for the terpenoid biosynthesis in this local herb that could be exploited for valuable production using metabolic engineering in both microbial and plant systems.
  9. Abdul Rahim R, Jayusman PA, Lim V, Ahmad NH, Abdul Hamid ZA, Mohamed S, et al.
    Front Pharmacol, 2021;12:796509.
    PMID: 35111063 DOI: 10.3389/fphar.2021.796509
    Blainvillea acmella (L.) Philipson [Asteraceae] (B. acmella) is an important medicinal plant native to Brazil, and it is widely known as a toothache plant. A plethora of studies have demonstrated the antioxidant activities of B. acmella and few studies on the stimulatory effects on alkaline phosphatase (ALP) secretion from bone cells; however, there is no study on its antioxidant and anabolic activity on bone cells. The study aimed to evaluate the phytochemical contents of aqueous and ethanol extracts of B. acmella using gas chromatography mass spectrometry (GCMS) and liquid chromatography time of flight mass spectrometry (LCTOFMS) along with the total phenolic (TPC) and flavonoid (TFC) contents using Folin-Ciocalteu and aluminum colorimetric methods. The extracts of B. acmella leaves were used to scavenge synthetic-free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. The bone anabolic effects of B. acmella extracts on MC3T3-E1 cells were measured with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoium bromide (MTT) at 1, 3, 5, and 7 days, Sirius-red and ALP at 7 and 14 days, and Alizarin Red S at 14 and 21 days. Comparatively, ethanol extract of B. acmella (BaE) contributed higher antioxidant activities (IC50 of 476.71 µg/ml and 56.01 ± 6.46 mg L-ascorbic acid/g against DPPH and FRAP, respectively). Anabolic activities in bone proliferation, differentiation, and mineralization were also higher in B. acmella of ethanol (BaE) than aqueous (BaA) extracts. Positive correlations were observed between phenolic content (TPC and TFC) to antioxidant (ABTS and FRAP) and anabolic activities. Conversely, negative correlations were present between phenolic content to antioxidant (DPPH) activity. These potential antioxidant and bone anabolic activities in BaE might be due to the phytochemicals confirmed through GCMS and LCTOFMS, revealed that terpenoids of α-cubebene, cryophyllene, cryophyllene oxide, phytol and flavonoids of pinostrobin and apigenin were the compounds contributing to both antioxidant and anabolic effects in BaE. Thus, B. acmella may be a valuable antioxidant and anti-osteoporosis agent. Further study is needed to isolate, characterize and elucidate the underlying mechanisms responsible for the antioxidant and bone anabolic effects.
  10. Alias NAR, Hoo WPY, Siak PY, Othman SS, Mohammed Alitheen NB, In LLA, et al.
    Int J Mol Sci, 2023 May 18;24(10).
    PMID: 37240273 DOI: 10.3390/ijms24108928
    Colorectal cancer (CRC) is often caused by mutations in the KRAS oncogene, making KRAS neoantigens a promising vaccine candidate for immunotherapy. Secreting KRAS antigens using live Generally Recognized as Safe (GRAS) vaccine delivery hosts such as Lactococcus lactis is deemed to be an effective strategy in inducing specific desired responses. Recently, through the engineering of a novel signal peptide SPK1 from Pediococcus pentosaceus, an optimized secretion system was developed in the L. lactis NZ9000 host. In this study, the potential of the L. lactis NZ9000 as a vaccine delivery host for the production of two KRAS oncopeptides (mutant 68V-DT and wild-type KRAS) through the use of the signal peptide SPK1 and its mutated derivative (SPKM19) was investigated. The expression and secretion efficiency analyses of KRAS peptides from L. lactis were performed in vitro and in vivo in BALB/c mice. Contradictory to our previous study using the reporter staphylococcal nuclease (NUC), the yield of secreted KRAS antigens mediated by the target mutant signal peptide SPKM19 was significantly lower (by ~1.3-folds) compared to the wild-type SPK1. Consistently, a superior elevation of IgA response against KRAS aided by SPK1 rather than mutant SPKM19 was observed. Despite the lower specific IgA response for SPKM19, a positive IgA immune response from mice intestinal washes was successfully triggered following immunization. Size and secondary conformation of the mature proteins are suggested to be the contributing factors for these discrepancies. This study proves the potential of L. lactis NZ9000 as a host for oral vaccine delivery due to its ability to evoke the desired mucosal immune response in the gastrointestinal tract of mice.
  11. Abdul Rahim R, Jayusman PA, Muhammad N, Mohamed N, Lim V, Ahmad NH, et al.
    PMID: 33805420 DOI: 10.3390/ijerph18073532
    Oxidative stress and inflammation are two common risk factors of various life-threatening disease pathogenesis. In recent years, medicinal plants that possess antioxidant and anti-inflammatory activities were extensively studied for their potential role in treating and preventing diseases. Spilanthes acmella (S. acmella), which has been traditionally used to treat toothache in Malaysia, contains various active metabolites responsible for its anti-inflammatory, antiseptic, and anesthetic bioactivities. These bioactivities were attributed to bioactive compounds, such as phenolic, flavonoids, and alkamides. The review focused on the summarization of in vitro and in vivo experimental reports on the antioxidant and anti-inflammatory actions of S. acmella, as well as how they contributed to potential health benefits in lowering the risk of diseases that were related to oxidative stress. The molecular mechanism of S. acmella in reducing oxidative stress and inflammatory targets, such as inducible nitric oxide synthase (iNOS), transcription factors of the nuclear factor-κB family (NF-κB), cyclooxygenase-2 (COX-2), and mitogen-activated protein kinase (MAPK) signaling pathways were discussed. Besides, the antioxidant potential of S. acmella was measured by total phenolic content (TPC), total flavonid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and superoxide anion radical scavenging (SOD) and thiobarbituric acid reactive substance (TBARS) assays. This review revealed that S. acmella might have a potential role as a reservoir of bioactive agents contributing to the observed antioxidant, anti-inflammatory, and health beneficial effects.
  12. Vaithilingam RD, Safii SH, Baharuddin NA, Karen-Ng LP, Saub R, Ariffin F, et al.
    Oral Dis, 2015 Jan;21(1):e62-9.
    PMID: 24930489 DOI: 10.1111/odi.12267
    Periodontal bio-repositories, which allow banking of clinically validated human data and biological samples, provide an opportunity to derive biomarkers for periodontal diagnosis, prognosis and therapeutic activities which are expected to improve patient management. This article presents the establishing of the Malaysian Periodontal Database and Biobank System (MPDBS) which was initiated in 2011 with the aim to facilitate periodontal research. Partnerships were established with collaborating centres. Policies on specimen access, authorship and acknowledgement policies were agreed upon by all participating centres before the initiation of the periodontal biobank. Ethical approval for the collection of samples and data were obtained from institutional ethics review boards. A broad-based approach for informed consent was used, which covered areas related to quality of life impacts, genetics and molecular aspects of periodontal disease. Sample collection and processing was performed using a standardized protocol. Biobanking resources such as equipment and freezers were shared with the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS). In the development of the MPDBS, challenges that were previously faced by the MOCDTBS were considered. Future challenges in terms of ethical and legal issues will be faced when international collaborations necessitate the transportation of specimens across borders.
  13. Ng AWR, Tan PJ, Hoo WPY, Liew DS, Teo MYM, Siak PY, et al.
    PeerJ, 2018;6:e5056.
    PMID: 30042874 DOI: 10.7717/peerj.5056
    Background: Somatic point substitution mutations in the KRAS proto-oncogene primarily affect codons 12/13 where glycine is converted into other amino acids, and are highly prevalent in pancreatic, colorectal, and non-small cell lung cancers. These cohorts are non-responsive to anti-EGFR treatments, and are left with non-specific chemotherapy regimens as their sole treatment options. In the past, the development of peptide vaccines for cancer treatment was reported to have poor AT properties when inducing immune responses. Utilization of bioinformatics tools have since become an interesting approach in improving the design of peptide vaccines based on T- and B-cell epitope predictions.

    Methods: In this study, the region spanning exon 2 from the 4th to 18th codon within the peptide sequence of wtKRAS was chosen for sequence manipulation. Mutated G12V and G13D K-ras controls were generated in silico, along with additional single amino acid substitutions flanking the original codon 12/13 mutations. IEDB was used for assessing human and mouse MHC class I/II epitope predictions, as well as linear B-cell epitopes predictions, while RNA secondary structure prediction was performed via CENTROIDFOLD. A scoring and ranking system was established in order to shortlist top mimotopes whereby normalized and reducing weighted scores were assigned to peptide sequences based on seven immunological parameters. Among the top 20 ranked peptide sequences, peptides of three mimotopes were synthesized and subjected to in vitro and in vivo immunoassays. Mice PBMCs were treated in vitro and subjected to cytokine assessment using CBA assay. Thereafter, mice were immunized and sera were subjected to IgG-based ELISA.

    Results: In silico immunogenicity prediction using IEDB tools shortlisted one G12V mimotope (68-V) and two G13D mimotopes (164-D, 224-D) from a total of 1,680 candidates. Shortlisted mimotopes were predicted to promote high MHC-II and -I affinities with optimized B-cell epitopes. CBA assay indicated that: 224-D induced secretions of IL-4, IL-5, IL-10, IL-12p70, and IL-21; 164-D triggered IL-10 and TNF-α; while 68-V showed no immunological responses. Specific-IgG sera titers against mutated K-ras antigens from 164-D immunized Balb/c mice were also elevated post first and second boosters compared to wild-type and G12/G13 controls.

    Discussion: In silico-guided predictions of mutated K-ras T- and B-cell epitopes were successful in identifying two immunogens with high predictive scores, Th-bias cytokine induction and IgG-specific stimulation. Developments of such immunogens are potentially useful for future immunotherapeutic and diagnostic applications against KRAS(+) malignancies, monoclonal antibody production, and various other research and development initiatives.

  14. De Simone B, Abu-Zidan FM, Chouillard E, Di Saverio S, Sartelli M, Podda M, et al.
    World J Emerg Surg, 2022 Dec 16;17(1):61.
    PMID: 36527038 DOI: 10.1186/s13017-022-00466-4
    BACKGROUND: The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not.

    METHODS: Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not.

    RESULTS: A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p 

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