Displaying publications 121 - 140 of 228 in total

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  1. Fulltext An interesting case of systemic lupus erythematosus presenting with hypercalcemia: A diagnostic dilemma
    Abdul Gafor AH, Cader RA, Das S, Masir N, Wahid FA
    Am J Case Rep, 2013;14:1-3.
    PMID: 23569551 DOI: 10.12659/AJCR.883849
    BACKGROUND: Hypercalcemia is common in primary hyperparathyroidism malignancies and even in tuberculosis. Interestingly, systemic lupus erythematosus (SLE) rarely presents with hypercalcemia.
    CASE REPORT: We describe an interesting case of SLE in a patient who was otherwise thought to have either tuberculosis or a malignancy. The patient initially presented with feeling unwell, with generalized lymphadenopathy, bilateral pleural effusion, and bilateral corneal calcium deposits secondary to severe hypercalcemia. The diagnosis of SLE was made based on positivity of antinuclear antibodies (ANA) and anti-dsDNA, the presence of serositis, lymphadenopathy, autoimmune hemolytic anemia, and constitutional symptoms. She was treated with steroids, with tremendous improvement in her general well-being, resolution of lymphadenopathy and pleural effusion, and normalization of her hemoglobin and serum calcium. The atypical presentation of SLE with hypercalcemia with pleural effusion is discussed.
    CONCLUSIONS: SLE should be one of the differential diagnoses in patients presenting with severe hypercalcemia.
    KEYWORDS: atypical presentation; hypercalcemia; systemic lupus erythematosus
  2. Effects of preeclampsia on the yield of hematopoietic stem cells obtained from umbilical cord blood at delivery
    Wahid FS, Nasaruddin MZ, Idris MR, Tusimin M, Tumian NR, Mahdy ZA
    J Obstet Gynaecol Res, 2012 Mar;38(3):490-7.
    PMID: 22381102 DOI: 10.1111/j.1447-0756.2011.01740.x
    To compare the numbers of cord blood CD34(+) hematopoietic stem cells (HSC) between preeclampsia (PE) and control (non-PE) subjects and to determine the factors that may influence this observation.
  3. Anti-amoebic properties of a Malaysian marine sponge Aaptos sp. on Acanthamoeba castellanii
    Nakisah MA, Ida Muryany MY, Fatimah H, Nor Fadilah R, Zalilawati MR, Khamsah S, et al.
    World J Microbiol Biotechnol, 2012 Mar;28(3):1237-44.
    PMID: 22805843 DOI: 10.1007/s11274-011-0927-8
    Crude methanol extracts of a marine sponge, Aaptos aaptos, collected from three different localities namely Kapas, Perhentian and Redang Islands, Terengganu, Malaysia, were tested in vitro on a pathogenic Acanthamoeba castellanii (IMR isolate) to examine their anti-amoebic potential. The examination of anti-Acanthamoebic activity of the extracts was conducted in 24 well plates for 72 h at 30 °C. All extracts possessed anti-amoebic activity with their IC(50) values ranging from 0.615 to 0.876 mg/mL. The effect of the methanol extracts on the surface morphology of A. castellanii was analysed under scanning electron microscopy. The ability of the extracts to disrupt the amoeba cell membrane was indicated by extensive cell's blebbing, changes in the surface morphology, reduced in cell size and with cystic appearance of extract-treated Acanthamoeba. Number of acanthapodia and food cup was also reduced in this Acanthamoeba. Morphological criteria of apoptosis in Acanthamoeba following treatment with the sponge's extracts was determined by acridine orange-propidium iodide staining and observed by fluorescence microscopy. By this technique, apoptotic and necrotic cells can be visualized and quantified. The genotoxic potential of the methanol extracts was performed by the alkaline comet assay. All methanol extracts used were significantly induced DNA damage compared to untreated Acanthamoeba by having high percentage of scores 1, 2, and 3 of the DNA damage. Results from cytotoxicity and genotoxicity studies carried out in the present study suggest that all methanol extracts of A. aaptos have anti-amoebic properties against A. castellanii.
  4. Real-time quantification for BCR-ABL transcripts in chronic myeloid leukaemia patients in UKMMC, Malaysia
    Wong FL, Hamidah NH, Hawa AA, Nurul AN, Leong CF, Saw F, et al.
    Malays J Pathol, 2011 Dec;33(2):107-12.
    PMID: 22299211
    Molecular pathogenesis of chronic myeloid leukemia (CML) is well established and molecular monitoring for patients with CML has become an important practice in the management of patients on imatinib therapy. In the present study, we report the use of RQ-PCR method for detection of BCR-ABL fusion gene for our CML cases. We performed a two-step RQ-PCR on bone marrow aspirates or peripheral blood of 37 CML patients. Quantitative expression of BCR-ABL fusion gene was carried out relative to the expression of a housekeeping gene as endogenous control to compensate for uneven cell numbers, RNA quality, or variations in reverse transcription efficiencies. Twenty-four of these patients were pre-treated with hydroxyurea or alpha interferon prior to the imatinib therapy. Their BCR-ABL fusion gene levels were monitored for 18 months. All samples processed were evaluable. The PCR amplification efficiency of the ABL gene is 90.5% (0.2158) and the BCR-ABL gene, 93.4% (0.1573).
  5. Roles of diet, lifetime physical activity and oxidative DNA damage in the occurrence of prostate cancer among men in Klang Valley, Malaysia
    Shahar S, Shafurah S, Hasan Shaari NS, Rajikan R, Rajab NF, Golkhalkhali B, et al.
    Asian Pac J Cancer Prev, 2011;12(3):605-11.
    PMID: 21627352
    BACKGROUND: There is a paucity of information on risk factors of prostate cancer, especially those related to dietary and lifestyle among Asian populations.

    OBJECTIVE: This study aimed to determine the relationship between dietary intake (macronutrients, fruits, vegetables and lycopene), lifetime physical activity and oxidative DNA damage with prostate cancer.

    DESIGN: A case control study was carried out among 105 subjects (case n=35, control n=70), matched for age and ethnicity. Data on sociodemographic, medical, dietary intake, consumption of lycopene rich food and lifetime physical activity were obtained through an interview based questionnaire. Anthropometric measurements including weight, height and waist hip circumferences were also carried out on subjects. A total of 3 mL fasting venous blood was drawn to assess lymphocyte oxidative DNA damage using the alkaline comet assay.

    RESULTS: Cases had a significantly higher intake of fat (27.7 ± 5.5%) as compared to controls (25.1 ± 5.9%) (p < 0.05). Mean intakes of fruits and vegetables (3.11 ± 1.01 servings/d)(p < 0.05), fruits (1.23 ± 0.59 servings/d) (p<0.05) and vegetables (1.97 ± 0.94 servings/d) were higher in controls than cases (2.53 ± 1.01, 0.91 ∓ 0.69, 1.62 ± 0.82 servings/d). A total of 71% of cases did not met the recommendation of a minimum of three servings of fruits and vegetables daily, as compared to 34% of controls (p < 0.05) (adjusted OR 6.52 (95% CI 2.3-17.8)) (p < 0.05). Estimated lycopene intake among cases (2,339 ∓ 1,312 mcg/d) were lower than controls (3881 ∓ 3120 mcg/d) (p< 0.01). Estimated lycopene intake of less than 2,498 mcg/day (50th percentile) increased risk of prostate cancer by double [Adjusted OR 2.5 (95%CI 0.99-6.31)]. Intake of tomatoes, watermelon, guava, pomelo, papaya, mango, oranges, dragon fruit, carrot, tomato sauce and barbeque sauce were higher in controls compared to cases. Intake of tomato sauce of more than 2.24 g/d (25th percentile), papaya more than 22.7 g/d (50th percentile) and oranges more than 19.1g/h (50th percentile) reduced prostate cancer risk by 7.4 (Adjusted OR 7.4 (95% CI 1.17-46.8)), 2.7 (adjusted OR 2.75 (95% CI 1.03-7.39)) and 2.6 times (adjusted OR = 2.6 (95% CI=1.01-6.67)), respectively (p < 0.05 for all parameters). No oxidative damage was observed among subjects. Past history of not engaging with any physical activities at the age of 45 to 54 years old increased risk of prostate cancer by approximately three folds (Adjusted OR 2.9(95% CI = 0.8-10.8)) (p < 0.05). In conclusion, low fat diet, high intake of fruits, vegetables and lycopene rich foods and being physical active at middle age were found to be protective. Thus, it is essential for Malaysian men to consume adequate fruits and vegetables, reduce fat intake and engage in physical activity in order to reduce prostate cancer risk.

  6. Fulltext Goniothalamin induces coronary artery smooth muscle cells apoptosis: the p53-dependent caspase-2 activation pathway
    Chan KM, Rajab NF, Siegel D, Din LB, Ross D, Inayat-Hussain SH
    Toxicol. Sci., 2010 Aug;116(2):533-48.
    PMID: 20498002 DOI: 10.1093/toxsci/kfq151
    Goniothalamin (GN), a styryl-lactone isolated from Goniothalamus andersonii, has been demonstrated to possess antirestenostic properties by inducing apoptosis on coronary artery smooth muscle cells (CASMCs). In this study, the molecular mechanisms of GN-induced CASMCs apoptosis were further elucidated. Apoptosis assessment based on the externalization of phosphatidylserine demonstrated that GN induces CASMCs apoptosis in a concentration-dependent manner. The GN-induced DNA damage occurred with concomitant elevation of p53 as early as 2 h, demonstrating an upstream signal for apoptosis. However, the p53 elevation in GN-treated CASMCs was independent of NAD(P)H: quinone oxidoreductase 1 and Mdm-2 expression. An increase in hydrogen peroxide and reduction in free thiols confirmed the role for oxidative stress in GN treatment. Pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-FMK) that significantly abrogated GN-induced CASMCs apoptosis suggested the involvement of caspase(s). The role of apical caspase-2, -8, and -9 was then investigated, and sequential activation of caspase-2 and -9 but not caspase-8 leading to downstream caspase-3 cleavage was observed in GN-treated CASMCs. Reduction of ATP level and decrease in oxygen consumption further confirmed the role of mitochondria in GN-induced apoptosis in CASMCs. The mitochondrial release of cytochrome c was seen without mitochondrial membrane potential loss and was independent of cardiolipin. These data provide insight into the mechanisms of GN-induced apoptosis, which may have important implications in the development of drug-eluting stents.
  7. Mutagenic and clastogenic characterization of poststerilized poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer biosynthesized by Delftia acidovorans
    Siew EL, Rajab NF, Osman AB, Sudesh K, Inayat-Hussain SH
    J Biomed Mater Res A, 2009 Dec;91(3):786-94.
    PMID: 19051306 DOI: 10.1002/jbm.a.32290
    Polyhydroxyalkanoates (PHA) are naturally occurring biopolyesters that have great potential in the medical field. However, the leachables resulting from sterilization process of the biomaterials may exert toxic effect including genetic damage. Here, we demonstrate that although gamma-irradiation of poly(3-hydroxybutyrate-co-50 mol % 4-hydroxybutyrate) [P(3HB-co-4HB)] did not cause any change in the morphology by scanning electron microscopy, there was a significant degradation of this copolymer where the molecular weight was reduced by 37% after sterilization indicating the generation of leachables. Therefore, further investigation on the ability of the extract of this poststerilized copolymer to induce mutagenic effect was performed using Ames test (S. typhimurium strains TA1535 and TA1537) and umu test (S. typhimurium strain TA1535/pSK1002). Additionally, the capability of the extract to induce clastogenic effect was determined using Chinese hamster lung V79 fibroblast cells. Our results showed that with and without the presence of S9 metabolic activation, no mutagenic effects were observed in both Ames and umu tests when treated with P(3HB-co-4HB) extract. Similarly, treatment of P(3HB-co-4HB) extract in V79 fibroblast cells showed no significant production of micronuclei when compared with the positive control (Mitomycin C). Together, these results indicate that leachables of poststerilized P(3HB-co-4HB) cause no mutagenic and clastogenic effects.
  8. In vitro biocompatibility evaluation of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer in fibroblast cells
    Siew EL, Rajab NF, Osman AB, Sudesh K, Inayat-Hussain SH
    J Biomed Mater Res A, 2007 May;81(2):317-25.
    PMID: 17120221
    Among the various biomaterials available for tissue engineering and therapeutic applications, microbial polyhydroxyalkanoates offer the most diverse range of thermal and mechanical properties. In this study, the biocompatibility of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB); containing 50 mol % of 4-hydroxybutyrate] copolymer produced by Delftia acidovorans was evaluated. The cytotoxicity, mode of cell death, and genotoxicity of P(3HB-co-4HB) extract against V79 and L929 fibroblast cells were assessed using MTT assay, acridine orange/propidium iodide staining, and alkaline comet assay, respectively. Our results demonstrate that P(3HB-co-4HB) treated on both cell lines were comparable with clinically-used Polyglactin 910, where more than 60% of viable cells were observed following 72-h treatment at 200 mg/mL. Further morphological investigation on the mode of cell death showed an increase in apoptotic cells in a time-dependent manner in both cell lines. On the other hand, P(3HB-co-4HB) at 200 mg/mL showed no genotoxic effects as determined by alkaline comet assay following 72-h treatment. In conclusion, our study indicated that P(3HB-co-4HB) compounds showed good biocompatibility in fibroblast cells suggesting that it has potential to be used for future medical applications.
  9. Microscopic evaluation of the natural coral (Porites spp.) post-implantation in sheep femur
    Fadilah A, Zuki AB, Loqman MY, Zamri-Saad M, Al-Salihi KA, Norimah Y, et al.
    Med J Malaysia, 2004 May;59 Suppl B:127-8.
    PMID: 15468851
    The study was carried out with the aim to evaluate natural coral (Porites spp.) implanted in sheep femur microscopically. Twelve adult, male sheep were used in this study. The defect area was implanted with coral and monitored for up to 12 weeks. The sheep were euthanased at 2,4,8, and 12 weeks post-implantation. Microscopically, natural coral implanted into bone tissue have shown gradual resorption and progressively replaced by new bone. At 12 weeks post-implantation, the implanted site was almost completely surrounded by mature bone. The results showed that natural coral was found to be a biodegradable and osteo-conductive biomaterial, which acted as a scaffold for a direct osteoblastic apposition.
  10. Fulltext Gelam honey protects against gamma-irradiation damage to antioxidant enzymes in human diploid fibroblasts
    Ahmad TA, Jubri Z, Rajab NF, Rahim KA, Yusof YA, Makpol S
    Molecules, 2013 Feb 11;18(2):2200-11.
    PMID: 23434870 DOI: 10.3390/molecules18022200
    The present study was designed to determine the radioprotective effects of Malaysian Gelam honey on gene expression and enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) of human diploid fibroblasts (HDFs) subjected to gamma-irradiation. Six groups of HDFs were studied: untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/mL of sterilized Gelam honey (w/v) for 24 h and exposed to 1 Gray (Gy) of gamma rays at the dose rate of 0.25 Gy/min. Gamma-irradiation was shown to down-regulate SOD1, SOD2, CAT and GPx1 gene expressions (p < 0.05). Conversely, HDFs treated with Gelam honey alone showed up-regulation of all genes studied. Similarly, SOD, CAT and GPx enzyme activities in HDFs decreased with gamma-irradiation and increased when cells were treated with Gelam honey (p < 0.05). Furthermore, of the three different stages of study treatment, pre-treatment with Gelam honey caused up-regulation of SOD1, SOD2 and CAT genes expression and increased the activity of SOD and CAT. As a conclusion, Gelam honey modulates the expression of antioxidant enzymes at gene and protein levels in irradiated HDFs indicating its potential as a radioprotectant agent.
  11. Fulltext Disseminated tuberculosis masquerading primary myelodysplastic syndrome
    Shaharir SS, Tumian NR, Yu Lin AB, Abdul Wahid SF
    J Infect Dev Ctries, 2013 Mar;7(3):286-8.
    PMID: 23493009 DOI: 10.3855/jidc.2691
    Tuberculosis is notoriously known to be a great mimicker of other diseases and may cause various haematologic abnormalities, especially with marrow involvement. A 61-year-old man who presented with right empyema and pancytopenia was diagnosed to have disseminated tuberculosis supported by the presence of caseating granuloma with Langhan's giant cells in the marrow and demonstration of acid-fast bacilli in the pleural fluid. Trilineage dysplasia from marrow aspirate was initially attributed to be reactive to the infection. A cytogenetic study was repeated after he showed poor response to a year of anti-tuberculosis treatment. The underlying primary myelodysplastic syndrome was unmasked when his cytogenetics showed trisomy 8. This case report has demonstrated the various haematological manifestations of tuberculosis and highlighted the importance of cytogenetic study in differentiating between primary and secondary myelodysplastic marrow changes.
  12. Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome
    Wan Jamaludin WF, Periyasamy P, Wan Mat WR, Abdul Wahid SF
    J Clin Virol, 2015 Aug;69:91-5.
    PMID: 26209387 DOI: 10.1016/j.jcv.2015.06.004
    Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin.
  13. Safety and efficacy of dermal fibroblast conditioned medium (DFCM) fortified collagen hydrogel as acellular 3D skin patch
    Maarof M, Mh Busra MF, Lokanathan Y, Bt Hj Idrus R, Rajab NF, Chowdhury SR
    Drug Deliv Transl Res, 2019 02;9(1):144-161.
    PMID: 30547385 DOI: 10.1007/s13346-018-00612-z
    Skin substitutes are one of the main treatments for skin loss, and a skin substitute that is readily available would be the best treatment option. However, most cell-based skin substitutes require long production times, and therefore, patients endure long waiting times. The proteins secreted from the cells and tissues play vital roles in promoting wound healing. Thus, we aimed to develop an acellular three-dimensional (3D) skin patch with dermal fibroblast conditioned medium (DFCM) and collagen hydrogel for immediate treatment of skin loss. Fibroblasts from human skin samples were cultured using serum-free keratinocyte-specific media (KM1 or KM2) and serum-free fibroblast-specific medium (FM) to obtain DFCM-KM1, DFCM-KM2, and DFCM-FM, respectively. The acellular 3D skin patch was soft, semi-solid, and translucent. Collagen mixed with DFCM-KM1 and DFCM-KM2 showed higher protein release compared to collagen plus DFCM-FM. In vitro and in vivo testing revealed that DFCM and collagen hydrogel did not induce an immune response. The implantation of the 3D skin patch with or without DFCM on the dorsum of BALB/c mice demonstrated a significantly faster healing rate compared to the no-treatment group 7 days after implantation, and all groups had complete re-epithelialization at day 17. Histological analysis confirmed the structure and integrity of the regenerated skin, with positive expression of cytokeratin 14 and type I collagen in the epidermal and dermal layer, respectively. These findings highlight the possibility of using fibroblast secretory factors together with collagen hydrogel in an acellular 3D skin patch that can be used allogeneically for immediate treatment of full-thickness skin loss.
  14. Fulltext Relationships between dietary nutrients intake and lipid levels with functional MRI dorsolateral prefrontal cortex activation
    Lau H, Shahar S, Mohamad M, Rajab NF, Yahya HM, Din NC, et al.
    Clin Interv Aging, 2019;14:43-51.
    PMID: 30613138 DOI: 10.2147/CIA.S183425
    Background: Dorsolateral prefrontal cortex (DLPFC) is a key node in the cognitive control network that supports working memory. DLPFC dysfunction is related to cognitive impairment. It has been suggested that dietary components and high-density lipoprotein cholesterol (HDL-C) play a vital role in brain health and cognitive function.

    Purpose: This study aimed to investigate the relationships between dietary nutrient intake and lipid levels with functional MRI (fMRI) brain activation in DLPFC among older adults with mild cognitive impairment.

    Participants and methods: A total of 15 community-dwelling older adults with mild cognitive impairment, aged ≥60 years, participated in this cross-sectional study at selected senior citizen clubs in Klang Valley, Malaysia. The 7-day recall Diet History Questionnaire was used to assess participants' dietary nutrient intake. Fasting blood samples were also collected for lipid profile assessment. All participants performed N-back (0- and 1-back) working memory tasks during fMRI scanning. DLPFC (Brodmann's areas 9 and 46, and inferior, middle, and superior frontal gyrus) was identified as a region of interest for analysis.

    Results: Positive associations were observed between dietary intake of energy, protein, cholesterol, vitamins B6 and B12, potassium, iron, phosphorus, magnesium, and HDL-C with DLPFC activation (P<0.05). Multivariate analysis showed that vitamin B6 intake, β=0.505, t (14)=3.29, P=0.023, and Digit Symbol score, β=0.413, t (14)=2.89, P=0.045; R2=0.748, were positively related to DLPFC activation.

    Conclusion: Increased vitamin B6 intake and cognitive processing speed were related to greater activation in the DLPFC region, which was responsible for working memory, executive function, attention, planning, and decision making. Further studies are needed to elucidate the mechanisms underlying the association.

  15. Bacterial cellulose/acrylic acid hydrogel synthesized via electron beam irradiation: accelerated burn wound healing in an animal model
    Mohamad N, Mohd Amin MCI, Pandey M, Ahmad N, Rajab NF
    Carbohydr Polym, 2014 Dec 19;114:312-320.
    PMID: 25263896 DOI: 10.1016/j.carbpol.2014.08.025
    Natural polymer-based hydrogels are of interest to health care professionals as wound dressings owing to their ability to absorb exudates and provide hydration for healing. The aims of this study were to develop and characterize bacterial cellulose/acrylic acid (BC/AA) hydrogels synthesized by electron beam irradiation and investigate its wound healing potential in an animal model. The BC/AA hydrogels were characterized by SEM, tensile strength, water absorptivity, and water vapor transmission rate (WVTR). The cytotoxicity of the hydrogels was investigated in L929 cells. Skin irritation and wound healing properties were evaluated in Sprague-Dawley rats. BC/AA hydrogels had a macroporous network structure, high swelling ratio (4000-6000% at 24h), and high WVTR (2175-2280 g/m(2)/day). The hydrogels were non-toxic in the cell viability assay. In vivo experiments indicated that hydrogels promoted faster wound-healing, enhanced epithelialization, and accelerated fibroblast proliferation compared to that in the control group. These results suggest that BC/AA hydrogels are promising materials for burn dressings.
  16. Fulltext In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors
    Zulkipli NN, Zakaria R, Long I, Abdullah SF, Muhammad EF, Wahab HA, et al.
    Molecules, 2020 Sep 02;25(17).
    PMID: 32887218 DOI: 10.3390/molecules25173991
    Natural products remain a popular alternative treatment for many ailments in various countries. This study aimed to screen for potential mammalian target of rapamycin (mTOR) inhibitors from Malaysian natural substance, using the Natural Product Discovery database, and to determine the IC50 of the selected mTOR inhibitors against UMB1949 cell line. The crystallographic structure of the molecular target (mTOR) was obtained from Protein Data Bank, with Protein Data Bank (PDB) ID: 4DRI. Everolimus, an mTOR inhibitor, was used as a standard compound for the comparative analysis. Computational docking approach was performed, using AutoDock Vina (screening) and AutoDock 4.2.6 (analysis). Based on our analysis, asiaticoside and its derivative, asiatic acid, both from Centella asiatica, revealed optimum-binding affinities with mTOR that were comparable to our standard compound. The effect of asiaticoside and asiatic acid on mTOR inhibition was validated with UMB1949 cell line, and their IC50 values were 300 and 60 µM, respectively, compared to everolimus (29.5 µM). Interestingly, this is the first study of asiaticoside and asiatic acid against tuberous sclerosis complex (TSC) disease model by targeting mTOR. These results, coupled with our in silico findings, should prompt further studies, to clarify the mode of action, safety, and efficacy of these compounds as mTOR inhibitors.
  17. Fulltext Intermittent Fasting Enhanced the Cognitive Function in Older Adults with Mild Cognitive Impairment by Inducing Biochemical and Metabolic changes: A 3-Year Progressive Study
    Ooi TC, Meramat A, Rajab NF, Shahar S, Ismail IS, Azam AA, et al.
    Nutrients, 2020 Aug 30;12(9).
    PMID: 32872655 DOI: 10.3390/nu12092644
    Intermittent fasting (IF) refers to various dietary regimens that cycle between a period of non-fasting and a period of total fasting. This study aimed to determine the effects of IF on cognitive function among elderly individuals who practice IF who have mild cognitive impairment (MCI). A total of 99 elderly subjects with MCI of Malay ethnicity without any terminal illness were recruited from a larger cohort study, LRGS TUA. The subjects were divided into three groups, comprising those who were regularly practicing IF (r-IF), irregularly practicing IF (i-IF), and non-fasters (n-IF). Upon 36 months of follow-up, more MCI subjects in the r-IF group reverted to successful aging with no cognitive impairment and diseases (24.3%) compared to those in i-IF (14.2%) and n-IF groups (3.7%). The r-IF group's subjects exhibited significant increment in superoxide dismutase (SOD) activity and reduction in body weight, levels of insulin, fasting blood glucose, malondialdehyde (MDA), C-reactive protein (CRP), and DNA damage. Moreover, metabolomics analysis showed that IF may modulate cognitive function via various metabolite pathways, including the synthesis and degradation of ketone bodies, butanoate metabolism, pyruvate metabolism, and glycolysis and gluconeogenesis pathways. Overall, the MCI-afflicted older adults who practiced IF regularly had better cognitive scores and reverted to better cognitive function at 36 months follow-up.
  18. Fulltext Urine Untargeted Metabolomic Profiling Is Associated with the Dietary Pattern of Successful Aging among Malaysian Elderly
    Nik Mohd Fakhruddin NNI, Shahar S, Ismail IS, Ahmad Azam A, Rajab NF
    Nutrients, 2020 Sep 23;12(10).
    PMID: 32977370 DOI: 10.3390/nu12102900
    Food intake biomarkers (FIBs) can reflect the intake of specific foods or dietary patterns (DP). DP for successful aging (SA) has been widely studied. However, the relationship between SA and DP characterized by FIBs still needs further exploration as the candidate markers are scarce. Thus, 1H-nuclear magnetic resonance (1H-NMR)-based urine metabolomics profiling was conducted to identify potential metabolites which can act as specific markers representing DP for SA. Urine sample of nine subjects from each three aging groups, SA, usual aging (UA), and mild cognitive impairment (MCI), were analyzed using the 1H-NMR metabolomic approach. Principal components analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were applied. The association between SA urinary metabolites and its DP was assessed using the Pearson's correlation analysis. The urine of SA subjects was characterized by the greater excretion of citrate, taurine, hypotaurine, serotonin, and melatonin as compared to UA and MCI. These urinary metabolites were associated with alteration in "taurine and hypotaurine metabolism" and "tryptophan metabolism" in SA elderly. Urinary serotonin (r = 0.48, p < 0.05) and melatonin (r = 0.47, p < 0.05) were associated with oat intake. These findings demonstrate that a metabolomic approach may be useful for correlating DP with SA urinary metabolites and for further understanding of SA development.
  19. The Roles of Tissue Rigidity and Its Underlying Mechanisms in Promoting Tumor Growth
    Zakaria MA, Rajab NF, Chua EW, Selvarajah GT, Masre SF
    Cancer Invest, 2020 Sep;38(8-9):445-462.
    PMID: 32713210 DOI: 10.1080/07357907.2020.1802474
    Tissues become more rigid during tumorigenesis and have been identified as a driving factor for tumor growth. Here, we highlight the concept of tissue rigidity, contributing factors that increase tissue rigidity, and mechanisms that promote tumor growth initiated by increased tissue rigidity. Various factors lead to increased tissue rigidity, promoting tumor growth by activating focal adhesion kinase (FAK) and Rho-associated kinase (ROCK). Consequently, result in recruitment of cancer-associated fibroblasts (CAFs), epithelial-mesenchymal transition (EMT) and tumor protection from immunosurveillance. We also discussed the rationale for targeting tumor tissue rigidity and its potential for cancer treatment.
  20. Fulltext Incidence and multidimensional predictors of occasional and recurrent falls among Malaysian community-dwelling older persons
    Ooi TC, Singh DKA, Shahar S, Rajab NF, Vanoh D, Sharif R, et al.
    BMC Geriatr, 2021 03 02;21(1):154.
    PMID: 33653312 DOI: 10.1186/s12877-021-02103-2
    BACKGROUND: Falls incidence rate and comprehensive data on factors that predict occasional and repeated falls from large population-based studies are scarce. In this study, we aimed to determine the incidence of falls and identify predictors of occasional and recurrent falls. This was done in the social, medical, physical, nutritional, biochemical, cognitive dimensions among community-dwelling older Malaysians.

    METHODS: Data from 1,763 Malaysian community-dwelling older persons aged ≥ 60 years were obtained from the LRGS-TUA longitudinal study. Participants were categorized into three groups according to the presence of a single fall (occasional fallers), ≥two falls (recurrent fallers), or absence of falls (non-fallers) at an 18-month follow-up.

    RESULTS: Three hundred and nine (17.53 %) participants reported fall occurrences at an 18-month follow-up, of whom 85 (27.51 %) had two or more falls. The incidence rate for occasional and recurrent falls was 8.47 and 3.21 per 100 person-years, respectively. Following multifactorial adjustments, being female (OR: 1.57; 95 % CI: 1.04-2.36), being single (OR: 5.31; 95 % CI: 3.36-37.48), having history of fall (OR: 1.86; 95 % CI: 1.19-2.92) higher depression scale score (OR: 1.10; 95 % CI: 1.02-1.20), lower hemoglobin levels (OR: 0.90; 95 % CI: 0.81-1.00) and lower chair stand test score (OR: 0.93; 95 % CI: 0.87-1.00) remained independent predictors of occasional falls. While, having history of falls (OR: 2.74; 95 % CI: 1.45-5.19), being a stroke survivor (OR: 8.57; 95 % CI: 2.12-34.65), higher percentage of body fat (OR: 1.04; 95 % CI: 1.01-1.08) and lower chair stand test score (OR: 0.87; 95 % CI: 0.77-0.97) appeared as recurrent falls predictors.

    CONCLUSIONS: Having history of falls and lower muscle strength were predictors for both occasional and recurrent falls among Malaysian community-dwelling older persons. Modifying these predictors may be beneficial in falls prevention and management strategies among older persons.

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