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Rapid treatment of full-thickness skin loss using ovine tendon collagen type I scaffold with skin cells

Mh Busra F, Rajab NF, Tabata Y, Saim AB, B H Idrus R, Chowdhury SR

J Tissue Eng Regen Med, 2019 05;13(5):874-891.
PMID: 30811090 DOI: 10.1002/term.2842

The full-thickness skin wound is a common skin complication affecting millions of people worldwide. Delayed treatment of this condition causes the loss of skin function and integrity that could lead to the development of chronic wounds or even death. This study was aimed to develop a rapid wound treatment modality using ovine tendon collagen type I (OTC-I) bio-scaffold with or without noncultured skin cells. Genipin (GNP) and carbodiimide (EDC) were used to cross-link OTC-I scaffold to improve the mechanical strength of the bio-scaffold. The physicochemical, biomechanical, biodegradation, biocompatibility, and immunogenicity properties of OTC-I scaffolds were investigated. The efficacy of this treatment approach was evaluated in an in vivo skin wound model. The results demonstrated that GNP cross-linked OTC-I scaffold (OTC-I_GNP) had better physicochemical and mechanical properties compared with EDC cross-linked OTC-I scaffold (OTC-I_EDC) and noncross-link OTC-I scaffold (OTC-I_NC). OTC-I_GNP and OTC-I_NC demonstrated no toxic effect on cells as it promoted higher cell attachment and proliferation of both primary human epidermal keratinocytes and human dermal fibroblasts compared with OTC-I_EDC. Both OTC-I_GNP and OTC-I_NC exhibited spontaneous formation of bilayer structure in vitro. Immunogenic evaluation of OTC-I scaffolds, in vitro and in vivo, revealed no sign of immune response. Finally, implantation of OTC-I_NC and OTC-I_GNP scaffolds with noncultured skin cells demonstrated enhanced healing with superior skin maturity and microstructure features, resembling native skin in contrast to other treatment (without noncultured skin cells) and control group. The findings of this study, therefore, suggested that both OTC-I scaffolds with noncultured skin cells could be promising for the rapid treatment of full-thickness skin wound.
Cell-based therapies for amyotrophic lateral sclerosis/motor neuron disease

Abdul Wahid SF, Law ZK, Ismail NA, Azman Ali R, Lai NM

Cochrane Database Syst Rev, 2016 11 08;11:CD011742.
PMID: 27822919

BACKGROUND: Amyotrophic lateral sclerosis (ALS), which is also known as motor neuron disease (MND) is a fatal disease associated with rapidly progressive disability, for which no definitive treatment as yet exists. Current treatment regimens largely focus on relieving symptoms to improve the quality of life of those affected. Based on data from preclinical studies, cell-based therapy is a promising treatment for ALS/MND.
OBJECTIVES: To assess the effects of cell-based therapy for people with ALS/MND, compared with placebo or no additional treatment.
SEARCH METHODS: On 21 June 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, and Embase. We also searched two clinical trials' registries for ongoing or unpublished studies.
SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs), quasi-RCTs and cluster RCTs that assigned people with ALS/MND to receive cell-based therapy versus a placebo or no additional treatment. Co-interventions were allowable, provided that they were given to each group equally.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology.
MAIN RESULTS: No studies were eligible for inclusion in the review. We identified four ongoing trials.
AUTHORS' CONCLUSIONS: Currently, there is a lack of high-quality evidence to guide practice on the use of cell-based therapy to treat ALS/MND.We need large, prospective RCTs to establish the efficacy of cellular therapy and to determine patient-, disease- and cell treatment-related factors that may influence the outcome of cell-based therapy. The major goals of future research should be to determine the appropriate cell source, phenotype, dose, and route of delivery, as these will be key elements in designing an optimal cell-based therapy programme for people with ALS/MND. Future research should also explore novel treatment strategies, including combinations of cellular therapy and standard or novel neuroprotective agents, to find the best possible approach to prevent or reverse the neurological deficit in ALS/MND, and to prolong survival in this debilitating and fatal condition.
Fulltext Evaluation of phytoestrogens in inducing cell death mediated by decreasing Annexin A1 in Annexin A1-knockdown leukemia cells

Hasan M, Kumolosasi E, Jasamai M, Jamal JA, Azmi N, Rajab NF

Daru, 2020 Jun;28(1):97-108.
PMID: 31912375 DOI: 10.1007/s40199-019-00320-0

BACKGROUND: Phytoestrogens are plant compounds that are structurally similar to estrogen and that possess anti-cancer properties. Previous studies have reported that coumestrol, daidzein and genistein could induce cell death by reducing Annexin A1 protein in leukemic cell lines. Annexin A1 (ANXA1) is involved in cell progression, metastasis, and apoptosis in several types of cancer cells. The present study sought to investigate if the effects of phytoestrogens on apoptosis, cell cycle arrest and phagocytosis in ANXA1-knockdown leukemic cells are mediated through ANXA1 or occurred independently.
METHODS: Transfection of ANXA1 siRNA was conducted to downregulate ANXA1 expression in Jurkat, K562 and U937 cells. Apoptosis and cell cycle assays were conducted using flow cytometry. Western blot was performed to evaluate ANXA1, caspases and Bcl-2 proteins expression. Phagocytosis was determined using hematoxylin and eosin staining.
RESULTS: The expression of ANXA1 after the knockdown was significantly downregulated in all cell lines. Genistein significantly induced apoptosis associated with an upregulation of procaspase-3, -9, and - 1 in Jurkat cells. The Bcl-2 expression showed no significant difference in Jurkat, K562 and U937 cells. Treatment with phytoestrogens increased procaspase-1 expression in Jurkat and U937 cells while no changes were detected in K562 cells. Flow cytometry analysis demonstrated that after ANXA1 knockdown, coumestrol and genistein caused cell cycle arrest at G2/M phase in selected type of cells. The percentage of phagocytosis and phagocytosis index increased after the treatment with phytoestrogens in all cell lines.
CONCLUSION: Phytoestrogens induced cell death in ANXA1-knockdown leukemia cells, mediated by Annexin A1 proteins. Graphical abstract.
Fulltext The effects of six months Persicaria minor extract supplement among older adults with mild cognitive impairment: a double-blinded, randomized, and placebo-controlled trial

Lau H, Shahar S, Mohamad M, Rajab NF, Yahya HM, Din NC, et al.

BMC Complement Med Ther, 2020 Oct 19;20(1):315.
PMID: 33076878 DOI: 10.1186/s12906-020-03092-2

BACKGROUND: Persicaria minor extract exhibits antioxidant and anti-inflammatory properties and has potential effects on cognitive function and mood. However, the effects of P.minor on brain activation and biomarkers have not been studied among older adults. This multicentre, randomized, double-blinded, placebo-controlled study aimed to investigate the effect of 6 months P.minor extract supplement (Biokesum®) on cognition, mood, biomarkers, and brain activation among older adults with Mild Cognitive Impairment (MCI).
METHOD: A total of 36 Malaysian community-dwelling older adults with MCI (60-75-year-old) were randomized into Biokesum® (n = 18) and placebo group (n = 18). Each subject consumed one capsule of Biokesum® (250 mg/capsule) or placebo (maltodextrin, 280 mg/capsule) twice daily for 6 months. Cognitive function and mood were assessed at baseline, 3rd, and 6th-month using neuropsychological tests (MMSE, Digit Span, RAVLT, Digit Symbol, and Visual Reproduction) and Profile of Mood State (POMS) questionnaire. Blood lipid profile, fasting blood glucose, and biomarkers (MDA, LPO, COX-2, iNOS, and BDNF) were measured at baseline and 6th month. By the end of the intervention, there were 30 compliers (Biokesum®: N = 15; Placebo: N = 15) and 6 dropouts. For brain activation assessment, 15 subsamples (Biokesum®: N = 8; Placebo: N = 7) completed N-back and Stroop tasks during fMRI scanning at baseline and 6th month. The dorsolateral prefrontal cortex (Brodmann's area 9 and 46) was identified as a region of interest (ROI) for brain activation analysis using SPM software.
RESULTS: Two-way mixed ANOVA analysis showed significant improvements in Visual Reproduction II (p = 0.012, partial η2 = 0.470), tension (p = 0.042, partial η2 = 0.147), anger (p = 0.010, partial η2 = 0.207), confusion (p = 0.041, partial η2 = 0.148), total negative subscales (p = 0.043, partial η2 = 0.145), BDNF (p = 0.020, partial η2 = 0.179) and triglyceride (p = 0.029, partial η2 = 0.237) following 6 months of Biokesum® supplementation. Preliminary finding also demonstrated significant improvement at 0-back task-induced right DLPFC activation (p = 0.028, partial η2 = 0.652) among subsamples in Biokesum® group. No adverse events were reported at the end of the study.
CONCLUSION: Six months Biokesum® supplementation potentially improved visual memory, negative mood, BDNF, and triglyceride levels among older adults with MCI. Significant findings on brain activation at the right DPLFC must be considered as preliminary.
TRIAL REGISTRATION: Retrospectively registered on 30th August 2019 [ ISRC TN12417552 ].
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.
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.
Fulltext In vitro toxicological assessment of gadolinium (III) chloride in V79-4 fibroblasts

Siew EL, Farris AF, Rashid N, Chan KM, Rajab NF

Genes Environ, 2020;42:22.
PMID: 32537035 DOI: 10.1186/s41021-020-00161-3

Background: Rare earth minerals of the lanthanide series are widely used in the field of medical and clinical application. Gadolinium (Gd), the most preferred rare earth mineral is frequently used as magnets, superconductors and magnetic resonance imaging (MRI) contrast agent. Increasing production of gadolinium waste, known potent toxicity of this element and lack of information on its Material Safety Data Sheet (MSDS) prompts health risk assessment on gadolinium. In this study, cytotoxicity and genotoxicity of Gadolinium (III) chloride (GdCl3) were investigated using MTT assay, Alkaline Comet assay and Micronucleus assay, respectively.
Results: Our results demonstrated that the viability of GdCl3 treated V79-4 cells was significantly (p 0.05) DNA damage both in the presence and absence of metabolic activation. However, it induced significant (p
Fulltext Bone Marrow Oxidative Stress and Acquired Lineage-Specific Genotoxicity in Hematopoietic Stem/Progenitor Cells Exposed to 1,4-Benzoquinone

Mathialagan RD, Abd Hamid Z, Ng QM, Rajab NF, Shuib S, Binti Abdul Razak SR

Int J Environ Res Public Health, 2020 08 13;17(16).
PMID: 32823552 DOI: 10.3390/ijerph17165865

Hematopoietic stem/progenitor cells (HSPCs) are susceptible to benzene-induced genotoxicity. However, little is known about the mechanism of DNA damage response affecting lineage-committed progenitors for myeloid, erythroid, and lymphoid. Here, we investigated the genotoxicity of a benzene metabolite, 1,4-benzoquinone (1,4-BQ), in HSPCs using oxidative stress and lineage-directed approaches. Mouse bone marrow cells (BMCs) were exposed to 1,4-BQ (1.25-12 μM) for 24 h, followed by oxidative stress and genotoxicity assessments. Then, the genotoxicity of 1,4-BQ in lineage-committed progenitors was evaluated using colony forming cell assay following 7-14 days of culture. 1,4-BQ exposure causes significant decreases (p < 0.05) in glutathione level and superoxide dismutase activity, along with significant increases (p < 0.05) in levels of malondialdehyde and protein carbonyls. 1,4-BQ exposure induces DNA damage in BMCs by significantly (p < 0.05) increased percentages of DNA in tail at 7 and 12 μM and tail moment at 12 μM. We found crucial differences in genotoxic susceptibility based on percentages of DNA in tail between lineage-committed progenitors. Myeloid and pre-B lymphoid progenitors appeared to acquire significant DNA damage as compared with the control starting from a low concentration of 1,4-BQ exposure (2.5 µM). In contrast, the erythroid progenitor showed significant damage as compared with the control starting at 5 µM 1,4-BQ. Meanwhile, a significant (p < 0.05) increase in tail moment was only notable at 7 µM and 12 µM 1,4-BQ exposure for all progenitors. Benzene could mediate hematological disorders by promoting bone marrow oxidative stress and lineage-specific genotoxicity targeting HSPCs.
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.
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.
Fulltext Serum Metabolomics Profiling of Commercially Mixed Functional Foods-Effects in Beta-Amyloid Induced Rats Measured Using 1H NMR Spectroscopy

Rosli NHM, Yahya HM, Ibrahim FW, Shahar S, Ismail IS, Azam AA, et al.

Nutrients, 2020 Dec 12;12(12).
PMID: 33322743 DOI: 10.3390/nu12123812

Functional foods such as pomegranate, dates and honey were shown by various previous studies to individually have a neuroprotective effect, especially in neurodegenerative disease such as Alzheimer's disease (AD). In this novel and original study, an 1H NMR spectroscopy tool was used to identify the metabolic neuroprotective mechanism of commercially mixed functional foods (MFF) consisting of pomegranate, dates and honey, in rats injected with amyloid-beta 1-42 (Aβ-42). Forty-five male albino Wistar rats were randomly divided into five groups: NC (0.9% normal saline treatment + phosphate buffer solution (PBS) solution injection), Abeta (0.9% normal saline treatment + 0.2 µg/µL Aβ-42 injection), MFF (4 mL/kg MFF treatment + PBS solution injection), Abeta-MFF (4 mL/kg MFF treatment + 0.2 µg/µL Aβ-42 injection) and Abeta-NAC (150 mg/kg N-acetylcysteine + 0.2 µg/µL Aβ-42 injection). Based on the results, the MFF and NAC treatment improved the spatial memory and learning using Y-maze. In the metabolic analysis, a total of 12 metabolites were identified, for which levels changed significantly among the treatment groups. Systematic metabolic pathway analysis found that the MFF and NAC treatments provided a neuroprotective effect in Aβ-42 injected rats by improving the acid amino and energy metabolisms. Overall, this finding showed that MFF might serve as a potential neuroprotective functional food for the prevention of AD.
Roles of Rho‑associated kinase in lung cancer (Review)

Zakaria MA, Rajab NF, Chua EW, Selvarajah GT, Masre SF

Int J Oncol, 2021 02;58(2):185-198.
PMID: 33491756 DOI: 10.3892/ijo.2020.5164

Lung cancer is one of the most lethal forms of cancer known to man, affecting millions of individuals worldwide. Despite advancements being made in lung cancer treatments, the prognosis of patients with the disease remains poor, particularly among patients with late‑stage lung cancer. The elucidation of the signaling pathways involved in lung cancer is a critical approach for the treatment of the disease. Over the past decades, accumulating evidence has revealed that Rho‑associated kinase (ROCK) is overexpressed in lung cancer and is associated with tumor growth. The present review discusses recent findings of ROCK signaling in the pathogenesis of lung cancer that were conducted in pre‑clinical studies. The significant role of ROCK in cancer cell apoptosis, proliferation, migration, invasion and angiogenesis is discussed. The present review also suggests the use of ROCK as a potential target for the development of lung cancer therapies, as ROCK inhibition can reduce multiple hallmarks of cancer, particularly by decreasing cancer cell migration, which is an initial step of metastasis.
Fulltext Rituximab-induced lung disease

Wan Zaidi WA, Wan Jamaludin WF, Tumian NR, Abdul Wahid F

Med J Malaysia, 2016 Aug;71(4):209-210.
PMID: 27770123 MyJurnal DOI: 10.1183/09031936.00080209

Pulmonary toxicity is a rare complication of Rituximab therapy. Although Rituximab is relatively safe and can be administered in an outpatient setting, Rituximab-associated lung disease has been reported and may cause mortality despite early detection. Typically the pulmonary toxicity occurs at around the fourth cycle of Rituximab. High index of suspicion is crucial and other concurrent pathology such as infective causes should be excluded. Radiological imaging and histological confirmation should be obtained and early treatment with corticosteroid should be initiated. Patients should receive counselling regarding respiratory symptoms and possible pulmonary toxicity.
Fulltext Immunomodulatory potential of Clinacanthus nutans extracts in the co-culture of triple-negative breast cancer cells, MDA-MB-231, and THP-1 macrophages

Nordin FJ, Pearanpan L, Chan KM, Kumolosasi E, Yong YK, Shaari K, et al.

PLoS One, 2021;16(8):e0256012.
PMID: 34379689 DOI: 10.1371/journal.pone.0256012

Triple-negative breast cancer is the main type of breast carcinoma that causes mortality among women because of the limited treatment options and high recurrence. Chronic inflammation has been linked with the tumor microenvironment (TME) in breast cancer progression. Clinacanthus nutans (CN) has gained much attention because of its anticancer properties, but its mechanism remains unclear. We aimed to study the qualitative phytochemical content and elucidate the cytotoxicity effects of CN on human triple-negative breast cancer (TNBC), MDA-MB-231 and human macrophage-like cells such as THP-1 by using sulforhodamine B (SRB) assay. As highly metastatic cells, MDA-MB-231 cells can migrate to the distal position, the effect of CN on migration were also elucidated using the scratch assay. The CN effects on ameliorating chronic inflammation in TME were studied following the co-culture of MDA-MB-231/THP-1 macrophages. The cytokine expression levels of IL-6, IL-1β and tumor necrosis factor-alpha (TNF-α) were determined using ELISA assays. The results showed that both ethanolic and aqueous CN extracts contained alkaloid, phenol and tannin, flavonoid, terpenoid, glycoside and steroid. However, saponin was only found in the aqueous extract of CN. CN was not cytotoxic to both MDA-MB-231 and THP-1 cells. The ability of MDA-MB-231 to migrate was also not halted by CN treatment. However, CN ethanol extract decreased IL-6 at 25 μg/mL (p = 0.02) and 100 μg/mL (p = 0.03) but CN aqueous extract increased IL-6 expression at 50 μg/mL (p = 0.08) and 100 μg/mL (p = 0.02). IL-1β showed decreased expression after treated with CN ethanol and CN aqueous both at 25 μg/mL (p = 0.03). TNF-α were significantly decreased after CN ethanol treatment at concentration 25- (p = 0.001), 50- (p = 0.000) and 100 μg/mL (p = 0.000). CN aqueous extract slightly inhibited TNF-α at all 25-50- and 100 μg/mL (p = 0.001, p = 0.000, p = 0.000, respectively). Overall, CN acts by ameliorating the pro-inflammatory condition in the TME and may be a potential strategy for its anticancer mechanism on highly metastatic breast cancer condition. The major pathways that link both cancer and inflammation were NF-κB and STATs thus further study on the upstream and downstream pathways is needed to fully understand the mechanism of CN extracts in cooling the inflamed TME in breast cancer.
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.
Higher levels of lead and aluminium are associated with increased risk of falls among community-dwelling older adults: An 18-month follow-up study

Ooi TC, Singh DKA, Shahar S, Rajab NF, Sharif R

Geriatr Gerontol Int, 2021 Nov;21(11):1026-1032.
PMID: 34590402 DOI: 10.1111/ggi.14284

AIM: The present study aims to determine the association of trace elements and oxidative and DNA damage biomarkers with fall incidence among community-dwelling older adults.
METHODS: This study is part of the Long-term Research Grant Scheme - Towards Useful Ageing cohort study in Malaysia. Of a total of 174 participants with complete trace elements and oxidative and DNA damage data during baseline, only 147 (84.5%) were successfully followed up after 18 months. Participants who experienced any fall events in the previous 18 months during the follow-up were categorized as fallers.
RESULTS: Thirty participants (20.4%) reported at least one fall in the previous 18 months. The mean concentrations of aluminium, lead and zinc were significantly higher (P
Fulltext Clastogenicity and Aneugenicity of 1,4-Benzoquinone in Different Lineages of Mouse Hematopoietic Stem/Progenitor Cells

Chow PW, Abd Hamid Z, Mathialagan RD, Rajab NF, Shuib S, Sulong S

Toxics, 2021 May 12;9(5).
PMID: 34065823 DOI: 10.3390/toxics9050107

Previous reports on hematotoxicity and leukemogenicity related to benzene exposure highlighted its adverse effects on hematopoiesis. Despite the reported findings, studies concerning the mechanism of benzene affecting chromosomal integrity in lineage-committed hematopoietic stem/progenitor cells (HSPCs) remain unclear. Here, we studied the clastogenicity and aneugenicity of benzene in lineage-committed HSPCs via karyotyping. Isolated mouse bone marrow cells (MBMCs) were exposed to the benzene metabolite 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, 5, 7, and 12 μM for 24 h, followed by karyotyping. Then, the chromosomal aberration (CA) in 1,4-BQ-exposed hematopoietic progenitor cells (HPCs) comprising myeloid, Pre-B lymphoid, and erythroid lineages were evaluated following colony-forming cell (CFC) assay. Percentage of CA, predominantly via Robertsonian translocation (Rb), was increased significantly (p < 0.05) in MBMCs and all progenitors at all concentrations. As a comparison, Pre-B lymphoid progenitor demonstrated a significantly higher percentage of CA (p < 0.05) than erythroid progenitor at 1.25, 2.5, and 7 μM as well as a significantly higher percentage (p < 0.05) than myeloid progenitor at 7 μM of 1,4-BQ. In conclusion, 1,4-BQ induced CA, particularly via Rb in both MBMCs and HPCs, notably via a lineage-dependent response. The role of lineage specificity in governing the clastogenicity and aneugenicity of 1,4-BQ deserves further investigation.
Neuroimaging Functional Magnetic Resonance Imaging Task-Based Dorsolateral Prefrontal Cortex Activation Following 12 Weeks of Cosmos caudatus Supplementation Among Older Adults With Mild Cognitive Impairment

You YX, Shahar S, Mohamad M, Rajab NF, Haron H, Che Din N, et al.

J Magn Reson Imaging, 2021 12;54(6):1804-1818.
PMID: 34080265 DOI: 10.1002/jmri.27762

BACKGROUND: Cosmos caudatus (CC) is traditional Asian vegetable, commonly consumed among the Southeast Asian population. It has been reported to be high in flavonoids and might potentially improve brain activity among older adults with mild cognitive impairment (MCI). The effect of CC in brain activation improvement using neuroimaging is yet to be discovered.
PURPOSE: To investigate the effects of CC supplement on brain activity using functional magnetic resonance imaging (fMRI) among older adults with MCI.
STUDY TYPE: Prospective, randomized, double-blind, placebo-controlled trial.
POPULATION/SUBJECTS: Twenty older adults with mild cognitive impairment (60-75 years old), 14 of them (70%) were female subjects.
FIELD STRENGTH/SEQUENCE: A 3.0-T, T1-weighted anatomical images, T2*-weighted imaging data, A single shot, gradient echo-echo planar imaging (EPI) sequence.
ASSESSMENT: All subjects were asked to consume two 500 mg capsules of either CC supplement or placebo (maltodextrin) daily for 12 weeks. Cognitive function was measured using validated neuropsychological tests (i.e. Mini-mental State Examination and Digit Span) and task-based fMRI (N-back and Stroop Color Word Test) at baseline and 12th week. Brodmann's area 9, 46 and anterior cingulate cortex were selected as the regions of interest to define dorsolateral prefrontal cortex (DLPFC) in fMRI analysis.
STATISTICAL TESTS: Normality test was performed with the Shapiro-Wilk test. Two-way repeated ANOVA determined the intervention effects of the CC supplementation on brain activity after adjustments for covariates. Significance level at P
Fulltext Denosumab as the Treatment of Recalcitrant Tuberculous Pleural Effusion-Associated Hypercalcemia

Abd Jalil AA, Wan Muhamad Hatta SF, Mohamad AF, Abdul Rani MF

Case Rep Med, 2021;2021:5544848.
PMID: 33986809 DOI: 10.1155/2021/5544848

Denosumab is a human monoclonal antibody that binds to RANKL (receptor activator of nuclear factor-kappa B ligand). It has mainly been used in the treatment of osteoporosis for a variety of causes especially in situations refractory to bisphosphonates or when kidney function is impaired. It is also used in cases of malignancy-associated hypercalcemia. There are many causes of hypercalcemia, but only rarely it is associated with granulomatous diseases such as tuberculous pleural effusion. We report a case of hypercalcemia from tuberculous pleural effusion that was initially admitted with left medium abundance pleural effusion and a serum corrected calcium level of 3.48 mmol/L. The calcium level was successfully normalized within 72 hours of subcutaneous denosumab administration after other interventions have failed.
Reply to the comments on "Higher levels of lead and aluminium are associated with increased risk of falls among community-dwelling older adults: An 18-month follow-up study"

Ooi TC, Singh DKA, Shahar S, Rajab NF, Sharif R

Geriatr Gerontol Int, 2022 02;22(2):183-185.
PMID: 34984783 DOI: 10.1111/ggi.14337

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