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Fulltext Gelam honey attenuated radiation-induced cell death in human diploid fibroblasts by promoting cell cycle progression and inhibiting apoptosis

Tengku Ahmad TA, Jaafar F, Jubri Z, Abdul Rahim K, Rajab NF, Makpol S

BMC Complement Altern Med, 2014;14:108.
PMID: 24655584 DOI: 10.1186/1472-6882-14-108

The interaction between ionizing radiation and substances in cells will induce the production of free radicals. These free radicals inflict damage to important biomolecules such as chromosomes, proteins and lipids which consequently trigger the expression of genes which are involved in protecting the cells or repair the oxidative damages. Honey has been known for its antioxidant properties and was used in medical and cosmetic products. Currently, research on honey is ongoing and diversifying. The aim of this study was to elucidate the role of Gelam honey as a radioprotector in human diploid fibroblast (HDFs) which were exposed to gamma-rays by determining the expression of genes and proteins involved in cell cycle regulation and cell death.
Fulltext Dietary Supplement Intake and Its Association with Cognitive Function, Physical Fitness, Depressive Symptoms, Nutritional Status and Biochemical Indices in a 3-Year Follow-Up Among Community Dwelling Older Adults: A Longitudinal Study

Vanoh D, Shahar S, Yahya HM, Che Din N, Mat Ludin AF, Ajit Singh DK, et al.

Clin Interv Aging, 2021;16:161-175.
PMID: 33531799 DOI: 10.2147/CIA.S266587

Purpose: Use of dietary supplements by older adults has been increasing for improving micronutrient deficiencies, cognitive function, and overall health status. Thus, the objective of this secondary investigation is to explore the longitudinal association of baseline supplement intake in improving cognitive function, biochemical parameters, anthropometric variables and physical fitness among older adults.
Methods: Towards Useful Aging (TUA) is a three-year longitudinal study conducted at baseline (2013-2014) and at follow-up (2015-2017) surveys. The number of participants dropped from 2322 during baseline study to 1787 and 1560 during the 18th and 36th month follow-up, respectively. Data on socio-demography, use of dietary supplement, biochemical indices, anthropometry, cognitive function, physical fitness and depressive symptoms were obtained. Longitudinal associations were done using the linear mixed model analysis among 1285 subjects with complete data.
Results: The most common vitamin and mineral supplementations consumed were multivitamin, B-complex, and calcium. Meanwhile, the herbal supplements consumed by participants were Eurycoma longifolia, Morinda citrifolia and Orthosiphon aristatus. Longitudinal analysis adjusted for multiple covariates showed improvement in both supplement users and non-users for global cognitive function, working memory, visual memory, 2-minute step test, chair stand test, chair sit and reach and time up and go test, waist circumference and hip circumference in both the supplement users and non-users.
Conclusion: Our findings indicated that dietary supplement intake is not associated with cognitive function, physical fitness, nutritional status, depressive symptoms or biochemical indices since improvement in the parameters was observed among both supplement users and non-users.
Fulltext Involvement of Seladin-1 in goniothalamin-induced apoptosis in urinary bladder cancer cells

Yen HK, Fauzi AR, Din LB, McKelvey-Martin VJ, Meng CK, Inayat-Hussain SH, et al.

BMC Complement Altern Med, 2014;14:295.
PMID: 25107315 DOI: 10.1186/1472-6882-14-295

Selective Alzheimer Disease Indicator-1 (or Seladin-1) is a multifunctional protein first discovered by downregulation of its expression in Alzheimer's disease. Interestingly, the expression of this protein is upregulated in several cancers, including primary bladder cancer. However, its role in cancer formation has yet to be discovered. Goniothalamin is a natural product that has been demonstrated to induce apoptosis in various cancer cell lines. In this study, we have elucidated the role of Seladin-1 in goniothalamin-induced cytotoxicity towards human urinary bladder cancer cell line RT4.
Fulltext Effects of 12 Weeks Cosmos caudatus Supplement among Older Adults with Mild Cognitive Impairment: A Randomized, Double-Blind and Placebo-Controlled Trial

You YX, Shahar S, Rajab NF, Haron H, Yahya HM, Mohamad M, et al.

Nutrients, 2021 Jan 29;13(2).
PMID: 33572715 DOI: 10.3390/nu13020434

Cosmos caudatus (CC) contains high flavonoids and might be beneficial in neuroprotection. It has the potential to prevent neurodegenerative diseases. Therefore, we aimed to investigate the effects of 12 weeks of Cosmos caudatus supplement on cognitive function, mood status, blood biochemical profiles and biomarkers among older adults with mild cognitive impairment (MCI) through a double-blind, placebo-controlled trial. The subjects were randomized into CC supplement (n = 24) and placebo group (n = 24). Each of them consumed one capsule of CC supplement (250 mg of CC/capsule) or placebo (500 mg maltodextrin/capsule) twice daily for 12 weeks. Cognitive function and mood status were assessed at baseline, 6th week, and 12th week using validated neuropsychological tests. Blood biochemical profiles and biomarkers were measured at baseline and 12th week. Two-way mixed analysis of variance (ANOVA) analysis showed significant improvements in mini mental state examination (MMSE) (partial η2 = 0.150, p = 0.049), tension (partial η2 = 0.191, p = 0.018), total mood disturbance (partial η2 = 0.171, p = 0.028) and malondialdehyde (MDA) (partial η2 = 0.097, p = 0.047) following CC supplementation. In conclusion, 12 weeks CC supplementation potentially improved global cognition, tension, total mood disturbance, and oxidative stress among older adults with MCI. Larger sample size and longer period of intervention with incorporation of metabolomic approach should be conducted to further investigate the underlying mechanism of CC supplementation in neuroprotection.
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 Is There Any Relationship Between Biochemical Indices and Anthropometric Measurements With Dorsolateral Prefrontal Cortex Activation Among Older Adults With Mild Cognitive Impairment?

You YX, Shahar S, Mohamad M, Rajab NF, Che Din N, Lau HJ, et al.

Front Hum Neurosci, 2021;15:765451.
PMID: 35046782 DOI: 10.3389/fnhum.2021.765451

Working memory is developed in one region of the brain called the dorsolateral prefrontal cortex (DLPFC). The dysfunction of this region leads to synaptic neuroplasticity impairment. It has been reported that several biochemical parameters and anthropometric measurements play a vital role in cognition and brain health. This study aimed to investigate the relationships between cognitive function, serum biochemical profile, and anthropometric measurements using DLPFC activation. A cross-sectional study was conducted among 35 older adults (≥60 years) who experienced mild cognitive impairment (MCI). For this purpose, we distributed a comprehensive interview-based questionnaire for collecting sociodemographic information from the participants and conducting cognitive tests. Anthropometric values were measured, and fasting blood specimens were collected. We investigated their brain activation using the task-based functional MRI (fMRI; N-back), specifically in the DLPFC region. Positive relationships were observed between brain-derived neurotrophic factor (BDNF) (β = 0.494, p < 0.01) and Mini-Mental State Examination (MMSE) (β = 0.698, p < 0.01); however, negative relationships were observed between serum triglyceride (β = -0.402, p < 0.05) and serum malondialdehyde (MDA) (β = -0.326, p < 0.05) with right DLPFC activation (R 2 = 0.512) while the participants performed 1-back task after adjustments for age, gender, and years of education. In conclusion, higher serum triglycerides, higher oxidative stress, and lower neurotrophic factor were associated with lower right DLPFC activation among older adults with MCI. A further investigation needs to be carried out to understand the causal-effect mechanisms of the significant parameters and the DLPFC activation so that better intervention strategies can be developed for reducing the risk of irreversible neurodegenerative diseases among older adults with MCI.
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.
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 Rigid Tissue Increases Cytoplasmic pYAP Expression in Pre-Malignant Stage of Lung Squamous Cell Carcinoma (SCC) In Vivo

Zakaria MA, Kiew MC, Rajab NF, Chua EW, Masre SF

Curr Issues Mol Biol, 2022 Sep 29;44(10):4528-4539.
PMID: 36286025 DOI: 10.3390/cimb44100310

Increased tissue rigidity is able to activate the Hippo signaling pathway, leading to YAP inactivation by phosphorylation and translocation into the cytoplasm. Accumulating evidence suggests that cytoplasmic pYAP serves as a tumor suppressor and could be a prognostic biomarker for several solid cancers. However, the relationship between tissue rigidity and cytoplasmic pYAP expression in the early stage of lung squamous cell carcinoma (SCC) remains elusive; this was determined in this study by using a mouse model. Female BALB/c mice were assigned into two groups (n = 6; the vehicle (VC) and the pre-malignant (PM) group, which received 70% acetone and 0.04 M N-nitroso-tris-chloroethylurea (NTCU) for 15 weeks, respectively. In this study, the formation of hyperplasia and metaplasia lesions was found in the PM group, indicating the pre-malignant stage of lung SCC. The pre-malignant tissue appeared to be more rigid as characterized by significantly higher (p < 0.05) epithelium thickness, proliferative activity, and collagen content than the VC group. The PM group also had a significantly higher (p < 0.05) cytoplasmic pYAP protein expression than the VC group. In conclusion, increased tissue rigidity may contribute to the upregulation of cytoplasmic pYAP expression, which may act as a tumor suppressor in the early stage of lung SCC.
Fulltext Tissue Rigidity Increased during Carcinogenesis of NTCU-Induced Lung Squamous Cell Carcinoma In Vivo

Zakaria MA, Aziz J, Rajab NF, Chua EW, Masre SF

Biomedicines, 2022 Sep 23;10(10).
PMID: 36289644 DOI: 10.3390/biomedicines10102382

Increased tissue rigidity is an emerging hallmark of cancer as it plays a critical role in promoting cancer growth. However, the field lacks a defined characterization of tissue rigidity in dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) in vivo. Pre-malignant and malignant lung SCC was developed in BALB/c mice using N-nitroso-tris-chloroethylurea (NTCU). Picro sirius red staining and atomic force microscopy were performed to measure collagen content and collagen (diameter and rigidity), respectively. Then, the expression of tenascin C (TNC) protein was determined using immunohistochemistry staining. Briefly, all tissue rigidity parameters were found to be increased in the Cancer group as compared with the Vehicle group. Importantly, collagen content (33.63 ± 2.39%) and TNC expression (7.97 ± 2.04%) were found to be significantly higher (p < 0.05) in the Malignant Cancer group, as compared with the collagen content (18.08 ± 1.75%) and TNC expression (0.45 ± 0.53%) in the Pre-malignant Cancer group, indicating increased tissue rigidity during carcinogenesis of lung SCC. Overall, tissue rigidity of lung SCC was suggested to be increased during carcinogenesis as indicated by the overexpression of collagen and TNC protein, which may warrant further research as novel therapeutic targets to treat lung SCC effectively.
Fulltext NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model

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

Sci Rep, 2021 Nov 18;11(1):22500.
PMID: 34795360 DOI: 10.1038/s41598-021-01988-8

Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P

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