ORCID Profile
0000-0002-1626-5308
Current Organisations
Universiti Putra Malaysia
,
Australian National University
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Publisher: China Anti-cancer Association
Date: 2018
Publisher: MDPI AG
Date: 09-01-2021
DOI: 10.3390/MOLECULES26020321
Abstract: Obesity is one of the risk factors associated with cardiovascular diseases, hypertension, abnormal liver function, diabetes, and cancers. Orlistat is currently available to treat obesity, but it is associated with adverse side effects. Natural resources are widely used for obesity treatment. Hence, this study aimed to investigate the anti-obesity activity of Elateriospermum tapos (E. tapos) shell extract in obesity induced Sprague Dawley rats. The rats’ obesity was induced by a high-fat (HF) diet made up of 50% standard rat pellet, 20% milk powder, 6% corn starch, and 24% ghee and a cafeteria (CAF) diet such as chicken rolls, salty biscuits, cakes, and cheese snacks. A hot aqueous method for the extraction of E. tapos shells was applied by using 500 mL of distilled water for about 24 h. Various dosages of E. tapos shell extract (10 mg/kg, 100 mg/kg, and 200 mg/kg) were used. At the end of the study, body weight, caloric intake, organ weight, lipid profile, lipoprotein lipase (LPL) activity, and histopathology analysis were carried out. E. tapos shell extract treated groups showed a reduction in body weight, positive lipid-lowering effect, decrements in triglyceride accumulation and LPL activity, and positive improvement in histopathology analysis. A dose of 200 mg/kg showed the most effective result compared to 10 mg/kg and 100 mg/kg doses.
Publisher: Academic Journals
Date: 21-11-2011
DOI: 10.5897/AJB11.699
Publisher: Friends Science Publishers
Date: 03-2018
Publisher: MDPI AG
Date: 23-08-2019
DOI: 10.3390/IJMS20174114
Abstract: A nanocomposite, phytic acid-chitosan-magnetic iron oxide nanoparticles (IP6-CS-MNPs) has been used to treat colon cancer in vitro, previously. However, its potential toxicity in vivo has yet to be elucidated. Hence, the present study aimed to evaluate the acute effects of oral administration of IP6-CS-MNPs in mice. In this study, 1000 and 2000 mg/kg body weight (b.w) of IP6-CS-MNPs were orally administered to two different groups of BALB/c mice, once. Additionally, the mice in the control group were given only deionized water. After 14 days of post-IP6-CS-MNPs administration, in a similar way to the untreated mice, the treated mice showed no sign of mortality and abnormalities. However, the serum urea level of mice receiving 2000 mg/kg b.w of IP6-CS-MNPs was significantly higher than the control group (p 0.05). The mice that received 1000 mg/kg IP6-CS-MNPs showed a significantly higher level of serum alkaline phosphatase (ALP) compared to the control group. However, there were no significant histopathological changes seen in the liver and kidneys of treated mice compared to the untreated group.
Publisher: Hindawi Limited
Date: 21-12-2019
DOI: 10.1155/2019/3480569
Abstract: Epigallocatechin-3-gallate (EGCG) is the most abundant bioactive polyphenolic compound among the green tea constituents and has been identified as a potential anticancer agent in colorectal cancer (CRC) studies. This study was aimed to determine the mechanism of actions of EGCG when targeting the endoplasmic reticulum (ER) stress pathway in CRC. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was performed on HT-29 cell line and normal cell line (3T3) to determine the EGCG toxicity. Next, western blot was done to observe the expression of the related proteins for the ER stress pathway. The Caspase 3/7 assay was performed to determine the apoptosis induced by EGCG. The results demonstrated that EGCG treatment was toxic to the HT-29 cell line. EGCG induced ER stress in HT-29 by upregulating immunoglobulin-binding (BiP), PKR-like endoplasmic reticulum kinase (PERK), phosphorylation of eukaryotic initiation factor 2 alpha subunit (eIF2 α ), activating transcription 4 (ATF4), and inositol-requiring kinase 1 alpha (IRE1 α ). Apoptosis was induced in HT-29 cells after the EGCG treatment, as shown by the Caspase 3/7 activity. This study indicates that green tea EGCG has the potential to inhibit colorectal cancer cells through the induction of ER stress.
Publisher: Springer Science and Business Media LLC
Date: 09-11-2016
DOI: 10.1007/S10439-016-1758-4
Abstract: Nerve monitoring is a safety mechanism to detect the proximity between surgical instruments and important nerves during surgical bone preparation. In temporal bone, this technique is highly specific and sensitive at distances below 0.1 mm, but remains unreliable for distances above this threshold. A deeper understanding of the patient-specific bone electric properties is required to improve this range of detection. A sheep animal model has been used to characterize bone properties in vivo. Impedance measurements have been performed at low frequencies (<1 kHz) between two electrodes placed inside holes drilled into the sheep mastoid bone. An electric circuit composed of a resistor and a Fricke constant phase element was able to accurately describe the experimental measurements. Bone resistivity was shown to be linearly dependent on the inter-electrode distance and the local bone density. Based on this model, the amount of bone material between the electrodes could be predicted with an error of 0.7 mm. Our results indicate that bone could be described as an ideal resistor while the electrochemical processes at the electrode-tissue interface are characterized by a constant phase element. These results should help increasing the safety of surgical drilling procedures by better predicting the distance to critical nerve structures.
Publisher: Hindawi Limited
Date: 06-03-2019
DOI: 10.1155/2019/2821597
Abstract: Lung cancer is the leading cause of cancer related deaths worldwide with about 40% occurring in developing countries. The two varieties of Momordica charantia , which are Chinese and Indian bitter melon, have been subjected to antiproliferative activity in human non-small cell lung cells A549. The A549 cells were treated with hot and cold aqueous extraction for both the bitter melon varieties, and the antiproliferative activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptotic mechanism of action on A549 human lung cancer cells was evaluated first morphologically using Hoechst 33358, and cytoskeleton staining using Filamentous-actin (F-actin) cytoskeleton FICT and DAPI followed by caspase-3/7, reactive oxygen species (ROS), and p53 activity. Chinese hot aqueous extraction (CHA) exhibited potent antiproliferative activity against A549 human lung cancer cells. The morphological analysis of mitochondria destruction and the derangement of cytoskeleton showed apoptosis-inducing activity. CHA increased the caspase-3/7 activity by 1.6-fold and the ROS activity by 5-fold. Flow cytometric analysis revealed 34.5% of apoptotic cells significantly (p .05) compared to cisplatin-treated A549 human cancer cells. CHA is suggested to induce apoptosis due to their rich bioactive chemical constituents. These findings suggest that the antiproliferative effect of CHA was due to apoptosis via ROS-mediated mitochondria injury.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.BCP.2016.04.001
Abstract: The endoplasmic reticulum (ER) plays a major role in the synthesis, maturation and folding of proteins and is a critical calcium (Ca(2+)) reservoir. Cellular stresses lead to an overwhelming accumulation of misfolded proteins in the ER, leading to ER stress and the activation of the unfolded protein response (UPR). In the stressful tumor microenvironment, the UPR maintains ER homeostasis and enables tumor survival. Thus, a novel strategy for cancer therapeutics is to overcome chronically activated ER stress by triggering pro-apoptotic pathways of the UPR. Considering this, the mechanisms by which the novel anti-cancer agent, Dp44mT, can target the ER stress response pathways were investigated in multiple cell-types. Our results demonstrate that the cytotoxic chelator, Dp44mT, which forms redox-active metal complexes, significantly: (1) increased ER stress-associated pro-apoptotic signaling molecules (i.e., p-eIF2α, ATF4, CHOP) (2) increased IRE1α phosphorylation (p-IRE1α) and XBP1 mRNA splicing (3) reduced expression of ER stress-associated cell survival signaling molecules (e.g., XBP1s and p58(IPK)) (4) increased cleavage of the transcription factor, ATF6, which enhances expression of its downstream targets (i.e., CHOP and BiP) and (5) increased phosphorylation of CaMKII that induces apoptosis. In contrast to Dp44mT, the iron chelator, DFO, which forms redox-inactive iron complexes, did not affect BiP, p-IRE1α, XBP1 or p58(IPK) levels. This study highlights the ability of a novel cancer therapeutic (i.e., Dp44mT) to target the pro-apoptotic functions of the UPR via cellular metal sequestration and redox stress. Assessment of ER stress-mediated apoptosis is fundamental to the understanding of the pharmacology of chelation for cancer treatment.
Publisher: Hindawi Limited
Date: 02-05-2019
DOI: 10.1155/2019/9152757
Abstract: Momordica charantia Linn., commonly known as bitter gourd, has many protective roles due to its medicinal value as it contains bioactive components. However, this extract showed possible toxicity effect on zebrafish embryo. Thus this study was designed to differentiate the toxicity activities in two types of M. charantia s le which are Indian and Chinese M. charantia , as well as to compare between two different aqueous extraction methods, hot and cold aqueous method, using zebrafish embryo assay assessment. It was observed that the survival rate of zebrafish embryo decreased as the concentration of test extract increased for all s les of M. charantia . The LC 50 values of hot aqueous Chinese M. charantia , hot aqueous Indian M. charantia , and cold aqueous Chinese M. charantia were 144.54 μ g/ml, 199.53 μ g/ml, and 251.19 μ g/ml, respectively. However, cold aqueous Indian M. charantia has a higher LC 50 which was not in the range of the tested concentration. Hatchability of Danio rerio embryo reduced as the concentration of M. charantia extract increased while no hatching was observed in the highest concentration (1000 μ g/ml). Scoliosis of zebrafish larvae was only seen in higher concentrations (125-1000 μ g/ml) of extract. The heartbeat of zebrafish larvae treated with M. charantia extract was within the normal range, 120-180 bpm, but at higher concentrations (125-1000 μ g/ml) the heartbeat differed for all s les of test extract. Hence, although this plant extract was safe to be consumed due to its pharmaceutical effect, it still exhibited mild toxicity effect at higher concentration when it was evaluated on zebrafish embryo.
Publisher: Informa UK Limited
Date: 09-08-2023
Publisher: Informa UK Limited
Date: 23-11-2022
Publisher: MDPI AG
Date: 09-10-2020
DOI: 10.3390/NU12103077
Abstract: The present study aimed to determine the effect of an ethyl acetate extract of Mikania micrantha stems (EAMMS) in hypercholesterolemia-induced rats. Rats were ided into a normal group (NC) and hypercholesterolemia induced groups: hypercholesterolemia control group (PC), simvastatin group (SV) (10 mg/kg) and EAMMS extract groups at different dosages of 50, 100 and 200 mg/kg, respectively. Blood serum and tissues were collected for haematological, biochemical, histopathological, and enzyme analysis. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, malondialdehyde (MDA) level, as well as enzymes of HMG-CoA reductase (HMGCR) and acetyl-CoA acetyltransferase 2 (ACAT2), were measured. Feeding rats with high cholesterol diet for eight weeks resulted in a significantly (p 0.05) increased of TC, TG, LDL-C, AST, ALT and MDA levels. Meanwhile, the administration of EAMMS extract (50, 100 and 200 mg/kg) and simvastatin (10 mg/kg) significantly reduced (p 0.05) the levels of TC, TG, LDL-C and MDA compared to rats in the PC group. Furthermore, all EAMMS and SV-treated groups showed a higher HDL-C level compared to both NC and PC groups. No significant difference was found in the level of ALT, AST, urea and creatinine between the different dosages in EAMMS extracts. Treatment with EAMMS also exhibited the highest inhibition activity of enzyme HMGCR and ACAT2 as compared to the control group. From the histopathological examination, liver tissues in the PC group showed severe steatosis than those fed with EAMMS and normal diet. Treatment with EAMMS extract ameliorated and reduced the pathological changes in the liver. No morphological changes showed in the kidney structure of both control and treated groups. In conclusion, these findings demonstrated that EAMMS extract has anti-hypercholesterolemia properties and could be used as an alternative treatment for this disorder.
Publisher: Informa UK Limited
Date: 04-05-2021
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.BBCAN.2014.01.005
Abstract: Cancer is a major public health issue and, despite recent advances, effective clinical management remains elusive due to intra-tumoural heterogeneity and therapeutic resistance. Iron is a trace element integral to a multitude of metabolic processes, including DNA synthesis and energy transduction. Due to their generally heightened proliferative potential, cancer cells have a greater metabolic demand for iron than normal cells. As such, iron metabolism represents an important "Achilles' heel" for cancer that can be targeted by ligands that bind and sequester intracellular iron. Indeed, novel thiosemicarbazone chelators that act by a "double punch" mechanism to both bind intracellular iron and promote redox cycling reactions demonstrate marked potency and selectivity in vitro and in vivo against a range of tumours. The general mechanisms by which iron chelators selectively target tumour cells through the sequestration of intracellular iron fall into the following categories: (1) inhibition of cellular iron uptake romotion of iron mobilisation (2) inhibition of ribonucleotide reductase, the rate-limiting, iron-containing enzyme for DNA synthesis (3) induction of cell cycle arrest (4) promotion of localised and cytotoxic reactive oxygen species production by copper and iron complexes of thiosemicarbazones (e.g., Triapine(®) and Dp44mT) and (5) induction of metastasis and tumour suppressors (e.g., NDRG1 and p53, respectively). Emerging evidence indicates that chelators can further undermine the cancer phenotype via inhibiting the epithelial-mesenchymal transition that is critical for metastasis and by modulating ER stress. This review explores the "expanding horizons" for iron chelators in selectively targeting cancer cells.
Publisher: MDPI AG
Date: 07-09-2022
Abstract: Women with previous gestational diabetes mellitus (post-GDM) have an increased risk of cardiometabolic diseases including type 2 diabetes (T2D). Current diabetes screening is based on the oral glucose tolerance test without nutritional assessments, even though unhealthy dietary patterns were found to expedite disease progression in women post-GDM. While a healthful dietary pattern reduces T2D risk, limited data support a dietary pattern tailored to the Asian population, especially in the Malaysian context. Metabolomic profiles associated with dietary patterns in this population are also lacking. The proposed study aims to investigate both components of dietary patterns and metabolomic profile, known as nutritype signatures, and their association with T2D in women post-GDM. The comparative cross-sectional study will involve a minimum of 126 Malaysian women post-GDM aged 18–49 years. Dietary patterns will be analysed using principal component analysis. Plasma and urinary metabolites will be quantified using one-dimensional proton nuclear magnetic resonance (1H NMR) spectroscopy. The aim of the study is identifying the nutritype signatures associated with T2D. The findings will support the development of early prevention measures against T2D in women post-GDM.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/681027
Abstract: Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP 6 extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were ided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal ( i.p. ) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP 6 was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/ β -catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis. β -Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP 6 markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP 6 had also markedly decreased β -catenin and COX-2 in colon tumors. Thus, the downregulation of β -catenin and COX-2 could play a role in inhibiting the CRC development induced by IP 6 and thereby act as a potent anticancer agent.
Publisher: Cambridge University Press (CUP)
Date: 06-2022
DOI: 10.1017/GLJ.2022.44
Abstract: Perpetuating Britain’s controversial administration of the Chagos Archipelago (BIOT – British Indian Ocean Territory) raises questions about the UK’s commitment to the rules-based order and international law. This interdisciplinary article examines British administration of the Chagos Archipelago by taking a legal-international relations perspective. It provides an overview to the rules-based order concept and its relation with international law, briefly examines the Territory’s history, and outlines how BIOT violates the principles enshrined in the rules-based order concept, specifically promotion of self-determination, prohibition of forced displacement and respect for international institutions. This study is significant due to its timing – set in a period of increased international pressure on the United Kingdom to cede sovereignty of the Chagos Archipelago to Mauritius – and also significant in a period of increased rules-based order strain throughout the Indo-Pacific. This article argues that, despite Britain’s assertion that it is a ch ion of the rules-based order, of which international law is a component, continued British administration of the Chagos Archipelago is in contravention of both. In an era of rules-based order strain, British BIOT policy provides fertile ground to criticisms of its foreign policy and international law selectivity and double standards.
Publisher: Hindawi Limited
Date: 21-03-2020
DOI: 10.1155/2020/7958041
Abstract: In many studies, green tea epigallocatechin-3-gallate (EGCG) has already shown its therapeutic effects in colorectal cancer cells (CRC). However, its mechanism of actions in CRC is poorly elucidated. Hence, this study attempts to elucidate the mechanism of actions of green tea ECGG via iron chelation activity in CRC. In order to investigate this property, HT-29 cell lines (CRC) were treated with EGCG for 24 h, 48 h, and 72 h. From western blot analysis, EGCG had upregulated transferrin receptor (TfR) protein and downregulated Ferritin-H (FtH) protein indicating that iron chelation activity has occurred in CRC. Meanwhile, the molecular docking study demonstrated that EGCG is able to strongly interact the ferritin protein with a high binding affinity (−7.3 kcal/mol) via strong hydrogen bindings to glutamic acid 64 and lysine 71 two moderate hydrogen bindings to asparagine 74 and a hydrophobic interaction to the hydrophobic pocket of lysine 71. The strong interaction predicted between EGCG to ferritin may lead to inhibition of ferritin by EGCG, thus supporting the downregulation of FtH observed in in vitro studies. Molecular docking study of TfR to EGCG cannot be modulated based on the in vitro results. In conclusion, EGCG possesses iron chelator property in CRC and this potential could be further exploited for CRC treatment.
Publisher: MDPI AG
Date: 09-03-2023
DOI: 10.3390/IJMS24065224
Abstract: Colorectal cancer (CRC) is responsible for a notable rise in the overall mortality rate. Obesity is found to be one of the main factors behind CRC development. Andrographis paniculata is a herbaceous plant famous for its medicinal properties, particularly in Southeast Asia for its anti-cancer properties. This study examines the chemopreventive impact of A. paniculata ethanolic extract (APEE) against a high-fat diet and 1,2-dimethylhydrazine-induced colon cancer in Sprague Dawley rats. Sprague Dawley rats were administered 1,2-dimethylhydrazine (40 mg/kg, i.p. once a week for 10 weeks) and a high-fat diet (HFD) for 20 weeks to induce colorectal cancer. APEE was administered at 125 mg/kg, 250 mg/kg, and 500 mg/kg for 20 weeks. At the end of the experiment, blood serum and organs were collected. DMH/HFD-induced rats had abnormal crypts and more aberrant crypt foci (ACF). APEE at a dose of 500 mg/kg improved the dysplastic state of the colon tissue and caused a 32% reduction in the total ACF. HFD increased adipocyte cell size, while 500 mg/kg APEE reduced it. HFD and DMH/HFD rats had elevated serum insulin and leptin levels. Moreover, UHPLC-QTOF-MS analysis revealed that APEE was rich in anti-cancer phytochemicals. This finding suggests that APEE has anti-cancer potential against HFD/DMH-induced CRC and anti-adipogenic and anti-obesity properties.
Publisher: MDPI AG
Date: 02-12-2013
Publisher: Wiley
Date: 03-12-2021
DOI: 10.1002/FSN3.2051
Publisher: Informa UK Limited
Date: 03-05-2020
No related grants have been discovered for Nurul Husna Shafie.