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Fulltext Correction: Vitamin D Deficiency and Its Association With Vitamin D Receptor Gene Variants Among Malaysian Women With Hypertensive Disorders in Pregnancy: Protocol for a Nutrigenomics Study

Ibrahim Y, Basri NI, Nordin N, Mohd Jamil AA

JMIR Res Protoc, 2024 Apr 11;13:e59300.
PMID: 38603774 DOI: 10.2196/59300

[This corrects the article DOI: 10.2196/53722.].
Fulltext Vitamin D Deficiency and Its Association With Vitamin D Receptor Gene Variants Among Malaysian Women With Hypertensive Disorders in Pregnancy: Protocol for a Nutrigenomics Study

Ibrahim Y, Basri NI, Nordin N, Mohd Jamil AA

JMIR Res Protoc, 2024 Mar 26;13:e53722.
PMID: 38530345 DOI: 10.2196/53722

BACKGROUND: Vitamin D deficiency has been associated with hypertensive disorders in pregnancy (HDP). The risk of developing HDP was reported to be further augmented among individuals with a vitamin D receptor (VDR) genetic variant. However, the reported roles of VDR variants in hypertensive disorders are inconsistent among different populations. Given the relatively higher incidence of vitamin D deficiency among Malaysian pregnant women and the high incidence of HDP in this population, we hypothesize that there may be associations between the risk of vitamin D deficiency and HDP with VDR genetic variants.
OBJECTIVE: This paper outlines the protocol for a study to determine the association of vitamin D status and VDR sequence variants among Malaysian pregnant women with HDP.
METHODS: This prospective study consists of two phases. The first phase is a cross-sectional study that will entail gathering medical records, a questionnaire survey, and laboratory testing for vitamin D status, with a planned recruitment of 414 pregnant women. The questionnaire will be utilized to assess the risk factors for vitamin D deficiency. The vitamin D status will be obtained from measurement of the vitamin D (25-hydroxyvitamin D3) level in the blood. The second phase is a case-control study involving a Malay ethnic cohort with vitamin D deficiency. Participants will be divided into two groups with and without HDP (n=150 per group). Genomic DNA will be extracted from the peripheral blood monocytes of participants using the Qiagen DNA blood kit, and VDR sequence variants will be determined using polymerase chain reaction-high-resolution melting (PCR-HRM) analysis. Sanger sequencing will then be used to sequence randomly selected samples corresponding to each identified variant to validate our PCR-HRM results. The VDR genotype and mutation frequencies of BsmI, ApaI, TaqI, and FokI will be statistically analyzed to evaluate their relationships with developing HDP.
RESULTS: As of December 2023, 340 subjects have been recruited for the phase 1 study, 63% of whom were determined to have vitamin D deficiency. In the phase 2 study, 50 and 22 subjects have been recruited from the control and case groups, respectively. Recruitment is expected to be completed by March 2024 and all analyses should be completed by August 2024.
CONCLUSIONS: The outcome of the study will identify the nonmodifiable genetic components contributing to developing vitamin D deficiency leading to HDP. This will in turn enable gaining a better understanding of the contribution of genetic variability to the development of HDP, thus providing more evidence for a need of customized vitamin D supplementation during pregnancy according to the individual variability in the response to vitamin D intake.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05659173; https://clinicaltrials.gov/study/NCT05659173.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53722.
Fulltext Ultrastructural Changes and Antitumor Effects of Doxorubicin/Thymoquinone-Loaded CaCO3 Nanoparticles on Breast Cancer Cell Line

Ibiyeye KM, Nordin N, Ajat M, Zuki ABZ

Front Oncol, 2019;9:599.
PMID: 31334120 DOI: 10.3389/fonc.2019.00599

Background: Combination chemotherapy of anticancer drugs is extensively being researched since it could reduce multidrug resistance and side effects as a result of lower dosage of each drug. In this study, we evaluated the effects of doxorubicin-loaded (Dox-ACNP), thymoquinone-loaded (TQ-ACNP) and a combined doxorubicin/thymoquinone-loaded cockle shell-derived aragonite calcium carbonate nanoparticles (Dox/TQ-ACNP) on breast cancer cell line and compared with their free drugs counterpart. Methods: Cell viability using MTT assay, apoptosis with Annexin V-PI kit, morphological changes using contrast light microscope, scanning electron microscope and transmission electron microscope, cell cycle analysis, invasion assay, and scratch assay were carried out. The cell viability was evaluated in breast cancer cell line (MDA MB231), normal breast cells (MDF10A) and normal fibroblast (3T3). Results: MDA MB231 IC50 dosages of drug-loaded nanoparticle were not toxic to the normal cells. The combination therapy showed enhanced apoptosis, reduction in cellular migration and invasion when compared to the single drug-loaded nanoparticle and the free drugs. Scanning electron microscope showed presence of cell shrinkage, cell membrane blebbing, while transmission electron microscope showed nuclear fragmentation, disruption of cell membrane, apoptotic bodies, and disruption of mitochondrial cistern. Conclusion: The results from this study showed that the combined drug-loaded cockle shell-derived aragonite calcium carbonate nanoparticles (Dox/TQ-ACNP) showed higher efficacy in breast cancer cells at lower dose of doxorubicin and thymoquinone.
Fulltext A comprehensive review of cystic fibrosis in Africa and Asia

Abubakar Bobbo K, Ahmad U, Chau DM, Nordin N, Abdullah S

Saudi J Biol Sci, 2023 Jul;30(7):103685.
PMID: 37313453 DOI: 10.1016/j.sjbs.2023.103685

Cystic fibrosis (CF) was earlier thought to be a disease prevalent in the West among Caucasians. However, quite a number of recent studies have uncovered CF cases outside of this region, and reported hundreds of unique and novel variant forms of CFTR. Here, we discuss the evidence of CF in parts of the world earlier considered to be rare; Africa, and Asia. This review also highlighted the CFTR mutation variations and new mutations discovered in these regions. This discovery implies that the CF data from these regions were earlier underestimated. The inadequate awareness of the disease in these regions might have contributed towards the poor diagnostic facilities, under-diagnosis or/and under-reporting, and the lack of CF associated health policies. Overall, these regions have a high rate of infant, childhood and early adulthood mortality due to CF. Therefore, there is a need for a thorough investigation of CF prevalence and to identify unique and novel variant mutations within these regions in order to formulate intervention plans, create awareness, develop mutation specific screening kits and therapies to keep CF mortality at bay.
Relationship standards and Malay Muslim couples' marital satisfaction

Nordin N, Halford WK, Barlow FK, Mastor KA

J Marital Fam Ther, 2023 Oct;49(4):825-841.
PMID: 37545186 DOI: 10.1111/jmft.12659

Relationship standards are beliefs about what is important in high-quality couple relationships. Clarifying standards cross-culturally informs theory about relationship quality and goals for culturally appropriate couple therapy. The current study assessed four standards (Couple Bond, Family Responsibility, Relationship Effort, and Religion) in n = 113 Malay Muslim couples, and the association of those standards with marital satisfaction. All four standards were strongly endorsed, Religion was the most strongly endorsed, and there were minimal sex differences. Separate actor-partner interdependence models showed actor effects of all four standards on own satisfaction for husbands and wives, partner effects of three of the four husbands' standards (not Relationship Effort) on wives' satisfaction, but no partner effects of female standards on male satisfaction. The findings underscore the importance of all four standards in Malay Muslim marriages and that attention to all these standards might need to be part of couple therapy with Malay couples.
Fulltext Vitamin E-Mediated Modulation of Glutamate Receptor Expression in an Oxidative Stress Model of Neural Cells Derived from Embryonic Stem Cell Cultures

Abd Jalil A, Khaza'ai H, Nordin N, Mansor N, Zaulkffali AS

Evid Based Complement Alternat Med, 2017;2017:6048936.
PMID: 29348770 DOI: 10.1155/2017/6048936

Glutamate is the primary excitatory neurotransmitter in the central nervous system. Excessive concentrations of glutamate in the brain can be excitotoxic and cause oxidative stress, which is associated with Alzheimer's disease. In the present study, the effects of vitamin E in the form of tocotrienol-rich fraction (TRF) and alpha-tocopherol (α-TCP) in modulating the glutamate receptor and neuron injury markers in an in vitro model of oxidative stress in neural-derived embryonic stem (ES) cell cultures were elucidated. A transgenic mouse ES cell line (46C) was differentiated into a neural lineage in vitro via induction with retinoic acid. These cells were then subjected to oxidative stress with a significantly high concentration of glutamate. Measurement of reactive oxygen species (ROS) was performed after inducing glutamate excitotoxicity, and recovery from this toxicity in response to vitamin E was determined. The gene expression levels of glutamate receptors and neuron-specific enolase were elucidated using real-time PCR. The results reveal that neural cells derived from 46C cells and subjected to oxidative stress exhibit downregulation of NMDA, kainate receptor, and NSE after posttreatment with different concentrations of TRF and α-TCP, a sign of neurorecovery. Treatment of either TRF or α-TCP reduced the levels of ROS in neural cells subjected to glutamate-induced oxidative stress; these results indicated that vitamin E is a potent antioxidant.
On the dual crosslinking for functionality enhancement of poly (acrylamide-co-acrylic acid)/chitosan-aluminum (III) ions and its characterization and sensory hydrogel fibers

Nordin N, Zairul Azman ZA, Adnan NA, Majid SR

Int J Biol Macromol, 2024 Aug;274(Pt 1):133383.
PMID: 38914395 DOI: 10.1016/j.ijbiomac.2024.133383

In this report, we present a dual crosslinking hydrogel fiber made from polyamine saccharides chitosan (CS), synthesized through UV polymerization. This process utilizes Irgacure 2959 and N,N'-Methylenebisacrylamide (MBAA) as initiators, followed by immersion in an aluminum chloride (AlCl3) solution. The resulting hydrogel incorporates a dual crosslinking mechanism, quantitatively studied via Nuclear Magnetic Resonance (NMR) spectroscopy. This mechanism involves chemical crosslinking through radical graft polymerization of acrylamide and acrylic acid onto CS in the presence of MBAA, and physical crosslinking through hydrogen bonding interactions between P(AAm-co-AA) and a metal coordination bond. The mechanical properties of the hydrogel fiber enable it to withstand stresses up to 656 kPa and strains exceeding 300 %. Additionally, the hydrogel fiber exhibits conductivity at 1.96 Scm-1. Serving as a multifunctional material, it acts as a strain sensor and finds utility in optics. Remarkably, it demonstrates the capability to detect human motions such as finger bending and minor deformations like vibrations of the vocal cords. Furthermore, its ability to guide dynamic light makes it promising for optical applications. Consequently, this multifunctional hydrogel fiber emerges as a highly promising candidate for diverse applications in fields such as bioengineering and electronics.
Efficient encapsulation of a model drug in chitosan cathodic electrodeposition: Preliminary analysis using FTIR, UV-vis, and NMR spectroscopy

Nordin N, Zaini Ambia NFA, Majid SR, Abu Bakar N

Carbohydr Polym, 2025 Jan 15;348(Pt A):122830.
PMID: 39562104 DOI: 10.1016/j.carbpol.2024.122830

This study investigates the preliminary efficacy of drug encapsulation in chitosan hydrogels by cathodic electrodeposition for the encapsulation of the aromatic dye methyl orange to enhance drug delivery in biological systems. Chitosan, a biocompatible and transparent polymer, is known for its ability to effectively encapsulate and transport therapeutic agents, which is critical for sustained and targeted drug release. Methyl orange was selected as a model drug to study the effects of deposition and immersion times on encapsulation efficiency. The effects of deposition and immersion times on encapsulation efficiency were analyzed by synthesizing multilayer hydrogels via electrochemical oxidation. Characterization techniques, including UV-visible spectroscopy, FTIR, and NMR, were employed; FTIR indicated an effective absorption of 4.34 % for Td50Ti60, while UV-Vis showed 46.41 % at Td60Ti50. NMR analysis revealed effective concentrations of 0.47 mM for Td70Ti60 and 0.38 mM for Td60Ti50, indicating that longer immersion times enhance absorption. These findings provide a foundation for further studies aimed at optimizing drug delivery strategies and improving the therapeutic efficacy of encapsulated agents in biological applications.
Fulltext TOPSIS prefabricated building construction evaluation based on interval-valued Pythagorean fuzzy numbers based on prospect theory

Chang L, Nordin N, Zhao S, Gu X, Zhao Y

Sci Rep, 2025 Jan 23;15(1):2913.
PMID: 39848985 DOI: 10.1038/s41598-025-85729-1

Prefabricated buildings have a series of advantages such as high efficiency, energy savings, and environmental protection, and are being strongly promoted by the Chinese government. However, due to the late start of prefabricated buildings in China, the installation process of prefabricated components is relatively complex, leading to difficulties in quality and safety control. A novel evaluation methodology integrating the technique for order preference by similarity to ideal solution (TOPSIS) with prospect theory and interval-valued Pythagorean fuzzy numbers (IVPFNs) is proposed. Fully considering the subjective value perceptions of decision-makers when faced with losses and gains, a risk evaluation model is established based on different types of decision-makers. This model is then compared with the weight correction coefficient model from a balanced perspective to prevent bias caused by over-reliance on decision-makers' subjective preferences. This study establishes an assessment index system for assembly construction risk, considering personnel, materials, machinery, management, and technology factors. By merging prospect theory with the TOPSIS method, the application of Pythagorean fuzzy numbers is refined, enhancing the group decision-making process for evaluating risks in prefabricated construction projects. On the other hand, the prospect theory approach can focus on the actual psychological state of managers during decision-making, addressing the research gap concerning the impact of managers' psychological states on the evaluation process. The study identifies critical risk factors and suggests specific risk management strategies to improve the risk mitigation capabilities of construction entities, offering a structured approach to enhancing the efficiency and safety of prefabricated construction projects.
Fulltext Psychometric properties of the 'Skala Kepuasan Interaksi Perubatan-11' to measure patient satisfaction with physician-patient interaction in Malaysia

Abd Aziz A, Izyan Farhana Nordin N, Mohd Noor N, Bachok N, Nor Ismalina Isa S

Fam Pract, 2014 Apr;31(2):236-44.
PMID: 24317538 DOI: 10.1093/fampra/cmt062

Background. Patient satisfaction influences the outcomes of the patient-physician encounter.
Objective. The objective of this study was to validate the Malay version patient satisfaction
(MISS-21) questionnaire using a confirmatory validity approach.
Methods. A cross-sectional study was conducted involving 252 patients attending primary health
clinic, Hospital Universiti Sains Malaysia. Construct validity (convergent and discriminant) using
confirmatory factor analysis and internal consistency were performed after the translation, content
validity and face validity processes. Criterion validity was assessed using Pearson correlations
with the scale of shared decision making 9-item questionnaire (SDMQ-9). The data was
analysed using Analysis of Moment Structure version 19.
Results. A total of 252 (100%) outpatients responded to this study. The final model that consists
of three domains with 11 items had a good fit; (χ2
(df) = 65.805 (32), P
Fulltext Acute toxicity and gastroprotective role of M. pruriens in ethanol-induced gastric mucosal injuries in rats

Golbabapour S, Hajrezaie M, Hassandarvish P, Abdul Majid N, Hadi AH, Nordin N, et al.

Biomed Res Int, 2013;2013:974185.
PMID: 23781513 DOI: 10.1155/2013/974185

The investigation was to evaluate gastroprotective effects of ethanolic extract of M. pruriens leaves on ethanol-induced gastric mucosal injuries in rats. Forty-eight rats were divided into 8 groups: negative control, extract control, ulcer control, reference control, and four experimental groups. As a pretreatment, the negative control and the ulcer control groups were orally administered carboxymethylcellulose (CMC). The reference control was administered omeprazole orally (20 mg/kg). The ethanolic extract of M. pruriens leaves was given orally to the extract control group (500 mg/kg) and the experimental groups (62.5, 125, 250, and 500 mg/kg). After 1 h, CMC was given orally to the negative and the extract control groups. The other groups received absolute ethanol. The rats were sacrificed after 1 h. The ulcer control group exhibited significant mucosal injuries with decreased gastric wall mucus and severe damage to the gastric mucosa. The extract caused upregulation of Hsp70 protein, downregulation of Bax protein, and intense periodic acid schiff uptake of glandular portion of stomach. Gastric mucosal homogenate showed significant antioxidant properties with increase in synthesis of PGE2, while MDA was significantly decreased. The ethanolic extract of M. pruriens leaves was nontoxic (<5 g/kg) and could enhance defensive mechanisms against hemorrhagic mucosal lesions.
Production and characterization of violacein by locally isolated Chromobacterium violaceum grown in agricultural wastes

Ahmad WA, Yusof NZ, Nordin N, Zakaria ZA, Rezali MF

Appl Biochem Biotechnol, 2012 Jul;167(5):1220-34.
PMID: 22278051 DOI: 10.1007/s12010-012-9553-7

The present work highlighted the production of violacein by the locally isolated Chromobacterium violaceum (GenBank accession no. HM132057) in various agricultural waste materials (sugarcane bagasse, solid pineapple waste, molasses, brown sugar), as an alternative to the conventional rich medium. The highest yield for pigment production (0.82 g L⁻¹) was obtained using free cells when grown in 3 g of sugarcane bagasse supplemented with 10% (v/v) of L-tryptophan. A much lower yield (0.15 g L⁻¹) was obtained when the cells were grown either in rich medium (nutrient broth) or immobilized onto sugarcane bagasse. Violacein showed similar chemical properties as other natural pigments based on the UV-Vis, Fourier transform infrared spectroscopy, thin-layer chromatography, nuclear magnetic resonance, and mass spectrometry analysis. The pigment is highly soluble in acetone and methanol, insoluble in water or non-polar organic solvents, and showed good stability between pH 5-9, 25-100 °C, in the presence of light metal ions and oxidant such as H₂O₂. However, violacein would be slowly degraded upon exposure to light. This is the first report on the use of cheap and easily available agricultural wastes as growth medium for violacein-producing C. violaceum.
Correlation of antioxidant activities with theoretical studies for new hydrazone compounds bearing a 3,4,5-trimethoxy benzyl moiety

Kareem HS, Ariffin A, Nordin N, Heidelberg T, Abdul-Aziz A, Kong KW, et al.

Eur J Med Chem, 2015 Oct 20;103:497-505.
PMID: 26402727 DOI: 10.1016/j.ejmech.2015.09.016

A new series of antioxidants, namely imines bearing the well-known free radical scavenger group 3,4,5-trimethoxybenzyloxy, was designed and synthesized. Theoretical calculations based on density functional theory (DFT) were performed to understand the antioxidant activities. Experimental studies evaluating the antioxidant activities of the compounds using DPPH and FRAP assays verified the predictions obtained by DMOL3 based on DFT.1. The DPPH radical scavenging activities depended on the substitution pattern of the aromatic aldehyde, with both the substitution type and position showing significant effects. Compounds 7b, 7c and 7d, which contain a phenolic hydroxyl group at the para position to the imine as well as, additional electron donating groups at the ortho-position to this hydroxyl group, exhibited IC₅₀ values of 62, 75 and 106 μg/mL, respectively, and potent antioxidant activities against DPPH, which were better than that of the reference compound BHT. With the exception of compounds 7a and 7h with a phenolic hydroxyl group at the ortho position, all of the investigated compounds exhibited ferric reducing activities above 1000 μM. Correlation analysis between the two antioxidant assays revealed moderate positive correlation (r = 0.59), indicating differing antioxidant activities based on the reaction mechanism. Therefore, imines bearing a 3,4,5-trimethoxybenzyloxy group can be proposed as potential antioxidants for tackling oxidative stress.
Cleistopholine isolated from Enicosanthellum pulchrum exhibits apoptogenic properties in human ovarian cancer cells

Nordin N, Majid NA, Mohan S, Dehghan F, Karimian H, Rahman MA, et al.

Phytomedicine, 2016 Apr 15;23(4):406-16.
PMID: 27002411 DOI: 10.1016/j.phymed.2016.02.016

Cleistopholine is a natural alkaloid present in plants with numerous biological activities. However, cleistopholine has yet to be isolated using modern techniques and the mechanism by which this alkaloid induces apoptosis in cancer cells remains to be elucidated.
Patterns of oviposition and development of Chrysomya megacephala (Fabricius) (Diptera: Calliphoridae) and Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) on burned rabbit carcasses

Mahat NA, Zainol-Abidin NL, Nordin NH, Abdul-Wahab R, Jayaprakash PT

Forensic Sci Int, 2016 Mar;260:9-13.
PMID: 26779962 DOI: 10.1016/j.forsciint.2015.12.047

Considering that crimes against animals such as illegal killing and cruelty have been alarmingly increasing and since burning is one of the common ways for disposing cadavers, ability to estimate minimum postmortem interval (PMI) using entomological data merits consideration. Chrysomya megacephala and Chrysomya rufifacies are common necrophagous species recovered from cadavers in many countries including Malaysia. Specific studies focusing on the oviposition and developmental patterns of both species on cadavers manifesting different levels of burn as described by the Crow-Glassman Scale (CGS) remain scarce. In four replicates, rabbit carcasses were burned to CGS levels #1, #2 and #3 by varying the amount of petrol used and duration of burning. Oviposition by C. megacephala and C. rufifacies was delayed by one day in the case of carcasses burned to the CGS level #3 (p<0.05) when compared with that of controls. Such delay in oviposition was not observed in the CGS level #1 and #2 carcasses. No significant differences (p>0.05) in the duration of development were found between control and burned carcasses. These findings deserve consideration while estimating minimum PMI since burning as a mean for disposing animal and human cadavers is gaining popularity.
A descriptive study of nasogastric tube feeding among geriatric inpatients in Malaysia: utilization, complications, and caregiver opinions

Nordin N, Kamaruzzaman SB, Chin AV, Poi PJ, Tan MP

J Nutr Gerontol Geriatr, 2015;34(1):34-49.
PMID: 25803603 DOI: 10.1080/21551197.2014.998326

The strong emphasis on feeding in Asian cultures may influence decisions for nasogastric (NG) tube feeding in geriatric inpatients. We evaluated the utility, complications, and opinions of caregivers toward NG tube feeding in an acute geriatric ward in a teaching hospital in Kuala Lumpur. Consecutive patients aged 65 years and older receiving NG tube feeding were included. Sociodemographic, clinical, and laboratory indices were recorded. Opinion on NG tube feeding were evaluated through face-to-face interviews with caregivers, recruited through convenience sampling. Of 432 patients admitted, 96 (22%), age ± standard deviation = 80.8 ± 7.4 years, received NG tube feeding. The complication and mortality rates were 69% and 38%, respectively. Diabetes (odds ratio [95% confidence interval] = 3.34 [1.07, 10.44], aspiration pneumonia (8.15 [2.43, 27.24]), impaired consciousness (3.13 [1.05, 9.36]), and albumin ≤26 g/dl (4.43 [1.46, 13.44]) were independent predictors of mortality. Other relatives were more likely than spouses (23.5 [3.59, 154.2]) and caregivers with tertiary education more likely than those with no formal education ( 18 [1.23, 262.7]) to agree to NG feeding. Sixty-four percent of caregivers felt NG tube feeding was appropriate at the end of life, mostly due to the fear of starvation. NG tube feeding is widely used in our setting, despite high complication and mortality rates, with likely influences from cultural emphasis on feeding.
Fulltext Liriodenine, an aporphine alkaloid from Enicosanthellum pulchrum, inhibits proliferation of human ovarian cancer cells through induction of apoptosis via the mitochondrial signaling pathway and blocking cell cycle progression

Nordin N, Majid NA, Hashim NM, Rahman MA, Hassan Z, Ali HM

Drug Des Devel Ther, 2015;9:1437-48.
PMID: 25792804 DOI: 10.2147/DDDT.S77727

Enicosanthellum pulchrum is a tropical plant from Malaysia and belongs to the Annonaceae family. This plant is rich in isoquinoline alkaloids. In the present study, liriodenine, an isoquinoline alkaloid, was examined as a potential anticancer agent, particularly in ovarian cancer. Liriodenine was isolated by preparative high-performance liquid chromatography. Cell viability was performed to determine the cytotoxicity, whilst the detection of morphological changes was carried out by acridine orange/propidium iodide assay. Initial and late apoptosis was examined by Annexin V-fluorescein isothiocyanate and DNA laddering assays, respectively. The involvement of pathways was detected via caspase-3, caspase-8, and caspase-9 analyses. Confirmation of pathways was further performed in mitochondria using a cytotoxicity 3 assay. Apoptosis was confirmed at the protein level, including Bax, Bcl-2, and survivin, while interruption of the cell cycle was used for final validation of apoptosis. The result showed that liriodenine inhibits proliferation of CAOV-3 cells at 37.3 μM after 24 hours of exposure. Changes in cell morphology were detected by the presence of cell membrane blebbing, chromatin condensation, and formation of apoptotic bodies. Early apoptosis was observed by Annexin V-fluorescein isothiocyanate bound to the cell membrane as early as 24 hours. Liriodenine activated the intrinsic pathway by induction of caspase-3 and caspase-9. Involvement of the intrinsic pathway in the mitochondria could be seen, with a significant increase in mitochondrial permeability and cytochrome c release, whereas the mitochondrial membrane potential was decreased. DNA fragmentation occurred at 72 hours upon exposure to liriodenine. The presence of DNA fragmentation indicates the CAOV-3 cells undergo late apoptosis or final stage of apoptosis. Confirmation of apoptosis at the protein level showed overexpression of Bax and suppression of Bcl-2 and survivin. Liriodenine inhibits progression of the CAOV-3 cell cycle in S phase. These findings indicate that liriodenine could be considered as a promising anticancer agent.
Fulltext Prospective role of mitochondrial apoptotic pathway in mediating GMG-ITC to reduce cytotoxicity in H2O2-induced oxidative stress in differentiated SH-SY5Y cells

Jaafaru MS, Nordin N, Rosli R, Shaari K, Bako HY, Noor NM, et al.

Biomed Pharmacother, 2019 Nov;119:109445.
PMID: 31541852 DOI: 10.1016/j.biopha.2019.109445

The antioxidant and neuroprotective activity of Glucomoringin isothiocyanate (GMG-ITC) have been reported in in vivo and in vitro models of neurodegenerative diseases. However, its neuroprotective role via mitochondrial-dependent pathway in a noxious environment remains unknown. The main objective of the present study was to unveil the mitochondrial apoptotic genes' profile and prospectively link with neuroprotective activity of GMG-ITC through its ROS scavenging. The results showed that pre-treatment of differentiated SH-SY5Y cells with 1.25 μg/mL purified isolated GMG-ITC, significantly reduced reactive oxygen species (ROS) production level, compared to H2O2 control group, as evidenced by flow cytometry-based evaluation of ROS generation. Presence of GMG-ITC prior to development of oxidative stress condition, downregulated the expression of cyt-c, p53, Apaf-1, Bax, CASP3, CASP8 and CASP9 genes with concurrent upregulation of Bcl-2 gene in mitochondrial apoptotic signalling pathway. Protein Multiplex revealed significant decreased in cyt-c, p53, Apaf-1, Bax, CASP8 and CASP9 due to GMG-ITC pre-treatment in oxidative stress condition. The present findings speculated that pre-treatment with GMG-ITC may alleviate oxidative stress condition in neuronal cells by reducing ROS production level and protect the cells against apoptosis via neurodegenerative disease potential pathways.
Crossing the Blood-Brain Barrier: A Review on Drug Delivery Strategies for Treatment of the Central Nervous System Diseases

Mansor NI, Nordin N, Mohamed F, Ling KH, Rosli R, Hassan Z

Curr Drug Deliv, 2019;16(8):698-711.
PMID: 31456519 DOI: 10.2174/1567201816666190828153017

Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases.
Fulltext Targeting of CD133+ Cancer Stem Cells by Mesenchymal Stem Cell Expressing TRAIL Reveals a Prospective Role of Apoptotic Gene Regulation in Non-Small Cell Lung Cancer

Fakiruddin KS, Lim MN, Nordin N, Rosli R, Zakaria Z, Abdullah S

Cancers (Basel), 2019 08 28;11(9).
PMID: 31466290 DOI: 10.3390/cancers11091261

Mesenchymal stem cells (MSCs) are emerging as vehicles for anti-tumor cytotherapy; however, investigation on its efficacy to target a specific cancer stem cell (CSC) population in non-small cell lung cancer (NSCLC) is lacking. Using assays to evaluate cell proliferation, apoptosis, and gene expression, we investigated the efficacy of MSCs expressing tumour necrosis factor (TNF)-related apoptosis inducing ligand (MSC-TRAIL) to target and destroy CD133+ (prominin-1 positive) NSCLC-derived CSCs. Characterization of TRAIL death receptor 5 (DR5) revealed that it was highly expressed in the CD133+ CSCs of both H460 and H2170 cell lines. The human MSC-TRAIL generated in the study maintained its multipotent characteristics, and caused significant tumor cell inhibition in NSCLC-derived CSCs in a co-culture. The MSC-TRAIL induced an increase in annexin V expression, an indicator of apoptosis in H460 and H2170 derived CD133+ CSCs. Through investigation of mitochondria membrane potential, we found that MSC-TRAIL was capable of inducing intrinsic apoptosis to the CSCs. Using pathway-specific gene expression profiling, we uncovered candidate genes such as NFKB1, BAG3, MCL1, GADD45A, and HRK in CD133+ CSCs, which, if targeted, might increase the sensitivity of NSCLC to MSC-TRAIL-mediated inhibition. As such, our findings add credibility to the utilization of MSC-TRAIL for the treatment of NSCLC through targeting of CD133+ CSCs.

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