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  1. Fulltext Effects of Reduced Gadolinium-Based Contrast Agents (GBCA) Volumes on MRI Image Quality: An Experimental Phantom Study
    Ismail, N., Bashah, F. A. A., Zakaria, F.
    Physics and Technology in Medicine, 2020;1(2):32-39.
    MyJurnal
    Many recent studies focused on the patient’s safety from the administration of gadolinium-based contrast agents (GBCAs), their concentration, the dose of administration and their effects on the image quality. The present study was aimed at evaluating the effects of reduced GBCAs (gadobutrol and gadoterate meglumine) volume on the image quality by using phantoms. Eight (8) human brain mimicking phantom made of nickel chloride (NiCl2) doped agarose gel were added with 0.00500 ml (100% volume), 0.00350 ml (75% volume), 0.00250 ml (50% volume) and 0.00125 ml (25% volume) of gadobutrol, 0.0100 ml (100% volume), 0.0075 ml (75% volume), 0.0050 ml (50% volume) and 0.0025 ml (25% volume) of gadoterate meglumine. The phantoms were scanned using a 1.5-T and a 3 T-MRI system. Signal-to-noise ratio (SNR) and the contrast agents enhancement were evaluated quantitatively and qualitatively. The 50% volume of gadobutrol and gadoterate meglumine at 3 T showed greater enhancement when compared with 50% and 100% volumes of gadobutrol and gadoterate meglumine at 1.5 T. It can be concluded that the volume of gadobutrol and gadoterate meglumine contrast agents can be reduced when using a higher field system
  2. Comparison study of the MRI shoulder PROPELLER technique with differential image quality by variation of shoulder coils
    Khairi M, Zakaria F, Supar R, Mohd Z
    Med J Malaysia, 2024 Mar;79(Suppl 1):74-81.
    PMID: 38555889
    INTRODUCTION: Motion and pulsation artifacts are the most prominent types of artifacts in Magnetic Resonance Imaging (MRI) of the shoulder. Therefore, this study examined the Periodically Rotating Overlapping Parallel Lines with Enhanced Reconstruction (PROPELLER) technique with small flex coil (SFC) and dedicated shoulder coil (DSC) for the reduction of motion and pulsation artifacts. The signalto- noise ratio (SNR) and contrast-to-noise ratio (CNR) of the standard proton density fat saturation (PDFS) pulse sequence and the PROPELLER proton density fat saturation (PROPELLER PDFS) pulse sequence were also evaluated.

    MATERIALS AND METHODS: Eighteen (18) participants who met the inclusion and exclusion criteria were scanned using a standard non-contrast MRI shoulder protocol including the PDFS pulse sequence and the PROPELLER PDFS pulse sequence using a small flex coil and a dedicated shoulder coil. Two experienced musculoskeletal (MSK) radiologists evaluated and graded the presence of artifacts on the MR images and the SNR and CNR were measured quantitatively.

    RESULTS: The non-parametric Wilcoxon Signed Rank test revealed a significant reduction in motion and pulsation artifacts between the PROPELLER PDFS pulse sequence and the standard PDFS pulse sequence. In addition, the nonparametric Mann-Whitney U test revealed that the mean rank of SNR for the standard sequence was statistically significant when compared to the PROPELLER sequence for both coil types. The CNR of the PROPELLER sequence was statistically significant between fat-fluid, bone-fluid, bonetendon, bone-muscle, and muscle-fluid when using SFC and DSC.

    CONCLUSION: This study proved that the PROPELLER-PDFS pulse sequence effectively eliminates motion and pulsation artifacts, regardless of the coils utilised. The PROPELLERPDFS pulse sequence can therefore be implemented into the standard MRI shoulder procedure.

  3. Anti-Proliferative Effects of Methanol and Water Extracts of Pyrrosia piloselloides on the Hela Human Cervical Carcinoma Cell Line
    Sul ‘ain MD, Zakaria F, Johan MF
    Asian Pac J Cancer Prev, 2019 Jan 25;20(1):185-192.
    PMID: 30678430
    Background: Cervical cancer is one of the most commonly diagnosed neoplasms and a leading cause of cancer
    death among females worldwide. Limitations with conventional medical treatments have driven researchers to
    search for alternative approaches using natural products. This study aimed to detemine potential anti-proliferative
    effects of methanol and water extracts of Pyrrosia piloselloides (P. piloselloides) on the HeLa cell line. Methods:
    3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine IC50
    concentrations and apoptosis analysis was by flow cytometry. To identify chemical compounds in the extracts, gas
    chromatography-mass spectrometry (GC-MS) was employed. Results: P. piloselloides methanol extracts (PPME) showed
    antiproliferative effects on HeL awith an IC50 of 16.25μg/mL while the P. piloselloides water extract (PPWE) was without
    influence. Neither extract showed any significant effects on apoptosis. GC-MS analysis, revealed 5-hydroxymethylfurfural
    (23.1%), allopurinol (8.66%) and 3, 5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (7.41%) as major components in
    the PPME, while sulfolan-3-ol (10.1%), linoleic acid (9.06%) and β-sitosterol acetate (7.98%) predominated in the
    PPWE case. Conclusion: This first study of P. piloselloides showed PPME to exert potent anti-proliferative effect on
    HeLa cell lines. Further research now needs to be performed to establish the mechanisms of inhibition.
  4. Fulltext A Link between Mitochondrial Dysregulation and Idiopathic Autism Spectrum Disorder (ASD): Alterations in Mitochondrial Respiratory Capacity and Membrane Potential
    Hassan H, Zakaria F, Makpol S, Karim NA
    Curr Issues Mol Biol, 2021 Dec 16;43(3):2238-2252.
    PMID: 34940131 DOI: 10.3390/cimb43030157
    Autism spectrum disorder (ASD) is a neurological disorder triggered by various factors through complex mechanisms. Research has been done to elucidate the potential etiologic mechanisms in ASD, but no single cause has been confirmed. The involvement of oxidative stress is correlated with ASD and possibly affects mitochondrial function. This study aimed to elucidate the link between mitochondrial dysregulation and idiopathic ASD by focusing on mitochondrial respiratory capacity and membrane potential. Our findings showed that mitochondrial function in the energy metabolism pathway was significantly dysregulated in a lymphoblastoid cell line (LCL) derived from an autistic child (ALCL). Respiratory capacities of oxidative phosphorylation (OXPHOS), electron transfer of the Complex I and Complex II linked pathways, membrane potential, and Complex IV activity of the ALCL were analyzed and compared with control cell lines derived from a developmentally normal non-autistic sibling (NALCL). All experiments were performed using high-resolution respirometry. Respiratory capacities of OXPHOS, electron transfer of the Complex I- and Complex II-linked pathways, and Complex IV activity of the ALCL were significantly higher compared to healthy controls. Mitochondrial membrane potential was also significantly higher, measured in the Complex II-linked pathway during LEAK respiration and OXPHOS. These results indicate the abnormalities in mitochondrial respiratory control linking mitochondrial function with autism. Correlating mitochondrial dysfunction and autism is important for a better understanding of ASD pathogenesis in order to produce effective interventions.
  5. Fulltext Prevalence and Pattern of Glomerulonephritis: An Experience of Two Tertiary Centers in Malaysia
    Maifata S, Hod R, Ghani FA, Zakaria F
    Saudi J Kidney Dis Transpl, 2023 Mar 01;34(2):167-177.
    PMID: 38146727 DOI: 10.4103/1319-2442.391896
    The prevalence of glomerulonephritis (GN), especially membranous GN (MGN), changes from time to time. This change may be due to genetic predisposition, environmental factors race, age, and indications for a renal biopsy. This study was conducted to evaluate the distribution and changing patterns of GN by further assessing the prevalence of MGN. A 1000, 123 biopsies were performed from January 2012 to October 2019 in Hospital Serdang and Hospital Kuala Lumpur. Electron microscopy, immunohistochemistry, and clinical presentations were used to differentiate primary and secondary MGN, from which 611 and 457 primary and secondary subjects were diagnosed with primary and secondary GN, respectively. Primary MGN accounts for 13% of all the primary GN, while lupus nephritis (LN) accounts for 44.2% of all secondary GN followed by diabetes mellitus (25.6%). The proportions of primary and secondary MGN were 64.8% and 35.2%, respectively, with a male-to-female ratio of 1:1.1 in favor of females. The renal biopsy obtained from the registry of two prominent hospitals in Malaysia provided valuable prevalence and demonstrated changes in the prevalence of GN in Malaysia. Notwithstanding, immunoglobulin A nephropathy and LN remain the most common causes of primary and secondary GN in Malaysia.
  6. Fulltext Hypoglycemic and Antidiabetic Effect of Pleurotus sajor-caju Aqueous Extract in Normal and Streptozotocin-Induced Diabetic Rats
    Ng SH, Mohd Zain MS, Zakaria F, Wan Ishak WR, Wan Ahmad WA
    Biomed Res Int, 2015;2015:214918.
    PMID: 26682215 DOI: 10.1155/2015/214918
    Pleurotus sajor-caju (PSC) is an edible oyster mushroom featuring high nutritional values and pharmacological properties. Objective. To investigate the hypoglycemic and antidiabetic effects of single and repeated oral administration of PSC aqueous extract in normal and diabetic rats.
  7. Behavioral and cortisol analysis of the anti-stress effect of Polygonum minus (Huds) extracts in chronic unpredictable stress (CUS) zebrafish model
    Abdul Rahim N, Nordin N, Ahmad Rasedi NIS, Mohd Kauli FS, Wan Ibrahim WN, Zakaria F
    Comp Biochem Physiol C Toxicol Pharmacol, 2022 Jun;256:109303.
    PMID: 35202824 DOI: 10.1016/j.cbpc.2022.109303
    The World Health Organization (WHO) recorded approximately 350 million people worldwide have suffered from mental health disorders, such as depression, anxiety, schizophrenia, and addictive behaviors. The search for new drugs from nature has drawn on many biological resources and human practices. In this study, leaves of Polygonum minus standardized extract (Biokesum®), 1 and 100 mg/L were used to evaluate the anti-stress effect in the chronic unpredictable stress (CUS) zebrafish model. Five groups of zebrafish were manipulated in this study, comprising control, chronic unpredictable stress (CUS), CUS + Biokesum® 1 mg/L (4 days, 20 min/day, immersion) CUS + Biokesum® 100 mg/L (4 days, 20 min/day, immersion) and CUS + fluoxetine 0.6 mg/L (4 days, 20 min/day, immersion). Four different behavioral tests were used, i.e. open-field test, social interaction test, light and dark test, and exploratory test. After four consecutive days of treatment, the zebrafish were sacrificed for whole-body cortisol analysis. The exploratory test showed a significant change upon P. minus treatment (one-way ANOVA; p = 0.0011). Cortisol analysis showed a decrease of cortisol level after treatment with the extract and fluoxetine, without significant difference. These results showed that zebrafish is a reliable model to study the anti-stress effect of compounds or herbal extract.
  8. Biomarker triterpenoids of Centella asiatica as potential antidepressant agents: Combining in vivo and in silico studies
    Mando Z, Mando H, Afzan A, Shaari K, Hassan Z, Mohamad Taib MNA, et al.
    Behav Brain Res, 2024 May 28;466:114976.
    PMID: 38599249 DOI: 10.1016/j.bbr.2024.114976
    Although there are various treatments available for depression, some patients may experience resistance to treatment or encounter adverse effects. Centella asiatica (C. asiatica) is an ancient medicinal herb used in Ayurvedic medicine for its rejuvenating, neuroprotective and psychoactive properties. This study aims to explore the antidepressant-like effects of the major constituents found in C. asiatica, i.e., asiatic acid, asiaticoside, madecassic acid, and madecassoside at three doses (1.25, 2.5, and 5 mg/kg, i.p), on the behavioural and cortisol level of unpredictable chronic stress (UCS) zebrafish model. Based on the findings from the behavioural study, the cortisol levels in the zebrafish body after treatment with the two most effective compounds were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, a molecular docking study was conducted to predict the inhibitory impact of the triterpenoid compounds on serotonin reuptake. The in vivo results indicate that madecassoside (1.25, 2.5, and 5 mg/kg), asiaticoside and asiatic acid (5 mg/kg) activated locomotor behaviour. Madecassoside at all tested doses and asiaticoside at 2.5 and 5 mg/kg significantly decreased cortisol levels compared to the stressed group, indicating the potential regulation effect of madecassoside and asiaticoside on the hypothalamic-pituitary-adrenal axis overactivity. This study highlights the potential benefits of madecassoside and asiaticoside in alleviating depressive symptoms through their positive effects on behaviour and the hypothalamic-pituitary-adrenal (HPA)- axis in a chronic unpredictable stress zebrafish model. Furthermore, the in silico study provided additional evidence to support these findings. These promising results suggest that C. asiatica may be a valuable and cost-effective therapeutic option for depression, and further research should be conducted to explore its potential benefits.
  9. Fulltext Medicinal plants' proposed nanocomposites for the management of endocrine disorders
    Al Zarzour RH, Kamarulzaman EE, Saqallah FG, Zakaria F, Asif M, Abdul Razak KN
    Heliyon, 2022 Sep;8(9):e10665.
    PMID: 36185142 DOI: 10.1016/j.heliyon.2022.e10665
    Extensive attention has been focused on herbal medicine for the treatment of different endocrine disorders. In fact, compelling scientific evidence indicates that natural compounds might act as endocrine modulators by mimicking, stimulating, or inhibiting the actions of different hormones, such as thyroid, sex, steroidal, and glucose regulating hormones. These potentials might be effectively employed for therapeutic purposes related to the endocrine system as novel complementary choices. Nevertheless, despite the remarkable therapeutic effects, inadequate targeting efficiency and low aqueous solubility of the bioactive components are still essential challenges in their clinical accreditation. On the other hand, nanotechnology has pushed the wheels of combining inorganic nanoparticles with biological structures of medicinal bioactive compounds as one of the utmost exciting fields of research. Nanoparticle conjugations create an inclusive array of applications that provide greater compliance, higher bioavailability, and lower dosage. This can safeguard the global availability of these wealthy natural sources, regardless of their biological occurrence. This review inspects future challenges of medicinal plants in various endocrine disorders for safe and alternative treatments with examples of their nanoparticle formulations.
  10. Fulltext Ultrasound-assisted extraction conditions optimisation using response surface methodology from Mitragyna speciosa (Korth.) Havil leaves
    Zakaria F, Tan JK, Mohd Faudzi SM, Abdul Rahman MB, Ashari SE
    Ultrason Sonochem, 2021 Dec;81:105851.
    PMID: 34864545 DOI: 10.1016/j.ultsonch.2021.105851
    The optimisation of the Ultrasound-Assisted Extraction (UAE) method was investigated by employing the Central Composite Rotatable Design (CCRD) of Response Surface Methodology (RSM). The UAE method was based on a simple ultrasound treatment using methanol as the extraction medium to facilitate the cell disruption of Mitragyna speciosa leaves for optimum extraction yield and Total Phenolic Content (TPC). Three different parameters comprising extraction temperature (X1: 25-50 °C), sonication time (X2: 15-50 min), and solvent to solid ratio (X3: 10-30 mL/g), and were selected as the independent variables, while two response variables were selected, namely extraction yield (Y1) and TPC (Y2). Based on the results, the developed quadratic polynomial model correlated with the experimental data is based on the coefficient of determination (R2) of extraction yield (0.9972, p 
  11. Perturbations in Amino Acid Metabolism in Reserpine-Treated Zebrafish Brain Detected by 1H Nuclear Magnetic Resonance-Based Metabolomics
    Zakaria F, Akhtar MT, Wan Ibrahim WN, Abu Bakar N, Muhamad A, Shohaimi S, et al.
    Zebrafish, 2021 02;18(1):42-54.
    PMID: 33538644 DOI: 10.1089/zeb.2020.1895
    Depression is a complex and disabling psychiatric disorder, which is expected to be a leading cause for disability by 2030. According to World Health Organization, about 350 million people are suffering with mental health disorders around the globe, especially depression. However, the mechanisms involved in stress-induced depression have not been fully elucidated. In this study, a stress-like state was pharmacologically induced in zebrafish using reserpine, a drug widely used to mediate depression in experimental animal models. Zebrafish received single intraperitoneal (i.p.) injections of 20, 40, and 80 mg/kg body weight reserpine doses and were subjected to open-field test at 2, 24, 48, 72, and 96 h after the treatment. Along with observed changes in behavior and measurement of cortisol levels, the fish were further examined for perturbations in their brain metabolites by 1H nuclear magnetic resonance (NMR)-based metabolomics. We found a significant increase in freezing duration, whereas total distance travelled was decreased 24 h after single intraperitoneal injection of reserpine. Cortisol level was also found to be higher after 48 h of reserpine treatment. The 1H NMR data showed that the levels of metabolites such as glutamate, glutamine, histamine, valine, leucine and histidine, lactate, l-fucose, betaine and γ-amino butyric acid (GABA), β-hydroxyisovalerate, and glutathione were significantly decreased in the reserpine-treated group. This study provided some insights into the molecular nature of stress that could contribute toward a better understanding of depression disorder.
  12. Fulltext In Vitro Modulation of Endogenous Antioxidant Enzyme Activities and Oxidative Stress in Autism Lymphoblastoid Cell Line (ALCL) by Stingless Bee Honey Treatment
    Nayan NS, Yazid MAM, Nallappan K, Amran AA, Zaidi NS, Zakaria F, et al.
    Oxid Med Cell Longev, 2020;2020:4539891.
    PMID: 33335642 DOI: 10.1155/2020/4539891
    Autism has been associated with a low antioxidant defense mechanism, while honey has been known for decades for its antioxidant and healing properties. Determination of stingless bee honey (KH) effects on antioxidant enzyme activities and oxidative damage in Autism Lymphoblastoid Cell Line (ALCL) was performed. ALCL and its normal sibling pair (NALCL) were cultured in RPMI-1640 medium at 37°C and 5% CO2. ALCL was treated with 400 μg/mL KH (24 h), and oxidative stress marker, malondialdehyde (MDA), and antioxidant enzyme activities (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured via enzyme-linked immunosorbent assay (ELISA), while deoxyribonucleic acid (DNA) damage was determined via comet assay. Low SOD activity (p < 0.05) and high MDA level (p < 0.05) were observed in ALCL compared to NALCL. Higher grade (Grades 2 and 3) of DNA damage was highly observed (p < 0.05) in ALCL compared to NALCL, whereas lower grade (Grades 0 and 1) DNA damage was highly detected (p < 0.05) in NALCL compared to ALCL. KH treatment caused a significant increase in SOD and GPx activities (p < 0.05) in ALCL compared to untreated ALCL. Correspondingly, KH treatment reduced the Grade 2 DNA damage (p < 0.05) in ALCL compared to untreated ALCL. CAT activity showed no significant difference between all three groups, while the MDA level showed no significant difference between treated and untreated ALCL. In conclusion, KH treatment significantly reduced the oxidative stress in ALCL by increasing the SOD and GPx antioxidant enzyme activities, while reducing the DNA damage.
  13. Centella asiatica (L.) Urb. Extract ameliorates branched-chain amino acid (BCAA) metabolism in acute reserpine-induced stress zebrafish model via 1H Nuclear Magnetic Resonance (NMR)-based metabolomics approach
    Zakaria F, Akhtar MT, Wan Norhamidah WI, Noraini AB, Muhamad A, Shohaimi S, et al.
    Comp Biochem Physiol C Toxicol Pharmacol, 2023 Feb;264:109501.
    PMID: 36336330 DOI: 10.1016/j.cbpc.2022.109501
    Depression is a common mental disorder that can adversely affect psychosocial function and quality of life. However, the exact aetiology and pathogenesis of depression are still unclear. Stress plays a major role in the pathogenesis of depression. The use of currently prescribed antidepressants has many side effects. Centella asiatica (C. asiatica) has shown promising antidepressant activity in rodent models. Here, we developed a reserpine-induced zebrafish stress-like model and performed behavioural analysis, cortisol measurement and 1H-Nuclear Magnetic Resonance (1H NMR) spectroscopy-based metabolomics analysis to test the anti-stress activity of ethanolic extract of C. asiatica (RECA). A significant increase in total distance travelled (F(8,8) = 8.905, p = 0.0054) and a reduction in freezing duration (F(9, 9) = 10.38, p = 0.0018) were found in the open field test (OFT). Asiaticoside, one of tested C.asiatica's triterpenoid gives a significant increase in contact duration (F(5,5) = 142.3, (p = 0.0330) at 2.5 mg/kg). Eight biomarkers were found, i.e. ß-hydroxyisovaleric acid, leucine, threonine, scylloinositol, lactate, betaine, valine, choline and l-fucose, to be responsible for the class separation between stress and RECA-treated groups. Metabolic pathway alteration in zebrafish brain upon treatment with RECA was identified as valine, leucine and isoleucine biosynthesis, while alanine, aspartate, glutamate and glycerophospholipid metabolism was involved after fluoxetine treatment.
  14. Antidepressant evaluation of Andrographis paniculata Nees extract and andrographolide in chronic unpredictable stress zebrafish model
    Aldurrah Z, Mohd Kauli FS, Abdul Rahim N, Zainal Z, Afzan A, Al Zarzour RH, et al.
    Comp Biochem Physiol C Toxicol Pharmacol, 2023 Sep;271:109678.
    PMID: 37301417 DOI: 10.1016/j.cbpc.2023.109678
    Andrographis paniculata (A. paniculata) showed an anti-depressive effect in rodent models. Zebrafish has recently emerged as a worthy complementary translational model for antidepressant drug discovery study. This study investigates the anti-depressive effect of A. paniculata extract and andrographolide in the chronic unpredictable stress (CUS)- zebrafish model. Four groups of zebrafish (n = 10/group), i.e. control, CUS (stressed, untreated), CUS + A. paniculata (100 mg/L) and CUS + fluoxetine (0.01 mg/L) were assessed in open-field and social interaction tests, 24 h after treatment. After extract screening, behavioural and cortisol analysis of andrographolide (5, 25 and 50 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) were evaluated. Before the behavioural study, acute toxicity and characterization of A. paniculata extract using UHPLC-ESI-MS/MS were performed. A significant reduction in freezing duration was found in A. paniculata- (t-test, p = 0.0234) and fluoxetine-treated groups (t-test, p 
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