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Brain magnetic resonance image segmentation using novel improvement for expectation maximizing

Balafar MA, Ramli AR, Mashohor S

Neurosciences (Riyadh), 2011 Jul;16(3):242-7.
PMID: 21677615

To improve the quality of expectation maximizing (EM) for brain image segmentation, and to evaluate the accuracy of segmentation results.
Epigenomic approach in understanding Alzheimer's disease and type 2 diabetes mellitus

Shaik MM, Gan SH, Kamal MA

CNS Neurol Disord Drug Targets, 2014 Mar;13(2):283-9.
PMID: 24074446 DOI: 10.2174/18715273113126660181

Cognitive decline is a debilitating feature of Alzheimer's disease (AD). The causes leading to such impairment are still poorly understood and effective treatments for AD are still unavailable. Type 2 diabetes mellitus (T2DM) has been identified as a risk factor for AD due to desensitisation of insulin receptors in the brain. Recent studies have suggested that epigenetic mechanisms may also play a pivotal role in the pathogenesis of both AD and T2DM. This article describes the correlation between AD and T2DM and provides the insights to the epigenetics of AD. Currently, more research is needed to clarify the exact role of epigenetic regulation in the course and development of AD and also in relation to insulin. Research conducted especially in the earlier stages of the disease could provide more insight into its underlying pathophysiology to help in early diagnosis and the development of more effective treatment strategies.
Targeting immunosuppressor cells with nanoparticles in autoimmunity: How far have we come to?

Ahmad S, Al-Hatamleh MAI, Mohamud R

Cell Immunol, 2021 10;368:104412.
PMID: 34340162 DOI: 10.1016/j.cellimm.2021.104412

Autoimmunity is the assault of immune response towards self-antigens, resulting to inflammation and tissue injury. It is staged into three phases and caused by malfunction of immune tolerance. In our body, immune tolerance is synchronized by several immunosuppressor cells such as regulatory T cells and B cells as well as myeloid-derived suppressor cells, which are prominently dysregulated in autoimmunity. Hence, targeting these cell populations serve as a significant potential in the therapy of autoimmunity. Nanotechnology with its advantageous properties is shown to be a remarkable tool as drug delivery system in this field. This review focused on the development of therapeutics in autoimmune diseases utilizing various nanoparticles formulation based on two targeting approaches in autoimmunity, passive and active targeting. Lastly, this review outlined the approved present nanomedicines as well as in clinical evaluations and issues regarding the lack of translation of these nanomedicines into the market, despite the abundant of positive experimental observations.
Fulltext A comparative study of antibacterial and antivirulence activities of four selected honeys to Manuka honey

Al-Kafaween MA, Nagi Al-Jamal HA

Iran J Microbiol, 2022 Apr;14(2):238-251.
PMID: 35765547 DOI: 10.18502/ijm.v14i2.9193

BACKGROUND AND OBJECTIVES: Honey has excellent antibacterial properties against various microorganisms of several different species. To date, there is no comparative evaluation of the antibacterial activity of Jarrah honey (JH), Kelulut Madu honey (KMH), Gelam honey (GH), and Acacia honey (AH) with that of Manuka honey (MH). The purpose of this study was to conduct such study and to compare the antibacterial activity of JH, KMH, GH, and AH with that of MH against Pseudomonas aeruginosa and Streptococcus pyogenes.
MATERIALS AND METHODS: Activity was assessed using broth microdilution, time kill viability, microtiter plate, scanning electron microscope (SEM) and Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR).
RESULTS: The susceptibility tests revealed promising antibacterial activities of all honeys against both bacteria. The MICs of JH, KMH, GH, and AH ranged from 20% to 25% compared to MH (12.5%) against both bacteria. The MBCs of JH, KMH, GH, and AH ranged from 20% to 50% compared to MH (20%) against both bacteria. Treatment of both bacteria with 2× MIC (Minimum inhibitory concentration) of MH, JH, KMH, GH, and AH for 9 hours resulted in reduction in colony-forming unit (CFU/ml). SEM images showed that the morphological changes, cell destruction, cell lysis and biofilm disruption in both bacteria after exposure to all honeys. RT-qPCR analysis revealed that the expression of all genes in both bacteria were downregulated following treatment with all honeys. Among the all-tested honeys, MH showed the highest total antibacterial and antivirulence activities.
CONCLUSION: Our results indicate that all honeys activity included inhibition of both bacteria due to a decrease in expression of essential genes associated with both bacteria, suggesting that all honeys could potentially be used as an alternative therapeutic agent against certain microorganisms particularly against P. aeruginosa and S. pyogenes.
Do folate, vitamins B₆ and B₁₂ play a role in the pathogenesis of migraine? The role of pharmacoepigenomics

Shaik MM, Tan HL, Kamal MA, Gan SH

CNS Neurol Disord Drug Targets, 2014;13(5):828-35.
PMID: 24040787

Migraine is a neurovascular disease that has classically been attributed to multifactorial aetiologies, with genetic components and environmental interactions considered the main influence. Genes such as flavoenzyme 5, 10- methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have been associated with elevated plasma homocysteine levels. This elevation in homocysteine results in an array of metabolic disorders and increased risk of complex diseases, including migraine. Catalysation of homocysteine requires the presence of vitamins B6, B12 and folate. Deficiencies in these cofactor vitamins result in hypomethylation, which triggers migraine. Because migraine predominantly affects females, it is hypothesised that fluctuating oestrogen levels, which are governed by oestrogen receptor 1 polymorphisms, are important. Another important factor is homocysteine, the production of which is dependent upon MTHFR and B vitamins. Gene expression is modulated through epigenetic mechanisms, which involve methionine. Additionally, folate plays a major role in DNA synthesis. We propose that vitamin B intake, coupled with MTHFR and oestrogen receptor 1 polymorphisms, causes differential DNA methylation and gene expression that may contribute to the occurrence of migraine.
Current Genetic and Epigenetic Insights into Type 2 Diabetes Mellitus

Alam F, Kamal MA, Islam MA, Banu S

Endocr Metab Immune Disord Drug Targets, 2019;19(6):717-718.
PMID: 31530259 DOI: 10.2174/187153031906190724104004
Fulltext Mushrooms: a potential natural source of anti-inflammatory compounds for medical applications

Elsayed EA, El Enshasy H, Wadaan MA, Aziz R

Mediators Inflamm, 2014;2014:805841.
PMID: 25505823 DOI: 10.1155/2014/805841

For centuries, macrofungi have been used as food and medicine in different parts of the world. This is mainly attributed to their nutritional value as a potential source of carbohydrates, proteins, amino acids, and minerals. In addition, they also include many bioactive metabolites which make mushrooms and truffles common components in folk medicine, especially in Africa, the Middle East, China, and Japan. The reported medicinal effects of mushrooms include anti-inflammatory effects, with anti-inflammatory compounds of mushrooms comprising a highly diversified group in terms of their chemical structure. They include polysaccharides, terpenoids, phenolic compounds, and many other low molecular weight molecules. The aims of this review are to report the different types of bioactive metabolites and their relevant producers, as well as the different mechanisms of action of mushroom compounds as potent anti-inflammatory agents.
Immune-mediated Pathogenesis and Therapies for Inflammatory Autoimmune Diseases

Islam MA, Kamal MA, Md Zulfiker AH, Gan SH

Curr Pharm Des, 2019;25(27):2907-2908.
PMID: 31621552 DOI: 10.2174/138161282527191007151037
Fulltext Curation of an international drug proprietary names dataset

Khaleel MA, Khan AH, Ghadzi SMS, Alshakhshir S

Data Brief, 2022 Feb;40:107701.
PMID: 34988273 DOI: 10.1016/j.dib.2021.107701

A drug dataset containing international proprietary names is essential for researchers investigating different drugs from different countries worldwide. However, many websites on the internet offer free access for a single drug searching service to identify international drug trade names, but not for a list of drugs to be searched and identified. Therefore, it will be problematic if the researcher has a list of hundreds or thousands of drug trade names to be identified. In this project, we have created an International Drug Dictionary (IDD) by curating collected drug lists from open access websites belonging to official drug regulatory agencies, official healthcare systems, or recognized scientific bodies from 44 countries around the world in addition to the European public assessment reports (EPAR) and the DRUGBANK vocabulary published in the public domain. Researchers interested in pharmacovigilance, pharmacoepidemiology, or pharmacoeconomics can benefit from this dataset, especially when identifying lists of proprietary drug names, particularly of multi-national origin. To enhance its adaptability, we also mapped the IDD to the standardized drug vocabulary RxNorm. The IDD can also be used as a tool for mapping international drug trade names to RxNorm. Each drug entity in the IDD mapped to a unique identification number for each entity called Atom Unique Identifier (RXAUI) from RxNorm.
Fulltext Comparison of the antimicrobial and antivirulence activities of Sidr and Tualang honeys with Manuka honey against Staphylococcus aureus

Al-Kafaween MA, Al-Groom RM, Hilmi ABM

Iran J Microbiol, 2023 Feb;15(1):89-101.
PMID: 37069905 DOI: 10.18502/ijm.v15i1.11923

BACKGROUND AND OBJECTIVES: Honey is one of the oldest traditional remedies that has been widely utilized to cure a variety of human ailments. The objective of this research was to test and compare the antibacterial activity of Sidr honey (SH) and Tualang honey (TH) to that of Manuka honey (MH) against Staphylococcus aureus.
MATERIALS AND METHODS: The antibacterial activity of MH, SH and TH against S. aureus was investigated by agar well diffusion, Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), time-kill curve, microtiter plate and RT-qPCR analysis.
RESULTS: Agar inhibition assay showed that MH possess highest total antibacterial activity against S. aureus with an inhibition zone 25.1 mm compared with that of SH (22.2 mm) and TH (21.3 mm). The findings showed that when compared to SH and TH (MIC: 25% and MBC: 50%), MH honey had the lowest MIC (12.5%) and MBC (25%). After S. aureus was exposed to MH, SH, and TH, there was a decrease in colony-forming unit as seen by the time-kill curve. The lowest concentration 20% of MH, SH and TH was significantly found to inhibit S. aureus biofilm. The RT-qPCR results revealed that all the selected genes in S. aureus were downregulated in gene expression following exposure to each of the tested honeys. Comparing the total antibacterial, antibiofilm, and antivirulence activities of all the tested honeys, MH demonstrated the greatest levels of these properties.
CONCLUSION: According to this study, various types of each evaluated honey have the capacity to effectively suppress and modify the virulence of S. aureus via a variety of molecular targets.
Synthesis and characterization of poly (methyl methacrylate)/SiO2 hybrid membranes: effect of solvents on thermal properties

Zulfikar MA, Mohammad AW

Med J Malaysia, 2004 May;59 Suppl B:141-2.
PMID: 15468858

Hybrid organic-inorganic membranes were fabricated using sol-gel technique using PMMA and TEOS with 80/20 (w/w) ratio at various solvents. The thin membrane films were then characterized using DSC and TGA. From DSC analysis, the Tg value of the PMMA moieties in hybrids membranes was in the order H-15-Toluene < Pure PMMA < H-15-THF < H-15-DMF. Furthermore, from TGA analysis it was found that the hybrid membranes have higher thermal stability compared to pure PMMA, and the type of solvents used play an important role in their degradation behavior.
Fulltext The HUKM Spinal Instrumentation System for adolescent idiopathic scoliosis. A biomechanical comparison study using finite element analysis

Azlan AM, Mohammad AR, Ariffin AK

Med J Malaysia, 2005 Jul;60 Suppl C:30-4.
PMID: 16381280 MyJurnal

This finite element analysis is aimed at comparing relative stiffness of three different posterior instrumentation constructs: the Hospital Universiti Kebangsaan Malaysia Spinal Instrumentation System (HUKM-SIS), the Cotrell-Dubousset Instrumentation (CDI) and Harrington Instrumentation System (HIS), used in the treatment of adolescent idiopathic scoliosis (AIS). The constructs were tested under various loads using MSC Patran 2001 r2a. Under increasing flexion loads, there was a linearly corresponding increase in deflection magnitudes for all constructs on the load-deflection curve. The CDI was the stiffest construct under axial, forward flexion and extension loads, followed by the HUKM-SIS and HIS. Under lateral bending loads, the HUKM-SIS construct was the stiffest followed by CDI and HIS. The HUKM-SIS construct was stiffer than HIS under torsional loads. We conclude that multiple pedicle screws increase the stiffness of posterior instrumentation constructs under all loads and inter-segmental spinous processes wiring increase the stiffness against lateral bending.
Fulltext The pattern of femoral diaphyseal fractures in children admitted in Sarawak General Hospital

Rasit AH, Mohammad AW, Pan KL

Med J Malaysia, 2006 Feb;61 Suppl A:79-82.
PMID: 17042236

Trend towards changing the face of management for pediatric femoral fractures tends to advocate operative treatment. This study was undertaken to review our current practice in the wake of recent progress in the management of pediatric femoral fractures. Fifty patients with femoral diaphyseal fracture treated in Sarawak General Hospital were reviewed retrospectively after an average follow-up of 2.6 years. There were 36 boys and 14 girls, with a mean age of 6.2 years (range five months to 14 years). Children under six years of age constituted the majority of the patients. Half of the fractures were caused by road traffic accident. Nine patients had associated injuries. The most common site of fracture was at the middle third (N=31). The treatment regimens were delayed hip spica (DHS) in 16, immediate hip spica (IHS) in 24, plate osteosynthesis (PO) in five, titanium elastic nailing (TEN) in five, and external fixation (EF) in one. The minimum hospital stay was two days, and the maximum 33 days (mean, 9.7 days). Malunion was the commonest complication. Conservative treatment is the preferred option for children under six years of age. It is cost-effective with minimal complication. The other treatment options are reserved for specific indication in older children. Diaphyseal fractures of the femur in children can be adequately managed non-operatively.
Recurrent parent genome recovery analysis in a marker-assisted backcrossing program of rice (Oryza sativa L.)

Miah G, Rafii MY, Ismail MR, Puteh AB, Rahim HA, Latif MA

C. R. Biol., 2015 Feb;338(2):83-94.
PMID: 25553855 DOI: 10.1016/j.crvi.2014.11.003

Backcross breeding is the most commonly used method for incorporating a blast resistance gene into a rice cultivar. Linkage between the resistance gene and undesirable units can persist for many generations of backcrossing. Marker-assisted backcrossing (MABC) along with marker-assisted selection (MAS) contributes immensely to overcome the main limitation of the conventional breeding and accelerates recurrent parent genome (RPG) recovery. The MABC approach was employed to incorporate (a) blast resistance gene(s) from the donor parent Pongsu Seribu 1, the blast-resistant local variety in Malaysia, into the genetic background of MR219, a popular high-yielding rice variety that is blast susceptible, to develop a blast-resistant MR219 improved variety. In this perspective, the recurrent parent genome recovery was analyzed in early generations of backcrossing using simple sequence repeat (SSR) markers. Out of 375 SSR markers, 70 markers were found polymorphic between the parents, and these markers were used to evaluate the plants in subsequent generations. Background analysis revealed that the extent of RPG recovery ranged from 75.40% to 91.3% and from 80.40% to 96.70% in BC1F1 and BC2F1 generations, respectively. In this study, the recurrent parent genome content in the selected BC2F2 lines ranged from 92.7% to 97.7%. The average proportion of the recurrent parent in the selected improved line was 95.98%. MAS allowed identification of the plants that are more similar to the recurrent parent for the loci evaluated in backcross generations. The application of MAS with the MABC breeding program accelerated the recovery of the RP genome, reducing the number of generations and the time for incorporating resistance against rice blast.
Isolation and characterization of bioactive compounds from the bark of Litsea costalis

Hosseinzadeh M, Mohamad J, Khalilzadeh MA, Zardoost MR, Haak J, Rajabi M

J. Photochem. Photobiol. B, Biol., 2013 Nov 5;128:85-91.
PMID: 24077497 DOI: 10.1016/j.jphotobiol.2013.08.002

The bark of Litsea costalis affords two new compounds named 4,4'-diallyl-5,5'-dimethoxy-[1,1'-biphennyl]-2,2'-diol, biseugenol A (1) and 2,2'-oxybis (4-allyl-1-methoxybenzene), biseugenol B (2) along with two known compounds (3-4), namely 5-methoxy-2-Hydroxy Benzaldehyde (3), and (E)-4-styrylphenol (4). The structures of 1 and 2 were determined using 1D and 2D NMR data. Also, the IR and NMR data were combined with quantum chemical calculations in the DFT approach using the hybrid B3LYP exchange-correlation function to confirm the structures of the compounds. Compounds showed fairly potent anticancer activity against cell lines and antioxidant (DPPH).
Sexual dysfunction and its determinants in Malaysian women with rheumatoid arthritis

Shahar MA, Hussein H, Sidi H, Shah SA, Mohamed Said MS

Int J Rheum Dis, 2012 Oct;15(5):468-77.
PMID: 23083037 DOI: 10.1111/j.1756-185X.2012.01753.x

AIM: To determine the prevalence of sexual dysfunction (FSD) among women with rheumatoid arthritis attending the Rheumatology Clinic in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) and Hospital Putrajaya, Malaysia, and to determine its associations with potential clinical and disease activity factors.
METHOD: This was a cross-sectional study involving women with rheumatoid arthritis between the ages of 20 and 60 years. A validated Malay Version Female Sexual Function Index (MVFSFI) was administered to diagnose FSD. Sociodemographic and disease activity profiles were obtained and those who had and did not have FSD were compared.
RESULTS: Among 63 respondents, 51 patients were included in the analysis for FSD. The prevalence of FSD in women with rheumatoid arthritis attending UKMMC and Hospital Putrajaya Rheumatology Clinic was 29.4%. Erythrocyte sedimentation rate (ESR) and Disease Activity Score in 28 joints (DAS28-ESR) correlates with MVFSFI score with r=-0.364 (P=0.009) and r=-0.268 (P=0.057), respectively. Sociodemographic factors that correlate with MVFSFI score were: patient's age (r=0.520, P<0.001); duration of marriage (r=-0.355, P=0.001); husband's age (r=-0.460, P=0.001); age of oldest child (r=-0.449, P=0.001); and age of youngest child (r=-0.627, P<0.001).
CONCLUSION: We found in this study that the prevalence of FSD in rheumatoid arthritis in our centers was 29.4%. Age and family dynamics appear to be more important predictors compared to disease activity.
Study site: Rheumatology Clinic, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) and Hospital Putrajaya, Malaysia
Flavonoids and linderone from Lindera oxyphylla and their bioactivities

Hosseinzadeh M, Hadi AH, Mohamad J, Khalilzadeh MA, Cheahd SC, Fadaeinasab M

Comb Chem High Throughput Screen, 2013 Feb;16(2):160-6.
PMID: 23173924

A new linderone A, namely 2-cinnamoyl-3-hydroxy-4, 5-dimethoxycyclopenta-2, 4-dienone (5), together with three known flavonoids (1-3) and one linderone (4), were isolated from the bark of Lindera oxyphylla. Extensive spectroscopic analysis including 1D and 2D-NMR spectra determined their sturctures. In addition, the antioxidant activity of all the compounds has been determined using 2, 2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), ferric reducing antioxidant power (FRAP) and ferrous ion chelating (FIC) methods. Compound 3 showed excellent DPPH scavenging activity with IC50% value of 8.5 ± 0.004% (μg/mL) which is comparable with vitamin C. This compound, also showed an absorbance value of 1.00 ± 0.06% through FRAP test when compared with Butyl Hydroxy Aniline (BHA). However, FIC showed low activity for all the isolated compounds (chelating activity less than 50%) in comparison with ethylene diamine tetra acetic acid (EDTA). Anticancer activity for all compounds has also been measured on A375 human melanoma, HT-29 colon adenocarcinoma, MCF-7 human breast adenocarcinoma cells, WRL-68 normal hepatic cells, A549 non-small cell lung cancer cells and PC-3 prostate adenocarcinoma cell line. Compound 1 showed A549=65.03%, PC-3=30.12%, MCF-7=47.67, compound 2 showed PC-3=90.13%, compound 3 showed MCF-7=79.57 and for compound 5 MCF-7 is 96.33.
Fulltext Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives

El-Faham A, Farooq M, Khattab SN, Abutaha N, Wadaan MA, Ghabbour HA, et al.

Molecules, 2015;20(8):14638-55.
PMID: 26287132 DOI: 10.3390/molecules200814638

Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 μM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 μM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 μM, but this compound was inactive in liver cancer and normal cell lines.
Current advance methods for the identification of blast resistance genes in rice

Tanweer FA, Rafii MY, Sijam K, Rahim HA, Ahmed F, Latif MA

C. R. Biol., 2015 May;338(5):321-34.
PMID: 25843222 DOI: 10.1016/j.crvi.2015.03.001

Rice blast caused by Magnaporthe oryzae is one of the most devastating diseases of rice around the world and crop losses due to blast are considerably high. Many blast resistant rice varieties have been developed by classical plant breeding and adopted by farmers in various rice-growing countries. However, the variability in the pathogenicity of the blast fungus according to environment made blast disease a major concern for farmers, which remains a threat to the rice industry. With the utilization of molecular techniques, plant breeders have improved rice production systems and minimized yield losses. In this article, we have summarized the current advanced molecular techniques used for controlling blast disease. With the advent of new technologies like marker-assisted selection, molecular mapping, map-based cloning, marker-assisted backcrossing and allele mining, breeders have identified more than 100 Pi loci and 350 QTL in rice genome responsible for blast disease. These Pi genes and QTLs can be introgressed into a blast-susceptible cultivar through marker-assisted backcross breeding. These molecular techniques provide timesaving, environment friendly and labour-cost-saving ways to control blast disease. The knowledge of host-plant interactions in the frame of blast disease will lead to develop resistant varieties in the future.
Fulltext Antiviral and Immunomodulatory Effects of Phytochemicals from Honey against COVID-19: Potential Mechanisms of Action and Future Directions

Al-Hatamleh MAI, Hatmal MM, Sattar K, Ahmad S, Mustafa MZ, Bittencourt MC, et al.

Molecules, 2020 Oct 29;25(21).
PMID: 33138197 DOI: 10.3390/molecules25215017

The new coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has recently put the world under stress, resulting in a global pandemic. Currently, there are no approved treatments or vaccines, and this severe respiratory illness has cost many lives. Despite the established antimicrobial and immune-boosting potency described for honey, to date there is still a lack of evidence about its potential role amid COVID-19 outbreak. Based on the previously explored antiviral effects and phytochemical components of honey, we review here evidence for its role as a potentially effective natural product against COVID-19. Although some bioactive compounds in honey have shown potential antiviral effects (i.e., methylglyoxal, chrysin, caffeic acid, galangin and hesperidinin) or enhancing antiviral immune responses (i.e., levan and ascorbic acid), the mechanisms of action for these compounds are still ambiguous. To the best of our knowledge, this is the first work exclusively summarizing all these bioactive compounds with their probable mechanisms of action as antiviral agents, specifically against SARS-CoV-2.

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