Displaying publications 1 - 20 of 118 in total

Abstract:
Sort:
  1. Najmuddin MF, Haris H, Othman N, Zahari F, Mohd-Ridwan AR, Md-Zain BM, et al.
    Data Brief, 2020 Aug;31:105727.
    PMID: 32548216 DOI: 10.1016/j.dib.2020.105727
    Morphism refer to polymorphic species, in which multiple colour variants coexist within a population. Morphism in primates is common and langurs also exhibit certain characteristics of morphism, such as conspicuous natal coats. Banded langurs (Presbytis femoralis) and dusky leaf monkey (Trachypithecus obscurus) exhibits the same characteristics of conspicuous natal coats, but these coats are only limited to infants and changed when they reached adulthood. This article reports the first discovery of rare brown morph of two adult male banded langurs and one leucistic adult female dusky leaf monkey in Malaysia. We also conducted a systematic literature search to review the diversity of morphism in leaf monkey globally.
  2. Othman I, Aklilu E
    Vet World, 2019;12(3):472-476.
    PMID: 31089320 DOI: 10.14202/vetworld.2019.472-476
    Aim: This study aimed to investigate the occurrence of Marek's disease (MD) in five poultry farms in Malaysia using postmortem examination, histopathology, and polymerase chain reaction (PCR).

    Materials and Methods: Tissue samples were collected from 24 broiler breeder chickens from four commercial broiler breeder farms and six layer chickens from one layer farm. Gross and histopathological examinations and PCR amplification of the gene encoding for avian MD herpesvirus (MDV-1) were conducted.

    Results: Gross pathological changes including hepatomegaly, splenomegaly, lymphomatous lesion at the mesentery, oviduct atrophy, and follicular atresia with lymphomatous were observed, whereas diffuse multifocal whitish infiltration of the spleen, neoplastic infiltration in the liver, intrafollicular lymphoid infiltration of the bursa of Fabricius, and lymphomatous tumor at the mesentery were seen on histopathological examinations. Confirmation by PCR showed that a total of 16 (53.33%) samples were positive for avian MDV-1. Although the outbreak involved a much larger number of birds in the respective farms, our investigation was limited based on resource and time frame allocated for the study.

    Conclusion: The findings from this study help in emphasizing the potential threats of MDV to the poultry industry globally, in general, and in Malaysia, in particular. As the scope of the current study is limited, future studies focusing on MDV pathogenesis, typing, and causes of vaccine failures are recommended.

  3. Rafindadi AD, Shafiq N, Othman I, Ibrahim A, Aliyu MM, Mikić M, et al.
    Heliyon, 2023 Feb;9(2):e13389.
    PMID: 36761825 DOI: 10.1016/j.heliyon.2023.e13389
    Accident analysis is used to discover the causes of workplace injuries and devise methods for preventing them in the future. There has been little discussion in the previous studies of the specific elements contributing to deadly construction accidents. In contrast to previous studies, this study focuses on the causes of fatal construction accidents based on management factors, unsafe site conditions, and workers' unsafe actions. The association rule mining technique identifies the hidden patterns or knowledge between the root causes of fatal construction accidents, and one hundred meaningful association rules were extracted from the two hundred and fifty-three rules generated. It was discovered that many fatal construction accidents were caused by management factors, unsafe site circumstances, and risky worker behaviors. These analyses can be used to demonstrate plausible cause-and-effect correlations, assisting in building a safer working environment in the construction sector. The study findings can be used more efficiently to design effective inspection procedures and occupational safety initiatives. Finally, the proposed method should be tested in a broader range of construction situations and scenarios to ensure that it is as accurate as possible.
  4. Dhanoa A, Hassan SS, Jahan NK, Reidpath DD, Fatt QK, Ahmad MP, et al.
    Infect Dis Poverty, 2018 Jan 16;7(1):1.
    PMID: 29335021 DOI: 10.1186/s40249-017-0384-1
    BACKGROUND: The frequency and magnitude of dengue epidemics continue to increase exponentially in Malaysia, with a shift in the age range predominance toward adults and an expansion to rural areas. Despite this, information pertaining to the extent of transmission of dengue virus (DENV) in the rural community is lacking. This community-based pilot study was conducted to establish DENV seroprevalence amongst healthy adults in a rural district in Southern Malaysia, and to identify influencing factors.

    METHODS: In this study undertaken between April and May 2015, a total of 277 adult participants were recruited from households across three localities in the Sungai Segamat subdistrict in Segamat district. Sera were tested for immunoglobulin G (IgG) (Panbio® Dengue Indirect IgG ELISA/high-titer capture) and immunoglobulin M (IgM) (Panbio®) antibodies. The plaque reduction neutralization test (PRNT) was conducted on random samples of IgG-positive sera for further confirmation. Medical history and a recall of previous history of dengue were collected through interviews, whereas sociodemographic information was obtained from an existing database.

    RESULTS: The overall seroprevalence for DENV infection was 86.6% (240/277) (95% CI: 83-91%). Serological evidence of recent infection (IgM/high-titer capture IgG) was noted in 11.2% (31/277) of participants, whereas there was evidence of past infection in 75.5% (209/277) of participants (indirect IgG minus recent infections). The PRNT assay showed that the detected antibodies were indeed specific to DENV. The multivariate analysis showed that the older age group was significantly associated with past DENV infections. Seropositivity increased with age; 48.5% in the age group of <25 years to more than 85% in age group of >45 years (P 

  5. Alkhorayef M, Sulieman A, Alzahrani K, Abuzaid M, Alomair OI, Almuwannis M, et al.
    Appl Radiat Isot, 2021 Feb;168:109520.
    PMID: 33307438 DOI: 10.1016/j.apradiso.2020.109520
    The various technological advancements in computed tomography (CT) have resulted in remarkable growth in the use of CT imaging in clinical practice, not the least of which has been its establishment as the most valuable imaging examination for the assessment of cardiovascular system disorders. The objective of this study was to assess the effective radiation dose and radiation risk for patients during cardiac CT procedures, based on studies from four different hospitals equipped with 128 slice CT equipment. A total of eighty-three patients were investigated in this study with different clinical indications. Effective doses were also calculated using software based on Monte Carlo simulation. The mean patient age (years), weight (kg), and body mass index (BMI (kg/m2)) were 49 ± 11, 82 ± 12, and 31 ± 6, respectively. The results of the study revealed that the tube voltage (kVp) and tube current-exposure time product (mAs) ranged between 100 to 140 and 50 to 840 respectively. The overall average patient dose values for the volume CT dose index [(CTDIvol), in mGy)] and dose length product (DLP) (in mGy·cm) were 34.8 ± 15 (3.7-117.0) and 383.8 ± 354 (46.0-3277.0) respectively. The average effective dose (mSv) was 15.2 ± 8 (1.2-61.8). The radiation dose values showed wide variation between different hospitals and even within the same hospital. The results indicate the need to optimize radiation dose and to establish diagnostic reference levels (DRLs) for patients undergoing coronary computed tomography angiography (CCTA), also to harmonize the imaging protocols to ensure reduced radiation risk.
  6. Alnaaimi M, Sulieman A, Tamam N, Alkhorayef M, Alduaij M, Mohammedzein T, et al.
    Appl Radiat Isot, 2021 Dec;178:109965.
    PMID: 34688024 DOI: 10.1016/j.apradiso.2021.109965
    The positron emitters (18F-Sodium Fluoride (NaF)) and X-rays used in Positron emission tomography (PET) combined with computed tomography (PET/CT) imaging have a high radiation dose, which results in a high patient dose. The present research intends to determine the radiation dose and risks associated with PET/CT- 18F-Sodium fluoride examinations in patients. The 18F-NaF PET/CT was used to investigate the doses of 86 patients. Patient exposure parameters and ImPACT software were used to calculate mean effective doses. The administered activity of 185 MBq (5.0 mCi) per procedure has a mean and range based on the patient's BMI (BMI). The range of patient effective doses per procedure was found to be 4-10 mSv, with a radiation risk of 1 × 10-5 per procedure. Patient doses are determined by the patient's size, scanner type, imaging protocol, and reconstruction method. For further dose reduction, proper justification and radiation dose optimization is required.
  7. Rusmili MRA, Othman I, Abidin SAZ, Yusof FA, Ratanabanangkoon K, Chanhome L, et al.
    PLoS One, 2019;14(12):e0227122.
    PMID: 31887191 DOI: 10.1371/journal.pone.0227122
    Malayan krait (Bungarus candidus) is a medically important snake species found in Southeast Asia. The neurotoxic effects of envenoming present as flaccid paralysis of skeletal muscles. It is unclear whether geographical variation in venom composition plays a significant role in the degree of clinical neurotoxicity. In this study, the effects of geographical variation on neurotoxicity and venom composition of B. candidus venoms from Indonesia, Malaysia and Thailand were examined. In the chick biventer cervicis nerve-muscle preparation, all venoms abolished indirect twitches and attenuated contractile responses to nicotinic receptor agonists, with venom from Indonesia displaying the most rapid neurotoxicity. A proteomic analysis indicated that three finger toxins (3FTx), phospholipase A2 (PLA2) and Kunitz-type serine protease inhibitors were common toxin groups in the venoms. In addition, venom from Thailand contained L-amino acid oxidase (LAAO), cysteine rich secretory protein (CRISP), thrombin-like enzyme (TLE) and snake venom metalloproteinase (SVMP). Short-chain post-synaptic neurotoxins were not detected in any of the venoms. The largest quantity of long-chain post-synaptic neurotoxins and non-conventional toxins was found in the venom from Thailand. Analysis of PLA2 activity did not show any correlation between the amount of PLA2 and the degree of neurotoxicity of the venoms. Our study shows that variation in venom composition is not limited to the degree of neurotoxicity. This investigation provides additional insights into the geographical differences in venom composition and provides information that could be used to improve the management of Malayan krait envenoming in Southeast Asia.
  8. Chaisakul J, Khow O, Wiwatwarayos K, Rusmili MRA, Prasert W, Othman I, et al.
    Toxins (Basel), 2021 Jul 26;13(8).
    PMID: 34437392 DOI: 10.3390/toxins13080521
    Acute kidney injury (AKI) following Eastern Russell's viper (Daboia siamensis) envenoming is a significant symptom in systemically envenomed victims. A number of venom components have been identified as causing the nephrotoxicity which leads to AKI. However, the precise mechanism of nephrotoxicity caused by these toxins is still unclear. In the present study, we purified two proteins from D. siamensis venom, namely RvPLA2 and RvMP. Protein identification using LCMS/MS confirmed the identity of RvPLA2 to be snake venom phospholipase A2 (SVPLA2) from Thai D. siamensis venom, whereas RvMP exhibited the presence of a factor X activator with two subunits. In vitro and in vivo pharmacological studies demonstrated myotoxicity and histopathological changes of kidney, heart, and spleen. RvPLA2 (3-10 µg/mL) caused inhibition of direct twitches of the chick biventer cervicis muscle preparation. After administration of RvPLA2 or RvMP (300 µg/kg, i.p.) for 24 h, diffuse glomerular congestion and tubular injury with minor loss of brush border were detected in envenomed mice. RvPLA2 and RvMP (300 µg/kg; i.p.) also induced congestion and tissue inflammation of heart muscle as well as diffuse congestion of mouse spleen. This study showed the significant roles of PLA2 and SVMP in snake bite envenoming caused by Thai D. siamensis and their similarities with observed clinical manifestations in envenomed victims. This study also indicated that there is a need to reevaluate the current treatment strategies for Thai D. siamensis envenoming, given the potential for irreversible nephrotoxicity.
  9. Patikorn C, Leelavanich D, Ismail AK, Othman I, Taychakhoonavudh S, Chaiyakunapruk N
    J Glob Health, 2020 Dec;10(2):020415.
    PMID: 33312499 DOI: 10.7189/jogh.10.020415
    Background: Snakebite envenoming, a high priority Neglected Tropical Disease categorized by the World Health Organization (WHO), has been considered as a poverty-related disease that requires greater global awareness and collaboration to establish strategies that effectively decrease economic burdens. This prompts the need for a comprehensive review of the global literature that summarizes the global economic burden and a description of methodology details and their variation. This study aimed to systematically identify studies on cost of illness and economic evaluation associated with snakebites, summarize study findings, and evaluate their methods to provide recommendations for future studies.

    Methods: We searched PubMed, EMBASE, Cochrane library, and Econlit for articles published from inception to 31 July 2019. Original articles reporting costs or full economic evaluation related with snakebites were included. The methods and reporting quality were assessed. Costs were presented in US dollars (US$) in 2018.

    Results: Twenty-three cost of illness studies and three economic evaluation studies related to snakebites were included. Majority of studies (18/23, 78.26%) were conducted in Low- and Middle-income countries. Most cost of illness studies (82.61%) were done using hospital-based data of snakebite patients. While, four studies (17.39%) estimated costs of snakebites in communities. Five studies (21.74%) used societal perspective estimating both direct and indirect costs. Only one study (4.35%) undertook incidence-based approach to estimate lifetime costs. Only three studies (13.04%) estimated annual national economic burdens of snakebite which varied drastically from US$126 319 in Burkina Faso to US$13 802 550 in Sri Lanka. Quality of the cost of illness studies were varied and substantially under-reported. All three economic evaluation studies were cost-effectiveness analysis using decision tree model. Two of them assessed cost-effectiveness of having full access to antivenom and reported cost-effective findings.

    Conclusions: Economic burdens of snakebite were underestimated and not extensively studied. To accurately capture the economic burdens of snakebites at both the global and local level, hospital data should be collected along with community survey and economic burdens of snakebites should be estimated both in short-term and long-term period to incorporate the lifetime costs and productivity loss due to premature death, disability, and consequences of snakebites.

  10. Othman I, Anuar AN, Ujang Z, Rosman NH, Harun H, Chelliapan S
    Bioresour Technol, 2013 Apr;133:630-4.
    PMID: 23453799 DOI: 10.1016/j.biortech.2013.01.149
    The present study demonstrated that aerobic granular sludge is capable of treating livestock wastewater from a cattle farm in a sequencing batch reactor (SBR) without the presence of support material. A lab scale SBR was operated for 80 d using 4 h cycle time with an organic loading rate (OLR) of 9 kg COD m(-3) d(-1). Results showed that the aerobic granules were growing from 0.1 to 4.1 mm towards the end of the experimental period. The sludge volume index (SVI) was 42 ml g(-1) while the biomass concentration in the reactor grew up to 10.3 g L(-1) represent excellent biomass separation and good settling ability of the granules. During this period, maximum COD, TN and TP removal efficiencies (74%, 73% and 70%, respectively) were observed in the SBR system, confirming high microbial activity in the SBR system.
  11. Chaisakul J, Rusmili MR, Hodgson WC, Hatthachote P, Suwan K, Inchan A, et al.
    Toxins (Basel), 2017 03 29;9(4).
    PMID: 28353659 DOI: 10.3390/toxins9040122
    Cardiovascular effects (e.g., tachycardia, hypo- and/or hypertension) are often clinical outcomes of snake envenoming. Malayan krait (Bungarus candidus) envenoming has been reported to cause cardiovascular effects that may be related to abnormalities in parasympathetic activity. However, the exact mechanism for this effect has yet to be determined. In the present study, we investigated thein vivoandin vitrocardiovascular effects ofB. candidusvenoms from Southern (BC-S) and Northeastern (BC-NE) Thailand. SDS-PAGE analysis of venoms showed some differences in the protein profile of the venoms.B. candidusvenoms (50 µg/kg-100 µg/kg, i.v.) caused dose-dependent hypotension in anaesthetised rats. The highest dose caused sudden hypotension (phase I) followed by a return of mean arterial pressure to baseline levels and a decrease in heart rate with transient hypertension (phase II) prior to a small decrease in blood pressure (phase III). Prior administration of monovalent antivenom significantly attenuated the hypotension induced by venoms (100 µg/kg, i.v.). The sudden hypotensive effect of BC-NE venom was abolished by prior administration of hexamethonium (10 mg/kg, i.v.) or atropine (5 mg/kg, i.v.). BC-S and BC-NE venoms (0.1 µg/kg-100 µg/ml) induced concentration-dependent relaxation (EC50= 8 ± 1 and 13 ± 3 µg/mL, respectively) in endothelium-intact aorta. The concentration-response curves were markedly shifted to the right by pre-incubation with L-NAME (0.2 mM), or removal of the endothelium, suggesting that endothelium-derived nitric oxide (NO) is likely to be responsible for venom-induced aortic relaxation. Our data indicate that the cardiovascular effects caused byB. candidusvenoms may be due to a combination of vascular mediators (i.e., NO) and autonomic adaptation via nicotinic and muscarinic acetylcholine receptors.
  12. Tiash S, Othman I, Rosli R, Chowdhury EH
    Curr Drug Deliv, 2014;11(2):214-22.
    PMID: 24328684
    Most of the classical drugs used today to destroy cancer cells lead to the development of acquired resistance in those cells by limiting cellular entry of the drugs or exporting them out by efflux pumps. As a result, higher doses of drugs are usually required to kill the cancer cells affecting normal cells and causing numerous side effects. Accumulation of the therapeutic level of drugs inside the cancer cells is thus required for an adequate period of time to get drugs' complete therapeutic efficacy minimizing the side effects on normal cells. In order to improve the efficacy of chemotherapeutic drugs, nanoparticles of carbonate apatite and its strontium (Sr(2+))-substituted derivative were used in this study to make complexes with three classical anticancer drugs, methotrexate, cyclophosphamide and 5-flurouracil. The binding affinities of these drugs to apatite were evaluated by absorbance and HPLC analysis and the therapeutic efficacy of drug-apatite complexes was determined by cell viability assay. Carbonate apatite demonstrated significant binding affinity towards methotrexate and cyclophosphamide leading to more cellular toxicity than free drugs in MCF-7 and 4T1 breast cancer cells. Moreover, Sr(2+) substitution in carbonate apatite with resulting tiny particles less than 100 nm in diameter further promoted binding of methotrexate to the nanocarriers indicating that Sr(2+)-substituted apatite nanoparticles have the high potential for loading substantial amount of anti-cancer drugs with eventual more therapeutic effectiveness.
  13. Fatemian T, Othman I, Chowdhury EH
    Drug Discov Today, 2014 Jan;19(1):71-8.
    PMID: 23974068 DOI: 10.1016/j.drudis.2013.08.007
    Resistance of cancer cells to anticancer drugs is the main reason for the failure of traditional cancer treatments. Various cellular components and different loops within the signaling pathways contribute to drug resistance which could be modulated with the aim to restore drug efficacy. Unveiling the molecular mechanisms for cancer drug resistance has now paved the way for the development of novel approaches to regulate the response rates to anticancer drugs at the genetic level. The recent progress on identification and validation of the vital genes directly or indirectly involved in development of cancer drug resistance with the aid of the specific knock down ability of RNA interference technology is discussed in this review.
  14. Ahmad A, Othman I, Md Zain AZ, Chowdhury EH
    Curr Drug Deliv, 2015;12(2):210-22.
    PMID: 22452407
    Diabetes mellitus is a chronic disease accompanied by a multitude of problems worldwide with subcutaneously administered insulin being the most common therapy currently. Controlledrelease insulin is assumed to be of high importance for long-term glycaemic control by reducing the number of daily injections. Long-acting insulin also mimics the basal insulin levels in normal individuals that may be lacking in diabetic patients. Nanoparticles of carbonate apatite as established for efficient intracellular transport of DNA and siRNA have the potential to be used for sustained release of insulin as responsive nano-carriers. The flexibility in the synthesis of the particles over a wide range of pHs with eventual adjustment of pH-dependent particle dissolution and the manageable variability of particle-integrity by incorporating selective ions into the apatite structure are the promising features that could help in the development of sustained release formulations for insulin. In particular strontium-incorporated carbonate apatite particles were formulated and compared with those of unsubstituted apatite in the context of insulin binding and subsequent release kinetics in DMEM, simulated buffer and finally human blood over a period of 20 hours. Clearly, the former demonstated to have a stronger electrostatic affinity towards the acidic insulin molecules and facilitate to some extent sustained release of insulin by preventing the initial burst effect at physiological pH in comparison with the latter. Thus, our findings suggest that optimization of the carbonate apatite particle composition and structure would serve to design an ideal insulin nano-carrier with a controlled release profile.
  15. Zaman R, Karim ME, Othman I, Zaini A, Chowdhury EH
    Pharmaceutics, 2020 Jul 29;12(8).
    PMID: 32751231 DOI: 10.3390/pharmaceutics12080710
    Oral delivery is considered as the most preferred and yet most challenging mode of drug administration; especially a fragile and sensitive peptide like insulin that shows extremely low bioavailability through the gastro-intestinal (GIT) route. To address this problem, we have designed a novel drug delivery system (DDS) using precipitation-induced Barium (Ba) salt particles. The DDS can load insulin molecules and transport them through the GIT route. There were several in vitro simulation tests carried out to prove the efficiency of Ba salt particles as oral delivery candidates. All three Ba salt particles (BaSO4, BaSO3, and BaCO3) showed very good loading of insulin (>70% in all formulations) and a degree of resistance throughout a wide range of pHs from basic to acidic conditions when assessed by spectrophotometry. Particles and insulin-associated particles were morphologically assessed and characterized using FE-SEM and FT-IR. A set of tests were designed and carried out with mucin to predict whether the particles are potentially capable of overcoming one of the barriers for crossing intestinal epithelium. The mucin binding experiment demonstrated 60-100% of mucin adhesion to the three different particles. FT-IR identifies the characteristic peaks for mucin protein, particles, and particle-mucin complex re-confirming mucin adhesion to the particles. Finally, the effectiveness of nano-insulin was tested on streptozotocin (STZ) induced diabetic rats. A short acting human insulin analog, insulin aspart, was loaded into Ba salt particles at a dose of 100 IU/Kg prior to oral administration. Among the three formulations, insulin aspart-loaded BaSO4 and BaCO3 particles dramatically reduced the existing hyperglycemia. BaSO4 with loaded Insulin showed an onset of glucose-lowering action within 1 hr, with blood glucose level measured significantly lower compared to the 2nd and 3rd h (p < 0.05). Insulin-loaded BaCO3 particles showed a significant decrease in blood glucose level at 1-2 h, although the glucose level started to show a slight rise at 3rd h and by 4th h, it was back to baseline level. However, although BaSO3 particles with loaded insulin showed a trend of reduction in blood glucose level, the reduction was not found to be significant (p < 0.05) at any point in time. Therefore, oral formulations of insulin/BaSO4 and insulin/BaCO3 particles were observed as effective as native insulin aspart subcutaneous formulation in terms of onset and duration of action. Further investigation will be needed to reveal bioavailability and mechanism of action of this novel Nano-Insulin formulations.
  16. Zaman R, Islam RA, Ibnat N, Othman I, Zaini A, Lee CY, et al.
    J Control Release, 2019 05 10;301:176-189.
    PMID: 30849445 DOI: 10.1016/j.jconrel.2019.02.016
    Macromolecular protein and peptide therapeutics have been proven to be effective in treating critical human diseases precisely. Thanks to biotechnological advancement, a huge number of proteins and peptide therapeutics were made their way to pharmaceutical market in past few decades. However, one of the biggest challenges to be addressed for protein therapeutics during clinical application is their fast degradation in serum and quick elimination owing to enzymatic degradation, renal clearance, liver metabolism and immunogenicity, attributing to the short half-lives. Size and hydrophobicity of protein molecules make them prone to kidney filtration and liver metabolism. On the other hand, proteasomes responsible for protein destruction possess the capability of specifically recognizing almost all kinds of foreign proteins while avoiding any unwanted destruction of cellular components. At present almost all protein-based drug formulations available in market are administered intravenously (IV) or subcutaneously (SC) with high dosing at frequent interval, eventually creating dose-fluctuation-related complications and reducing patient compliance vastly. Therefore, artificially increasing the therapeutic half-life of a protein by attaching to it a molecule that increases the overall size (eg, PEG) or helps with receptor mediated recycling (eg, albumin), or manipulating amino acid chain in a way that makes it more prone towards aggregate formation, are some of the revolutionary approaches to avoid the fast degradation in vivo. Half-life extension technologies that are capable of dramatically enhancing half-lives of proteins in circulation (2-100 folds) and thus improving their overall pharmacokinetic (PK) parameters have been successfully applied on a wide range of protein therapeutics from hormones and enzymes, growth factor, clotting factor to interferon. The focus of the review is to assess the technological advancements made so far in enhancing circulatory half-lives and improving therapeutic potency of proteins.
  17. Haque ST, Karim ME, Abidin SAZ, Othman I, Holl MMB, Chowdhury EH
    Nanomaterials (Basel), 2020 Apr 27;10(5).
    PMID: 32349272 DOI: 10.3390/nano10050834
    Breast cancer is the abnormal, uncontrollable proliferation of cells in the breast. Conventional treatment modalities like chemotherapy induce deteriorating side effects on healthy cells. Non-viral inorganic nanoparticles (NPs) confer exclusive characteristics, such as, stability, controllable shape and size, facile surface modification, and unique magnetic and optical properties which make them attractive drug carriers. Among them, carbonate apatite (CA) particles are pH-responsive in nature, enabling rapid intracellular drug release, but are typically heterogeneous with the tendency to self-aggregate. Here, we modified the nano-carrier by partially substituting Ca2+ with Mg2+ and Fe3+ into a basic lattice structure of CA, forming Fe/Mg-carbonate apatite (Fe/Mg-CA) NPs with the ability to mitigate self-aggregation, form unique protein corona in the presence of serum and efficiently deliver doxorubicin (DOX), an anti-cancer drug into breast cancer cells. Two formulations of Fe/Mg-CA NPs were generated by adding different concentrations of Fe3+ and Mg2+ along with a fixed amount of Ca2+ in bicarbonate buffered DMEM (Dulbecco's Modified Eagle's Medium), followed by 30 min incubation at 37 °C. Particles were characterized by turbidity analysis, z-average diameter and zeta potential measurement, optical microscopy, field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), flame atomic absorption spectroscopy (FAAS), pH dissolution, drug binding, cellular uptake, thiazolyl blue tetrazolium bromide (MTT) assay, stability analysis, and protein corona study by LCMS (Liquid chromatography-mass spectrometry). Both formulations of Fe/Mg-CA displayed mostly uniform nano-sized particles with less tendency to aggregate. The EDX and FAAS elemental analysis confirmed the weight (%) of Ca, Fe and Mg, along with their Ca/P ratio in the particles. A constant drug binding efficiency was noticed with 5 μM to 10 μM of initial DOX concentration. A pH dissolution study of Fe/Mg-CA NPs revealed the quick release of DOX in acidic pH. Enhancement of cytotoxicity for the chemotherapy drug was greater for Fe/Mg-CA NPs as compared to CA NPs, which could be explained by an increase in cellular internalization as a result of the small z-average diameter of the former. The protein corona study by LCMS demonstrated that Fe/Mg-CA NPs exhibited the highest affinity towards transport proteins without binding with opsonins. Biodistribution study was performed to study the effect of DOX-loaded Fe/Mg-CA NPs on the tissue distribution of DOX in Balb/c 4T1 tumor-bearing mice. Both formulations of Fe/Mg-CA NPs have significantly increased the accumulation of DOX in tumors. Interestingly, high Fe/Mg-CA NPs exhibited less off-target distribution compared to low Fe/Mg-CA NPs. Furthermore, the blood plasma analysis revealed prolonged blood circulation half-life of DOX-loaded low and high Fe/Mg-CA NPs compared to free DOX solution. Modifying CA NPs with Fe3+ and Mg2+, thereby, led to the generation of nano-sized particles with less tendency to aggregate, enhancing the drug binding efficiency, cellular uptake, and cytotoxicity without hampering drug release in acidic pH, while improving the circulation half-life and tumor accumulation of DOX. Therefore, Fe/Mg-CA which predominantly forms a transport protein-related protein corona could be a proficient carrier for therapeutic delivery in breast cancer.
  18. Karim ME, Tha KK, Othman I, Borhan Uddin M, Chowdhury EH
    Pharmaceutics, 2018 May 26;10(2).
    PMID: 29861465 DOI: 10.3390/pharmaceutics10020065
    RNA Interference (RNAi) has brought revolutionary transformations in cancer management in the past two decades. RNAi-based therapeutics including siRNA and shRNA have immense scope to silence the expression of mutant cancer genes specifically in a therapeutic context. Although tremendous progress has been made to establish catalytic RNA as a new class of biologics for cancer management, a lot of extracellular and intracellular barriers still pose a long-lasting challenge on the way to clinical approval. A series of chemically suitable, safe and effective viral and non-viral carriers have emerged to overcome physiological barriers and ensure targeted delivery of RNAi. The newly invented carriers, delivery techniques and gene editing technology made current treatment protocols stronger to fight cancer. This review has provided a platform about the chronicle of siRNA development and challenges of RNAi therapeutics for laboratory to bedside translation focusing on recent advancement in siRNA delivery vehicles with their limitations. Furthermore, an overview of several animal model studies of siRNA- or shRNA-based cancer gene therapy over the past 15 years has been presented, highlighting the roles of genes in multiple cancers, pharmacokinetic parameters and critical evaluation. The review concludes with a future direction for the development of catalytic RNA vehicles and design strategies to make RNAi-based cancer gene therapy more promising to surmount cancer gene delivery challenges.
  19. Chai HC, Phipps ME, Othman I, Tan LP, Chua KH
    Lupus, 2013 Feb;22(2):198-204.
    PMID: 23257407 DOI: 10.1177/0961203312470183
    BACKGROUND: Human leukocyte antigen (HLA) antigens and genes have long been reported associated with systemic lupus erythematosus (SLE) susceptibility in many populations. With the advance in technologies such as genome-wide association studies, many newly discovered SLE-associated single-nucleotide polymorphisms (SNPs) have been reported in recent years. These include HLA-DRB1/HLA-DQA1 rs9271366 and HLA-DQB1/HLA-DQA2 rs9275328. Our aim was to investigate these SNPs in a Malaysian SLE cohort.
    MATERIALS AND METHODS: SNPs rs9271366 and rs9275328 were screened across 790 Malaysian citizens from three ethnic groups (360 patients and 430 healthy volunteers) by Taqman SNP genotyping assays. Allele and genotyping frequencies, Hardy-Weinberg equilibrium, Fisher's exact test and odds ratio were calculated for each SNP and ethnic group. Linkage disequilibrium and interaction between the two SNPs were also evaluated.
    RESULTS: The minor allele G and its homozygous genotype GG of HLA-DRB1/HLA-DQA1 rs9271366 significantly increased the SLE susceptibility in Malaysian patients, including those of Malay and Chinese ethnicity (odds ratio (OR) > 1, p 
  20. Buniya MK, Othman I, Sunindijo RY, Karakhan AA, Kineber AF, Durdyev S
    Int J Occup Saf Ergon, 2023 Mar;29(1):129-140.
    PMID: 35125068 DOI: 10.1080/10803548.2022.2038419
    Implementing a safety program is an essential step toward improving safety performance. This research aims to develop an overall project success (OPS) model for building projects through investigating the direct and indirect impact of safety critical success factors (CSFs) on OPS mediated by safety program elements. First, interviews were carried out with experts in the Iraqi construction industry, and then a questionnaire survey was utilized to obtain feedback from construction professionals. The results revealed that 20 elements are needed to confirm and improve effectiveness. These elements were categorized into four constructs: management commitment and employee involvement, worksite analysis, hazard and prevention control, and health and safety training. The analysis confirms that the relationship between safety CSFs and OPS are mediated by safety program elements. These findings offer a glimmer of hope for implementing safety programs in the Iraqi construction sector, and can also be used to enhance safety performance.
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links