Displaying publications 81 - 100 of 118 in total

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  1. Wan Mohd Tajuddin WNB, Lajis NH, Abas F, Othman I, Naidu R
    Nutrients, 2019 Dec 06;11(12).
    PMID: 31817718 DOI: 10.3390/nu11122989
    Lung cancer is among the most common cancers with a high mortality rate worldwide. Despite the significant advances in diagnostic and therapeutic approaches, lung cancer prognoses and survival rates remain poor due to late diagnosis, drug resistance, and adverse effects. Therefore, new intervention therapies, such as the use of natural compounds with decreased toxicities, have been considered in lung cancer therapy. Curcumin, a natural occurring polyphenol derived from turmeric (Curcuma longa) has been studied extensively in recent years for its therapeutic effects. It has been shown that curcumin demonstrates anti-cancer effects in lung cancer through various mechanisms, including inhibition of cell proliferation, invasion, and metastasis, induction of apoptosis, epigenetic alterations, and regulation of microRNA expression. Several invitro and invivo studies have shown that these mechanisms are modulated by multiple molecular targets such as STAT3, EGFR, FOXO3a, TGF-β, eIF2α, COX-2, Bcl-2, PI3KAkt/mTOR, ROS, Fas/FasL, Cdc42, E-cadherin, MMPs, and adiponectin. In addition, limitations, strategies to overcome curcumin bioavailability, and potential side effects as well as clinical trials were also reviewed.
  2. Abd Wahab NA, Lajis NH, Abas F, Othman I, Naidu R
    Nutrients, 2020 Mar 02;12(3).
    PMID: 32131560 DOI: 10.3390/nu12030679
    Prostate cancer (PCa) is a heterogeneous disease and ranked as the second leading cause of cancer-related deaths in males worldwide. The global burden of PCa keeps rising regardless of the emerging cutting-edge technologies for treatment and drug designation. There are a number of treatment options which are effectively treating localised and androgen-dependent PCa (ADPC) through hormonal and surgery treatments. However, over time, these cancerous cells progress to androgen-independent PCa (AIPC) which continuously grow despite hormone depletion. At this particular stage, androgen depletion therapy (ADT) is no longer effective as these cancerous cells are rendered hormone-insensitive and capable of growing in the absence of androgen. AIPC is a lethal type of disease which leads to poor prognosis and is a major contributor to PCa death rates. A natural product-derived compound, curcumin has been identified as a pleiotropic compound which capable of influencing and modulating a diverse range of molecular targets and signalling pathways in order to exhibit its medicinal properties. Due to such multi-targeted behaviour, its benefits are paramount in combating a wide range of diseases including inflammation and cancer disease. Curcumin exhibits anti-cancer properties by suppressing cancer cells growth and survival, inflammation, invasion, cell proliferation as well as possesses the ability to induce apoptosis in malignant cells. In this review, we investigate the mechanism of curcumin by modulating multiple signalling pathways such as androgen receptor (AR) signalling, activating protein-1 (AP-1), phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), wingless (Wnt)/ß-catenin signalling, and molecular targets including nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and cyclin D1 which are implicated in the development and progression of both types of PCa, ADPC and AIPC. In addition, the role of microRNAs and clinical trials on the anti-cancer effects of curcumin in PCa patients were also reviewed.
  3. 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.
  4. Bhuvanendran S, Hanapi NA, Ahemad N, Othman I, Yusof SR, Shaikh MF
    Front Neurosci, 2019;13:495.
    PMID: 31156375 DOI: 10.3389/fnins.2019.00495
    Embelin is well-known in ethnomedicine and reported to have central nervous system activities. However, there is no report on blood-brain barrier (BBB) permeability of embelin. Here the BBB permeability of embelin was evaluated using in vitro primary porcine brain endothelial cell (PBEC) model of the BBB. Embelin was also evaluated for acetylcholinesterase (AChE) inhibitory activity and docking prediction for interaction with AChE and amyloid beta (Aβ) binding sites. Embelin was found to be non-toxic to the PBECs and did not disturb the PBEC barrier function. The PBECs showed restrictive tight junctions with average transendothelial electrical resistance of 365.37 ± 113.00 Ω.cm2, for monolayers used for permeability assays. Permeability assays were conducted from apical-to-basolateral direction (blood-to-brain side). Embelin showed apparent permeability (Papp) value of 35.46 ± 20.33 × 10-6 cm/s with 85.53% recovery. In vitro AChE inhibitory assay demonstrated that embelin could inhibit the enzyme. Molecular docking study showed that embelin binds well to active site of AChE with CDOCKER interaction energy of -65.75 kcal/mol which correlates with the in vitro results. Docking of embelin with Aβ peptides also revealed the promising binding with low CDOCKER interaction energy. Thus, findings from this study indicate that embelin could be a suitable molecule to be further developed as therapeutic molecule to treat neurological disorders particularly Alzheimer's disease.
  5. Paudel YN, Angelopoulou E, Piperi C, Balasubramaniam VRMT, Othman I, Shaikh MF
    Eur J Pharmacol, 2019 Sep 05;858:172487.
    PMID: 31229535 DOI: 10.1016/j.ejphar.2019.172487
    High mobility group box 1 (HMGB1) is a ubiquitous protein, released passively by necrotic tissues or secreted actively by stressed cells. Extracellular HMGB1 is a typical damage-associated molecular pattern (DAMP) molecule which generates different redox types through binding with several receptors and signalling molecules, aggravating a range of cellular responses, including inflammation. HMGB1 is reported to participate in the pathogenesis of inflammatory diseases, through the interaction with pivotal transmembrane receptors, including the receptor for advanced glycation end products (RAGE) and toll-like receptor-4 (TLR-4). This review aims to highlight the role of HMGB1 in the innate inflammatory response describing its interaction with several cofactors and receptors that coordinate its downstream effects. Novel and underexplored HMGB1 binding molecules that have been actively involved in HMGB1-mediated inflammatory diseases/conditions with therapeutic potential are further discussed.
  6. Chung YS, Choo BKM, Ahmed PK, Othman I, Shaikh MF
    Front Pharmacol, 2020;11:692.
    PMID: 32477146 DOI: 10.3389/fphar.2020.00692
    Orthosiphon stamineus (OS) or Orthosiphon aristatus var. aristatus (OAA) is commonly known as cat's whiskers or "misai kucing". It is an herbaceous shrub that is popular in many different traditional and complementary medicinal systems. Its popularity has been justified by the plethora of studies that have shown that the secondary metabolites of the plant has effects that range from anti-inflammatory and gastroprotective to anorexic and antihypertensive. As such, OS could also be a potential treatment for Central Nervous System (CNS) disorders. However, a cohesive synthesis of the protective actions of OS was lacking. This systematic review was therefore commenced to elaborate on the various protective mechanisms of OS in the CNS. The PRISMA model was used and five databases (Google Scholar, SCOPUS, SpringerLink, ScienceDirect, and PubMed) were searched with relevant keywords to finally identify four articles that met the inclusion criteria. The articles described the protective effects of OS extracts on Alzheimer's disease, epilepsy, learning and memory, oxidative stress, and neurotoxicity. All the articles found were experimental or preclinical studies on animal models or in vitro systems. The reported activities demonstrated that OS could be a potential neuroprotective agent and might improve CNS conditions like neurodegeneration, neuroinflammation, and oxidative stress.
  7. 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.
  8. Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Ong CE
    Drug Metab Pers Ther, 2021 Apr 09;36(4):259-270.
    PMID: 34821124 DOI: 10.1515/dmpt-2020-0182
    OBJECTIVES: Glucosamine, chondroitin and diacerein are natural compounds commonly used in treating osteoarthritis. Their concomitant intake may trigger drug-natural product interactions. Cytochrome P450 (CYP) has been implicated in such interactions. Cytochrome P450 2D6 (CYP2D6) is a major hepatic CYP involved in metabolism of 25% of the clinical drugs. This study aimed to investigate the inhibitory effect of these antiarthritic compounds on CYP2D6.

    METHODS: CYP2D6 was heterologously expressed in Escherichia coli. CYP2D6-antiarthritic compound interactions were studied using in vitro enzyme kinetics assay and molecular docking.

    RESULTS: The high-performance liquid chromatography (HPLC)-based dextromethorphan O-demethylase assay was established as CYP2D6 marker. All glucosamines and chondroitins weakly inhibited CYP2D6 (IC50 values >300 µM). Diacerein exhibited moderate inhibition with IC50 and K i values of 34.99 and 38.27 µM, respectively. Its major metabolite, rhein displayed stronger inhibition potencies (IC50=26.22 μM and K i =32.27 μM). Both compounds exhibited mixed-mode of inhibition. In silico molecular dockings further supported data from the in vitro study. From in vitro-in vivo extrapolation, rhein presented an area under the plasma concentration-time curve (AUC) ratio of 1.5, indicating low potential to cause in vivo inhibition.

    CONCLUSIONS: Glucosamine, chondroitin and diacerein unlikely cause clinical interaction with the drug substrates of CYP2D6. Rhein, exhibits only low potential to cause in vivo inhibition.

  9. Sudhesh Dev S, Zainal Abidin SA, Farghadani R, Othman I, Naidu R
    Front Pharmacol, 2021;12:772510.
    PMID: 34867402 DOI: 10.3389/fphar.2021.772510
    Receptor tyrosine kinases (RTKs) are transmembrane cell-surface proteins that act as signal transducers. They regulate essential cellular processes like proliferation, apoptosis, differentiation and metabolism. RTK alteration occurs in a broad spectrum of cancers, emphasising its crucial role in cancer progression and as a suitable therapeutic target. The use of small molecule RTK inhibitors however, has been crippled by the emergence of resistance, highlighting the need for a pleiotropic anti-cancer agent that can replace or be used in combination with existing pharmacological agents to enhance treatment efficacy. Curcumin is an attractive therapeutic agent mainly due to its potent anti-cancer effects, extensive range of targets and minimal toxicity. Out of the numerous documented targets of curcumin, RTKs appear to be one of the main nodes of curcumin-mediated inhibition. Many studies have found that curcumin influences RTK activation and their downstream signaling pathways resulting in increased apoptosis, decreased proliferation and decreased migration in cancer both in vitro and in vivo. This review focused on how curcumin exhibits anti-cancer effects through inhibition of RTKs and downstream signaling pathways like the MAPK, PI3K/Akt, JAK/STAT, and NF-κB pathways. Combination studies of curcumin and RTK inhibitors were also analysed with emphasis on their common molecular targets.
  10. Zulazmi NA, Arulsamy A, Ali I, Zainal Abidin SA, Othman I, Shaikh MF
    CNS Neurosci Ther, 2021 04;27(4):381-402.
    PMID: 33539662 DOI: 10.1111/cns.13590
    Traumatic brain injury (TBI) is the leading cause of death and disability worldwide and has complicated underlying pathophysiology. Numerous TBI animal models have been developed over the past decade to effectively mimic the human TBI pathophysiology. These models are of mostly mammalian origin including rodents and non-human primates. However, the mammalian models demanded higher costs and have lower throughput often limiting the progress in TBI research. Thus, this systematic review aims to discuss the potential benefits of non-mammalian TBI models in terms of their face validity in resembling human TBI. Three databases were searched as follows: PubMed, Scopus, and Embase, for original articles relating to non-mammalian TBI models, published between January 2010 and December 2019. A total of 29 articles were selected based on PRISMA model for critical appraisal. Zebrafish, both larvae and adult, was found to be the most utilized non-mammalian TBI model in the current literature, followed by the fruit fly and roundworm. In conclusion, non-mammalian TBI models have advantages over mammalian models especially for rapid, cost-effective, and reproducible screening of effective treatment strategies and provide an opportunity to expedite the advancement of TBI research.
  11. Abdullah NAH, Rusmili MRA, Zainal Abidin SA, Shaikh MF, Hodgson WC, Othman I
    Toxins (Basel), 2021 12 02;13(12).
    PMID: 34941697 DOI: 10.3390/toxins13120859
    Phospholipase A2 (PLA2) toxins are one of the main toxin families found in snake venom. PLA2 toxins are associated with various detrimental effects, including neurotoxicity, myotoxicity, hemostatic disturbances, nephrotoxicity, edema, and inflammation. Although Naja sumatrana venom contains substantial quantities of PLA2 components, there is limited information on the function and activities of PLA2 toxins from the venom. In this study, a secretory PLA2 from the venom of Malaysian N. sumatrana, subsequently named A2-EPTX-Nsm1a, was isolated, purified, and characterized. A2-EPTX-Nsm1a was purified using a mass spectrometry-guided approach and multiple chromatography steps. Based on LC-MSMS, A2-EPTX-Nsm1a was found to show high sequence similarity with PLA2 from venoms of other Naja species. The PLA2 activity of A2-EPTX-Nsm1 was inhibited by 4-BPB and EDTA. A2-EPTX-Nsm1a was significantly less cytotoxic in a neuroblastoma cell line (SH-SY5Y) compared to crude venom and did not show a concentration-dependent cytotoxic activity. To our knowledge, this is the first study that characterizes and investigates the cytotoxicity of an Asp49 PLA2 isolated from Malaysian N. sumatrana venom in a human neuroblastoma cell line.
  12. Tan BH, Ahemad N, Pan Y, Palanisamy UD, Othman I, Yiap BC, et al.
    Biopharm Drug Dispos, 2018 Apr;39(4):205-217.
    PMID: 29488228 DOI: 10.1002/bdd.2127
    Many dietary supplements are promoted to patients with osteoarthritis (OA) including the three naturally derived compounds, glucosamine, chondroitin and diacerein. Despite their wide spread use, research on interaction of these antiarthritic compounds with human hepatic cytochrome P450 (CYP) enzymes is limited. This study aimed to examine the modulatory effects of these compounds on CYP2C9, a major CYP isoform, using in vitro biochemical assay and in silico models. Utilizing valsartan hydroxylase assay as probe, all forms of glucosamine and chondroitin exhibited IC50 values beyond 1000 μM, indicating very weak potential in inhibiting CYP2C9. In silico docking postulated no interaction with CYP2C9 for chondroitin and weak bonding for glucosamine. On the other hand, diacerein exhibited mixed-type inhibition with IC50 value of 32.23 μM and Ki value of 30.80 μM, indicating moderately weak inhibition. Diacerein's main metabolite, rhein, demonstrated the same mode of inhibition as diacerein but stronger potency, with IC50 of 6.08 μM and Ki of 1.16 μM. The docking of both compounds acquired lower CDOCKER interaction energy values, with interactions dominated by hydrogen and hydrophobic bondings. The ranking with respect to inhibition potency for the investigated compounds was generally the same in both in vitro enzyme assay and in silico modeling with order of potency being diacerein/rhein > various glucosamine/chondroitin forms. In vitro-in vivo extrapolation of inhibition kinetics (using 1 + [I]/Ki ratio) demonstrated negligible potential of diacerein to cause interaction in vivo, whereas rhein was predicted to cause in vivo interaction, suggesting potential interaction risk with the CYP2C9 drug substrates.
  13. Zainal Abidin SA, Rajadurai P, Chowdhury ME, Ahmad Rusmili MR, Othman I, Naidu R
    Toxins (Basel), 2016 10 18;8(10).
    PMID: 27763534
    Tropidolaemus wagleri and Cryptelytrops purpureomaculatus are venomous pit viper species commonly found in Malaysia. Tandem mass spectrometry analysis of the crude venoms has detected different proteins in T. wagleri and C. purpureomaculatus. They were classified into 13 venom protein families consisting of enzymatic and nonenzymatic proteins. Enzymatic families detected in T. wagleri and C. purpureomaculatus venom were snake venom metalloproteinase, phospholipase A₂, ʟ-amino acid oxidase, serine proteases, 5'-nucleotidase, phosphodiesterase, and phospholipase B. In addition, glutaminyl cyclotransferase was detected in C. purpureomaculatus. C-type lectin-like proteins were common nonenzymatic components in both species. Waglerin was present and unique to T. wagleri-it was not in C. purpureomaculatus venom. In contrast, cysteine-rich secretory protein, bradykinin-potentiating peptide, and C-type natriuretic peptide were present in C. purpureomaculatus venom. Composition of the venom proteome of T. wagleri and C. purpureomaculatus provides useful information to guide production of effective antivenom and identification of proteins with potential therapeutic applications.
  14. Choo BKM, Kundap UP, Kumari Y, Hue SM, Othman I, Shaikh MF
    Front Pharmacol, 2018;9:139.
    PMID: 29527169 DOI: 10.3389/fphar.2018.00139
    Epileptic seizures result from abnormal brain activity and can affect motor, autonomic and sensory function; as well as, memory, cognition, behavior, or emotional state. Effective anti-epileptic drugs (AEDs) are available but have tolerability issues due to their side effects. The Malaysian herbOrthosiphon stamineus, is a traditional epilepsy remedy and possesses anti-inflammatory, anti-oxidant and free-radical scavenging abilities, all of which are known to protect against seizures. This experiment thus aimed to explore if an ethanolic leaf extract ofO. stamineushas the potential to be a novel symptomatic treatment for epileptic seizures in a zebrafish model; and the effects of the extract on the expression levels of several genes in the zebrafish brain which are associated with seizures. The results of this study indicate thatO. stamineushas the potential to be a novel symptomatic treatment for epileptic seizures as it is pharmacologically active against seizures in a zebrafish model. The anti-convulsive effect of this extract is also comparable to that of diazepam at higher doses and can surpass diazepam in certain cases. Treatment with the extract also counteracts the upregulation of NF-κB, NPY and TNF-α as a result of a Pentylenetetrazol (PTZ) treated seizure. The anti-convulsive action for this extract could be at least partially due to its downregulation of TNF-α. Future work could include the discovery of the active anti-convulsive compound, as well as determine if the extract does not cause cognitive impairment in zebrafish.
  15. Patikorn C, Ismail AK, Zainal Abidin SA, Othman I, Chaiyakunapruk N, Taychakhoonavudh S
    PLoS Negl Trop Dis, 2022 Nov;16(11):e0010915.
    PMID: 36383562 DOI: 10.1371/journal.pntd.0010915
    BACKGROUND: Despite domestic production of antivenoms in the Association of Southeast Asian Nations (ASEAN) countries, not all victims with snakebite envenomings indicated for antivenom received the appropriate or adequate effective dose of antivenom due to insufficient supply and inadequate access to antivenoms. We aimed to conduct a cost-effectiveness analysis to project the potential economic and clinical impact of improving access to antivenoms when all snakebite envenomings in ASEAN countries were hypothetically treated with geographically appropriate antivenoms.

    METHODOLOGY: Using a decision analytic model with input parameters from published literature, local data, and expert opinion, we projected the impact of "full access" (100%) to antivenom, compared to "current access" in five most impacted ASEAN countries, including Indonesia (10%), Philippines (26%), Vietnam (37%), Lao PDR (4%), and Myanmar (64%), from a societal perspective with a lifetime time horizon. Sensitivity analyses were performed.

    PRINCIPAL FINDINGS: In base-case analyses, full access compared to current access to snake antivenom in the five countries resulted in a total of 9,362 deaths averted (-59%), 230,075 disability-adjusted life years (DALYs) averted (-59%), and cost savings of 1.3 billion USD (-53%). Incremental cost-effectiveness ratios (ICERs) of improving access to antivenom found higher outcomes but lower costs in all countries. Probabilistic sensitivity analyses of 1,000 iterations found that 98.1-100% of ICERs were cost-saving.

    CONCLUSION/SIGNIFICANCE: Improving access to snake antivenom will result in cost-saving for ASEAN countries. Our findings emphasized the importance of further strengthening regional cooperation, investment, and funding to improve the situation of snakebite victims in ASEAN countries.

  16. Chen WN, Shaikh MF, Bhuvanendran S, Date A, Ansari MT, Radhakrishnan AK, et al.
    Curr Neuropharmacol, 2022;20(4):799-808.
    PMID: 34077349 DOI: 10.2174/1570159X19666210528155801
    Poloxamer 188 (P188) is an FDA-approved biocompatible block copolymer composed of repeating units of Poly(Ethylene Oxide) (PEO) and poly(propylene oxide) (PPO). Due to its amphiphilic nature and high Hydrophile-Lipophile Balance (HLB) value of 29, P188 is used as a stabilizer/emulsifier in many cosmetics and pharmaceutical preparations. While the applications of P188 as an excipient are widely explored, the data on the pharmacological activity of P188 are scarce. Notably, the neuroprotective potential of P188 has gained a lot of interest. Therefore, this systematic review is aimed at summarizing evidence of neuroprotective potential of P188 in CNS disorders. The PRISMA model was used, and five databases (Google Scholar, Scopus, Wiley Online Library, ScienceDirect, and PubMed) were searched with relevant keywords. The search resulted in 11 articles, which met the inclusion criteria. These articles described the protective effects of P188 on traumatic brain injury or mechanical injury in cells, neurotoxicity, Parkinson's disease, Amyotrophic lateral sclerosis (ALS), and ischemia/ reperfusion injury from stroke. All the articles were original research in experimental or pre-clinical stages using animal models or in vitro systems. The reported activities demonstrated the potential of P188 as a neuroprotective agent in improving CNS conditions such as neurodegeneration.
  17. 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.
  18. 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.
  19. Siddiqui A, Abidin SAZ, Shah ZA, Othman I, Kumari Y
    PMID: 37100105 DOI: 10.1016/j.cbpc.2023.109636
    Globally around 24 million elderly population are dealing with dementia, and this pathological characteristic is commonly seen in people suffering from Alzheimer's disease (AD). Despite having multiple treatment options that can mitigate AD symptoms, there is an imperative call to advance our understanding of the disease pathogenesis to unfold disease-modifying treatments/therapies. To explore the driving mechanisms of AD development, we stretch out further to study time-dependant changes after Okadaic acid (OKA)-induced AD-like conditions in zebrafish. We evaluated the pharmacodynamics of OKA at two-time points, i.e., after 4-days and 10-days exposure to zebrafish. T-Maze was utilized to observe the learning and cognitive behaviour, and inflammatory gene expressions such as 5-Lox, Gfap, Actin, APP, and Mapt were performed in zebrafish brains. To scoop everything out from the brain tissue, protein profiling was performed using LCMS/MS. Both time course OKA-induced AD models have shown significant memory impairment, as evident from T-Maze. Gene expression studies of both groups have reported an overexpression of 5-Lox, GFAP, Actin, APP, and OKA 10D group has shown remarkable upregulation of Mapt in zebrafish brains. In the case of protein expression, the heatmap suggested an important role of some common proteins identified in both groups, which can be explored further to investigate their mechanism in OKA-induced AD pathology. Presently, the preclinical models available to understand AD-like conditions are not completely understood. Hence, utilizing OKA in the zebrafish model can be of great importance in understanding the pathology of AD progression and as a screening tool for drug discovery.
  20. 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.
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