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Fulltext Behavioural, genomics and proteomic approach to examine Alzheimer's disease in zebrafish

Siddiqui A, Abidin SAZ, Shah ZA, Othman I, Kumari Y

Comp Biochem Physiol C Toxicol Pharmacol, 2023 Sep;271:109636.
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.
Fulltext Applications of AI in oil and gas projects towards sustainable development: a systematic literature review

Waqar A, Othman I, Shafiq N, Mansoor MS

Artif Intell Rev, 2023 Mar 23.
PMID: 37362898 DOI: 10.1007/s10462-023-10467-7

Oil and gas construction projects are critical for meeting global demand for fossil fuels, but they also present unique risks and challenges that require innovative construction approaches. Artificial Intelligence (AI) has emerged as a promising technology for tackling these challenges, and this study examines its applications for sustainable development in the oil and gas industry. Using a systematic literature review (SLR), this research evaluates research trends from 2011 to 2022. It provides a detailed analysis of how AI suits oil and gas construction. A total of 115 research articles were reviewed to identify original contributions, and the findings indicate a positive trend in AI research related to oil and gas construction projects, especially after 2016. The originality of this study lies in its comprehensive analysis of the latest research on AI applications in the oil and gas industry and its contribution to developing recommendations for improving the sustainability of oil and gas projects. This research's originality is in providing insight into the most promising AI applications and methodologies that can help drive sustainable development in the oil and gas industry.
Contributions of safety critical success factors and safety program elements to overall project success

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.
Fulltext Impact of 3D Printing on the Overall Project Success of Residential Construction Projects Using Structural Equation Modelling

Waqar A, Othman I, Pomares JC

Int J Environ Res Public Health, 2023 Feb 21;20(5).
PMID: 36900821 DOI: 10.3390/ijerph20053800

After a decade of research and development, 3D printing is now an established technique in the construction sector, complete with its own set of accepted standards. The use of 3D printing in construction might potentially improve the outcome of the project as a whole. However, traditional strategies are often used in the residential construction industry in Malaysia, which causes serious public safety and health issues along with a negative impact on the environment. In the context of project management, overall project success (OPS) has five dimensions, such as cost, time, quality, safety, and environment. Understanding the role of 3D printing in relation to OPS dimensions in Malaysian residential construction projects would allow construction professionals to adopt 3D printing more easily. The aim of the study was to find the impact of 3D construction printing on OPS while considering the implications for all five dimensions. Fifteen professionals were interviewed to first evaluate and summarise the impact factors of 3D printing using the current literature. Then, a pilot survey was conducted, and the results were checked using exploratory factor analysis (EFA). The feasibility of 3D printing in the building sector was investigated by surveying industry experts. Partial least squares structural equation modelling was used to investigate and validate the fundamental structure and linkages between 3D printing and OPS (PLS-SEM). A strong correlation was found between 3D printing in residential projects and OPS. Highly positive implications are indicated by the environmental and safety dimensions of OPS. Malaysian decision-makers may look to the outcomes of introducing 3D printing into the residential construction industry as a modern method for increasing environmental sustainability, public health and safety, reducing cost and time, and increasing the quality of construction work. With this study's findings in hand, construction engineering management in Malaysia's residential building sector might benefit from a deeper understanding of how 3D printing is used for improving environmental compliance, public health and safety, and project scope.
Data mining of the essential causes of different types of fatal construction accidents

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.
Fulltext Potential economic and clinical implications of improving access to snake antivenom in five ASEAN countries: A cost-effectiveness analysis

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.
Fulltext Embelin prevents amyloid-beta accumulation via modulation of SOD1 in a Streptozotocin-induced AD-like condition: An evidence from in vitro investigation

Bhuvanendran S, Paudel YN, Kumari Y, Othman I, Shaikh MF

Curr Res Neurobiol, 2022;3:100032.
PMID: 36518345 DOI: 10.1016/j.crneur.2022.100032

Embelin is a neuroprotective compound with therapeutic benefit against experimental Alzheimer's disease (AD)-like condition. In the quest of untangling the underlying mechanism behind the neuroprotective effect of Embelin in AD, an in-vitro study of Embelin against neuronal damage induced by Streptozotocin (STZ) in rat hippocampal neuronal culture was performed. Current findings demonstrated that Embelin (2.5-10 μM) has efficiently protected hippocampal neurons against STZ (8 mM)-induced neurotoxicity. An increase in amyloid precursor protein (APP), microtubule-associated protein tau (MAPT), glycogen synthase kinase 3 alpha (GSK-3α) and glycogen synthase kinase 3 beta (GSK-3β) expression levels was observed when STZ (8 mM) stimulation was done for 24 h in the hippocampal neurons. A significant downregulation in the mRNA expression levels of APP, MAPT, GSK-3α, and GSK-3β upon pre-treatment with different doses of Embelin (2.5 μM, 5 μM and 10 μM) reflects that Embelin attenuated STZ-induced dysfunction of insulin signaling (IR). Embelin significantly modulated the mRNA expression of scavenger enzyme Superoxide dismutase (SOD1). Furthermore, STZ had significantly upregulates an expression of Aβ. On the contrary, pre-treatment with three doses of Embelin reversed an Aβ-induced neuronal death. Our findings suggest that, Embelin prevents Aβ accumulation via SOD1 pathway to protect against AD-like condition.
Fulltext Poloxamer 188 (P188), A Potential Polymeric Protective Agent for Central Nervous System Disorders: A Systematic Review

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.
Fulltext Isolation and Characterization of A2-EPTX-Nsm1a, a Secretory Phospholipase A2 from Malaysian Spitting Cobra (Naja sumatrana) Venom

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.
Estimation of patient effective doses in PET/CT- 18F-Sodium Fluoride examinations

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.
Fulltext Mechanistic role of boswellic acids in Alzheimer's disease: Emphasis on anti-inflammatory properties

Siddiqui A, Shah Z, Jahan RN, Othman I, Kumari Y

Biomed Pharmacother, 2021 Dec;144:112250.
PMID: 34607104 DOI: 10.1016/j.biopha.2021.112250

The resin/gum of Boswellia species belonging to the family of Burseraceae is a naturally occurring mixture of bioactive compounds, which was traditionally used as a folk medicine to treat conditions like chronic inflammation. Several research studies have also explored its' therapeutic potential against multiple neurodegenerative diseases such as Alzheimer's disease (AD). The main chemical constituents of this gum include boswellic acids (BAs) like 3-O-acetyl-11-keto-β boswellic acid (AKBA) that possess potent anti-inflammatory and neuroprotective properties in AD. It is also involved in inhibiting the acetylcholinesterase (AChE) activity in the cholinergic pathway and improve choline levels as well as its binding with nicotinic receptors to produce anti-inflammatory effects. Multiple shreds of evidence have demonstrated that BAs modulate key molecular targets and signalling pathways like 5-lipoxygenase/cyclooxygenase, Nrf2, NF-kB, cholinergic, amyloid-beta (Aβ), and neurofibrillary tangles formation (NFTs) that are involved in AD progression. The present review focuses on the possible mechanistic therapeutic role of BAs in modulating the 5-LOX/COX pathway in arachidonic acid metabolism, activating Nrf2 through binding of ARE, inhibiting NF-kB and AChE activity. In addition, an inhibition of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) induced neurotoxicity and neuroinflammation in AD by BAs is also discussed in this review. We have also highlighted that BAs possess beneficial effects in AD by targeting multiple molecular pathways and makes it an emerging drug candidate for treating neurodegenerative diseases.
Naturally Occurring HMGB1 Inhibitor, Glycyrrhizin, Modulates Chronic Seizures-Induced Memory Dysfunction in Zebrafish Model

Paudel YN, Khan SU, Othman I, Shaikh MF

ACS Chem Neurosci, 2021 09 15;12(18):3288-3302.
PMID: 34463468 DOI: 10.1021/acschemneuro.0c00825

Glycyrrhizin (GL) is a well-known pharmacological inhibitor of high mobility group box 1 (HMGB1) and is abundantly present in the licorice root (Glycyrrhiza radix). HMGB1 protein, a key mediator of neuroinflammation, has been implicated in several neurological disorders, including epilepsy. Epilepsy is a devastating neurological disorder with no effective disease-modifying treatment strategies yet, suggesting a pressing need for exploring novel therapeutic options. In the current investigation, using a second hit pentylenetetrazol (PTZ) induced chronic seizure model in adult zebrafish, regulated mRNA expression of HMGB1 was inhibited by pretreatment with GL (25, 50, and 100 mg/kg, ip). A molecular docking study suggests that GL establishes different binding interactions with the various amino acid chains of HMGB1 and Toll-like receptor-4 (TLR4). Our finding suggests that GL pretreatment reduces/suppresses second hit PTZ induced seizure, as shown by the reduction in the seizure score. GL also regulates the second hit PTZ induced behavioral impairment and rescued second hit PTZ related memory impairment as demonstrated by an increase in the inflection ratio (IR) at the 3 h and 24 h T-maze trial. GL inhibited seizure-induced neuronal activity as demonstrated by reduced C-fos mRNA expression. GL also modulated mRNA expression of BDNF, CREB-1, and NPY. The possible mechanism underlying the anticonvulsive effect of GL could be attributed to its anti-inflammatory activity, as demonstrated by the downregulated mRNA expression level of HMGB1, TLR4, NF-kB, and TNF-α. Overall, our finding suggests that GL exerts an anticonvulsive effect and ameliorates seizure-related memory disruption plausibly through regulating of the HMGB1-TLR4-NF-kB axis.
Fulltext Antimicrobial Resistance Patterns and Risk Factors Associated with Salmonella spp. Isolates from Poultry Farms in the East Coast of Peninsular Malaysia: A Cross-Sectional Study

Osman AY, Elmi SA, Simons D, Elton L, Haider N, Khan MA, et al.

Pathogens, 2021 Sep 09;10(9).
PMID: 34578192 DOI: 10.3390/pathogens10091160

The burden of antimicrobial use in agricultural settings is one of the greatest challenges facing global health and food security in the modern era. Malaysian poultry operations are a relevant but understudied component of epidemiology of antimicrobial resistance. We aimed to identify the prevalence, resistance patterns, and risk factors associated with Salmonella isolates from poultry farms in three states of East Coast Peninsular Malaysia. Between 8 February 2019 and 23 February 2020, a total of 371 samples (cloacal swabs = 259; faecal = 84; Sewage = 14, Tap water = 14) was collected from poultry operations. Characteristics of the sampled farms and associated risk factors were obtained using semi-structured questionnaires. Presumptive Salmonella spp. isolates were identified based on colony morphology with subsequent biochemical and PCR confirmation. Susceptibility of isolates was tested against a panel of 12 antimicrobials using disk diffusion method. Our findings revealed that the proportion of Salmonella spp.-positive isolates across sample source were as following: cloacal swab (46.3%, 120/259); faecal (59.5%, 50/84); in tap water (14.3%, 2/14); and in sewage sample (35.7%, 5/14). Isolates from faecal (15.5%, 13/84), cloacal (1.2%, 3/259), and sewage (7.1%, 1/14) samples were significantly resistant to at least five classes of antimicrobials. Resistance to Sulfonamides class (52%, 92/177) was predominantly observed followed by tetracycline (39.5%, 70/177) and aminoglycosides (35.6%, 63/177). Multivariate regression analysis identified intensive management system (OR = 1.55, 95% CI = 1.00-2.40) as a leading driver of antimicrobial resistance (AMR) acquisition. A prevalence of resistance to common antimicrobials was recorded for sulfamethoxazole (33.9%), tetracycline (39.5%), and trimethoprim-sulphamethoxazole (37.9%). A close association between different risk factors and the prevalence of AMR of Salmonella strains suggests a concern over rising misuse of veterinary antimicrobials that may contribute to the emergence and evolution of multidrug-resistant pathogen isolates. One Health approach is recommended to achieve a positive health outcome for all species.
Fulltext Role of Inflammatory Mediators, Macrophages, and Neutrophils in Glioma Maintenance and Progression: Mechanistic Understanding and Potential Therapeutic Applications

Basheer AS, Abas F, Othman I, Naidu R

Cancers (Basel), 2021 Aug 23;13(16).
PMID: 34439380 DOI: 10.3390/cancers13164226

Gliomas are the most common, highly malignant, and deadliest forms of brain tumors. These intra-cranial solid tumors are comprised of both cancerous and non-cancerous cells, which contribute to tumor development, progression, and resistance to the therapeutic regimen. A variety of soluble inflammatory mediators (e.g., cytokines, chemokines, and chemotactic factors) are secreted by these cells, which help in creating an inflammatory microenvironment and contribute to the various stages of cancer development, maintenance, and progression. The major tumor infiltrating immune cells of the tumor microenvironment include TAMs and TANs, which are either recruited peripherally or present as brain-resident macrophages (microglia) and support stroma for cancer cell expansion and invasion. These cells are highly plastic in nature and can be polarized into different phenotypes depending upon different types of stimuli. During neuroinflammation, glioma cells interact with TAMs and TANs, facilitating tumor cell proliferation, survival, and migration. Targeting inflammatory mediators along with the reprogramming of TAMs and TANs could be of great importance in glioma treatment and may delay disease progression. In addition, an inhibition of the key signaling pathways such as NF-κB, JAK/STAT, MAPK, PI3K/Akt/mTOR, and TLRs, which are activated during neuroinflammation and have an oncogenic role in glioblastoma (GBM), can exert more pronounced anti-glioma effects.
Fulltext Critical Success Factors of Safety Program Implementation in Construction Projects in Iraq

Buniya MK, Othman I, Sunindijo RY, Kashwani G, Durdyev S, Ismail S, et al.

Int J Environ Res Public Health, 2021 08 11;18(16).
PMID: 34444218 DOI: 10.3390/ijerph18168469

The construction sector is recognized as one of the most dangerous industries in the world. The situation is worsening in Iraq, as a result of a lack of attention to safety in the building industry and the poor implementation of safety programs. This research aims to identify the critical safety factors (CSFs) of safety program implementation in the Iraqi construction industry. The CSFs were first identified from a review of literature before being verified by construction practitioners, using semi-structured interviews. A questionnaire, based on the verified CSFs, was distributed to construction practitioners in Iraq. Exploratory factor analysis (EFA) was used to analyze the quantitative data, and the results show that the CSFs can be categorized into four constructs: worker involvement, safety prevention and control system, safety arrangement, and management commitment. Following that, partial least square structural equation modelling (PLS-SEM) was executed to establish the connection between safety program implementation and overall project success. The result confirms that safety program implementation has a significant, positive impact on project success. This article contributes to knowledge and practice by identifying the CSFs for implementing safety programs in the Iraqi construction industry. The successful implementation of a safety program not only improves safety performance, but also helps to meet other project goals.
Fulltext A Biochemical and Pharmacological Characterization of Phospholipase A2 and Metalloproteinase Fractions from Eastern Russell's Viper (Daboia siamensis) Venom: Two Major Components Associated with Acute Kidney Injury

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.
Fulltext Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells

Wan Mohd Tajuddin WNB, Abas F, Othman I, Naidu R

Int J Mol Sci, 2021 Jul 10;22(14).
PMID: 34299042 DOI: 10.3390/ijms22147424

Diarylpentanoid (DAP), an analog that was structurally modified from a naturally occurring curcumin, has shown to enhance anticancer efficacy compared to its parent compound in various cancers. This study aims to determine the cytotoxicity, antiproliferative, and apoptotic activity of diarylpentanoid MS13 on two subtypes of non-small cell lung cancer (NSCLC) cells: squamous cell carcinoma (NCI-H520) and adenocarcinoma (NCI-H23). Gene expression analysis was performed using Nanostring PanCancer Pathways Panel to determine significant signaling pathways and targeted genes in these treated cells. Cytotoxicity screening revealed that MS13 exhibited greater inhibitory effect in NCI-H520 and NCI-H23 cells compared to curcumin. MS13 induced anti-proliferative activity in both cells in a dose- and time-dependent manner. Morphological analysis revealed that a significant number of MS13-treated cells exhibited apoptosis. A significant increase in caspase-3 activity and decrease in Bcl-2 protein concentration was noted in both MS13-treated cells in a time- and dose-dependent manner. A total of 77 and 47 differential expressed genes (DEGs) were regulated in MS13 treated-NCI-H520 and NCI-H23 cells, respectively. Among the DEGs, 22 were mutually expressed in both NCI-H520 and NCI-H23 cells in response to MS13 treatment. The top DEGs modulated by MS13 in NCI-H520-DUSP4, CDKN1A, GADD45G, NGFR, and EPHA2-and NCI-H23 cells-HGF, MET, COL5A2, MCM7, and GNG4-were highly associated with PI3K, cell cycle-apoptosis, and MAPK signaling pathways. In conclusion, MS13 may induce antiproliferation and apoptosis activity in squamous cell carcinoma and adenocarcinoma of NSCLC cells by modulating DEGs associated with PI3K-AKT, cell cycle-apoptosis, and MAPK pathways. Therefore, our present findings could provide an insight into the anticancer activity of MS13 and merits further investigation as a potential anticancer agent for NSCLC cancer therapy.
Fulltext Orthosiphon stamineus Proteins Alleviate Hydrogen Peroxide Stress in SH-SY5Y Cells

Chung YS, Ahmed PK, Othman I, Shaikh MF

Life (Basel), 2021 Jun 20;11(6).
PMID: 34202937 DOI: 10.3390/life11060585

The neuroprotective potential of Orthosiphon stamineus leaf proteins (OSLPs) has never been evaluated in SH-SY5Y cells challenged by hydrogen peroxide (H2O2). This work thus aims to elucidate OSLP neuroprotective potential in alleviating H2O2 stress. OSLPs at varying concentrations were evaluated for cytotoxicity (24 and 48 h) and neuroprotective potential in H2O2-induced SH-SY5Y cells (24 h). The protective mechanism of H2O2-induced SH-SY5Y cells was also explored via mass-spectrometry-based label-free quantitative proteomics (LFQ) and bioinformatics. OSLPs (25, 50, 125, 250, 500, and 1000 µg/mL; 24 and 48 h) were found to be safe. Pre-treatments with OSLP doses (250, 500, and 1000 µg/mL, 24 h) significantly increased the survival of SH-SY5Y cells in a concentration-dependent manner and improved cell architecture-pyramidal-shaped cells, reduced clumping and shrinkage, with apparent neurite formations. OSLP pre-treatment (1000 µg/mL, 24 h) lowered the expressions of two major heat shock proteins, HSPA8 (heat shock protein family A (Hsp70) member 8) and HSP90AA1 (heat shock protein 90), which promote cellular stress signaling under stress conditions. OSLP is, therefore, suggested to be anti-inflammatory by modulating the "signaling of interleukin-4 and interleukin-13" pathway as the predominant mechanism in addition to regulating the "attenuation phase" and "HSP90 chaperone cycle for steroid hormone receptors" pathways to counteract heat shock protein (HSP)-induced damage under stress conditions.
Fulltext Digital Technologies in the Architecture, Engineering and Construction (AEC) Industry-A Bibliometric-Qualitative Literature Review of Research Activities

Manzoor B, Othman I, Pomares JC

Int J Environ Res Public Health, 2021 06 06;18(11).
PMID: 34204147 DOI: 10.3390/ijerph18116135

Digital technologies (DTs) are proven helpful in the Architecture, Engineering and Construction (AEC) industry due to their varied benefits to project stakeholders, such as enhanced visualization, better data sharing, reduction in building waste, increased productivity, sustainable performance and safety improvement. Therefore, researchers have conducted various studies on DTs in the AEC industry over the year; however, this study explores the state-of-the-art research on DTs in the AEC industry by means of a bibliometric-qualitative review method. This research would uncover new knowledge gaps and practical needs in the domain of DTs in the AEC industry. In addition, bibliometric analysis was carried out by utilizing academic publications from Scopus (i.e., 11,047 publications for the AEC industry, 1956 for DTs and 1778 for DTs in the AEC industry). Furthermore, a qualitative review was further conducted on 200 screened selected research publications in the domain of DTs. This study brings attention to the body of knowledge by envisioning trends and patterns by defining key research interests, journals, countries, new advancements, challenges, negative attitudes and future directions towards DTs in the AEC industry. However, this study is the first in its vital importance and uniqueness by providing a broad updated review of DTs in the AEC literature. Furthermore, this research laid a foundation for future researchers, policy makers and practitioners to explore the limitations in future research.
In vitro inhibitory effects of glucosamine, chondroitin and diacerein on human hepatic CYP2D6

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.

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