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Human topoisomerase II alpha as a prognostic biomarker in cancer chemotherapy

Ali Y, Abd Hamid S

Tumour Biol., 2016 Jan;37(1):47-55.
PMID: 26482620 DOI: 10.1007/s13277-015-4270-9

Topoisomerases are nuclear enzymes that regulate topology of DNA by facilitating the temporary cleavage and ligation cycle of DNA. Among all forms of topoisomerases, TOP-IIA is extensively associated with cell proliferation and therefore is an important therapeutic target in diseases that involved cellular proliferation such as cancers. Nearly half of present-day antitumor regimens contain at least one prescription that act as a topoisomerase inhibitor. Generally, tumor cells show divergent expression of TOP-IIA compared to normal cells. The remarkable expression of TOP-IIA in various carcinomas provides a significant biomarker toward understanding the nature of malignancy. TOP-IIA expression and amplification studies help in diagnosing cancer and to observe the disease progression, overall survival (OS) of patients, and response to therapy. This review highlights the research output and analysis in exploring the standing of TOP-IIA in various carcinomas. As some reports show contradiction within the same field of interest, the outline of that may help to induce researchers for further investigation and clarification. To the best of our knowledge, this is the first overview briefly summarizing the prognostic feature of TOP-IIA in various types of cancer.
Biomedical Applications of Aromatic Azo Compounds

Ali Y, Hamid SA, Rashid U

Mini Rev Med Chem, 2018;18(18):1548-1558.
PMID: 29792144 DOI: 10.2174/1389557518666180524113111

Azo dyes are widely used in textile, fiber, cosmetic, leather, paint and printing industries. Besides their characteristic coloring function, azo compounds are reported as antibacterial, antiviral, antifungal and cytotoxic agents. They have the ability to be used as drug carriers, either by acting as a 'cargo' that entrap therapeutic agents or by prodrug approach. The drug is released by internal or external stimuli in the region of interest, as observed in colon-targeted drug delivery. Besides drug-like and drug carrier properties, a number of azo dyes are used in cellular staining to visualize cellular components and metabolic processes. However, the biological significance of azo compounds, especially in cancer chemotherapy, is still in its infancy. This may be linked to early findings that declared azo compounds as one of the possible causes of cancer and mutagenesis. Currently, researchers are screening the aromatic azo compounds for their potential biomedical use, including cancer diagnosis and therapy. In this review, we highlight the medical applications of azo compounds, particularly related to cancer research. The biomedical significance of cis-trans interchange and negative implications of azo compounds are also discussed in brief.
Insights into the structure and drug design of benzimidazole derivatives targeting the epidermal growth factor receptor (EGFR)

Abdullah MN, Ali Y, Abd Hamid S

Chem Biol Drug Des, 2022 Dec;100(6):921-934.
PMID: 34651438 DOI: 10.1111/cbdd.13974

Tyrosine kinase overexpression could result in an unfavourable consequence of cancer progression in the body. A number of kinase inhibitor drugs targeting various cancer-related protein kinases have been developed and proven successful in clinical therapy. Benzimidazole is one of the most studied scaffolds in the search for effective anticancer drugs. The association of various functional groups and the structural design of the compounds may influence the binding towards the receptor. Despite numerous publications on the design, synthesis and biological assays of benzimidazole derivatives, their inhibitory activities against epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK), have not been specifically analysed. This review covers recent research reports on the anticancer activity of benzimidazole derivatives focusing on EGFR expression cell lines, based on their structure-activity relationship study. We believe it would aid researchers to envision the challenges and explore benzimidazole's potentials as tyrosine kinase inhibitors.
Fulltext Larvicidal efficacy screening of Anacardaciae crude extracts on the dengue hemorrhagic vector, Aedes aegypti

Zuharah WF, Fadzly N, Ali Y, Zakaria R, Juperi S, Asyraf M, et al.

Trop Biomed, 2014 Jun;31(2):297-304.
PMID: 25134898 MyJurnal

Vector-borne diseases are still rife because of the re-emergence of diseases transmitted by mosquitoes. The objective of this paper is to evaluate the larvicidal efficacy of crude leaf extract of Mangifera indica, Gluta renghas, and Melanochyla fasciculiflora against vector of dengue hemorrhagic fever, Aedes aegypti. These plant species are endemic species and widely distributed in Malaysian forests. Leaves of Ma. indica, G. renghas and M. fascculiflora were collected from Teluk Bahang National Park, Penang Malaysia. Fractions of leaves were segregated, air-dried, powdered and extracted using Soxhlet with methanol. The solvent was removed by using rotary evaporator to obtain the crude extract. Using WHO standard larval bioassay test method, third instar larvae of Aedes aegypti were exposed to concentration ranging from 200- 4500 ppm of methanol extract for all plant species. Larval mortality was observed after 24 hours exposure. The highest susceptibility and toxicity was recorded by Mangifera indica with the lowest concentration at 800 ppm followed by M. fasciculiflora and G. renghas. This indicates that crude plant extract is very effective in killing Ae. aegypti mosquitoes. This finding may lead to new low cost alternative, environmentally friendly method for mosquito control programs. To our knowledge, this is the first report on larvicidal bioefficacy from endemic Malaysian plants.
Fulltext Economic perspective of coronavirus (COVID-19)

Usman M, Ali Y, Riaz A, Riaz A, Zubair A

J Public Aff, 2020 Aug 07.
PMID: 32837324 DOI: 10.1002/pa.2252

This study aims to present a quick overview of the novel coronavirus (afterward COVID-19) which triggers from Wuhan, spread approximately 213 countries and territories around the globe, and still currently ongoing. Particularly, we are interested to investigate the economic perspective of COVID-19. This paper uses data from online published articles and current media sources, as the COVID-19 situation is unfolding yet. To deeply explore the said matter, we divide the economic impact into six dimensions that is, Chinese economy, Central Asian economies, South Asian economies, South East and West Asian economies, European economies, Northern African, and Middle Eastern economies. The paper concludes that epidemic situations like COVID-19 severely affect economies around the globe. The basic reasons behind such severity are immobility of labor, reduction in productivity, discontinuation of the supply chain, a decline in exports, uncertainty, and so on. This study is quite important for businesses and policymakers to estimate and plan current and post-COVID-19 situations.
Fulltext Macromolecules as targeted drugs delivery vehicles: an overview

Ali Y, Alqudah A, Ahmad S, Abd Hamid S, Farooq U

Des Monomers Polym, 2019;22(1):91-97.
PMID: 31007637 DOI: 10.1080/15685551.2019.1591681

Targeted drug delivery system improves the efficiency and safety of the therapeutic agents by managing the pharmacokinetics and pharmacodynamics of drugs. Currently, numerous drug carrier systems have been developed with different sizes, architectures and characteristics surface properties. Among different systems, macromolecules have a wide range of applications in targeted drug delivery system. The optimal drug loading potential, smooth drug releasing ability and biocompatibility are the distinguishing features that ensure the drugs delivery ability of macromolecules. This review briefly introduces some of the most commonly studied macromolecules which have been recommended as drugs delivery vehicles.
Polyphenols: Potential Future Arsenals in the Treatment of Diabetes

Solayman M, Ali Y, Alam F, Islam MA, Alam N, Khalil MI, et al.

Curr Pharm Des, 2016;22(5):549-65.
PMID: 26601968

Diabetes mellitus (DM) is one of the most common endocrine metabolic disorders. In addition to exercise and diet, oral anti-diabetic drugs have been used as a part of the management strategy worldwide. Unfortunately, none of the conventional anti-diabetic drugs are without side effects, and these drugs pose an economic burden. Therefore, the investigation of novel anti-diabetic regimens is a major challenge for researchers, in which nature has been the primary resource for the discovery of potential therapeutics. Many plants have been shown to act as anti-diabetic agents, in which the main active constituents are believed to be polyphenols. Natural products containing high polyphenol levels can control carbohydrate metabolism by various mechanisms, such as protecting and restoring beta-cell integrity, enhancing insulin releasing activity, and increasing cellular glucose uptake. Blackberries, red grapes, apricots, eggplant and popular drinks such as coffee, cocoa and green tea are all rich in polyphenols, which may dampen insulin resistance and be natural alternatives in the treatment of diabetes. Therefore, the aim of this review is to report on the available anti-diabetic polyphenols (medicinal plants, fruits and vegetables), their mechanisms in the various pathways of DM and their correlations with DM. Additionally, this review emphasizes the types of polyphenols that could be potential future resources in the treatment of DM via either novel regimens or as supplementary agents.
Physicochemical Properties, Minerals, Trace Elements, and Heavy Metals in Honey of Different Origins: A Comprehensive Review

Solayman M, Islam MA, Paul S, Ali Y, Khalil MI, Alam N, et al.

Compr Rev Food Sci Food Saf, 2016 Jan;15(1):219-233.
PMID: 33371579 DOI: 10.1111/1541-4337.12182

Honey is a popular natural food product with a very complex composition mainly consisting of both organic and inorganic constituents. The composition of honey is strongly influenced by both natural and anthropogenic factors, which vary based on its botanical and geographical origins. Although minerals and heavy metals are minor constituents of honey, they play vital role in determining its quality. There are several different analytical methods used to determine the chemical elements in honey. These methods are typically based on spectroscopy or spectrometry techniques (including atomic absorption spectrometry, atomic emission spectrometry, inductively coupled plasma mass spectrometry, and inductively coupled plasma optical emission spectrometry). This review compiles available scientific information on minerals and heavy metals in honey reported from all over the world. To date, 54 chemical elements in various types of honey have been identified and can be divided into 3 groups: major or macroelements (Na, K, Ca, Mg, P, S, Cl), minor or trace elements (Al, Cu, Pb, Zn, Mn, Cd, Tl, Co, Ni, Rb, Ba, Be, Bi, U, V, Fe, Pt, Pd, Te, Hf, Mo, Sn, Sb, La, I, Sm, Tb, Dy, Sd, Th, Pr, Nd, Tm, Yb, Lu, Gd, Ho, Er, Ce, Cr, As, B, Br, Cd, Hg, Se, Sr), and heavy metals (trace elements that have a specific gravity at least 5 times higher than that of water and inorganic sources). Chemical elements in honey samples throughout the world vary in terms of concentrations and are also influenced by environmental pollution.
Fulltext Design of an FPGA-Based Fuzzy Feedback Controller for Closed-Loop FES in Knee Joint Model

Noorsal E, Arof S, Yahaya SZ, Hussain Z, Kho D, Mohd Ali Y

Micromachines (Basel), 2021 Aug 16;12(8).
PMID: 34442590 DOI: 10.3390/mi12080968

Functional electrical stimulation (FES) device has been widely used by spinal cord injury (SCI) patients in their rehab exercises to restore motor function to their paralysed muscles. The major challenge of muscle contraction induced by FES is early muscle fatigue due to the open-loop stimulation strategy. To reduce the early muscle fatigue phenomenon, a closed-loop FES system is proposed to track the angle of the limb's movement and provide an accurate amount of charge according to the desired reference angle. Among the existing feedback controllers, fuzzy logic controller (FLC) has been found to exhibit good control performance in handling complex non-linear systems without developing any complex mathematical model. Recently, there has been considerable interest in the implementation of FLC in hardware embedded systems. Therefore, in this paper, a digital fuzzy feedback controller (FFC) embedded in a field-programmable gate array (FPGA) board was proposed. The digital FFC mainly consists of an analog-to-digital converter (ADC) Data Acquisition and FLC sub-modules. The FFC was designed to monitor and control the progress of knee extension movement by regulating the stimulus pulse width duration to meet the target angle. The knee is expected to extend to a maximum reference angle setting (70°, 40° or 30°) from its normal position of 0° once the stimulus charge is applied to the muscle by the FES device. Initially, the FLC was modelled using MATLAB Simulink. Then, the FLC was hardcoded into digital logic using hardware description language (HDL) Verilog codes. Thereafter, the performance of the digital FLC was tested with a knee extension model using the HDL co-simulation technique in MATLAB Simulink. Finally, for real-time verification, the designed digital FFC was downloaded to the Intel FPGA (DE2-115) board. The digital FFC utilized only 4% of the total FPGA (Cyclone IV E) logic elements (LEs) and required 238 µs to regulate stimulus pulse width data, including 3 µs for the FLC computation. The high processing speed of the digital FFC enables the stimulus pulse width duration to be updated every stimulation cycle. Furthermore, the implemented digital FFC has demonstrated good control performance in accurately controlling the stimulus pulse width duration to reach the desired reference angle with very small overshoot (1.4°) and steady-state error (0.4°). These promising results are very useful for a real-world closed-loop FES application.
Fulltext Synthesis, in-Vitro and in Silico Studies of Azo-Based Calix[4]arenes as Antibacterial Agent and Neuraminidase Inhibitor: A New Look Into an Old Scaffold

Ali Y, Muhamad Bunnori N, Susanti D, Muhammad Alhassan A, Abd Hamid S

Front Chem, 2018;6:210.
PMID: 29946538 DOI: 10.3389/fchem.2018.00210

Calixarene derivatives are reported as potential therapeutic agents. Azo derivatives of calixarenes have not been given much consideration to explore their biomedical applications. In the present study, some azo-based derivatives of calix[4]arene were synthesized and characterized and their antibacterial and antiviral potentials were studied. The mono azo products of sulphanilamide, sulfaguanidine and 2-methyl-4-aminobenzoic acid showed good activity against bacterial strains with minimum inhibition concentration values ranging from 0.97 to 62.5 μg/mL. For mono azo products, the diazotized salt was applied as a limiting reagent. The use of calix[4]arene and sodium acetate trihydrate in 1:3 (molar ratio) helped in partial substitution. Molecular docking was performed to see the interaction of the designed compounds with two bacterial and one viral (neuraminidase) receptor. Some of the derivatives showed good interaction with the active site of bacterial and neuraminidase enzymes through hydrogen, hydrophobic and pi-pi interactions, and could inhibit the activity of the selected enzymes.
Fulltext Isolation, Characterization and Neuroprotective Activity of Folecitin: An In Vivo Study

Farooq U, Khan T, Shah SA, Hossain MS, Ali Y, Ullah R, et al.

Life (Basel), 2021 Aug 12;11(8).
PMID: 34440569 DOI: 10.3390/life11080825

Neurodegenerative diseases (NDs) extend the global health burden. Consumption of alcohol as well as maternal exposure to ethanol can damage several neuronal functions and cause cognition and behavioral abnormalities. Ethanol induces oxidative stress that is linked to the development of NDs. Treatment options for NDs are yet scarce, and natural product-based treatments could facilitate ND management since plants possess plenty of bioactive metabolites, including flavonoids, which typically demonstrate antioxidant and anti-inflammatory properties. Hypericum oblongifolium is an important traditional medicinal plant used for hepatitis, gastric ulcer, external wounds, and other gastrointestinal disorders. However, it also possesses multiple bioactive compounds and antioxidant properties, but the evaluation of isolated pure compounds for neuroprotective efficacy has not been done yet. Therefore, in the current study, we aim to isolate and characterize the bioactive flavonoid folecitin and evaluate its neuroprotective activity against ethanol-induced oxidative-stress-mediated neurodegeneration in the hippocampus of postnatal day 7 (PND-7) rat pups. A single dose of ethanol (5 g/kg body weight) was intraperitoneally administered after the birth of rat pups on PND-7. This caused oxidative stress accompanied by the activation of phosphorylated-c-Jun N-terminal kinase (p-JNK), nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cysteine-aspartic acid protease-1 (caspase-1) proteins to form a complex called the NLRP3-inflammasome, which converts pro-interleukin 1 beta (IL-1B) to activate IL-1B and induce widespread neuroinflammation and neurodegeneration. In contrast, co-administration of folecitin (30 mg/kg body weight) reduced ethanol-induced oxidative stress, inhibited p-JNK, and deactivated the NLRP3-inflammasome complex. Furthermore, folecitin administration reduced neuroinflammatory and neurodegenerative protein markers, including decreased caspase-3, BCL-2-associated X protein (BAX), B cell CLL/lymphoma 2 (BCL-2), and poly (ADP-ribose) polymerase-1 (PARP-1) expression in the immature rat brain. These findings conclude that folecitin is a flavone compound, and it might be a novel, natural and safe agent to curb oxidative stress and its downstream harmful effects, including inflammasome activation, neuroinflammation, and neurodegeneration. Further evaluation in a dose-dependent manner would be worth it in order to find a suitable dose regimen for NDs.
Design, synthesis, in vitro Evaluation and docking studies on dihydropyrimidine-based urease inhibitors

Iftikhar F, Ali Y, Ahmad Kiani F, Fahad Hassan S, Fatima T, Khan A, et al.

Bioorg Chem, 2017 10;74:53-65.
PMID: 28753459 DOI: 10.1016/j.bioorg.2017.07.003

In our previous report, we have identified 3,4-dihydropyrimidine scaffold as promising class of urease inhibitor in a structure based virtual screen (SBVS) experiment. In present study, we attempted to optimize the scaffold by varying C-5 substituent. The elongation of the C-5 chain was achieved by the reaction of C-5 ester with hydrazine leading to C-5 carbohydrazides which were further used as building blocks for the synthesis of fifteen new compounds having diverse moieties. A significantly higher in vitro urease inhibitory activity with IC50 values in submicromolar range was observed for semithiocarbazide derivatives (4a-c, 0.58-0.79µM) and isatin Schiff base derivative 5a (0.23µM). Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its key amino acid residues. The overall results of urease inhibition have shown that these compounds can be further optimized and developed as lead urease inhibitors.
Fulltext Don't close the book on tocilizumab for the treatment of severe COVID-19 pneumonia-the jury is still out: The Kuwait experience

Al-Shamali Y, M Ali Y, Al-Shamali RA, Al-Melahi M, Al-Shammari FR, Alsaber A, et al.

PLoS One, 2021;16(8):e0254379.
PMID: 34428204 DOI: 10.1371/journal.pone.0254379

PURPOSE: This cross-sectional observational study aims to report preliminary data from the first experience using tocilizumab for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in three of Kuwait's largest public hospitals City.
PATIENTS AND METHODS: This chart review study examined the benefits of tocilizumab treatment among 127 patients diagnosed with severe coronavirus disease of 2019 (COVID-19) pneumonia.
RESULTS: 90 of 127 patients (71%) survived. Mortality was highest in the elderly with multiple medical conditions.
CONCLUSION: Despite the small sample size and retrospective nature of the work, our findings are consistent with recent studies suggesting tocilizumab administration in patients presenting with severe COVID pneumonia with associated hyperinflammatory features conferred mortality benefit.
Evaluation of potential bacterial protease inhibitor properties of selected hydroxyquinoline derivatives: an in silico docking and molecular dynamics simulation approach

Riaz F, Hossain MS, Roney M, Ali Y, Qureshi S, Muhammad R, et al.

J Biomol Struct Dyn, 2023 Nov;41(19):9756-9769.
PMID: 36399018 DOI: 10.1080/07391102.2022.2146200

Antimicrobial drug resistance (AMR) is a severe global threat to public health. The increasing emergence of drug-resistant bacteria requires the discovery of novel antibacterial agents. Quinoline derivatives have previously been reported to exhibit antimalarial, antiviral, antitumor, antiulcer, antioxidant and, most interestingly, antibacterial properties. In this study, we evaluated the binding affinity of three newly designed hydroxyquinolines derived from sulfanilamide (1), 4-amino benzoic acid (2) and sulfanilic acid (3) towards five bacterial protein targets (PDB ID: 1JIJ, 3VOB, 1ZI0, 6F86, 4CJN). The three derivatives were designed considering the amino acid residues identified at the active site of each protein involved in the binding of each co-crystallized ligand and drug-likeness properties. The ligands displayed binding energy values with the target proteins ranging from -2.17 to -8.45 kcal/mol. Compounds (1) and (3) showed the best binding scores towards 1ZI0/3VOB and 1JIJ/4CJN, respectively, which may serve as new antibiotic scaffolds. Our in silico results suggest that sulfanilamide (1) or sulfanilic acid (3) hydroxyquinoline derivatives have the potential to be developed as bacterial inhibitors, particularly MRSA inhibitors. But before that, it must go through the proper preclinical and clinical trials for further scientific validation. Further experimental studies are warranted to explore the antibacterial potential of these compounds through preclinical and clinical studies.Communicated by Ramaswamy H. Sarma.
Fulltext Is Serum Uric Acid Level Associated with Disease Activity in Rheumatoid Arthritis Patients

Alkhudir D, Al-Herz A, Saleh K, Alawadhi A, Al-Kandari W, Hasan E, et al.

Open Access Rheumatol, 2023;15:223-230.
PMID: 38026718 DOI: 10.2147/OARRR.S418814

BACKGROUND: An association between serum uric acid (UA) and disease activity in rheumatoid arthritis (RA) patients has not been well studied. We describe RA patients with high and normal UA and study its association with RA activity.
METHODS: Adult RA patients from the Kuwait Registry for Rheumatic Diseases (KRRD) were studied from February 2012 through March 2022. Patients with documented UA levels were included. UA of >357 µmol/L (6mg/dL) was considered high. Statistical comparison and correlation were made using multivariate logistic regression.
RESULTS: Overall, 1054 patients with documented UA. A total of 158 patients (15%) had high UA level with a mean of 409± 44.4µmol/L. The mean age for the high UA group and low UA group were 59.3 ± 10.7 years and 54.5 ± 12.4 years, respectively (p<0.001). 49.4% were female in high UA group, and 62.2% were female in low UA group, respectively (p<0.05). Logistic analysis showed an inverse relation between DAS28 and UA, as lower DAS28 score was associated with higher UA level (p=0.032) OR 1.39. There was a direct relation with HAQ, creatinine and UA. A higher HAQ is associated with a higher UA level (p=0.019) OR 0.78. High creatinine level is also associated with high UA level (p<0.001) OR 0.24. The use of antirheumatic drugs was similar among patients with high and normal UA.
CONCLUSION: RA patients with a higher UA had a lower disease activity despite using similar antirheumatic drugs. The reasons behind this association need to be further studied.
Adherence to the Mediterranean diet is associated with a reduced DAS28 index among patients with rheumatoid arthritis: Case study from KRRD

Alawadhi B, Alsaber A, Shatawan I, Al-Herz A, Setiya P, Saleh K, et al.

Int J Rheum Dis, 2023 Dec;26(12):2430-2440.
PMID: 37784239 DOI: 10.1111/1756-185X.14928

BACKGROUND: Rheumatoid arthritis (RA) is a chronic, autoimmune disease that mostly affects the synovial joints. It has been hypothesized that dietary and other environmental and lifestyle factors contribute to the development of RA and its severity.
OBJECTIVE: The present study aims to measure the effect of the Mediterranean diet (MedDiet) on the disease activity scores (DAS28) among patients with RA.
METHODS: Adult patients who satisfied the American College of Rheumatology (ACR) classification criteria for RA from major hospitals in Kuwait were evaluated. A cross-sectional study conducted on 754 RA patients visits aged (21-79) years. Patients were evaluated using the DAS28. Patients' levels of adherence to the MedDiet are assessed using a validated 14-item Questionnaire (paper or web-based). The data was analyzed using both multivariate and univariate statistics. Multivariate logistic regression was used to analyze the statistical relationship between MedDiet and RA disease activity.
RESULTS: The finding suggests that a MedDiet can have a positive impact on DAS28 among patients with RA. In the DAS28 cohort (DAS28

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