Displaying publications 1 - 20 of 161 in total

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  1. Mannan Baig A, Khan NA, Effendi V, Rana Z, Ahmad HR, Abbas F
    Anticancer Drugs, 2017 01;28(1):75-87.
    PMID: 27606721
    Recent reports on acetylcholine muscarinic receptor subtype 3 (CHRM3) have shown its growth-promoting role in prostate cancer. Additional studies report the proliferative effect of the cholinergic agonist carbachol on prostate cancer by its agonistic action on CHRM3. This study shows that the type 1 acetylcholine muscarinic receptor (CHRM1) contributes toward the proliferation and growth of prostate cancer. We used growth and cytotoxic assays, the prostate cancer microarray database and CHRM downstream pathways' homology of CHRM subtypes to uncover multiple signals leading to the growth of prostate cancer. Growth assays showed that pilocarpine stimulates the proliferation of prostate cancer. Moreover, it shows that carbachol exerts an additional agonistic action on nicotinic cholinergic receptor of prostate cancer cells that can be blocked by tubocurarine. With the use of selective CHRM1 antagonists such as pirenzepine and dicyclomine, a considerable inhibition of proliferation of prostate cancer cell lines was observed in dose ranging from 15-60 µg/ml of dicyclomine. The microarray database of prostate cancer shows a dominant expression of CHRM1 in prostate cancer compared with other cholinergic subtypes. The bioinformatics of prostate cancer and CHRM pathways show that the downstream signalling include PIP3-AKT-CaM-mediated growth in LNCaP and PC3 cells. Our study suggests that antagonism of CHRM1 may be a potential therapeutic target against prostate cancer.
  2. Chia TY, Murugaiyah V, Khan NA, Sattar MA, Abdulla MH, Johns EJ, et al.
    Physiol Res, 2021 03 17;70(1):13-26.
    PMID: 33728924
    Reactive oxygen species (ROS) such as superoxide (O2-) generated by NAD(P)H oxidases have emerged as important molecules in blood pressure regulation. This study investigated the effect of apocynin and catalase on blood pressure and renal haemodynamic and excretory function in an L-NAME induced hypertension model. Forty Male Wistar-Kyoto (WKY) rats (n=8 per group) were treated with either: vehicle (WKY-C); L-NAME (WKY-L, 15 mg/kg/day in drinking fluid); WKY-L given apocynin to block NAD(P)H oxidase (WKY-LApo, 73 mg/kg/day in drinking water.); WKY-L given catalase to enhance ROS scavenging (WKY-LCat, 10000 U/kg/day i.p.); and WKY-L receiving apocynin plus catalase (WKY-LApoCat) daily for 14 days. L-NAME elevated systolic blood pressure (SBP), 116+/-1 to 181±4 mmHg, reduced creatinine clearance, 1.69+/-0.26 to 0.97+/-0.05 ml/min/kg and fractional sodium excretion, 0.84+/-0.09 to 0.55+/-0.09 % at day 14. Concomitantly, plasma malondialdehyde (MDA) increased six fold, while plasma total superoxide dismutase (T-SOD), plasma nitric oxide (NO) and plasma total antioxidant capacity (T-AOC) were decreased by 60-70 % and Nox 4 mRNA expression was increased 2-fold. Treatment with apocynin and catalase attenuated the increase in SBP and improved renal function, enhanced antioxidative stress capacity and reduced the magnitude of Nox4 mRNAs expression in the L-NAME treated rats. This study demonstrated that apocynin and catalase offset the development of L-NAME induced hypertension, renal dysfunction and reduced oxidative stress status, possibly contributed by a reduction in Nox4 expression during NOS inhibition. These findings would suggest that antioxidant compounds such as apocynin and catalase have potential in treating cardiovascular diseases.
  3. Mohd Hussain RH, Afiqah WN, Abdul Ghani MK, Khan NA, Siddiqui R, Anuar TS
    Saudi J Biol Sci, 2021 Apr;28(4):2352-2359.
    PMID: 33911949 DOI: 10.1016/j.sjbs.2021.01.030
    The incidence of Acanthamoeba keratitis has been increasing since the previous decades, especially among contact lens users. This infection is majorly caused by the use of ineffective contact lens disinfecting solution. Thus, this study was conducted to evaluate the in vitro effects of multi-purpose disinfecting solutions (MPDS) against Acanthamoeba trophozoites and cysts. Acanthamoeba genotype T4 isolated from contact lens paraphernalia and an environmental strains were propagated for trophozoite or cyst-containing culture and adjusted in final concentration of 1 × 105 cells/ml. Amoebicidal and cysticidal assays were conducted by incubating trophozoites and cysts with OPTI-FREE® Express®, ReNu® Fresh™, Complete® Multi-Purpose Solution and AVIZOR Unica® Sensitive according to the manufacturer's minimum recommended disinfectant time (MMRDT) for up to 12 h at 30 ⁰C. Trypan blue hemocytometer-based microscopic counts determined amoebicidal and cysticidal effects. The viability of Acanthamoeba trophozoites and cysts was confirmed by re-inoculated them in the 1.5% non-nutrient agar plates. It was found that none of the MPDS showed amoebicidal and cysticidal effects during the MMRDT. However, OPTI-FREE® Express® demonstrated a significant differences in average cell reduction for both stages within MMRDT. When subjected to 12 h exposure, both OPTI-FREE® Express® and ReNu® Fresh™ led to significant reduction in the number of trophozoite and cyst cells. Notably, Complete® Multi-Purpose Solution and AVIZOR Unica® Sensitive did appreciably improve the solution effectiveness towards trophozoite cells when incubated for 12 h. All MPDS were largely ineffective, with 100% survival of all isolates at MMRDT, while OPTI-FREE® Express® showed limited amoebicidal activity against the contact lens paraphernalia isolate, however, it was more against the environmental strains after 12 h incubation time. The commercially available MPDS employed in this research offered minimal effectiveness against the protozoa despite the contact time. Improvement or development of new solution should consider the adjustment of the appropriate disinfectant concentration, adequate exposure time or the incorporation of novel chemical elements, which are effective against Acanthamoeba for accelerated disinfecting and more reduction of potential exposure of contact lens users to Acanthamoeba keratitis.
  4. Mohd Hussain RH, Abdul Ghani MK, Khan NA, Siddiqui R, Anuar TS
    J Water Health, 2022 Jan;20(1):54-67.
    PMID: 35100154 DOI: 10.2166/wh.2021.128
    The present study identifies the Acanthamoeba genotypes and their pathogenic potential in five marine waters in Malaysia. Fifty water samples were collected between January and May 2019. Physical parameters of water quality were measured in situ, whereas chemical and microbiological analyses were conducted in the laboratory. All samples had undergone filtration using nitrocellulose membrane and were tested for Acanthamoeba using cultivation and polymerase chain reaction by targeting the 18S ribosomal RNA gene. The pathogenic potential of all positive isolates was identified using physiological tolerance tests. Thirty-six (72.0%) samples were positive for Acanthamoeba. Total coliforms (p = 0.013) and pH level (p = 0.023) displayed significant correlation with Acanthamoeba presence. Phylogenetic analysis showed that 27 samples belonged to genotype T4, four (T11), two (T18) and one from each genotype T5, T15 and T20. Thermo- and osmo-tolerance tests signified that three (8.3%) Acanthamoeba strains displayed highly pathogenic attributes. This study is the first investigation in Malaysia describing Acanthamoeba detection in marine water with molecular techniques and genotyping. The study outcomes revealed that the marine water in Malaysia could be an integral source of Acanthamoeba strains potentially pathogenic in humans. Thus, the potential risk of this water should be monitored routinely in each region.
  5. Mohd Hussain RH, Abdul Ghani MK, Khan NA, Siddiqui R, Aazmi S, Halim H, et al.
    Pathogens, 2022 Dec 05;11(12).
    PMID: 36558808 DOI: 10.3390/pathogens11121474
    Amoebic keratitis and encephalitis are mainly caused by free-living amoebae of the genus Acanthamoeba, which consists of both pathogenic and nonpathogenic species. The global distribution, amphizoic properties and the severity of the disease caused by Acanthamoeba species have inspired the scientific community to put more effort into the isolation of Acanthamoeba, besides exploring the direct and indirect parameters that could signify a pathogenic potential. Therefore, this study was performed to characterize the pathogenic potential of Acanthamoeba isolated from contact lens paraphernalia and water sources in Malaysia. Various methodologies were utilized to analyze the thermotolerance and osmotolerance, the secretion level of proteases and the cytopathic effect of trophozoites on the cell monolayer. In addition, the in vitro cytopathogenicity of these isolates was assessed using the LDH-release assay. A total of 14 Acanthamoeba isolates were classified as thermo- and osmotolerant and had presence of serine proteases with a molecular weight of 45-230 kDa. Four T4 genotypes isolated from contact lens paraphernalia recorded the presence of serine-type proteases of 107 kDa and 133 kDa. In contrast, all T3 genotypes isolated from environmental samples showed the presence of a 56 kDa proteolytic enzyme. Remarkably, eight T4 and a single T3 genotype isolates demonstrated a high adhesion percentage of greater than 90%. Moreover, the use of the HeLa cell monolayer showed that four T4 isolates and one T3 isolate achieved a cytopathic effect in the range of 44.9-59.4%, indicating an intermediate-to-high cytotoxicity level. Apart from that, the LDH-release assay revealed that three T4 isolates (CL5, CL54 and CL149) and one T3 isolate (SKA5-SK35) measured an exceptional toxicity level of higher than 40% compared to other isolates. In short, the presence of Acanthamoeba T3 and T4 genotypes with significant pathogenic potential in this study reiterates the essential need to reassess the functionality of other genotypes that were previously classified as nonpathogenic isolates in past research.
  6. Abdelnasir S, Mungroo MR, Shahabuddin S, Siddiqui R, Khan NA, Anwar A
    ACS Chem Neurosci, 2021 Oct 06;12(19):3579-3587.
    PMID: 34545742 DOI: 10.1021/acschemneuro.1c00179
    Free-living amoebae include Acanthamoeba castellanii and Naegleria fowleri that are opportunistic protozoa responsible for life-threatening central nervous system infections with mortality rates over 90%. The rising number of cases and high mortality rates are indicative of the critical unmet need for the development of efficient drugs in order to avert future deaths. In this study, we assess the anti-amoebic capacity of a conducting polymer nanocomposite comprising polyaniline (PANI) and hexagonal boron nitride (hBN) against A. castellanii and N. fowleri. We observed significant amoebicidal and cysticidal effects using 100 μg/mL PANI/hBN (P < 0.05). Further, the nanocomposite demonstrated negligible cytotoxicity toward HaCaT and primary human corneal epithelial cells (pHCECs). In evaluating the mode of inhibition of A. castellanii due to treatment with PANI/hBN, increased intracellular reactive oxygen species (ROS) was measured and scanning microscopy visualized the formation of pores in the amoebae. Overall, this study is suggestive of the potential of the PANI/hBN nanocomposite as a promising therapy for amoeba infections.
  7. Abdelnasir S, Mungroo MR, Chew J, Siddiqui R, Khan NA, Ahmad I, et al.
    ACS Omega, 2023 Mar 07;8(9):8237-8247.
    PMID: 36910978 DOI: 10.1021/acsomega.2c06050
    Primary amoebic meningoencephalitis and granulomatous amoebic encephalitis are distressing infections of the central nervous system caused by brain-eating amoebae, namely, Naegleria fowleri and Acanthamoeba spp., respectively, and present mortality rates of over 90%. No single drug has been approved for use against these infections, and current therapy is met with an array of obstacles including high toxicity and limited specificity. Thus, the development of alternative effective chemotherapeutic agents for the management of infections due to brain-eating amoebae is a crucial requirement to avert future mortalities. In this paper, we synthesized a conducting polymer-based nanocomposite entailing polyaniline (PANI) and molybdenum disulfide (MoS2) and explored its anti-trophozoite and anti-cyst potentials against Acanthamoeba castellanii and Naegleria fowleri. The intracellular generation of reactive oxygen species (ROS) and ultrastructural appearances of amoeba were also evaluated with treatment. Throughout, treatment with the 1:2 and 1:5 ratios of PANI/MoS2 at 100 μg/mL demonstrated significant anti-amoebic effects toward A. castellanii as well as N. fowleri, appraised to be ROS mediated and effectuate physical alterations to amoeba morphology. Further, cytocompatibility toward human keratinocyte skin cells (HaCaT) and primary human corneal epithelial cells (pHCEC) was noted. For the first time, polymer-based nanocomposites such as PANI/MoS2 are reported in this study as appealing options in the drug discovery for brain-eating amoebae infections.
  8. Ahmed U, Manzoor M, Qureshi S, Mazhar M, Fatima A, Aurangzeb S, et al.
    Acta Trop, 2023 Mar;239:106824.
    PMID: 36610529 DOI: 10.1016/j.actatropica.2023.106824
    Pathogenic A. castellanii and N. fowleri are opportunistic free-living amoebae. Acanthamoeba spp. are the causative agents of granulomatous amebic encephalitis (GAE) and amebic keratitis (AK), whereas Naegleria fowleri causes a very rare but severe brain infection called primary amebic meningoencephalitis (PAM). Acridinone is an important heterocyclic scaffold and both synthetic and naturally occurring derivatives have shown various valuable biological properties. In the present study, ten synthetic Acridinone derivatives (I-X) were synthesized and assessed against both amoebae for anti-amoebic and cysticidal activities in vitro. In addition, excystation, encystation, cytotoxicity, host cell pathogenicity was also performed in-vitro. Furthermore, molecular docking studies of these compounds with three cathepsin B paralogous enzymes of N. fowleri were performed in order to predict the possible docking mode with pathogen. Compound VII showed potent anti-amoebic activity against A. castellanii with IC50 53.46 µg/mL, while compound IX showed strong activity against N. fowleri in vitro with IC50 72.41 µg/mL. Compounds II and VII showed a significant inhibition of phenotypic alteration of A. castellanii, while compound VIII significantly inhibited N. fowleri cysts. Cytotoxicity assessment showed that these compounds caused minimum damage to human keratinocyte cells (HaCaT cells) at 100 µg/mL, while also effectively reduced the cytopathogenicity of Acanthamoeba to HaCaT cells. Moreover, Cathepsin B protease was investigated in-silico as a new molecular therapeutic target for these compounds. All compounds showed potential interactions with the catalytic residues. These results showed that acridine-9(10H)-one derivatives, in particular compounds II, VII, VIII and IX hold promise in the development of therapeutic agents against these free-living amoebae.
  9. Ahmed U, Sivasothy Y, Khan KM, Khan NA, Wahab SMA, Awang K, et al.
    Acta Trop, 2023 Dec;248:107033.
    PMID: 37783284 DOI: 10.1016/j.actatropica.2023.107033
    Acanthamoeba castellanii is an opportunistic free-living amoeba (FLA) pathogen which can cause fatal central nervous system (CNS) infection, granulomatous amoebic encephalitis (GAE) and potentially blinding ocular infection, Acanthamoeba keratitis (AK). Acanthamoeba species remain a challenging protist to treat due to the unavailability of safe and effective therapeutic drugs and their ability to protect themselves in the cyst stage. Natural products and their secondary metabolites play a pivotal role in drug discovery against various pathogenic microorganisms. In the present study, the ethyl acetate extract of Myristica cinnamomea King fruit was evaluated against A. castellanii (ATCC 50492), showing an IC50 of 45.102 ± 4.62 µg/mL. Previously, the bio-guided fractionation of the extract resulted in the identification of three active compounds, namely Malabaricones (A-C). The isolated and thoroughly characterized acylphenols were evaluated for their anti-amoebic activity against A. castellanii for the first time. Among tested compounds, Malabaricone B (IC50 of 101.31 ± 17.41 µM) and Malabaricone C (IC50 of 49.95 ± 6.33 µM) showed potent anti-amoebic activity against A. castellanii trophozoites and reduced their viability up-to 75 and 80 %, respectively. Moreover, both extract and Malabaricones also significantly (p < 0.05) inhibit the encystation and excystation of A. castellanii, while showed minimal toxicity against human keratinocyte cells (HaCaT cells) at lower tested concentrations. Following that, the explanation of the possible mechanism of action of purified compounds were assessed by detection of the state of chromatin. Hoechst/PI 33342 double staining showed that necrotic cell death occurred in A. castellanii trophozoites after 8 h treatment of Malabaricones (A-C). These findings demonstrate that Malabaricones B and C could serve as promising therapeutic options against A. castellanii infections.
  10. Ahmed U, Ong SK, Tan KO, Khan KM, Khan NA, Siddiqui R, et al.
    Int Microbiol, 2023 Nov 28.
    PMID: 38015290 DOI: 10.1007/s10123-023-00450-1
    Acanthamoeba are free living amoebae that are the causative agent of keratitis and granulomatous amoebic encephalitis. Alpha-Mangostin (AMS) is a significant xanthone; that demonstrates a wide range of biological activities. Here, the anti-amoebic activity of α-Mangostin and its silver nano conjugates (AMS-AgNPs) were evaluated against pathogenic A. castellanii trophozoites and cysts in vitro. Amoebicidal assays showed that both AMS and AMS-AgNPs inhibited the viability of A. castellanii dose-dependently, with an IC50 of 88.5 ± 2.04 and 20.2 ± 2.17 μM, respectively. Both formulations inhibited A. castellanii-mediated human keratinocyte cell cytopathogenicity. Functional assays showed that both samples caused apoptosis through the mitochondrial pathway and reduced mitochondrial membrane potential and ATP production, while increasing reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome-c reductase in the cytosol. Whole transcriptome sequencing of A. castellanii showed the expression of 826 genes, with 447 genes being up-regulated and 379 genes being down-regulated post treatment. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the majority of genes were linked to apoptosis, autophagy, RAP1, AGE-RAGE and oxytocin signalling pathways. Seven genes (PTEN, H3, ARIH1, SDR16C5, PFN, glnA GLUL, and SRX1) were identified as the most significant (Log2 (FC) value 4) for molecular mode of action in vitro. Future in vivo studies with AMS and nanoconjugates are needed to realize the clinical potential of this work.
  11. Simau FA, Ahmed U, Khan KM, Khan NA, Siddiqui R, Alharbi AM, et al.
    Parasitol Res, 2024 Jan 31;123(2):117.
    PMID: 38294565 DOI: 10.1007/s00436-024-08131-2
    The free living Acanthamoeba spp. are ubiquitous amoebae associated with potentially blinding disease known as Acanthamoeba keratitis (AK) and a fatal central nervous system infection granulomatous amoebic encephalitis (GAE). With the inherent ability of cellular differentiation, it can phenotypically transform to a dormant cyst form from an active trophozoite form. Acanthamoeba cysts are highly resistant to therapeutic agents as well as contact lens cleaning solutions. One way to tackle drug resistance against Acanthamoeba is by inhibiting the formation of cysts from trophozoites. The biochemical analysis showed that the major component of Acanthamoeba cyst wall is composed of carbohydrate moieties such as galactose and glucose. The disaccharide of galactose and glucose is lactose. In this study, we analyzed the potential of lactase enzyme to target carbohydrate moieties of cyst walls. Amoebicidal assessment showed that lactase was ineffective against trophozoite of A. castellanii but enhanced amoebicidal effects of chlorhexidine. The lactase enzyme did not show any toxicity against normal human keratinocyte cells (HaCaT) at the tested range. Hence, lactase can be used for further assessment for development of potential therapeutic agents in the management of Acanthamoeba infection as well as formulation of effective contact lens disinfectants.
  12. Rao K, Abdullah M, Ahmed U, Wehelie HI, Shah MR, Siddiqui R, et al.
    Arch Microbiol, 2024 Mar 04;206(4):134.
    PMID: 38433145 DOI: 10.1007/s00203-024-03854-3
    Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.
  13. Younas M, Zou H, Laraib T, Rajpoot NA, Khan NA, Zaidi AA, et al.
    PLoS One, 2021;16(9):e0256449.
    PMID: 34529693 DOI: 10.1371/journal.pone.0256449
    Mungbean yellow mosaic virus (MYMV) is an important constraint in successful production of mungbean (Vigna radiata L.) in many countries, including Pakistan. The MYMV spreads by insect vector whitefly (Bemisia tabaci Gennadius). The use of resistant cultivars is the most effective management tactics for MYMV. Twenty mungbean varieties/lines were screened against insect vector of MYMV under field condition in the current study. Resistance levels for varieties/lines were assessed through visual scoring of typical disease symptoms. Furthermore, the impacts of two insecticides 'Imidacloprid' and 'Thiamethoxam' and two plant extracts, i.e., neem (Azadirachta indica), and Eucalyptus (Eucalyptus camaldulensis) were tested on the suppression of whitefly. Field screening indicated that none of the tested varieties/lines proved immune/highly resistant, while significant variations were recorded among varieties/lines for resistance level. All varieties/lines were systemically infected with MYMV. The varieties 'AARI-2006' and 'Mung-14043' were considered as resistant to MYMV based on visual symptoms and the lowest vector population. These varieties were followed by 'NM-2006' and 'NL-31', which proved as moderately resistant to MYMV. All remaining varieties/lines were grouped as moderately to highly susceptible to MYMV based on visual symptoms' scoring. These results revealed that existing mungbean germplasm do not possess high resistance level MYMV. However, the lines showing higher resistance in the current study must be exploited in breeding programs for the development of resistant mungbean varieties/lines against MYMV. Imidacloprid proved as the most effective insecticide at all concentrations to manage whitefly population. Therefore, use of the varieties with higher resistance level and spraying Imidacloprid could lower the incidence of MYMV.
  14. Khan NA, Khalaf OI, Romero CAT, Sulaiman M, Bakar MA
    Entropy (Basel), 2021 Aug 16;23(8).
    PMID: 34441192 DOI: 10.3390/e23081053
    In this study, a novel application of neurocomputing technique is presented for solving nonlinear heat transfer and natural convection porous fin problems arising in almost all areas of engineering and technology, especially in mechanical engineering. The mathematical models of the problems are exploited by the intelligent strength of Euler polynomials based Euler neural networks (ENN's), optimized with a generalized normal distribution optimization (GNDO) algorithm and Interior point algorithm (IPA). In this scheme, ENN's based differential equation models are constructed in an unsupervised manner, in which the neurons are trained by GNDO as an effective global search technique and IPA, which enhances the local search convergence. Moreover, a temperature distribution of heat transfer and natural convection porous fin are investigated by using an ENN-GNDO-IPA algorithm under the influence of variations in specific heat, thermal conductivity, internal heat generation, and heat transfer rate, respectively. A large number of executions are performed on the proposed technique for different cases to determine the reliability and effectiveness through various performance indicators including Nash-Sutcliffe efficiency (NSE), error in Nash-Sutcliffe efficiency (ENSE), mean absolute error (MAE), and Thiel's inequality coefficient (TIC). Extensive graphical and statistical analysis shows the dominance of the proposed algorithm with state-of-the-art algorithms and numerical solver RK-4.
  15. Khan NA, Ibrahim Khalaf O, Andrés Tavera Romero C, Sulaiman M, Bakar MA
    Comput Intell Neurosci, 2022;2022:2710576.
    PMID: 35096038 DOI: 10.1155/2022/2710576
    In this study, the intelligent computational strength of neural networks (NNs) based on the backpropagated Levenberg-Marquardt (BLM) algorithm is utilized to investigate the numerical solution of nonlinear multiorder fractional differential equations (FDEs). The reference data set for the design of the BLM-NN algorithm for different examples of FDEs are generated by using the exact solutions. To obtain the numerical solutions, multiple operations based on training, validation, and testing on the reference data set are carried out by the design scheme for various orders of FDEs. The approximate solutions by the BLM-NN algorithm are compared with analytical solutions and performance based on mean square error (MSE), error histogram (EH), regression, and curve fitting. This further validates the accuracy, robustness, and efficiency of the proposed algorithm.
  16. Ling SS, Magosso E, Khan NA, Yuen KH, Barker SA
    Drug Dev Ind Pharm, 2006 Mar;32(3):335-45.
    PMID: 16556538
    A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.
  17. Sunil Kumar Naik TS, Singh S, N P, Varshney R, Uppara B, Singh J, et al.
    Chemosphere, 2023 Jan;311(Pt 2):137104.
    PMID: 36347345 DOI: 10.1016/j.chemosphere.2022.137104
    In the present study, a simple and sensitive method for detecting bisphenol A (BPA) in various environments, including groundwater, was described using a widespread electrochemical method. BPA is well-known for its endocrine-disrupting properties, which may cause potential toxicological effects oon the nervous, reproductive, and immune systems. A novel metal-organic framework (UiO-66-NDC/GO) was synthesized, and its existence was confirmed by several characterization techniques like FTIR, UV-visible, XRD, SEM-EDX, Raman spectroscopy, and TGA. Due to the excellent electrocatalytic nature, UiO-66-NDC/GO was chosen as the sensor material and integrated on the surface of the bare carbon paste electrode (BCPE). The UiO-66-NDC/GO modified carbon paste electrode (MCPE) was engaged for the detection of BPA using techniques like cyclic Voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectroscopy (EIS). The applied sensor exhibited an astonishing outcome for BPA detection with high sensitivity and selectivity. The lower detection limit (LLOD) of 0.025 μM was achieved at the modified sensor with a linear concentration range of 10-70 μM. Moreover, the practical applicability of the sensor was tested on tap water, drinking water, and fresh liquid milk, giving an excellent recovery of BPA in the range of 94.8-99.3 (v.%). The proposed method could be employed for electrochemical device or a solid state device fabrication for the onsite monitoring of BPA.
  18. Alsubih M, El Morabet R, Khan RA, Khan NA, Ul Haq Khan M, Ahmed S, et al.
    Environ Sci Pollut Res Int, 2021 Nov;28(44):63017-63031.
    PMID: 34218378 DOI: 10.1007/s11356-021-15062-3
    Groundwater is a primary natural water source in the absence of surface water bodies. Groundwater in urban environments experiences unprecedented stress from urban growth, population increase, and industrial activities. This study assessed groundwater quality in terms of arsenic and heavy metal contamination in three industrial areas (Shahdara, Jhilmil, and Patparganj), Delhi, India. The water quality was assessed over a 3-year time interval (i.e., 2015 and 2018). The groundwater constituents investigated were As, Fe, Cr, Cd, Ni, Zn, Mn, Cu, and Pb. Metal index and heavy metal pollution indexes were estimated to assess groundwater pollution. The health risk was evaluated in terms of non-carcinogenic and carcinogenic risk assessment. Patparganj industrial area saw increment in concentration for Cu 0.23 mg/L (2015)-0.85 mg/L (2018), Zn 0.51 mg/L (2015)-7.2 mg/L (2018), Fe 0.32 mg/L (2015)-0.9 mg/L (2018), Cr 0.21 mg/L (2015)-0.26 mg/L (2018), Mn 0.14 mg/L (2015)-0.25 mg/L (2018), Ni 0.04 mg/L (2015)-0.34 mg/L (2018), and As 0.01 mg/L (2015)-0.18 mg/L (2018). Cd and Pb concentrations were observed to decrease by 40-90 % and 85-99% for all the three industrial areas. Metal index and heavy metal index values were found to be >1 for all locations. The risk quotient value > 1 was observed for all locations in the year 2015 but was found to increase further to a range of RQ 10-62 in the year 2018, inferring increased non-carcinogenic risk to consumers. The carcinogenic risk was significant with respect to Fe (0.2-0.7), Zn (0.001-0.007), and As (0.002-0.003) for all locations in the year 2015. This study concludes that groundwater in the three industrial areas is highly polluted and is not fit for human consumption. Further studies are required to explore possible control measures and develop methods to mitigate groundwater pollution, sustainable management, and optimized use to conserve it for future generations.
  19. Kamsani YS, Rajikin MH, Mohamed Nor Khan NA, Abdul Satar N, Chatterjee A
    Med Sci Monit Basic Res, 2013 Mar 06;19:87-92.
    PMID: 23462735 DOI: 10.12659/MSMBR.883822
    BACKGROUND: This study aimed to evaluate the adverse effects of various doses of nicotine and protective effects of different concentrations of gamma-tocotrienol (gamma-TCT) on in vitro embryonic development and lipid peroxidation in mice.

    MATERIAL AND METHODS: A) Effects of various doses of nicotine on in vitro embryonic development: Female mice were treated with 1.0, 3.0, or 5.0 mg/kg/day nicotine for 7 consecutive days. Animals were superovulated, cohabited overnight, and sacrificed. Embryos were cultured in vitro. Plasma was assayed. B) Effects of concomitant treatment of nicotine concurrently with various doses of gamma-TCT on in vitro embryonic development: Female mice were treated with nicotine (5.0 mg/kg/day), gavaged gamma-TCT of 30, 60, or 90 mg/kg/day or nicotine concurrently with gamma-TCT of 3 different doses for 7 consecutive days. Animals were superovulated, cohabited overnight, and sacrificed. Embryos were cultured and plasma was assayed.

    RESULTS: A) Effects of various doses of nicotine on in vitro embryonic development: Number of hatched blastocysts decreased in 1.0 and 3.0 mg/kg/day nicotine groups. Nicotine at 5.0 mg/kg/day stopped embryo development at morula. MDA concentrations increased following all nicotine doses. B) Effects of concomitant treatment of nicotine concurrently with various doses of gamma-TCT on in vitro embryonic development: Embryo development was completed in all groups. MDA concentration increased only in the group treated with nicotine concurrently with 30 mg/kg/day gamma-TCT.

    CONCLUSIONS: Nicotine impairs in vitro embryo development and increases MDA in plasma. The deleterious impact of nicotine on embryo development is reversed by supplementing gamma-TCT concurrently with nicotine.

  20. Jusof WH, Khan NA, Rajikin MH, Satar NA, Mustafa MF, Jusoh N, et al.
    Int J Fertil Steril, 2015 07 27;9(2):221-9.
    PMID: 26246881
    BACKGROUND: Timing of the first zygotic cleavage is an accurate predictor of embryo quality. Embryos that cleaved early (EC) have been shown to exhibit higher develop- mental viability compared to those that cleaved at a later period (LC). However, the vi- ability of EC embryos in comparison to LC embryos after vitrification is unknown. The present study aims to investigate the post-vitrification developmental viability of murine EC versus LC embryos.

    MATERIALS AND METHODS: In this experimental study, female ICR mice (6-8 weeks old) were superovulated and cohabited with fertile males for 24 hours. Afterwards, their ovi- ducts were excised and embryos harvested. Embryos at the 2-cell stage were catego- rized as EC embryos, while zygotes with two pronuclei were categorized as LC embryos. Embryos were cultured in M16 medium supplemented with 3% bovine serum albumin (BSA) in a humidified 5% CO2atmosphere. Control embryos were cultured until the blastocyst stage without vitrification. Experimental embryos at the 2-cell stage were vitri- fied for one hour using 40% v/v ethylene glycol, 18% w/v Ficoll-70 and 0.5 M sucrose as the cryoprotectant. We recorded the numbers of surviving embryos from the control and experimental groups and their development until the blastocyst stage. Results were analyzed using the chi-square test.

    RESULTS: A significantly higher proportion of EC embryos (96.7%) from the control group developed to the blastocyst stage compared with LC embryos (57.5%, P<0.0001). Similarly, in the experimental group, a significantly higher percentage of vitrified EC embryos (69.4%) reached the blastocyst stage compared to vitrified LC embryos (27.1%, P<0.0001).

    CONCLUSION: Vitrified EC embryos are more vitrification tolerant than LC embryos. Prese- lection of EC embryos may be used as a tool for selection of embryos that exhibit higher developmental competence after vitrification.

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