Displaying publications 1 - 20 of 44 in total

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  1. Sayani JKS, English NJ, Khan MS, Lal B, Kamireddi VR
    ACS Omega, 2023 Feb 21;8(7):6218-6224.
    PMID: 36844557 DOI: 10.1021/acsomega.2c02823
    This work presents the effect of hydrogen sulfide gas on the phase behavior of both methane gas hydrate formation and CO2 gas hydrate formation. For this, the thermodynamic equilibrium conditions for various gas mixtures containing CH4/H2S and CO2/H2S are initially found by simulation using PVTSim software. These simulated results are compared using an experimental approach and the available literature. Then, the thermodynamic equilibrium conditions generated by simulation are used for generating Hydrate Liquid-Vapor-Equilibrium (HLVE) curves to understand the phase behavior of gases. Further, the effect of hydrogen sulfide on the thermodynamic stability of methane and carbon dioxide hydrates was studied. It was clearly observed from the results that an increase in H2S composition in the gas mixture decreases the stability of CH4 and CO2 hydrates.
  2. Abubakar AA, Ibrahim SM, Ali AK, Handool KO, Khan MS, Noordin Mustapha M, et al.
    Animal Model Exp Med, 2019 Mar;2(1):34-43.
    PMID: 31016285 DOI: 10.1002/ame2.12051
    BACKGROUND: Chondrocytes in the growth plate (GP) undergo increases in volume during different cascades of cell differentiation during longitudinal bone growth. The volume increase is reported to be the most significant variable in understanding the mechanism of long bone growth.

    METHODS: Forty-five postnatal Sprague-Dawley rat pups, 7-15 days old were divided into nine age groups (P7-P15). Five pups were allocated to each group. The rats were sacrificed and tibia and metatarsal bones were harvested. Bone lengths were measured after 0, 24, 48, and 72 hours of ex vivo incubation. Histology of bones was carried out, and GP lengths and chondrocyte densities were determined.

    RESULTS: There were significant differences in bone length among the age groups after 0 and 72 hours of incubation. Histological sectioning was possible in metatarsal bone from all age groups, and in tibia from 7- to 13-day-old rats. No significant differences in tibia and metatarsal GP lengths were seen among different age groups at 0 and 72 hours of incubation. Significant differences in chondrocyte densities along the epiphyseal GP of the bones between 0 and 72 hours of incubation were observed in most of the age groups.

    CONCLUSION: Ex vivo growth of tibia and metatarsal bones of rats aged 7-15 days old is possible, with percentage growth rates of 23.87 ± 0.80% and 40.38 ± 0.95% measured in tibia and metatarsal bone, respectively. Histological sectioning of bones was carried out without the need for decalcification in P7-P13 tibia and P7-P15 metatarsal bone. Increases in chondrocyte density along the GP influence overall bone elongation.

  3. Akbar SM, Al-Mahtab M, Khan MS, Raihan R, Shrestha A
    Ann Transl Med, 2016 Sep;4(18):335.
    PMID: 27761439
    Although several antiviral drugs are now available for treatment of patients with chronic hepatitis B (CHB), sustained off-treatment clinical responses and containment of CHB-related complications are not achieved in majority of CHB patients by antiviral therapy. In addition, use of these drugs is endowed with substantial long term risk of viral resistance and drug toxicity. The infinite treatment regimens of antiviral drugs for CHB patients are also costly and usually unbearable by most patients of developing and resource-constrained countries. Taken together, there is a pressing need to develop new and innovative therapeutic approaches for CHB patients. Immune therapy seems to be an alternate therapeutic approach for CHB patients because impaired or distorted or diminished immune responses have been detected in most of these patients. Also, investigators have shown that restoration or induction of proper types of immune responses may have therapeutic implications in CHB. Various immunomodulatory agents have been used to treat patients with CHB around the world and the outcomes of these clinical trials show that the properties of immune modulators and nature and designing of immune therapeutic regimens seem to be highly relevant in the context of treatment of CHB patients. In this review, the general properties and specific features of immune therapy for CHB have been discussed for developing the guidelines of effective regimens of immune therapy for CHB.
  4. Ali Khan MS, Nazan S, Mat Jais AM
    Arq Gastroenterol, 2017 Jul-Sep;54(3):183-191.
    PMID: 28492713 DOI: 10.1590/S0004-2803.201700000-21
    BACKGROUND: Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. from family Combretaceae is used in Ayurveda and Siddha traditional systems of medicine to heal ulcers.

    OBJECTIVE: The present study was conducted to assess the gastroprotective effect and understand the fundamental mechanism of action of Leathery Murdah, Terminalia coriacea (Roxb.) Wight & Arn. Leaf Methanolic Extract.

    METHODS: The test extract was screened for anti-ulcer activity by Aspirin induced ulcerogenesis in pyloric ligation and ethanol induced gastric ulcers at three doses - 125, 250, and 500 mg/kg, p.o. using Ranitidine 50 mg/kg and Misoprostol 100 μg/kg as standard drug in respective models. Seven parameters were carefully examined, that is, ulcer index, total protein, mucin, catalase, malondialdehyde, and superoxide dismutase levels and histopathology. High Performance Liquid Chromatographic - Ultra Violet profiling and Liquid Chromatography - Mass Spectral analysis of crude Terminalia coriacea leaves methanolic extract were carried out as a part of chemical characterization to identify bioactive compounds.

    RESULTS: All the test doses exhibited significant gastroprotective function, particularly the higher doses demonstrated improved action. The results revealed a significant increase in the levels of catalase, superoxide dismutase, and Mucin with reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also illustrated the gastroprotective effect of Terminalia coriacea leaves methanolic extract.

    CONCLUSION: Terminalia coriacea leaves methanolic extract exhibited strong anti-oxidant and anti-secretory activities mediated gastroprotection besides inducing the gastric mucosal production. The observed pharmacological response can be attributed to the flavonoidal compounds namely - Quercetin-3-O-rutinoside, Luteolin-7-O-glucoside, Myricetin hexoside, Quercetin-3-O-glucoside, Isorhamnetin-3-O-rhamnosylglucoside and Isorhamnetin-3-O-glucoside identified in the extract for the first time with High Performance Liquid Chromatographic - Ultra Violet and Liquid Chromatography - Mass Spectral analysis.
  5. Irfan B, Zahid I, Khan MS, Khan OAA, Zaidi S, Awan S, et al.
    BMC Health Serv Res, 2019 Nov 21;19(1):865.
    PMID: 31752855 DOI: 10.1186/s12913-019-4676-y
    BACKGROUND: Basic Life Support (BLS) is the recognition of sudden cardiac arrest and activation of the emergency response system, followed by resuscitation, and rapid defibrillation. According to WHO, Pakistan has one of the highest mortality rates from accidental deaths therefore assessment and comparison of BLS knowledge in health professionals is crucial. We thereby aim to assess and compare the knowledge of BLS in doctors, dentists and nurses.

    METHODS: A multi-centric cross-sectional survey was conducted in Karachi at different institutions belonging to the private as well as government sector from January to March 2018. We used a structured questionnaire which was adapted from pretested questionnaires that have been used previously in similar studies. Descriptive statistics were analyzed using SPSS v22.0, where adequate knowledge was taken as a score of at least 50%. P 

  6. Ali Khan MS, Mat Jais AM, Afreen A
    Biomed Res Int, 2013;2013:185476.
    PMID: 24350249 DOI: 10.1155/2013/185476
    The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses--125, 250, and 500 mg/kg--orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization--high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous.
  7. Gangurde R, Jagota V, Khan MS, Sakthi VS, Boppana UM, Osei B, et al.
    Biomed Res Int, 2023;2023:6970256.
    PMID: 36760472 DOI: 10.1155/2023/6970256
    The application of computational approaches in medical science for diagnosis is made possible by the development in technical advancements connected to computer and biological sciences. The current cancer diagnosis system is becoming outmoded due to the new and rapid growth in cancer cases, and new, effective, and efficient methodologies are now required. Accurate cancer-type prediction is essential for cancer diagnosis and treatment. Understanding, diagnosing, and identifying the various types of cancer can be greatly aided by knowledge of the cancer genes. The Convolution Neural Network (CNN) and neural pattern recognition (NPR) approaches are used in this study paper to detect and predict the type of cancer. Different Convolution Neural Networks (CNNs) have been proposed by various researchers up to this point. Each model concentrated on a certain set of parameters to simulate the expression of genes. We have developed a novel CNN-NPR architecture that predicts cancer type while accounting for the tissue of origin using high-dimensional gene expression inputs. The 5000-person sample of the 1-D CNN integrated with NPR is trained and tested on the gene profile, mapping with various cancer kinds. The proposed model's accuracy of 94% suggests that the suggested combination may be useful for long-term cancer diagnosis and detection. Fewer parameters are required for the suggested model to be efficiently trained before prediction.
  8. Younus HA, Hameed A, Mahmood A, Khan MS, Saeed M, Batool F, et al.
    Bioorg Chem, 2020 07;100:103827.
    PMID: 32402802 DOI: 10.1016/j.bioorg.2020.103827
    Medicinal importance of the sulfonylhydrazones is well-evident owing to their binding ability with zinc containing metalloenzymes. In the present study, we have synthesized different series of sulfonylhydrazones by using facile synthetic methods in good to excellent yield. All the successfully prepared sulfonylhydrazones were screened for ectonucleotidase (ALP & e5'NT) inhibitory activity. Among the chromen-2-one scaffold based sulfonylhydrazones, the compounds 7 was found to be most potent inhibitor for h-TNAP (human tissue non-specific alkaline phosphatase) and h-IAP (human intestinal alkaline phosphatase) with IC50 values of 1.02 ± 0.13 and 0.32 ± 0.0 3 µM respectively, compared with levamisole (IC50 = 25.2 ± 1.90 µM for h-TNAP) and l-phenylalanine (IC50 = 100 ± 3.00 µM for h-IAP) as standards. Further, the chromen-2-one based molecule 5a showed excellent activity against h-ecto 5'-NT (human ecto-5'-nucleotidase) with IC50 value of 0.29 ± 0.004 µM compared to standard, sulfamic acid (IC50 = 42.1 ± 7.8 µM). However, among the series of phenyl ring based sulfonylhydrazones, compound 9d was found to be most potent against h-TNAP and h-IAP with IC50 values of 0.85 ± 0.08 and 0.52 ± 0.03 µM, respectively. Moreover, in silico studies were also carried to demonstrate their putative binding with the target enzymes. The potent compounds 5a, 7, and 9d against different ectonucleotidases (h-ecto 5'-NT, h-TNAP, h-IAP) could potentially serve as lead for the development of new therapeutic agents.
  9. Yusufzai SK, Khan MS, Sulaiman O, Osman H, Lamjin DN
    Chem Cent J, 2018 Dec 04;12(1):128.
    PMID: 30515636 DOI: 10.1186/s13065-018-0497-z
    Coumarins are the phytochemicals, which belong to the family of benzopyrone, that display interesting pharmacological properties. Several natural, synthetic and semisynthetic coumarin derivatives have been discovered in decades for their applicability as lead structures as drugs. Coumarin based conjugates have been described as potential AChE, BuChE, MAO and β-amyloid inhibitors. Therefore, the objective of this review is to focus on the construction of these pharmacologically important coumarin analogues with anti-Alzheimer's activities, highlight their docking studies and structure-activity relationships based on their substitution pattern with respect to the selected positions on the chromen ring by emphasising on the research reports conducted in between year 1968 to 2017.
  10. Yusufzai SK, Osman H, Khan MS, Abd Razik BM, Ezzat MO, Mohamad S, et al.
    Chem Cent J, 2018 Jun 12;12(1):69.
    PMID: 29896651 DOI: 10.1186/s13065-018-0435-0
    A series of novel 4-thiazolidinone inhibitors SKYa-SKYg, containing coumarin as a core structure were synthesized via facile and efficient method. The structures of the synthesized compounds were established by extensive spectroscopic studies (FT IR, 1D NMR, 2D NMR, LC-MS) and elemental analysis. All the synthesized hybrids were further evaluated for their potential as anti-tubercular agents against Mycobacterium tuberculosis H37Rv ATCC 25618, and anti-bacterial agents against Escherichia coli, Enterobacter aerogenes, Salmonella typhi, Streptococcus pneumoniae and Staphylococcus aureus. Interestingly, the hybrids displayed potent bioactivity. However, compounds SKYc, SKYd, and SKYe appeared to be more effective against the tested bacterial strains, among which compound SKYb showed the highest inhibition against all the bacterial strains ranging from 41 to 165 μg/mL, as compared to the standards, streptomycin, kanamycin and vancomycin. Moreover, derivative SKYa was found to be the strongest against M. tuberculosis (83 μg/mL). Additionally, the anti-dengue potential of the coumarin hybrids as two-component NS2B/NS3 DENV flavivirus serine protease inhibitors was calculated using computational molecular docking approach, with reference to the standards 4-hydroxypanduratin, panduratin and ethyl 3-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy)propanoate with DS of - 3.379, - 3.189 and - 3.381, respectively. The docking results revealed that the synthesized hybrids exhibited potent anti-dengue activity among which compounds SKYf, SKYd, SKYc and SKYe were found to be the best ones with docking scores of - 4.014, - 3.964, - 3.905 and - 3.889. In summary, we discovered 4-thiazolidinone coumarin derivatives as a new scaffold that may eventually yield useful compounds in the treatment of bacterial and viral infections.
  11. Almashwali AA, Khan MS, Lal B, Jin QC, Sabil KM, Khor SF
    Chemosphere, 2023 Jan;312(Pt 2):137325.
    PMID: 36423723 DOI: 10.1016/j.chemosphere.2022.137325
    This experimental study evaluates the inhibition performance of kinetic hydrates inhibitors (KHIs) of three amino acids, namely: glycine, proline, and alanine. It includes the performance comparison with the conventional inhibitor i.e., polyvinyl pyrrolidine (PVP) on methane (CH4) hydrate in oil systems in two different systems, i.e., deionized and brine water systems. The experiments were conducted in a high-pressure hydrate reactor replicating subsea pipeline conditions, i.e., the temperature of 274 K, pressure 8 MPa, and concentration of 1 wt%, by applying the isochoric cooling technique. The formation kinetics results suggest that all the studied amino acids effectively worked as kinetic inhibitors by potentially delaying CH4 hydrate formations due to their steric hindrance abilities. The interesting phenomenon was observed that the different studied amino acids behave differently in the brine-oil and deionized water-oil systems due to their side chain interaction. In a deionized water-oil system, glycine gives the highest inhibition performance by reducing the hydrate formation risk. On the contrary, in the brine-oil system, proline showed a significant inhibition effect. It should be noted that both glycine and proline were giving almost similar inhibition performance compared to the conventional hydrate inhibitor PVP, however glycine and proline significantly reduced CH4 consumption into hydrate due to their high surface active under CH4 conditions, which strengths the surface tension of the liquid/CH4 interface. Furthermore, according to the findings, it shows that increased side alkyl chain lengths of amino acids increase the efficacy of their kinetic hydration inhibition performance due to better surface adsorption abilities. The amino acids' ability to suppress growth is also linked strongly with hydrophobicity and alkyl side chain length. The findings of this study contribute significantly to current efforts to limit gas hydrate formation in offshore pipelines, particularly in oil-dominant pipelines.
  12. Krishna Sahith Sayani J, English NJ, Khan MS, Ali A
    Chemosphere, 2023 Feb;313:137550.
    PMID: 36521742 DOI: 10.1016/j.chemosphere.2022.137550
    Gas Hydrate modelling has gained huge attention in the past decade due to its increase in usage for various energy as well as environmental applications at an industrial scale. As the experimental approach is highly expensive and time-consuming, modelling is the best way to predict the conditions before the actual applications at industrial scales. The commercial software currently existing uses the equation of states (EOS) to predict the thermodynamic conditions of gas hydrates. But, in certain cases, the prediction by using EOS fails to predict the hydrate conditions accurately. Therefore, there arose a need for an accurate prediction model to estimate the hydrate formation conditions. So, in this work, an accurate prediction model has been proposed to predict the thermodynamic equilibrium conditions of the gas hydrate formation. The performance of prediction accuracy for the proposed model is compared with those of the SRK equation of state and Peng Robinson (PR) Equation of state. It was observed that in most of the cases the proposed model has predicted the thermodynamic conditions more accurately than the PR and SRK equation of state. This work helps in understanding the limitations of EOS for the prediction hydrate conditions. Also, the current work helps in strengthening the conventional statistical modelling technique to predict the hydrate conditions for a broader range.
  13. Rahman T, Khandakar A, Qiblawey Y, Tahir A, Kiranyaz S, Abul Kashem SB, et al.
    Comput Biol Med, 2021 May;132:104319.
    PMID: 33799220 DOI: 10.1016/j.compbiomed.2021.104319
    Computer-aided diagnosis for the reliable and fast detection of coronavirus disease (COVID-19) has become a necessity to prevent the spread of the virus during the pandemic to ease the burden on the healthcare system. Chest X-ray (CXR) imaging has several advantages over other imaging and detection techniques. Numerous works have been reported on COVID-19 detection from a smaller set of original X-ray images. However, the effect of image enhancement and lung segmentation of a large dataset in COVID-19 detection was not reported in the literature. We have compiled a large X-ray dataset (COVQU) consisting of 18,479 CXR images with 8851 normal, 6012 non-COVID lung infections, and 3616 COVID-19 CXR images and their corresponding ground truth lung masks. To the best of our knowledge, this is the largest public COVID positive database and the lung masks. Five different image enhancement techniques: histogram equalization (HE), contrast limited adaptive histogram equalization (CLAHE), image complement, gamma correction, and balance contrast enhancement technique (BCET) were used to investigate the effect of image enhancement techniques on COVID-19 detection. A novel U-Net model was proposed and compared with the standard U-Net model for lung segmentation. Six different pre-trained Convolutional Neural Networks (CNNs) (ResNet18, ResNet50, ResNet101, InceptionV3, DenseNet201, and ChexNet) and a shallow CNN model were investigated on the plain and segmented lung CXR images. The novel U-Net model showed an accuracy, Intersection over Union (IoU), and Dice coefficient of 98.63%, 94.3%, and 96.94%, respectively for lung segmentation. The gamma correction-based enhancement technique outperforms other techniques in detecting COVID-19 from the plain and the segmented lung CXR images. Classification performance from plain CXR images is slightly better than the segmented lung CXR images; however, the reliability of network performance is significantly improved for the segmented lung images, which was observed using the visualization technique. The accuracy, precision, sensitivity, F1-score, and specificity were 95.11%, 94.55%, 94.56%, 94.53%, and 95.59% respectively for the segmented lung images. The proposed approach with very reliable and comparable performance will boost the fast and robust COVID-19 detection using chest X-ray images.
  14. Khan MS, Ibrahim SM, Adamu AA, Rahman MBA, Bakar MZA, Noordin MM, et al.
    Cryobiology, 2020 02 01;92:26-33.
    PMID: 31580830 DOI: 10.1016/j.cryobiol.2019.09.012
    A number of living creatures in the Antarctic region have developed characteristic adaptation of cold weather by producing antifreeze proteins (AFP). Antifreeze peptide (Afp1m) fragment have been designed in the sequence of strings from native proteins. The objectives of this study were to assess the properties of Afp1m to cryopreserve skin graft at the temperature of -10 °C and -20 °C and to assess sub-zero injuries in Afp1m cryopreserved skin graft using light microscopic techniques. In the present study, a process was developed to cryopreserve Sprague-Dawley (SD) rat skin grafts with antifreeze peptide, Afp1m, α-helix peptide fragment derived from Glaciozyma antractica yeast. Its viability assessed by different microscopic techniques. This study also described the damages caused by subzero temperatures (-10 and -20 °C) on tissue cryopreserved in different concentrations of Afp1m (0.5, 1, 2, 5 and 10 mg/mL) for 72 h. Histological scores of epidermis, dermis and hypodermis of cryopreserved skin grafts showed highly significant difference (p 
  15. Ibrahim SM, Kareem OH, Saffanah KM, Adamu AA, Khan MS, Rahman MBA, et al.
    Cryobiology, 2018 06;82:27-36.
    PMID: 29679551 DOI: 10.1016/j.cryobiol.2018.04.012
    The objective of this study was to evaluate the use of Afp1m as a cryopreservative agent for skin by examining the transplanted skin histological architecture and mechanical properties following subzero cryopreservation. Thirty four (34) rats with an average weight of 208 ± 31 g (mean ± SD), were used. Twenty four (n = 24) rats were equally divided into four groups: (i) immediate non-cryopreserved skin autografts (onto same site), (ii) immediate non-cryopreserved skin autografts (onto different sites), (iii) skin autografts cryopreserved with glycerol for 72 h and (iv) skin autografts cryopreserved with Afp1m for 72 h at -4 °C. Rounded shaped full-thickness 1.5-2.5 cm in diameter skin was excised from backs of rats for the autograft transplantation. Non-cryopreserved or cryopreserved auto skin graft were positioned onto the wound defects and stitched. Non-transplanted cryopreserved and non-cryopreserved skin strips from other ten rats (n = 10) were allowed for comparative biomechanical test. All skin grafts were subjected to histological and mechanical examinations at the end of day 21. Histological results revealed that tissue architecture especially the epidermal integrity and dermal-epidermal junction of the Afp1m cryopreserved skin grafts exhibited better histological appearance, good preservation of tissue architecture and structural integrity than glycerolized skin. However, there was no significant difference among these groups in other histological criteria. There were no significant differences among the 4 groups in skin graft mechanical properties namely maximum load. In conclusion, Afp1m were found to be able to preserve the microstructure as well as the viability and function of the skin destined for skin transplantation when was kept at -4 °C for 72 h.
  16. Rahman MS, Rahman HR, Prithula J, Chowdhury MEH, Ahmed MU, Kumar J, et al.
    Diagnostics (Basel), 2023 Jun 02;13(11).
    PMID: 37296800 DOI: 10.3390/diagnostics13111948
    Heart failure is a devastating disease that has high mortality rates and a negative impact on quality of life. Heart failure patients often experience emergency readmission after an initial episode, often due to inadequate management. A timely diagnosis and treatment of underlying issues can significantly reduce the risk of emergency readmissions. The purpose of this project was to predict emergency readmissions of discharged heart failure patients using classical machine learning (ML) models based on Electronic Health Record (EHR) data. The dataset used for this study consisted of 166 clinical biomarkers from 2008 patient records. Three feature selection techniques were studied along with 13 classical ML models using five-fold cross-validation. A stacking ML model was trained using the predictions of the three best-performing models for final classification. The stacking ML model provided an accuracy, precision, recall, specificity, F1-score, and area under the curve (AUC) of 89.41%, 90.10%, 89.41%, 87.83%, 89.28%, and 0.881, respectively. This indicates the effectiveness of the proposed model in predicting emergency readmissions. The healthcare providers can intervene pro-actively to reduce emergency hospital readmission risk and improve patient outcomes and decrease healthcare costs using the proposed model.
  17. Khan MS, Majid AM, Iqbal MA, Majid AS, Al-Mansoub M, Haque RS
    Eur J Pharm Sci, 2016 Oct 10;93:304-18.
    PMID: 27552907 DOI: 10.1016/j.ejps.2016.08.032
    Glioblastoma multiforme is a highly malignant, heterogenic, and drug resistant tumor. The blood-brain barrier (BBB), systemic cytotoxicity, and limited specificity are the main obstacles in designing brain tumor drugs. In this study a computational approach was used to design brain tumor drugs that could downregulate VEGF and IL17A in glioblastoma multiforme type four. Computational screening tools were used to evaluate potential candidates for antiangiogenic activity, target binding, BBB permeability, and ADME physicochemical properties. Additionally, in vitro cytotoxicity, migration, invasion, tube formation, apoptosis, ROS and ELISA assays were conducted for molecule 6 that was deemed most likely to succeed. The efflux ratio of membrane permeability and calculated docking scores of permeability to glycoproteins (P-gps) were used to determine the BBB permeability of the molecules. The results showed BBB permeation for molecule 6, with the predicted efficiency of 0.55kcal/mol and binding affinity of -37kj/mol corresponding to an experimental efflux ratio of 0.625 and predicted -15kj/mol of binding affinity for P-gps. Molecule 6 significantly affected the angiogenesis pathways by 2-fold downregulation of IL17A and VEGF through inactivation of active sites of HSP90 (predicted binding: -37kj/mol, predicted efficiency: 0.55kcal/mol) and p23 (predicted binding: 12kj/mol, predicted efficiency: 0.17kcal/mol) chaperon proteins. Additionally, molecule 6 activated the 17.38% relative fold of ROS level at 18.3μg/mL and upregulated the caspase which lead the potential synergistic apoptosis through the antiangiogenic activity of molecule 6 and thereby the highly efficacious anticancer upshot. The results indicate that the binding of the molecules to the therapeutic target is not essential to produce a lethal effect on cancer cells of the brain and that antiangiogenic efficiency is much more important.
  18. Ali Khan MS, Misbah, Ahmed N, Arifuddin M, Rehman A, Ling MP
    Food Chem Toxicol, 2018 Jun 05.
    PMID: 29883785 DOI: 10.1016/j.fct.2018.06.007
    Flowers of Tabernaemontana divaricata (L.) R. Br., (Apocynaceae) are used in traditional medicine for analgesic property. The present study was performed to isolate the active principles and investigate the mechanisms involved in the anti-nociception caused by T. divaricata flower methanolic extract (TDFME). The extract in the doses of 125, 250 and 500 mg/kg, p.o was subjected to various assays in acetic acid induced abdominal writhing and formalin induced paw licking test models. Naloxone, L-Arginine, Glibenclamide and Glutamate were used as inducers while Morphine, L-NAME, Methylene blue and Aspirin served as standard drugs. The phytochemical analysis led to the isolation of three indole alkaloids namely Voacangine, Catharanthine and O-acetyl Vallesamine. The anti-nociception produced by TDFME was attenuated significantly (p< 0.001) by the intra-peritoneal pretreatment of naloxone, L-Arginine and glibenclamide. The nociception produced by glutamate was inhibited by TDFME. TDFME also enhanced the antinociceptive activity of L-NAME when given in combination. However TDFME co-administration did not produce significant results with methylene blue indicating lack of cGMP involvement. These results indicate that TDFME produces anti-nociception action mediated by opioid, nitric oxide, K+-ATP and glutamate mechanisms and the effect is largely related to the indole alkaloids.
  19. Ali Khan MS, Ahmed N, Misbah, Arifuddin M, Zakaria ZA, Al-Sanea MM, et al.
    Food Chem Toxicol, 2018 May;115:523-531.
    PMID: 29555329 DOI: 10.1016/j.fct.2018.03.021
    In view of the report on anti-nociceptive activity of Leathery Murdah, Terminalia coriacea {Roxb.} Wight & Arn. (Combretaceae) leaves, the present study was conducted to isolate the active constituents and identify the underlying mechanisms. The methanolic extract of T. coriacea leaves (TCLME) at doses 125, 250 and 500 mg/kg orally, was subjected to various in-vivo assays in acetic acid induced writhing and formalin induced paw-licking tests with aspirin (100 mg/kg) and morphine (5 mg/kg) as reference drugs. Three flavonoids, rutin, robinin and gossypetin 3-glucuronide 8-glucoside were isolated and characterized from TCLME for the first time. The extract showed significant (p 
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