Displaying publications 1 - 20 of 67 in total

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  1. Isa MR, Mohd Noor N, Nawawi H, Kaur M., Rahman T, Mohd Kornain NK, et al.
    MyJurnal
    Imaging techniques involving optical coherence tomography, computed tomography (CT) and high-resolution magnetic resonance imaging (MRI) are used as tools to identify atherosclerotic plaques. However, the effects of water-based contrast media used in Post Mortem Computed Tomography Angiography (PMCTA) on the histopathology of atherosclerotic plaques have not been widely explored. The objective of this study is to determine the effects of water-based contrast media used in PMCTA on the histopathology of atherosclerotic plaques and biomarkers of atherosclerosis in experimentally induced established atherosclerotic rabbits. MATERIALS AND METHODS: Twenty male New Zealand white rabbits were divided into 2 groups. One group was given a high cholesterol diet (HCD) for 12 weeks to establish atherosclerosis and the control group normal diet (ND). Five rabbits from each group were then given intravenous water-based contrast media before being sacrificed. The entire length of aorta was dissected and submitted for histopathological examination and determination of tissue biomarkers α-SMA and MMP-9. RESULTS:Histopathological examination of the aorta including percentage of area covered by plaque and foam cell formation showed no significant difference in atheromatous plaque formation in both groups of HCD rabbits with or without intravenous contrast media injection (plaque: 55±41 vs. 63±15, p=0.731; foam cells: 124±83 vs. 171±55, p=0.325). Similarly, α-SMA and MMP-9 protein expression also showed no significant difference in both groups (α-SMA: 70±20 vs. 67±26, p=0.807; MMP-9: 60±12 vs. 57±17, p=0.785). CONCLUSION:Water-based contrast media used in PMCTA does not affect the morphology or the immunohistochemistry staining of SMA and MMP-9 in atherosclerotic plaques.
  2. Hoh BP, Abdul Rahman T, Yusoff K
    Hereditas, 2019;156:1.
    PMID: 30636949 DOI: 10.1186/s41065-019-0080-1
    Prevalence of hypertension (HTN) varies substantially across different populations. HTN is not only common - affecting at least one third of the world's adult population - but is also the most important driver for cardiovascular diseases. Yet up to a third of hypertensive patients are resistant to therapy, contributed by secondary hypertension but more commonly the hitherto inability to precisely predict response to specific antihypertensive agents. Population and individual genomics information could be useful in guiding the selection and predicting the response to treatment - an approach known as precision medicine. However this cannot be achieved without the knowledge of genetic variations that influence blood pressure (BP). A number of evolutionary factors including population demographics and forces of natural selection may be involved. This article explores some ideas on how natural selection influences BP regulation in ethnically and geographically diverse populations that could lead to them being susceptible to HTN. We explore how such evolutionary factors could impact the implementation of precision medicine in HTN. Finally, in order to ensure the success of precision medicine in HTN, we call for more initiatives to understand the genetic architecture within and between diverse populations with ancestry from different parts of the world, and to precisely classify the intermediate phenotypes of HTN.
  3. Gunasinghe KKJ, Rahman T, Chee Wezen X
    ACS Omega, 2024 Jan 16;9(2):2250-2262.
    PMID: 38250404 DOI: 10.1021/acsomega.3c05822
    The protein c-Myc is a transcription factor that remains largely intrinsically disordered and is known to be involved in various biological processes and is overexpressed in various cancers, making it an attractive drug target. However, intrinsically disordered proteins such as c-Myc do not show funnel-like basins in their free-energy landscapes; this makes their druggability a challenge. For the first time, we propose a heterodimer model of c-Myc/Max in full length in this work. We used Gaussian-accelerated molecular dynamics (GaMD) simulations to explore the behavior of c-Myc and its various regions, including the transactivation domain (TAD) and the basic helix-loop-helix-leucine-zipper (bHLH-Zipper) motif in three different conformational states: (a) monomeric c-Myc, (b) c-Myc when bound to its partner protein, Max, and (c) when Max was removed after binding. We analyzed the GaMD trajectories using root-mean-square deviation (RMSD), radius of gyration, root-mean-square fluctuation, and free-energy landscape (FEL) calculations to elaborate the behaviors of these regions. The results showed that the monomeric c-Myc structure showed a higher RMSD fluctuation as compared with the c-Myc/Max heterodimer in the bHLH-Zipper motif. This indicated that the bHLH-Zipper motif of c-Myc is more stable when it is bound to Max. The TAD region in both monomeric and Max-bound states showed similar plasticity in terms of RMSD. We also conducted residue decomposition calculations and showed that the c-Myc and Max interaction could be driven mainly by electrostatic interactions and the residues Arg299, Ile403, and Leu420 seemed to play important roles in the interaction. Our work provides insights into the behavior of c-Myc and its regions that could support the development of drugs that target c-Myc and other intrinsically disordered proteins.
  4. Rahman S, Rahman T, Ismail AA, Rashid AR
    Diabetes Obes Metab, 2007 Nov;9(6):767-80.
    PMID: 17924861 DOI: 10.1111/j.1463-1326.2006.00655.x
    The complications associated with diabetic vasculopathy are commonly grouped into two categories: microvascular and macrovascular complications. In diabetes, macrovascular disease is the commonest cause of mortality and morbidity and is responsible for high incidence of vascular diseases such as stroke, myocardial infarction and peripheral vascular diseases. Macrovascular diseases are traditionally thought of as due to underlying obstructive atherosclerotic diseases affecting major arteries. Pathological changes of major blood vessels leading to functional and structural abnormalities in diabetic vessels include endothelial dysfunction, reduced vascular compliance and atherosclerosis. Besides, advanced glycation end product formation interacts with specific receptors that lead to overexpression of a range of cytokines. Haemodynamic pathways are activated in diabetes and are possibly amplified by concomitant systemic hypertension. Apart from these, hyperglycaemia, non-enzymatic glycosylation, lipid modulation, alteration of vasculature and growth factors activation contribute to development of diabetic vasculopathy. This review focuses on pathophysiology and pathogenesis of diabetes-associated macrovasculopathy.
  5. Hindia MN, Rahman TA, Ojukwu H, Hanafi EB, Fattouh A
    PLoS One, 2016;11(5):e0155077.
    PMID: 27152423 DOI: 10.1371/journal.pone.0155077
    As the enterprise of the "Internet of Things" is rapidly gaining widespread acceptance, sensors are being deployed in an unrestrained manner around the world to make efficient use of this new technological evolution. A recent survey has shown that sensor deployments over the past decade have increased significantly and has predicted an upsurge in the future growth rate. In health-care services, for instance, sensors are used as a key technology to enable Internet of Things oriented health-care monitoring systems. In this paper, we have proposed a two-stage fundamental approach to facilitate the implementation of such a system. In the first stage, sensors promptly gather together the particle measurements of an android application. Then, in the second stage, the collected data are sent over a Femto-LTE network following a new scheduling technique. The proposed scheduling strategy is used to send the data according to the application's priority. The efficiency of the proposed technique is demonstrated by comparing it with that of well-known algorithms, namely, proportional fairness and exponential proportional fairness.
  6. Shazia Q, Mohammad ZH, Rahman T, Shekhar HU
    Anemia, 2012;2012:270923.
    PMID: 22645668 DOI: 10.1155/2012/270923
    Beta thalassemia major is an inherited disease resulting from reduction or total lack of beta globin chains. Patients with this disease need repeated blood transfusion for survival. This may cause oxidative stress and tissue injury due to iron overload, altered antioxidant enzymes, and other essential trace element levels. The aim of this review is to scrutinize the relationship between oxidative stress and serum trace elements, degree of damage caused by oxidative stress, and the role of antioxidant enzymes in beta thalassemia major patients. The findings indicate that oxidative stress in patients with beta thalassemia major is mainly caused by tissue injury due to over production of free radical by secondary iron overload, alteration in serum trace elements and antioxidant enzymes level. The role of trace elements like selenium, copper, iron, and zinc in beta thalassemia major patients reveals a significant change of these trace elements. Studies published on the status of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione S-transferase in beta thalassemia patients also showed variable results. The administration of selective antioxidants along with essential trace elements and minerals to reduce the extent of oxidative damage and related complications in beta thalassemia major still need further evaluation.
  7. Cheng Z, Hwang SS, Bhave M, Rahman T, Chee Wezen X
    J Chem Inf Model, 2023 Nov 13;63(21):6912-6924.
    PMID: 37883148 DOI: 10.1021/acs.jcim.3c01252
    Polo-like kinase 1 (PLK1) and p38γ mitogen-activated protein kinase (p38γ) play important roles in cancer pathogenesis by controlling cell cycle progression and are therefore attractive cancer targets. The design of multitarget inhibitors may offer synergistic inhibition of distinct targets and reduce the risk of drug-drug interactions to improve the balance between therapeutic efficacy and safety. We combined deep-learning-based quantitative structure-activity relationship (QSAR) modeling and hybrid-based consensus scoring to screen for inhibitors with potential activity against the targeted proteins. Using this combination strategy, we identified a potent PLK1 inhibitor (compound 4) that inhibited PLK1 activity and liver cancer cell growth in the nanomolar range. Next, we deployed both our QSAR models for PLK1 and p38γ on the Enamine compound library to identify dual-targeting inhibitors against PLK1 and p38γ. Likewise, the identified hits were subsequently subjected to hybrid-based consensus scoring. Using this method, we identified a promising compound (compound 14) that could inhibit both PLK1 and p38γ activities. At nanomolar concentrations, compound 14 inhibited the growth of human hepatocellular carcinoma and hepatoblastoma cells in vitro. This study demonstrates the combined screening strategy to identify novel potential inhibitors for existing targets.
  8. Awuah WA, Tenkorang PO, Ng JC, Abdul-Rahman T
    Neurosurgery, 2023 Jul 01;93(1):e16.
    PMID: 37097024 DOI: 10.1227/neu.0000000000002515
  9. Alicezah MK, Razali R, Rahman T, Hoh BP, Suhana NH, Muid S, et al.
    Malays J Pathol, 2014 Aug;36(2):131-7.
    PMID: 25194536 MyJurnal
    We report a rare case of homozygous familial hypercholesterolemia (HoFH), a 22-year-old Malay woman who presented initially with minor soft tissue injury due to a cycling accident. She was then incidentally found to have severe xanthelasma and hypercholesterolemia (serum TC 15.3 mmol/L and LDL-C 13.9 mmol/L). She was referred to the Specialized Lipid Clinic and was diagnosed with familial hypercholesterolemia (FH) based on the Simon Broome (SB) diagnostic criteria. There was a family history of premature coronary heart disease (CHD) in that three siblings had sudden cardiac death, and of consanguineous marriage in that her parents are cousins. DNA screening of LDLR and APOB genes was done by Polymerase Chain Reaction (PCR), followed by Denaturing High Performance Liquid Chromatography (DHPLC). Homozygous mutation C255S in Exon 5 of her LDLR gene was found. There was no mutation was found in Exon 26 and Exon 29 of the APOB gene. This report is to emphasize the importance of identifying patients with FH and cascade screening through established diagnostic criteria and genetic studies in order to ensure early detection and early treatment intervention to minimize the risk of developing CHD and related complications.
  10. Ansarudin F, Abd Rahman T, Yamada Y, Rahman NHA, Kamardin K
    Sensors (Basel), 2020 Oct 16;20(20).
    PMID: 33081110 DOI: 10.3390/s20205849
    In the 5G mobile system, new features such as millimetre wave operation, small cell size and multi beam are requested at base stations. At millimetre wave, the base station antennas become very small in size, which is about 30 cm; thus, dielectric lens antennas that have excellent multi beam radiation pattern performance are suitable candidates. For base station application, the lens antennas with small thickness and small curvature are requested for light weight and ease of installation. In this paper, a new lens shaping method for thin and small lens curvature is proposed. In order to develop the thin lens antenna, comparisons of antenna structures with conventional aperture distribution lens and Abbe's sine lens are made. Moreover, multi beam radiation pattern of three types of lenses are compared. As a result, the thin and small curvature of the proposed lens and an excellent multi beam radiation pattern are ensured.
  11. Sahlan N, Fadzilah MN, Muslim A, Shaari SA, Abdul Rahman T, Hoh BP
    Med J Malaysia, 2019 08;74(4):320-325.
    PMID: 31424040
    INTRODUCTION: Prevalence of Hepatitis B virus (HBV) infection among the non-indigenous people in Malaysia has been well established and range between 3% and 5%. However, data from the indigenous (Orang Asli) people is still lacking. The Negrito population is the most remotely located Orang Asli tribe with limited access to health care facilities. This study was undertaken to determine the epidemiology and seroprevalence of HBV infection among the Negrito.

    METHODS: Surveys were conducted in five Negrito settlements in Kelantan and Perak states in Malaysia. A total of 150 participants were recruited. Clinical history was taken and physical examination was performed. Five millilitres of whole blood were collected and tested for hepatitis B surface antigen (HBsAg) using electrochemiluminescence immunoassay.

    RESULTS: Participants were mainly from the Bateq (49.3%) and Mendriq (29.4%) sub-tribes. Overall, 13 subjects (8.7 %); nine males and four females were HBsAg positive. Nine of the HBsAg positive subjects were ≥35 years old. All of them had history of home deliver without evidence of antenatal record. Six (46%) of the HBsAg positive subjects had tattoo and body piercing in the past.

    CONCLUSION: The prevalence of HBV infection rate amongst the Negrito tribe is almost three-fold compared to the national rates. The reason for this finding remains unclear. Tattooing, body piercing and vertical transmission could be the main possible routes of transmission of HBV among the Negrito population in Malaysia.

  12. Al-Samman AM, Rahman TA, Azmi MH, Hindia MN, Khan I, Hanafi E
    PLoS One, 2016 Sep 21;11(9):e0163034.
    PMID: 27654703 DOI: 10.1371/journal.pone.0163034
    This paper presents an experimental characterization of millimeter-wave (mm-wave) channels in the 6.5 GHz, 10.5 GHz, 15 GHz, 19 GHz, 28 GHz and 38 GHz frequency bands in an indoor corridor environment. More than 4,000 power delay profiles were measured across the bands using an omnidirectional transmitter antenna and a highly directional horn receiver antenna for both co- and cross-polarized antenna configurations. This paper develops a new path-loss model to account for the frequency attenuation with distance, which we term the frequency attenuation (FA) path-loss model and introduce a frequency-dependent attenuation factor. The large-scale path loss was characterized based on both new and well-known path-loss models. A general and less complex method is also proposed to estimate the cross-polarization discrimination (XPD) factor of close-in reference distance with the XPD (CIX) and ABG with the XPD (ABGX) path-loss models to avoid the computational complexity of minimum mean square error (MMSE) approach. Moreover, small-scale parameters such as root mean square (RMS) delay spread, mean excess (MN-EX) delay, dispersion factors and maximum excess (MAX-EX) delay parameters were used to characterize the multipath channel dispersion. Multiple statistical distributions for RMS delay spread were also investigated. The results show that our proposed models are simpler and more physically-based than other well-known models. The path-loss exponents for all studied models are smaller than that of the free-space model by values in the range of 0.1 to 1.4 for all measured frequencies. The RMS delay spread values varied between 0.2 ns and 13.8 ns, and the dispersion factor values were less than 1 for all measured frequencies. The exponential and Weibull probability distribution models best fit the RMS delay spread empirical distribution for all of the measured frequencies in all scenarios.
  13. Rahman T, Hamzan NS, Mokhsin A, Rahmat R, Ibrahim ZO, Razali R, et al.
    Lipids Health Dis, 2017 Apr 24;16(1):81.
    PMID: 28438163 DOI: 10.1186/s12944-017-0470-1
    BACKGROUND: Familial hypercholesterolaemia (FH) leads to premature coronary artery diseases (CAD) which pathophysiologically can be measured by inflammation, endothelial activation and oxidative stress status. However, the status of these biomarkers among related unaffected relatives of FH cases and whether FH is an independent predictor of these biomarkers have not been well established. Thus, this study aims to (1) compare the biomarkers of inflammation, endothelial activation and oxidative stress between patients with FH, their related unaffected relatives (RUC) and normolipaemic subjects (NC) (2)determine whether FH is an independent predictor of these biomarkers.

    METHODS: One hundred thirty-one FH patients, 68 RUC and 214 matched NC were recruited. Fasting lipid profile, biomarkers of inflammation (hsCRP), endothelial activation (sICAM-1 and E-selectin) and oxidative stress [oxidized LDL (oxLDL), malondialdehyde (MDA) and F2-isoprostanes (ISP)] were analyzed and independent predictor was determined using binary logistic regression analysis.

    RESULTS: hsCRP was higher in FH and RUC compared to NC (mean ± SD = 1.53 ± 1.24 mg/L and mean ± SD = 2.54 ± 2.30 vs 1.10 ± 0.89 mg/L, p  0.05). FH was an independent predictor for sICAM-1 (p = 0.007), ox-LDL (p 

  14. Mohd Nor NS, Saimin H, Rahman T, Abdul Razak S, Mohd Nasir N, Ismail Z, et al.
    J Obes, 2018;2018:8508549.
    PMID: 29785305 DOI: 10.1155/2018/8508549
    Objective: There is limited data comparing prothrombogenic or fibrinolysis biomarkers (tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1)) simultaneously in subjects with Metabolic Syndrome (MS), simple central obesity without MS (COB) and normal controls (NC). We investigated the concentrations of fibrinolysis biomarkers in subjects with MS, COB and NC.

    Methods: A cross-sectional study involving 503 drug naive subjects (163 males, aged 30-65 years old (mean age ± SD = 47.4 ± 8.3 years)) divided into MS, COB and NC groups. COB was defined as central obesity (waist circumference (WC) males ≥90 cm, females ≥80 cm) in the absence of MS according to the International Diabetes Federation 2006. Fasting blood levels of tPA and PAI-1were analyzed.

    Results: MS and COB had significantly higher concentration of all biomarkers compared to NC. The MS group had significantly higher concentration of tPA and PAI-1 compared to COB. WC and HDL-c had significant correlation with all biomarkers (tPA p < 0.001, PAI-1 p < 0.001). Fasting plasma glucose and diastolic blood pressure were independent predictors after correcting for confounding factors.

    Conclusion: Central obesity with or without MS both demonstrated enhanced prothrombogenesis. This suggests that simple obesity possibly increases the risk of coronary artery disease in part, via increased susceptibility to thrombogenesis.

  15. Al-Samman AM, Azmi MH, Rahman TA, Khan I, Hindia MN, Fattouh A
    PLoS One, 2016;11(12):e0164944.
    PMID: 27992445 DOI: 10.1371/journal.pone.0164944
    This work proposes channel impulse response (CIR) prediction for time-varying ultra-wideband (UWB) channels by exploiting the fast movement of channel taps within delay bins. Considering the sparsity of UWB channels, we introduce a window-based CIR (WB-CIR) to approximate the high temporal resolutions of UWB channels. A recursive least square (RLS) algorithm is adopted to predict the time evolution of the WB-CIR. For predicting the future WB-CIR tap of window wk, three RLS filter coefficients are computed from the observed WB-CIRs of the left wk-1, the current wk and the right wk+1 windows. The filter coefficient with the lowest RLS error is used to predict the future WB-CIR tap. To evaluate our proposed prediction method, UWB CIRs are collected through measurement campaigns in outdoor environments considering line-of-sight (LOS) and non-line-of-sight (NLOS) scenarios. Under similar computational complexity, our proposed method provides an improvement in prediction errors of approximately 80% for LOS and 63% for NLOS scenarios compared with a conventional method.
  16. Muid S, Abu Bakar NA, Abdul Rahman T, Tengku Ismail TS, Kholin SF, Suvorov AV, et al.
    Malays J Pathol, 2019 Dec;41(3):283-292.
    PMID: 31901913
    INTRODUCTION: Apart from inflammation and endothelial dysfunction, other key components in the development of atherogenesis include prothrombogenesis and oxidative stress. The effects of long-term confinement and isolation, exposure to radiation and different gravity forces during space travel could potentially increase the long-term risk of atherosclerosis. To the best of our knowledge, this is the first study determining the status of prothrombogenesis and oxidative stress in six cosmonauts subjected to the longest duration of confined isolation period of 520 days in preparation for prospective undetermined manned space travel to Mars.

    MATERIALS AND METHODS: This collaborative research between the National Space Agency (ANGKASA), Universiti Teknologi MARA, Malaysia and Institute of Biomedical Problems (IBMP), Russia was conducted at the Russian Academy of Sciences IBMP, Moscow, Russia. Six multi-national cosmonauts were assigned to live in a ground-based confined module for 520 days. Standard exercise and diet regime were instituted throughout the isolation phase. Six age, ethnic and gender-matched healthy, free-living ground controls were recruited in parallel. Serial serum and whole blood were analysed for biomarkers of prothrombogenesis [plasminogen activator inhibitor-1 (PAI-1) and homocysteine] and oxidative stress [oxidised low-density lipoprotein (ox-LDL) and malondialdehyde (MDA)].

    RESULTS: There were significantly lower concentrations of PAI-1 and homocysteine in cosmonauts during confinement compared to the controls. There were no significant differences seen in the concentrations of biomarkers of oxidative stress during confinement but there was a significant percentage change increment for serum MDA in cosmonauts.

    CONCLUSION: Long-term confinement decreased the risk of prothrombogenesis and this could be attributed to the exercise and diet regime which includes omega-3 fatty acids supplementation given to the crew members during their confinement period. However, oxidative damage could not be excluded and may be attributed to the influence of psychological stress during this prolonged confinement.

  17. Muid S, Froemming GR, Rahman T, Ali AM, Nawawi HM
    Food Nutr Res, 2016;60:31526.
    PMID: 27396399 DOI: 10.3402/fnr.v60.31526
    BACKGROUND: Tocotrienols (TCTs) are more potent antioxidants than α-tocopherol (TOC). However, the effectiveness and mechanism of the action of TCT isomers as anti-atherosclerotic agents in stimulated human endothelial cells under inflammatory conditions are not well established.

    AIMS: 1) To compare the effects of different TCT isomers on inflammation, endothelial activation, and endothelial nitric oxide synthase (eNOS). 2) To identify the two most potent TCT isomers in stimulated human endothelial cells. 3) To investigate the effects of TCT isomers on NFκB activation, and protein and gene expression levels in stimulated human endothelial cells.

    METHODS: Human umbilical vein endothelial cells were incubated with various concentrations of TCT isomers or α-TOC (0.3-10 µM), together with lipopolysaccharides for 16 h. Supernatant cells were collected and measured for protein and gene expression of cytokines (interleukin-6, or IL-6; tumor necrosis factor-alpha, or TNF-α), adhesion molecules (intercellular cell adhesion molecule-1, or ICAM-1; vascular cell adhesion molecule-1, or VCAM-1; and e-selectin), eNOS, and NFκB.

    RESULTS: δ-TCT is the most potent TCT isomer in the inhibition of IL-6, ICAM-1, VCAM-1, and NFκB, and it is the second potent in inhibiting e-selectin and eNOS. γ-TCT isomer is the most potent isomer in inhibiting e-selectin and eNOS, and it is the second most potent in inhibiting is IL-6, VCAM-1, and NFκB. For ICAM-1 protein expression, the most potent is δ-TCT followed by α-TCT. α- and β-TCT inhibit IL-6 at the highest concentration (10 µM) but enhance IL-6 at lower concentrations. γ-TCT markedly increases eNOS expression by 8-11-fold at higher concentrations (5-10 µM) but exhibits neutral effects at lower concentrations.

    CONCLUSION: δ- and γ-TCT are the two most potent TCT isomers in terms of the inhibition of inflammation and endothelial activation whilst enhancing eNOS, possibly mediated via the NFκB pathway. Hence, there is a great potential for TCT isomers as anti-atherosclerotic agents.

  18. Ha CHX, Lee NK, Rahman T, Hwang SS, Yam WK, Chee XW
    J Biomol Struct Dyn, 2023 Apr;41(6):2146-2159.
    PMID: 35067186 DOI: 10.1080/07391102.2022.2028677
    The Human Immunodeficiency Virus (HIV) infection is a global pandemic that has claimed 33 million lives to-date. One of the most efficacious treatments for naïve or pretreated HIV patients is the HIV integrase strand transfer inhibitors (INSTIs). However, given that HIV treatment is life-long, the emergence of HIV strains resistant to INSTIs is an imminent challenge. In this work, we showed two best regression QSAR models that were constructed using a boosted Random Forest algorithm (r2 = 0.998, q210CV = 0.721, q2external_test = 0.754) and a boosted K* algorithm (r2 = 0.987, q210CV = 0.721, q2external_test = 0.758) to predict the pIC50 values of INSTIs. Subsequently, the regression QSAR models were deployed against the Drugbank database for drug repositioning. The top-ranked compounds were further evaluated for their target engagement activity using molecular docking studies and accelerated Molecular Dynamics simulation. Lastly, their potential as INSTIs were also evaluated from our literature search. Our study offers the first example of a large-scale regression QSAR modelling effort for discovering highly active INSTIs to combat HIV infection.Communicated by Ramaswamy H. Sarma.
  19. Adebusoye FT, Awuah WA, Swaminathan N, Ghosh S, Wellington J, Abdul-Rahman T, et al.
    Neurosurgery, 2023 Aug 01;93(2):e30-e31.
    PMID: 37192472 DOI: 10.1227/neu.0000000000002527
  20. Vadlamani VMK, Gunasinghe KKJ, Chee XW, Rahman T, Harper MT
    Sci Rep, 2023 Jun 02;13(1):8958.
    PMID: 37268726 DOI: 10.1038/s41598-023-36257-3
    CD39 (ectonucleoside triphosphate diphosphohydrolase-1; ENTPD1) metabolizes extracellular ATP and ADP to AMP. AMP is subsequently metabolized by CD79 to adenosine. CD39 activity is therefore a key regulator of purinergic signalling in cancer, thrombosis, and autoimmune diseases. In this study we demonstrate that soluble, recombinant CD39 shows substrate inhibition with ADP or ATP as the substrate. Although CD39 activity initially increased with increasing substrate concentration, at high concentrations of ATP or ADP, CD39 activity was markedly reduced. Although the reaction product, AMP, inhibits CD39 activity, insufficient AMP was generated under our conditions to account for the substrate inhibition seen. In contrast, inhibition was not seen with UDP or UTP as substrates. 2-methylthio-ADP also showed no substrate inhibition, indicating the nucleotide base is an important determinant of substrate inhibition. Molecular dynamics simulations revealed that ADP can undergo conformational rearrangements within the CD39 active site that were not seen with UDP or 2-methylthio-ADP. Appreciating the existence of substrate inhibition of CD39 will help the interpretation of studies of CD39 activity, including investigations into drugs that modulate CD39 activity.
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