Displaying publications 81 - 100 of 110 in total

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  1. Bhawani SA, Albishri HM, Khan ZA, Mohamad Ibrahim MN, Mohammad A
    J Anal Methods Chem, 2013;2013:973280.
    PMID: 24455427 DOI: 10.1155/2013/973280
    This review incorporates a large number of chromatographic systems modified by the surfactants. A large number of solvent systems and stationary phases are summarized in this paper. Three different kinds of surfactants (anionic, cationic, and nonionic) are used as modifiers for stationary phases as well as solvent systems. Surfactants are used at all the three different concentration levels (below, above, and at critical micelle concentration) where surfactants behave differently. Modifications of both stationary phases and solvent systems by surfactants produced a new generation of chromatographic systems. Microemulsion solvent systems are also incorporated in this paper. Microemulsion thin-layer chromatography is a new approach in the field of chromatography.
  2. Khan KM, Mesaik MA, Abdalla OM, Rahim F, Soomro S, Halim SA, et al.
    Bioorg Chem, 2016 Feb;64:21-8.
    PMID: 26637945 DOI: 10.1016/j.bioorg.2015.11.004
    Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objective of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9 μM compared to that of the standard drug, prednisolone <1.5 μM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8 μM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between <4.0 and 15.2 μM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4, 8, 9, and 18 at a concentration of 25 μg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5, 8, 12, and 18 showed significant (P<0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC50 range of <4.0 to 40.3 μM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases.
  3. Hatmal MM, Alshaer W, Mahmoud IS, Al-Hatamleh MAI, Al-Ameer HJ, Abuyaman O, et al.
    PLoS One, 2021;16(10):e0257857.
    PMID: 34648514 DOI: 10.1371/journal.pone.0257857
    CD36 (cluster of differentiation 36) is a membrane protein involved in lipid metabolism and has been linked to pathological conditions associated with metabolic disorders, such as diabetes and dyslipidemia. A case-control study was conducted and included 177 patients with type-2 diabetes mellitus (T2DM) and 173 control subjects to study the involvement of CD36 gene rs1761667 (G>A) and rs1527483 (C>T) polymorphisms in the pathogenesis of T2DM and dyslipidemia among Jordanian population. Lipid profile, blood sugar, gender and age were measured and recorded. Also, genotyping analysis for both polymorphisms was performed. Following statistical analysis, 10 different neural networks and machine learning (ML) tools were used to predict subjects with diabetes or dyslipidemia. Towards further understanding of the role of CD36 protein and gene in T2DM and dyslipidemia, a protein-protein interaction network and meta-analysis were carried out. For both polymorphisms, the genotypic frequencies were not significantly different between the two groups (p > 0.05). On the other hand, some ML tools like multilayer perceptron gave high prediction accuracy (≥ 0.75) and Cohen's kappa (κ) (≥ 0.5). Interestingly, in K-star tool, the accuracy and Cohen's κ values were enhanced by including the genotyping results as inputs (0.73 and 0.46, respectively, compared to 0.67 and 0.34 without including them). This study confirmed, for the first time, that there is no association between CD36 polymorphisms and T2DM or dyslipidemia among Jordanian population. Prediction of T2DM and dyslipidemia, using these extensive ML tools and based on such input data, is a promising approach for developing diagnostic and prognostic prediction models for a wide spectrum of diseases, especially based on large medical databases.
  4. Aljabali AAA, Alzoubi L, Hamzat Y, Alqudah A, Obeid MA, Al Zoubi MS, et al.
    Comb Chem High Throughput Screen, 2021;24(10):1557-1571.
    PMID: 32928083 DOI: 10.2174/1386207323666200914110012
    BACKGROUND: Virus nanoparticles have been extensively studied over the past decades for theranostics applications. Viruses are well-characterized, naturally occurring nanoparticles that can be produced in high quantity with a high degree of similarity in both structure and composition.

    OBJECTIVES: The plant virus Cowpea Mosaic Virus (CPMV) has been innovatively used as a nanoscaffold. Utilization of the internal cavity of empty Virus-Like Particles (VLPs) for the inclusion of therapeutics within the capsid has opened many opportunities in drug delivery and imaging applications.

    METHODS: The encapsidation of magnetic materials and anticancer drugs was achieved. SuperscriptCPMV denotes molecules attached to the external surface of CPMV and CPMVSubscript denotes molecules within the interior of the capsid.

    RESULTS: Here, the generation of novel VLPs incorporating iron-platinum nanoparticles TCPMVFePt and cisplatin (Cis) (TCPMVCis) is reported. TCPMVCis exhibited a cytotoxic IC50 of TCPMVCis on both A549 and MDA-MB-231 cell lines of 1.8 μM and 3.9 μM, respectively after 72 hours of incubation. The TCPMVFePt were prepared as potential MRI contrast agents.

    CONCLUSION: Cisplatin loaded VLP (TCPMVCis) is shown to enhance cisplatin cytotoxicity in cancer cell lines with its potency increased by 2.3-folds.

  5. Alam S, Dhar A, Hasan M, Richi FT, Emon NU, Aziz MA, et al.
    Molecules, 2022 Dec 08;27(24).
    PMID: 36557843 DOI: 10.3390/molecules27248709
    Diabetes mellitus is a life-threatening disorder affecting people of all ages and adversely disrupts their daily functions. Despite the availability of numerous synthetic-antidiabetic medications and insulin, the demand for the development of novel antidiabetic medications is increasing due to the adverse effects and growth of resistance to commercial drugs in the long-term usage. Hence, antidiabetic phytochemicals isolated from fruit plants can be a very nifty option to develop life-saving novel antidiabetic therapeutics, employing several pathways and MoAs (mechanism of actions). This review focuses on the antidiabetic potential of commonly available Bangladeshi fruits and other plant parts, such as seeds, fruit peals, leaves, and roots, along with isolated phytochemicals from these phytosources based on lab findings and mechanism of actions. Several fruits, such as orange, lemon, amla, tamarind, and others, can produce remarkable antidiabetic actions and can be dietary alternatives to antidiabetic therapies. Besides, isolated phytochemicals from these plants, such as swertisin, quercetin, rutin, naringenin, and other prospective phytochemicals, also demonstrated their candidacy for further exploration to be established as antidiabetic leads. Thus, it can be considered that fruits are one of the most valuable gifts of plants packed with a wide spectrum of bioactive phytochemicals and are widely consumed as dietary items and medicinal therapies in different civilizations and cultures. This review will provide a better understanding of diabetes management by consuming fruits and other plant parts as well as deliver innovative hints for the researchers to develop novel drugs from these plant parts and/or their phytochemicals.
  6. Alroomi M, Rajan R, Omar AA, Alsaber A, Pan J, Fatemi M, et al.
    Immun Inflamm Dis, 2021 Dec;9(4):1648-1655.
    PMID: 34438471 DOI: 10.1002/iid3.517
    INTRODUCTION: This study aims to investigate in-hоsрitаl mоrtаlity in severe асute resрirаtоry syndrоme соrоnаvirus 2 раtients strаtified by serum ferritin levels.

    METHODS: Patients were stratified based on ferritin levels (ferritin levels ≤ 1000 or >1000).

    RESULTS: Approximately 89% (118) of the patients with ferritin levels > 1000 had pneumonia, and 51% (67) had hypertension. Fever (97, 73.5%) and shortness of breath (80, 61%) were two major symptoms among the patients in this group. Logistic regression analysis indicated that ferritin level (odds ratio [OR] = 0.36, 95% confidence interval [CI] = 0.21-0.62; p  1000.

    CONCLUSION: In this study, higher levels of serum ferritin were found to be an independent predictor of in-hоsрitаl mоrtаlity.

  7. Rajan R, Hui JMH, Al Jarallah MA, Tse G, Chan JSK, Satti DI, et al.
    Ann Med Surg (Lond), 2024 Apr;86(4):1843-1849.
    PMID: 38576988 DOI: 10.1097/MS9.0000000000001646
    BACKGROUND: The dimensionless Rajan's heart failure (R-hf) risk score was proposed to predict all-cause mortality in patients hospitalized with chronic heart failure (HF) and reduced ejection fraction (EF) (HFrEF).

    PURPOSE: To examine the association between the modified R-hf risk score and all-cause mortality in patients with HFrEF.

    METHODS: Retrospective cohort study included adults hospitalized with HFrEF, as defined by clinical symptoms of HF with biplane EF less than 40% on transthoracic echocardiography, at a tertiary centre in Dalian, China, between 1 November 2015, and 31 October 2019. All patients were followed up until 31 October 2020. A modified R-hf risk score was calculated by substituting brain natriuretic peptide (BNP) for N-terminal prohormone of BNP (NT-proBNP) using EF× estimated glomerular filtration rate (eGFR)× haemoglobin (Hb))/BNP. The patients were stratified into tertiles according to the R-hf risk score. The measured outcome was all-cause mortality. The score performance was assessed using C-statistics.

    RESULTS: A total of 840 patients were analyzed (70.2% males; mean age, 64±14 years; median (interquartile range) follow-up 37.0 (27.8) months). A lower modified R-hf risk score predicted a higher risk of all-cause mortality, independent of sex and age [1st tertile vs. 3rd tertile: adjusted hazard ratio (aHR), 3.46; 95% CI: 2.11-5.67; P<0.001]. Multivariate Cox regression analysis indicated that a lower modified R-hf risk score was associated with increased cumulative all-cause mortality [univariate: (1st tertile vs. 3rd tertile: aHR, 3.45; 95% CI: 2.11-5.65; P<0.001) and multivariate: (1st tertile vs. 3rd tertile: aHR 2.21, 95% CI: 1.29-3.79; P=0.004)]. The performance of the model, as reported by C-statistic was 0.67 (95% CI: 0.62-0.72).

    CONCLUSION: The modified R-hf risk score predicted all-cause mortality in patients hospitalized with HFrEF. Further validation of the modified R-hf risk score in other cohorts of patients with HFrEF is needed before clinical application.

  8. Al-Hatamleh MAI, Hatmal MM, Alshaer W, Rahman ENSEA, Mohd-Zahid MH, Alhaj-Qasem DM, et al.
    Eur J Pharmacol, 2021 Apr 05;896:173930.
    PMID: 33545157 DOI: 10.1016/j.ejphar.2021.173930
    The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection.
  9. Mohammad A, Falahi E, Barakatun-Nisak MY, Hanipah ZN, Redzwan SM, Yusof LM, et al.
    Diabetes Metab Syndr, 2021 05 31;15(4):102158.
    PMID: 34186370 DOI: 10.1016/j.dsx.2021.05.031
    BACKGROUND AND AIMS: The studies have shown that α-tocopherol supplementation could improve lipid profile in diabetes mellitus (DM) patients. Nonetheless, the result remains inconsistent. Therefore, this meta-analysis was performed to evaluate the efficacy of α-tocopherol supplement on lipid parameters in DM patients.

    METHODS: We conducted an extensive search via Cochrane Library, PubMed, Scopus, and Web of Science databases to acquire the reported RCTs up to October 2020.

    RESULTS: The results showed no effects of α-tocopherol supplementation on lipid profile in DM patients except when used ≥12 weeks.

    CONCLUSIONS: α-tocopherol supplementation in DM patients had no significant effect on lipid profiles.

  10. Harith AA, Mohamed Z, Mohammad A, Lim KK, Reffin N, Mohd Fadzil M, et al.
    Med J Malaysia, 2023 Sep;78(5):653-660.
    PMID: 37775494
    INTRODUCTION: Healthcare drivers, including ambulance drivers, were less concerned about health and safety during the COVID-19 pandemic, with not only the risk of COVID-19 infection but also a higher risk of prolonged states of alertness, stress, burnout, fatigue and road traffic accident. This study aimed to determine the prevalence of stress and its associated factors among healthcare drivers, especially during the COVID-19 pandemic.

    MATERIALS AND METHODS: This study employs a crosssectional study design and utilises self-reported data obtained from locally validated personal stress inventory questionnaires. The data collection period spanned from August 1 to 31, 2020. The study sample consisted of 163 healthcare drivers affiliated with the Negeri Sembilan State Health Department. The Chi-square test and Fisher's exact test were the first used to determine the association between variables prior to conducting multiple logistic regression to predict the relationship between dependent and independent variables.

    RESULTS: In COVID-19's first year, 7.4% (n = 12) of healthcare drivers reported perceived stress with ambulance drivers reporting more stress (10.6%; n = 5) than non-ambulance drivers (6.0%; n = 7). Simple statistical analysis identified perceived stress significantly associated with household income, smoking status and performing on-call. Further analysis by multiple logistic regression found that perceived stress was significantly related to smoking (aOR 19.9, 95% CI: 1.86-213.90), and performing on-call (aOR 8.69, 95% CI 1.21-62.28). Nevertheless, no association was found between perceived stress and age, ethnicity, marital status, education, household income, co-morbidities, driving assignment, employment duration, needing a part-time job or motor vehicle accident history.

    CONCLUSION: The study found that the perceived stress amongst Malaysian healthcare drivers during the COVID-19 pandemic was relatively low. This could be due to fewer lifethreatening tasks, emergencies, assigned tasks and increase income due to overtime during the COVD-19 pandemic. The OSH team's efforts to provide consistent safety and health training, including stress management, may have contributed to the healthcare driver's ability to effectively manage the stressful circumstances encountered during the pandemic. In order to enhance salary competitiveness, employers should provide financial management education alongside subsidised housing and childcare provisions. Healthcare drivers who smoke should be taught different stress reduction techniques so that they can handle their stress in a healthy way.

  11. Pandrangi SL, Chittineedi P, Chalumuri SS, Meena AS, Neira Mosquera JA, Sánchez Llaguno SN, et al.
    Molecules, 2022 May 07;27(9).
    PMID: 35566360 DOI: 10.3390/molecules27093011
    Iron is a crucial element required for the proper functioning of the body. For instance, hemoglobin is the vital component in the blood that delivers oxygen to various parts of the body. The heme protein present in hemoglobin comprises iron in the form of a ferrous state which regulates oxygen delivery. Excess iron in the body is stored as ferritin and would be utilized under iron-deficient conditions. Surprisingly, cancer cells as well as cancer stem cells have elevated ferritin levels suggesting that iron plays a vital role in protecting these cells. However, apart from the cytoprotective role iron also has the potential to induce cell death via ferroptosis which is a non-apoptotic cell death dependent on iron reserves. Apoptosis a caspase-dependent cell death mechanism is effective on cancer cells however little is known about its impact on cancer stem cell death. This paper focuses on the molecular characteristics of apoptosis and ferroptosis and the importance of switching to ferroptosis to target cancer stem cells death thereby preventing cancer relapse. To the best of our knowledge, this is the first review to demonstrate the importance of intracellular iron in regulating the switching of tumor cells and therapy resistant CSCs from apoptosis to ferroptosis.
  12. Sayaf AM, Ullah Khalid S, Hameed JA, Alshammari A, Khan A, Mohammad A, et al.
    Front Pharmacol, 2023;14:1202128.
    PMID: 37670941 DOI: 10.3389/fphar.2023.1202128
    Introduction: Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) enzymes are major therapeutic targets of anemia and ischemic/hypoxia diseases. To overcome safety issues, liver failure, and problems associated with on-/off-targets, natural products due to their novel and unique structures offer promising alternatives as drug targets. Methods: In the current study, the Marine Natural Products, North African, South African, East African, and North-East African chemical space was explored for HIF-PHD inhibitors discovery through molecular search, and the final hits were validated using molecular simulation and free energy calculation approaches. Results: Our results revealed that CMNPD13808 with a docking score of -8.690 kcal/mol, CID15081178 with a docking score of -8.027 kcal/mol, CID71496944 with a docking score of -8.48 kcal/mol and CID11821407 with a docking score of -7.78 kcal/mol possess stronger activity than the control N-[(4-hydroxy-8-iodoisoquinolin-3-yl)carbonyl]glycine, 4HG (-6.87 kcal/mol). Interaction analysis revealed that the target compounds interact with Gln239, Tyr310, Tyr329, Arg383 and Trp389 residues, and chelate the active site iron in a bidentate manner in PHD2. Molecular simulation revealed that these target hits robustly block the PHD2 active site by demonstrating stable dynamics. Furthermore, the half-life of the Arg383 hydrogen bond with the target ligands, which is an important factor for PHD2 inhibition, remained almost constant in all the complexes during the simulation. Finally, the total binding free energy of each complex was calculated as CMNPD13808-PHD2 -72.91 kcal/mol, CID15081178-PHD2 -65.55 kcal/mol, CID71496944-PHD2 -68.47 kcal/mol, and CID11821407-PHD2 -62.06 kcal/mol, respectively. Conclusion: The results show the compounds possess good activity in contrast to the control drug (4HG) and need further in vitro and in vivo validation for possible usage as potential drugs against HIF-PHD2-associated diseases.
  13. Al-Qattan H, Al-Omairah H, Al-Hashash K, Al-Mutairi F, Al-Mutairat M, Al-Ajmi M, et al.
    Front Neurol, 2021;12:620799.
    PMID: 33889122 DOI: 10.3389/fneur.2021.620799
    Background: Obstructive sleep apnea (OSA) affects a considerable proportion of adults globally and is associated with elevated morbidity and mortality. Given the lack of epidemiologic data on the burden of OSA in Kuwait, this study sought to estimate its prevalence, associated risk factors, and comorbid conditions among a working population in Kuwait. Methods: This was a cross-sectional study of a sample of working adults (n = 651) from public institutions in Kuwait. High/low risk for OSA was ascertained according to the Berlin Questionnaire criteria. Participants self-reported their coexisting health conditions. Associations were assessed using Poisson regression with robust variance estimation; adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were estimated. Results: Overall, 20.0% (130/651) of participants were classified as being at high risk for OSA, with more male than female subjects being at high risk (24.0% [56/233] vs. 17.7% [74/418], P = 0.053), though this difference did not gain statistical significance. Moreover, a high risk for OSA was more common among older and obese subjects. Factors associated with increased prevalence of a high risk for OSA included current smoking status (aPR = 1.58, 95% CI: 1.02-2.06), longer hours spent watching television (1.76, 1.10-2.81), and lower self-perceived physical health (2.11, 1.15-3.87). However, decreasing trends in the prevalence of high risk for OSA were observed with frequent engagement in vigorous physical activity and longer nightly sleep duration. Compared to those at a low risk for OSA, the subjects at high risk for OSA were more likely to have insomnia disorder (2.83, 1.81-4.41), diabetes (1.94, 1.15-3.27), hypertension (3.00, 1.75-5.16), and depression (4.47, 1.80-11.08). Conclusion: This study estimated that 1/5 of working adults in Kuwait were at high risk for OSA, and the prevalence varied according to personal characteristics and lifestyle factors. Also, a high risk for OSA classification was associated with multiple comorbid health conditions.
  14. Mohammad A, Zheoat A, Oraibi A, Manaithiya A, S Almaary K, Allah Nafidi H, et al.
    Front Mol Biosci, 2023;10:1306179.
    PMID: 38516396 DOI: 10.3389/fmolb.2023.1306179
    Introduction: The pursuit of effective therapeutic solutions for SARS-CoV-2 infections and COVID-19 necessitates the repurposing of existing compounds. This study focuses on the detailed examination of the central protease, 3-chymotrypsin-like protease (3CLpro), a pivotal player in virus replication. The combined approach of molecular dynamics simulations and virtual screening is employed to identify potential inhibitors targeting 3CLpro. Methods: A comprehensive virtual screening of 7120 compounds sourced from diverse databases was conducted. Four promising inhibitors, namely EN1036, F6548-4084, F6548-1613, and PUBT44123754, were identified. These compounds exhibited notable attributes, including high binding affinity (ranging from -5.003 to -5.772 Kcal/mol) and superior Induced Fit Docking scores (ranging from -671.66 to -675.26 Kcal/mol) compared to co-crystallized ligands. Results: In-depth analysis revealed that F6548-1613 stood out, demonstrating stable hydrogen bonds with amino acids His41 and Thr62. Notably, F6548-1613 recorded a binding energy of -65.72 kcal/mol in Molecular Mechanics Generalized Born Surface Area (MMGBSA) simulations. These findings were supported by Molecular Dynamics simulations, highlighting the compound's efficacy in inhibiting 3CLpro. Discussion: The identified compounds, in compliance with Lipinski's rule of five and exhibiting functional molecular interactions with 3CLpro, present promising therapeutic prospects. The integration of in silico methodologies significantly expedites drug discovery, laying the foundation for subsequent experimental validation and optimization. This approach holds the potential to develop effective therapeutics for SARS-CoV-2.
  15. Ali I, Wei DQ, Khan A, Feng Y, Waseem M, Hussain Z, et al.
    Biotechnol Appl Biochem, 2024 Apr;71(2):402-413.
    PMID: 38287712 DOI: 10.1002/bab.2548
    Malonyl-CoA serves as the main building block for the biosynthesis of many important polyketides, as well as fatty acid-derived compounds, such as biofuel. Escherichia coli, Corynebacterium gultamicum, and Saccharomyces cerevisiae have recently been engineered for the biosynthesis of such compounds. However, the developed processes and strains often have insufficient productivity. In the current study, we used enzyme-engineering approach to improve the binding of acetyl-CoA with ACC. We generated different mutations, and the impact was calculated, which reported that three mutations, that is, S343A, T347W, and S350W, significantly improve the substrate binding. Molecular docking investigation revealed an altered binding network compared to the wild type. In mutants, additional interactions stabilize the binding of the inner tail of acetyl-CoA. Using molecular simulation, the stability, compactness, hydrogen bonding, and protein motions were estimated, revealing different dynamic properties owned by the mutants only but not by the wild type. The findings were further validated by using the binding-free energy (BFE) method, which revealed these mutations as favorable substitutions. The total BFE was reported to be -52.66 ± 0.11 kcal/mol for the wild type, -55.87 ± 0.16 kcal/mol for the S343A mutant, -60.52 ± 0.25 kcal/mol for T347W mutant, and -59.64 ± 0.25 kcal/mol for the S350W mutant. This shows that the binding of the substrate is increased due to the induced mutations and strongly corroborates with the docking results. In sum, this study provides information regarding the essential hotspot residues for the substrate binding and can be used for application in industrial processes.
  16. Mohamad N, Pahrol MA, Shaharudin R, Md Yazin NKR, Osman Y, Toha HR, et al.
    Front Public Health, 2022;10:878396.
    PMID: 35923958 DOI: 10.3389/fpubh.2022.878396
    Healthcare workers (HCWs) are at risk of contracting coronavirus disease-2019 (COVID-19) in their workplace. Infection prevention guidelines and standard operating procedures were introduced to reduce risk of exposure and prevent transmission. Safe practices during interaction with patients with COVID-19 are crucial for infection prevention and control (IPC). This study aimed to assess HCWs' compliance to IPC and to determine its association with sociodemographic and organizational factors. A cross-sectional study was conducted between March and April 2021 at public healthcare facilities in the east coast of Peninsular Malaysia. HCWs who were involved with COVID-19-related works were invited to participate in the online survey. The questionnaire was adapted from the World Health Organization (WHO) Interim Guidance: WHO Risk Assessment and Management of Exposure of Healthcare Workers in the Context of COVID-19. Respondents were categorized as compliant or non-compliant to IPC. A total of 600 HCWs involved in COVID-19-related works participated in the survey. Most of them (63.7%) were compliant to IPC as they responded to all items as "always, as recommended" during interaction with patients with COVID-19. The multivariate analysis showed that non-compliance was significantly associated with working in the emergency department (AOR = 3.16; 95% CI = 1.07-9.31), working as laboratory personnel (AOR = 15.13; 95% CI = 1.36-168.44), health attendant (AOR = 4.42; 95% CI = 1.74-11.24), and others (AOR = 3.63; 95% CI = 1.1-12.01), as well as work experience of more than 10 years (AOR = 4.71; 95% CI = 1.28-17.27). The odds of non-compliance among respondents without adequate new norms and personal protective equipment training were 2.02 (95% CI = 1.08-3.81) more than those with adequate training. Although most of the respondents complied to IPC protocols, compliance status differed according to department, work category, and years of service. Ensuring adequate training that will hopefully lead to behavioral change is crucial to prevent breach in IPC and thus minimize the risk of exposure to and transmission of COVID-19 in healthcare facilities.
  17. Sayaf AM, Kousar K, Suleman M, Albekairi NA, Alshammari A, Mohammad A, et al.
    BMC Chem, 2024 Nov 26;18(1):236.
    PMID: 39593151 DOI: 10.1186/s13065-024-01347-4
    Hypoxia-inducible factors (HIFs) are transcription factors that regulate erythropoietin (EPO) synthesis and red blood cell (RBC) production. Prolyl-4-hydroxylase domain (PHD) enzymes are key regulators of HIF's stability and activity. Inhibiting PHD enzymes can enhance HIF-mediated responses and have therapeutic potential for diseases such as anemia, cancer, stroke, ischemia, neurodegeneration, and inflammation. In this study, we searched for novel PHD inhibitors from four databases of natural products and synthetic compounds: AfroDb Natural Products, AnalytiCon Discovery Natural Product (NP), HIM-Herbal Ingredients In-Vivo Metabolism, and Herbal Ingredients' Targets, with a total number of 13,597 compounds. We screened the candidate compounds by molecular docking and validated them by molecular dynamics simulations and free energy calculations. We identified four target hits (ZINC36378940, ZINC2005305, ZINC31164438, and ZINC67910437) that showed stronger binding affinity to PHD2 compared to the positive control, Vadadustat (AKB-6548), with docking scores of - 13.34 kcal/mol, - 12.76 kcal/mol, - 11.96 kcal/mol, - 11.41 kcal/mol, and - 9.04 kcal/mol, respectively. The target ligands chelated the active site iron and interacted with key residues (Arg 383, Tyr329, Tyr303) of PHD2, in a similar manner as Vadadustat. Moreover, the dynamic stability-based assessment revealed that they also exhibited stable dynamics and compact trajectories. Then the total binding free energy was calculated for each complex which revealed that the control has a TBE of - 31.26 ± 0.30 kcal/mol, ZINC36378940 reported a TBE of - 38.65 ± 0.51 kcal/mol, for the ZINC31164438 the TBE was - 26.16 ± 0.30 kcal/mol while the ZINC2005305 complex reported electrostatic energy of - 32.75 ± 0.58 kcal/mol. This shows that ZINC36378940 is the best hit than the other and therefore further investigation should be performed for the clinical usage. Our results suggest that these target hits are promising candidates that reserve further in vitro and in vivo validations as potential PHD inhibitors for the treatment of renal anemia, cancer, stroke, ischemia, neurodegeneration, and inflammation.
  18. Noor Shafina MN, Nor Azizah A, Mohammad AR, Faisal MF, Mohamad Ikhsan S, Hafizah Z, et al.
    Med J Malaysia, 2015 Jun;70(3):153-7.
    PMID: 26248777 MyJurnal
    INTRODUCTION: Urinary tract infection (UTI) is a common bacterial infection affecting children and therefore, prompt recognition and accurate antimicrobial management are vital to prevent kidney damage. This study aims to determine the bacterial pathogens and their patterns of antimicrobial resistance in children presenting with UTI.
    METHODS: A retrospective study of 721 cases, involving children between the ages of 1-day old to 13 years old with culture-proven UTI in Selayang Hospital, Malaysia between January 2007 and December 2011. The bacterial pathogens and antibiotic resistance patterns in the total population, prophylaxis and no prophylaxis groups were studied.
    RESULTS: The 3 most common organisms isolated in the total population were E.Coli (41.6%), Klebsiella spp. (21.2%) and Enterococcus spp. (11.0%). With regards to the antibiotic resistance, E.Coli resistance rates to ampicillin, cefuroxime and gentamicin were 67.7%, 15.3% and 7.3% respectively. Ampicillin-resistance was also highest in Klebsiella spp. (84.3%), Enterococcus spp. (15.5%) and Proteus spp. (55.5%).
    CONCLUSION: E.coli remains to be the leading bacterial pathogen causing UTI in children, with ampicillin-resistance occurring in more than half of these cases. Therefore, accurate choice of antibiotics is important to ensure optimal outcome. In our study, cefuroxime and gentamicin have lower antibiotic resistance rates and can be used in the treatment of UTI in children.
  19. Khan A, Randhawa AW, Balouch AR, Mukhtar N, Sayaf AM, Suleman M, et al.
    RSC Adv, 2022 Mar 01;12(12):7318-7327.
    PMID: 35424688 DOI: 10.1039/d2ra00277a
    A new variant of SARS-CoV-2 known as the omicron variant (B.1.1.529) reported in South Africa with 30 mutations in the whole spike protein, among which 15 mutations are in the receptor-binding domain, is continuously spreading exponentially around the world. The omicron variant is reported to be highly contagious with antibody-escaping activity. The emergence of antibody-escaping variants is alarming, and thus the quick discovery of small molecule inhibitors is needed. Hence, the current study uses computational drug screening and molecular dynamics simulation approaches (replicated) to identify novel drugs that can inhibit the binding of the receptor-binding domain (RBD) with hACE2. Screening of the North African, East African and North-East African medicinal compound databases by employing a multi-step screening approach revealed four compounds, namely (-)-pipoxide (C1), 2-(p-hydroxybenzyl) benzofuran-6-ol (C2), 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol (C3), and Rhein (C4), with excellent anti-viral properties against the RBD of the omicron variant. Investigation of the dynamics demonstrates stable behavior, good residue flexibility profiles, and structural compactness. Validation of the top hits using computational bioactivity analysis, binding free energy calculations and dissociation constant (K D) analysis also indicated the anti-viral properties of these compounds. In conclusion, this study will help in the design and discovery of novel drug therapeutics, which may be used against the emerging omicron variant of SARS-CoV-2.
  20. Khan PA, Mohammad A, Bansal SL, Lal B, Singh P, Singh R, et al.
    Mol Biotechnol, 2024 Jan 09.
    PMID: 38195817 DOI: 10.1007/s12033-023-01022-4
    Solid waste generation is a huge contributor to environmental pollution issues, and food wastes are prominent in this category due to their large generation on a day-to-day basis. Thus, the settlement of daily food waste is one of the major constraints and needs innovative manufacturing sheme to valorize solid waste in sustainable manner. Moreover, these food wastes are rich in organic content, which has promising scope for their value-added products. In the present study, raw mango seed waste has been biotransformed to produce bacterial hydrolytic enzymes as feedstock. On investigating the impact of substrate, the highest bacterial cellulase production was recorded to be 18 IU/gds FP (filter paper) in 24 h of microbial incubation at 5 g of substrate in solid-state fermentation (SSF). Furthermore, at 40 °C and pH 6.0, 23 IU/gds FP enzyme could be produced in 24 h of SSF. Beside this, on comparing the influence of inorganic and organic nitrogen sources, urea has been found to provide better cellulase production, which yielded 28 IU/gds FP in 24 h of incubation, along with 77 IU/gds BG (β-glucosidase) and 89 IU/gds EG (endoglucanase). On the other hand, Tween-40 and Tween-80, two different surfactants, were employed at a 1.0% concentration for 24 h of incubation. It was noticed that Tween-80 showed complete enzyme activity at 24 h, which was found to be relatively superior to that of Tween-40. This study may have potential utility in enzyme production using mango seed as a food waste for various industrial applications.
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