Displaying publications 61 - 80 of 184 in total

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  1. Kandel S, Zaidi STR, Wanandy ST, Ming LC, Castelino RL, Sud K, et al.
    Perit Dial Int, 2017 11 21;38(1):49-56.
    PMID: 29162678 DOI: 10.3747/pdi.2017.00115
    BACKGROUND: Intraperitoneal (IP) administration of ceftazidime is recommended for the treatment of peritoneal dialysis-associated peritonitis (PDAP) from Pseudomonas. Patients with PDAP may also need IP heparin to overcome problems with drainage of turbid peritoneal dialysis (PD) fluids and blockage of catheters with fibrin. Physico-chemical stability of ceftazidime and heparin, and biological stability of heparin in many types of PD solutions is unknown. Therefore, we investigated the stability of ceftazidime and heparin in 4 types of PD solutions.

    METHODS: A total of 12 PD bags (3 for each type of solution) containing ceftazidime and heparin were prepared and stored at 4°C for 120 hours, and then at 25°C for 6 hours, and finally at 37°C for 12 hours. An aliquot was withdrawn after predefined time points and analyzed for the concentration of ceftazidime and heparin using high-performance liquid-chromatography (HPLC). Samples were assessed for pH, color changes, particle content, and anticoagulant activity of heparin.

    RESULTS: Ceftazidime and heparin retained more than 91% of their initial concentration when stored at 4°C for 120 hours followed by storage at 25°C for 6 hours and then at 37°C for 12 hours. Heparin retained more than 95% of its initial activity throughout the study period. Particle formation was not detected at any time under the storage conditions. The pH and color remained essentially unchanged throughout the study.

    CONCLUSIONS: Ceftazidime-heparin admixture retains its stability over long periods of storage at different temperatures, allowing its potential use for PDAP treatment in outpatient and remote settings.

  2. Chooi WH, Ng PW, Hussain Z, Ming LC, Ibrahim B, Koh D
    Vaccine, 2022 Mar 15;40(12):1699-1701.
    PMID: 35210120 DOI: 10.1016/j.vaccine.2022.02.034
  3. Jarrar Q, Ayoub R, Alhussine K, Goh KW, Moshawih S, Ardianto C, et al.
    J Pers Med, 2022 Nov 17;12(11).
    PMID: 36422097 DOI: 10.3390/jpm12111921
    BACKGROUND: The elevated plus maze (EPM) and the marble burying (MB) tests are common behavioral tests used for behavioral phenotyping in mouse models for neurodevelopmental disorders. However, the behavioral effects of maternal separation (MS), a standard paradigm for early life stress in animals, in both the EPM and MB tests remain incompletely known.

    OBJECTIVES: This study aimed to investigate the behavioral effects of prolonged MS in the offspring of mice using the EPM and MB tests.

    METHODS: Male BALB/c mice were isolated from their mothers for 4 h each day during the first 30 days after birth. On day 50 postnatal, groups of separated and non-separated mice (n = 18/each group) were subjected to the EPM and MB tests for comparative behavioral evaluations. In addition, the locomotor activity of mice was evaluated using the actophotometer test.

    RESULTS: The findings of the EPM test revealed that separated mice exhibited anxiolytic-like behaviors, as evidenced by a significant increase in the latency to closed arms and the time spent in the open arms compared with non-separated mice. Separated mice also showed compulsive burying activity in the MB test, as determined by a significant increase in the number of buried marbles. The results of the actophotometer test did not show any significant change in locomotor activity.

    CONCLUSIONS: Prolonged MS caused the adult offspring of mice to exhibit a decrease in anxiety state and increased compulsive burying activity, which were not associated with a change in locomotor activity. Further investigations with validated tests are needed to support these findings.

  4. Moshawih S, Hadikhani P, Fatima A, Goh HP, Kifli N, Kotra V, et al.
    J Mol Graph Model, 2022 Dec;117:108307.
    PMID: 36096064 DOI: 10.1016/j.jmgm.2022.108307
    A Laplacian scoring algorithm for gene selection and the Gini coefficient to identify the genes whose expression varied least across a large set of samples were the state-of-the-art methods used here. These methods have not been trialed for their feasibility in cheminformatics. This was a maiden attempt to investigate a complete comparative analysis of an anthraquinone and chalcone derivatives-based virtual combinatorial library. This computational "proof-of-concept" study illustrated the combinatorial approach used to explain how the structure of the selected natural products (NPs) undergoes molecular diversity analysis. A virtual combinatorial library (1.6 M) based on 20 anthraquinones and 24 chalcones was enumerated. The resulting compounds were optimized to the near drug-likeness properties, and the physicochemical descriptors were calculated for all datasets including FDA, Non-FDA, and NPs from ZINC 15. UMAP and PCA were applied to compare and represent the chemical space coverage of each dataset. Subsequently, the Laplacian score and Gini coefficient were applied to delineate feature selection and selectivity among properties, respectively. Finally, we demonstrated the diversity between the datasets by employing Murcko's and the central scaffolds systems, calculating three fingerprint descriptors and analyzing their diversity by PCA and SOM. The optimized enumeration resulted in 1,610,268 compounds with NP-Likeness, and synthetic feasibility mean scores close to FDA, Non-FDA, and NPs datasets. The overlap between the chemical space of the 1.6 M database was more prominent than with the NPs dataset. A Laplacian score prioritized NP-likeness and hydrogen bond acceptor properties (1.0 and 0.923), respectively, while the Gini coefficient showed that all properties have selective effects on datasets (0.81-0.93). Scaffold and fingerprint diversity indicated that the descending order for the tested datasets was FDA, Non-FDA, NPs and 1.6 M. Virtual combinatorial libraries based on NPs can be considered as a source of the combinatorial compound with NP-likeness properties. Furthermore, measuring molecular diversity is supposed to be performed by different methods to allow for comparison and better judgment.
  5. Wahab MSA, Jalani MM, Goh KW, Ming LC, Faller EM
    Int J Environ Res Public Health, 2022 Sep 02;19(17).
    PMID: 36078707 DOI: 10.3390/ijerph191710994
    Herbal and dietary supplements (HDSs) are frequently obtained from community pharmacies, but community pharmacists (CPs) have been underutilized for information regarding them. This study aimed to determine the prevalence of, factors behind, and reasons for consultation with CPs among HDS consumers in Malaysia. A cross-sectional study using an online survey was conducted among conveniently sampled individuals in Malaysia. Reasons for consultation or non-consultation with CPs about HDSs were sought from the respondents. A logistic regression analysis was conducted to determine the predictors of consultation with CPs. Overall, 40.3% (239/593) of participants consulted CPs about the HDSs that they purchased. The participants were predominantly unmarried (362/588, 61.6%) and belonged to the 18-29 age group (332/593, 56%). The multivariate analysis showed that a suburban residential setting was the only significant predictor for consultation with CPs (adjusted odds ratio = 0.390, 95% CI = 0.260-0.583). Respondents who consulted CPs generally agreed that the CPs were the right people to consult on HDSs (mean = 4.37, SD = 0.73). However, their discussion with CPs regarding HDSs mostly revolved around the benefits and directions for use, but little on the potential risks. Meanwhile, most respondents who did not consult CPs agreed that they had never thought of consulting CPs about their HDS use (mean = 3.45, SD = 1.02). The majority of them referred to the Internet (61.3%, 217/354) and social media (59.9%, 212/354) for information about HDSs. The findings from this study show that more efforts are warranted in encouraging consumers to consult CPs about their HDS use and to enhance their awareness of the roles of CPs in ensuring the safe use of HDSs.
  6. Bashir MA, Khan A, Shah SI, Ullah M, Khuda F, Abbas M, et al.
    Drug Des Devel Ther, 2023;17:261-272.
    PMID: 36726738 DOI: 10.2147/DDDT.S377686
    BACKGROUND: Self-emulsifying drug-delivery systems (SEDDSs) are designed to improve the oral bioavailability of poorly water-soluble drugs. This study aimed at formulating and characterization of SEDDS-based tablets for simvastatin using castor and olive oils as solvents and Tween 60 as surfactant.

    METHODS: The liquids were adsorbed on microcrystalline cellulose, and all developed formulations were compressed using 10.5 mm shallow concave round punches.

    RESULTS: The resulting tablets were evaluated for different quality-control parameters at pre- and postcompression levels. Simvastatin showed better solubility in a mixture of oils and Tween 60 (10:1). All the developed formulations showed lower self-emulsification time (˂200 seconds) and higher cloud point (˃60°C). They were free of physical defects and had drug content within the acceptable range (98.5%-101%). The crushing strength of all formulations was in the range of 58-96 N, and the results of the friability test were within the range of USP (≤1). Disintegration time was within the official limits (NMT 15 min), and complete drug release was achieved within 30 min.

    CONCLUSION: Using commonly available excipients and machinery, SEDDS-based tablets with better dissolution profile and bioavailability can be prepared by direct compression. These S-SEDDSs could be a better alternative to conventional tablets of simvastatin.

  7. Zafar R, Rehman IU, Shah Y, Ming LC, Goh HP, Goh KW
    PLoS One, 2023;18(9):e0291417.
    PMID: 37773947 DOI: 10.1371/journal.pone.0291417
    INTRODUCTION: Chronic kidney disease (CKD) is a significant public health challenge due to its rising incidence, mortality, and morbidity. Patients with kidney diseases often suffer from various comorbid conditions, making them susceptible to potential drug-drug interactions (pDDIs) due to polypharmacy and multiple prescribers. Inappropriate prescriptions for CKD patients and their consequences in the form of pDDIs are a major challenge in Pakistan.

    AIM: This study aimed to compare the incidence and associated risk factors of pDDIs among a public and private sector hospital in Khyber Pakhtunkhwa, Pakistan.

    METHOD: A retrospective cross-sectional study design was conducted to compare pDDIs among public and private sector hospitals from January 2023 to February 2023. Patients profile data for the full year starting from January 1 2022 to December 302022, was accessed All adult patients aged 18 years and above, of both genders, who currently have or have previously been diagnosed with end-stage renal disease (ESRD) were included. For assessing pDDIs, patient data was retrieved and checked using Lexicomp UpToDate® for severity and documentation of potential drug-drug interactions.

    RESULTS: A total of 358 patients' data was retrieved (with n = 179 in each hospital); however, due to incomplete data, n = 4 patients were excluded from the final analysis. The prevalence of pDDIs was found to be significantly higher in private hospitals (84.7%) than in public hospitals (26.6%), with a p-value <0.001. Patients in the age category of 41-60 years (AOR = 6.2; p = 0.008) and those prescribed a higher number of drugs (AOR = 1.2; p = 0.027) were independently associated with pDDIs in private hospitals, while the higher number of prescribed drugs (AOR = 2.9; p = <0.001) was an independent risk factor for pDDIs in public hospitals. The majority of pDDIs (79.0%) were of moderate severity, and a significant number of patients (15.1%) also experienced major pDDIs, with a p-value <0.001. The majority of pDDIs had fair documentation for reliability rating in both public and private hospitals.

    CONCLUSION: The prevalence of pDDIs was higher among CKD patients at private hospitals, and most of the pDDIs were of moderate severity. A considerable number of patients also experienced major pDDIs. The risk of experiencing pDDIs was found to be higher in older patients and among those prescribed a higher number of drugs.

  8. Zafar R, Rehman IU, Shah Y, Ali Z, Ming LC, Khan TM
    J Pharm Policy Pract, 2023 Sep 19;16(1):102.
    PMID: 37726861 DOI: 10.1186/s40545-023-00606-4
    BACKGROUND: Chronic kidney disease (CKD) poses a significant public health challenge. CKD patients have compromised renal function, which not only alters the pharmacokinetics of drugs but also their pharmacodynamics. Adjusting drug doses for these patients is essential to achieve the intended clinical outcomes, prevent adverse drug events, and halt further progression of the disease. Pharmacists play a pivotal role in ensuring safe and appropriate therapy for CKD patients. However, there is a noticeable absence of national dosing guidelines for CKD in Pakistan, coupled with a scarcity of studies exploring the knowledge, attitude, and perception of renal dose adjustments in the country. This study aimed to evaluate the knowledge, attitudes, and perceptions of pharmacists in the Khyber Pakhtunkhwa province and Islamabad regarding renal dose adjustments.

    METHODOLOGY: A cross-sectional study was conducted to gauge the knowledge, attitude, and perception of pharmacists working in various cities of Khyber Pakhtunkhwa and the capital city, Islamabad, from February to May 2023. The Renal Dosing Questionnaire-13 (RDQ-13) scale was employed for this purpose. The survey link was disseminated through emails, and the RDQ-13 scale was also completed in person by pharmacists from hospitals, clinics, community, and retail settings who interact with CKD patients. Univariate linear regression was employed, and factors with a p value 

  9. Xue Qin QN, Ming LC, Abd Wahab MS, Tan CS, Yuda A, Hermansyah A
    Res Social Adm Pharm, 2023 Jun;19(6):873-881.
    PMID: 36914513 DOI: 10.1016/j.sapharm.2023.02.015
    INTRODUCTION: Dementia is a disorder that causes a decline of cognitive function, and it affects millions of people worldwide. Increased availability of medications used to treat dementia will inevitably increase the likelihood of drug-related problems (DRPs).

    OBJECTIVE: This systematic review sought to identify DRPs due to medication misadventures, including adverse drug reactions (ADRs), and use of inappropriate medications, among patients with dementia or cognitive impairments.

    METHODS: The included studies were retrieved from the electronic databases PubMed and SCOPUS, and a preprint platform (MedRXiv) which were searched from their inception through August 2022. The English-language publications that reported DRPs among dementia patients were included. The JBI Critical Appraisal Tool for quality assessment was used to evaluate the quality of studies included in the review.

    RESULTS: Overall, 746 distinct articles were identified. Fifteen studies met the inclusion criteria and reported the most common DRPs, which comprised medication misadventures (n = 9), such as ADRs, inappropriate prescription use, and potentially inappropriate medication use (n = 6).

    CONCLUSION: This systematic review provides evidence that DRPs are prevalent among dementia patients, particularly the older people. It indicates that medication misadventures such as ADRs and inappropriate drug use, as well as potentially inappropriate medications, are the most prevalent DRPs among older people with dementia. Due to the small number of included studies, however, additional studies are required to improve comprehension about the issue.

  10. Awang Jihadi MH, Yuda A, Sukorini AI, Hermansyah A, Shafqat N, Tan CS, et al.
    Explor Res Clin Soc Pharm, 2023 Dec;12:100348.
    PMID: 37885436 DOI: 10.1016/j.rcsop.2023.100348
    INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the non-communicable diseases which continues to rise in prevalence and mortality rate throughout the years. Drug-related problems (DRPs) are more prevalent among T2DM patients especially those with co-morbidities.

    OBJECTIVE: The objective of this study was to review and assess the prevalence and characteristics of DRPs among hospitalized type 2 diabetes mellitus patients.

    METHODS: The systematic review of the literature was carried out using five online databases: PubMed, Scopus, Google Scholar, Web of Science, and Cochrane Library from the inception of the database until June 2022. Studies included in the review were published in English or Malay language. The data were extracted and assessed using the Joanna Briggs Institute (JBI) critical appraisal tools.

    RESULTS: A total of 939 studies were identified with 20 studies that met inclusion criteria and were included in this systematic review. The overall prevalence of DRPs in all 20 studies ranged from 7% to 94%. The most common DRPs included drug-drug interaction (DDI), adverse drug reaction (ADR), therapeutic effectiveness problems, and inappropriate medication use.

    CONCLUSION: The most common drug classes involved were antidiabetics (metformin), antihypertensives, antiplatelets and antibiotics. The risk factors contributing to DRPs included the presence of comorbidities, the number of medications, and polypharmacy. To conclude, the rate of DRPs incidence in hospitalized T2DM patients was observed to be high. Further future studies with appropriate study designs and methods of detecting DRPs will be necessary to reduce and prevent DRPs occurrences.

  11. Mohidin SRNSP, Moshawih S, Hermansyah A, Asmuni MI, Shafqat N, Ming LC
    J Evid Based Integr Med, 2023;28:2515690X231206227.
    PMID: 37822215 DOI: 10.1177/2515690X231206227
    Cassava (Manihot esculenta Crantz) is considered one of the essential tuber crops, serving as a dietary staple food for various populations. This systematic review provides a comprehensive summary of the nutritional and therapeutic properties of cassava, which is an important dietary staple and traditional medicine. The review aims to evaluate and summarize the phytochemical components of cassava and their association with pharmacological activities, traditional uses, and nutritional importance in global food crises. To collect all relevant information, electronic databases; Cochrane Library, PubMed, Scopus, Web of Science, Google Scholar, and Preprint Platforms were searched for studies on cassava from inception until October 2022. A total of 1582 studies were screened, while only 34 were included in this review. The results of the review indicate that cassava has diverse pharmacological activities, including anti-bacterial, anti-cancer, anti-diabetic, anti-diarrheal, anti-inflammatory, hypocholesterolemic effects, and wound healing properties. However, more studies that aim to isolate the phytochemicals in cassava extracts and evaluate their pharmacological property are necessary to further validate their medical and nutritional values.
  12. Juperi RNAA, Goh HP, Rehman IU, Lee KS, Ming LC, Hermansyah A
    J Pharm Policy Pract, 2023 Aug 24;16(1):101.
    PMID: 37620839 DOI: 10.1186/s40545-023-00594-5
    BACKGROUND: Pharmacy medicine (P) is obtained exclusively from a pharmacy under the supervision of a pharmacist. This study aims to understand the perception of healthcare professionals towards the dispensing separation, as well as the dispensing of pharmacy medicine by community pharmacies to enhance patient health outcomes in Brunei Darussalam.

    METHODS: A cross-sectional study was conducted between 1st March 2023 and 20th April 2023 among healthcare professionals. A newly designed and validated questionnaire was used. Its face and content validity, along with internal consistency, was adequately established. Convenient sampling was employed to recruit participants for the study. Statistical analysis using one-way ANOVA was performed, considering a p-value 

  13. Loh HC, Looi I, Ch'ng ASH, Goh KW, Ming LC, Ang KH
    GeoJournal, 2021 Jul 23.
    PMID: 34316088 DOI: 10.1007/s10708-021-10475-6
    Global environmental change is mainly due to human behaviours and is a major threat to sustainability. Despite all the health and economic consequences, the impact of the COVID-19 pandemic lockdown on environmental health warrants the scientific community's attention. Thus, this article examined and narratively reviewed the impact of several drastic measures taken on the macro environment and holistic planetary health. We note that the amount of pollution in the air, water, soil, and noise showed a significant decline during the pandemic. Global air quality improved due to lower anthropogenic emissions of air pollutants and atmospheric particles. Water ecosystems also demonstrated signs of recuperation in many countries. Less commercial fishing internationally resulted in the restoration of some aquatic life. Additionally, significant reduction of solid and water waste led to less soil pollution. Some places experienced cleaner beaches and ocean water while wildlife sightings in urban areas across the world occurred more often. Lastly, the COVID-19 pandemic lockdown also led to a worldwide decline in noise pollution. However, the beneficial environmental effects will not be permanent as the world gradually returns to its pre-pandemic status quo. Therefore, behavioural changes such as adopting a lifestyle that reduces carbon footprint are needed to make a positive impact on the environment. In addition, world leaders should consider the national policy changes necessary to ensure continuity of as many of the positive environmental impacts from the COVID-19 pandemic lockdown as possible. Those changes would also serve to lessen the likelihood of another zoonotic calamity.
  14. Alruwaili M, Jarrar B, Jarrar Q, Alruwaili M, Goh KW, Moshawih S, et al.
    Front Biosci (Landmark Ed), 2023 Jul 13;28(7):137.
    PMID: 37525906 DOI: 10.31083/j.fbl2807137
    BACKGROUND: Hydroxychloroquine (HCQ) toxicity can adversely affect vital organs, cause pathologic ocular damage, and can have direct cardiovascular effects. This study aims to identify the biochemical, hematological, and histological alterations of the vital organs associated with the effects of HCQ.

    METHODS: Male albino rats were exposed to the equivalent of HCQ therapeutic doses given to human patients being affected by malaria, lupus erythematosus, and COVID-19. The animal blood samples were subjected to hematological analysis, biochemical analysis, liver function tests, kidney function tests, and cardiac biomarkers. Liver, kidney, heart, spleen, and testis biopsies were subjected to histological examination.

    RESULTS: HCQ significantly lowered the values of erythrocytes, hemoglobin, hematocrit, platelets, leucocytes, and lymphocytes but significantly increased the values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase, alkaline phosphatase, lactate dehydrogenase, cholesterol, and chlorine ions. The renal tissues of HCQ-treated animals demonstrated glomerular fragmentation, partial atrophy degeneration, renal tubules hydropic degeneration, hyaline cast formation, and interstitial edema formation. Additionally, the heart exhibited myofiber necrosis, myolysis, wavy appearance, disorganization, and disarray. The testicular tissues also demonstrated spermatocyte degeneration, spermatogenic cell sloughing, testicular interstitial edema, and occasional spermatogenic arrest. Additionally, the spleen showed a decrease in the number and size of the white pulp follicles, a decrease in the number of apoptotic activity, and a decline in the number of T-rich cells. However, the red pulp demonstrated a diffuse decline in B rich-lymphocytes and macrophages. The liver was also the least affected but showed Kupffer cell hyperplasia and occasional hepatocyte dysplasia.

    CONCLUSIONS: The results indicate that chronic exposure to HCQ could alter the structures and functions of the vital organs.

  15. Massud A, Khan AH, Syed Sulaiman SA, Ahmad N, Shafqat M, Ming LC
    PLoS One, 2023;18(8):e0287966.
    PMID: 37561810 DOI: 10.1371/journal.pone.0287966
    INTRODUCTION: Tuberculosis (TB), a curable and preventable infectious disease, becomes difficult to treat if resistance against most effective and tolerable first line anti-TB drugs is developed. The objective of the present study was to evaluate the treatment outcomes and predictors of poor outcomes among drug-resistant tuberculosis (DR-TB) patients treated at a programmatic management unit of drug resistant tuberculosis (PMDT) unit, Punjab, Pakistan.

    METHODS: This prospective observational study was conducted at a a PMDT unit in Multan, Punjab, Pakistan. A total of 271 eligible culture positive DR-TB patients enrolled for treatment at the study site between January 2016 and May 2017 were followed till their treatment outcomes were recorded. World Health Organization's (WHO) defined criteria was used for categorizing treatment outcomes. The outcomes of cured and treatment completed were collectively placed as successful outcomes, while death, lost to follow-up (LTFU) and treatment failure were grouped as unsuccessful outcomes. Multivariable binary logistic regression analysis was employed for getting predictors of unsuccessful treatment outcomes. A p-value <0.05 was considered statistically significant.

    RESULTS: Of the 271 DR-TB patients analysed, nearly half (51.3%) were males. The patient's (Mean ± SD) age was 36.75 ± 15.69 years. A total of 69% patients achieved successful outcomes with 185 (68.2%) patients being cured and 2 (0.7%) completed therapy. Of the remaining 84 patients with unsuccessful outcomes, 48 (17.7%) died, 2 (0.7%) were declared treatment failure, 34 (12.5%) were loss to follow up. After adjusting for confounders, patients' age > 50 years (OR 2.149 (1.005-4.592) with p-value 0.048 and baseline lung cavitation (OR 7.798 (3.82-15.919) with p-value <0.001 were significantly associated with unsuccessful treatment outcomes.

    CONCLUSIONS: The treatment success rate (69%) in the current study participants was below the target set by WHO (>75%). Paying special attention and timely intervention in patients with high risk of unsuccessful treatment outcomes may help in improving treatment outcomes at the study site.

  16. Ming LC, Halim M, Rahim RA, Wan HY, Ariff AB
    Food Sci Biotechnol, 2016;25(5):1393-1398.
    PMID: 30263421 DOI: 10.1007/s10068-016-0217-1
    The potential use of fed-batch cultivation (FBC) for improvement of the production of Lactobacillus salivarius I 24 biomass for subsequent use as probiotics was studied using a 2-L stirredtank bioreactor. Three different constant feeding rates (0.1, 0.05, and 0.033 L/h) were applied in FBCs and their effect on carbon metabolism was evaluated. The carbon flux for cell built-up with reduction in lactic acid synthesis was observed in the fed-batch as compared to the batch cultivation mode. The viable cell number obtained in the constant FBC (CFBC) operated at a feeding rate of 0.05 L/h was 8 times higher (10.7×1010 CFU/mL) than that recorded in the batch cultivation. This gave the viable cell yield based on glucose consumed for CFBC of 26 times higher (11.3×1012 CFU/gGlucose) than the batch cultivation. This study demonstrated CFBC, which is simple with minimal use of process control equipment, has an industrial potential for improvement of probiotic production.
  17. Moshawih S, Goh HP, Kifli N, Darwesh MAE, Ardianto C, Goh KW, et al.
    J Biomol Struct Dyn, 2023 Sep 11.
    PMID: 37697727 DOI: 10.1080/07391102.2023.2256870
    Virtual screening aims to identify and rank compounds with drug/lead-like properties based on their affinity for the protein target. We developed a methodology that integrates structure- and ligand-based screening approaches to enhance hit rates against the TDP1 protein within a database of anthraquinone and chalcone derivatives, followed by evaluation of prioritized compounds through molecular simulations. This technique is particularly useful for training set imbalances. Four screening methods were used: QSAR, pharmacophore, shape similarity, and docking. Each method was individually trained to score compounds, and the scores were fused to create parallel Z-score fusion. The QSAR models exhibited satisfactory R2 values (0.84 to 0.75), whereas the pharmacophoric and shape similarity models demonstrated excellent performance (ROC:0.82-0.88). Docking enrichment analysis identified 6N0D as the optimal TDP1 crystal structure (ROC = 0.73). Remarkably, the consensus scoring method surpassed other screening methods, achieving the highest ROC value of 0.98. Docking screening prioritized compounds with binding modes resembling the co-crystallized ligands, whereas MMGBSA, consensus, and docking produced dynamic simulations that were as stable as the co-crystallized ligands. Additionally, the QSAR-selected compounds exhibited binding modes similar to those of commercially available TDP1 inhibitors. In this study, a strong correlation was found between the inhibitory concentrations and binding energy values of commercialized TDP1 inhibitors, indicating that the top-ranked compounds are expected to have potent inhibitory effects in the nano-/micromolar range. The results of this study establish that consensus scoring can be used as an adaptable mainstay virtual screening methodology, pending subsequent experimental validation for affirmation.Communicated by Ramaswamy H. Sarma.
  18. Chua HM, Moshawih S, Goh HP, Ming LC, Kifli N
    PLoS One, 2023;18(9):e0290948.
    PMID: 37656730 DOI: 10.1371/journal.pone.0290948
    There is still unmet medical need in cancer treatment mainly due to drug resistance and adverse drug events. Therefore, the search for better drugs is essential. Computer-aided drug design (CADD) and discovery tools are useful to streamline the lengthy and costly drug development process. Anthraquinones are a group of naturally occurring compounds with unique scaffold that exert various biological properties including anticancer activities. This protocol describes a systematic review that provide insights into the computer-aided drug design and discovery based on anthraquinone scaffold for cancer treatment. It was prepared in accordance with the "Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 guidelines, and published in the "International prospective register of systematic reviews" database (PROSPERO: CRD42023432904). Search strategies will be developed based on the combination of relevant keywords and executed in PubMed, Scopus, Web of Science and MedRxiv. Only original studies that employed CADD as primary tool in virtual screening for the purpose of designing or discovering anti-cancer drugs involving anthraquinone scaffold published in English language will be included. Two independent reviewers will be involved to screen and select the papers, extract the data and assess the risk of bias. Apart from exploring the trends and types of CADD methods used, the target proteins of these compounds in cancer treatment will also be revealed in this review. It is believed that the outcome of this study could be utilized to support the ongoing research in similar area with better quality and greater probability of success, consequently optimizing the resources in subsequent in vitro, in vivo, non-clinical and clinical development. It will also serve as an evidence based scientific guide for new research to design novel anthraquinone-derived drug with improved efficacy and safety profile for cancer treatment.
  19. Kow CS, Lee LH, Ramachandram DS, Hasan SS, Ming LC, Goh HP
    Immun Inflamm Dis, 2022 Feb;10(2):255-264.
    PMID: 34970856 DOI: 10.1002/iid3.562
    BACKGROUND: Overactivation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome can lead to severe illness in patients with coronavirus disease-2019 (COVID-19). The NLRP3 inhibitor, colchicine, therefore, appears to be promising for the treatment of COVID-19.

    AIMS: We aimed to perform a meta-analysis of randomized trials investigating the effect of colchicine in patients with COVID-19.

    MATERIALS & METHODS: We systematically searched electronic databases and clinical trial registries (up to October 17, 2021) for eligible studies. The outcomes of interest were all-cause mortality and duration of hospital stay. Meta-analysis with the random-effects model was used to estimate the pooled odds ratio (OR) of mortality and 95% confidence interval (CI). The pooled standardized mean difference of duration of hospital stay with 95% CI between colchicine users and non-colchicine users was estimated using Cohen's d index.

    RESULTS: The meta-analyses revealed no significant difference in the odds of mortality (pooled OR = 0.76; 95% CI: 0.53-1.07), but a significant reduction in the duration of hospital stay with the use of colchicine (pooled standardized mean difference = -0.59; 95% CI: -1.06 to -0.13).

    DISCUSSION AND CONCLUSION: The ability of colchicine to reduce the length of stay in hospitalized patients with COVID-19 is consistent with its potential to prevent clinical deterioration via inhibition of NLRP3 inflammasome. Nevertheless, such beneficial effects of colchicine did not translate into mortality benefits in patients with COVID-19.

  20. Ooi PL, Zainal H, Lean QY, Ming LC, Ibrahim B
    Pharmacy (Basel), 2021 Oct 01;9(4).
    PMID: 34698254 DOI: 10.3390/pharmacy9040161
    Background: The emergence of new technologies in the area of health information and communication helps pharmacists to check the safety of medications used via electronic prescribing. Objectives: The study aimed to identify the rate and types of problems with electronic prescriptions (e-prescriptions) that required pharmacist intervention at an inpatient pharmacy, and to evaluate prescribers' acceptance of these interventions. Methods: A retrospective cross-sectional study on the interventions of e-prescriptions documented by pharmacists was conducted in a public hospital inpatient pharmacy. Data were collected for descriptive analysis using a collection form, including the e-prescription interventions, types of wards, drugs involved, and acceptance of intervention by prescribers. A chi-square test was used to evaluate the association between ward pharmacist availability and the rate of interventions. Results: A total number of 11,922 (3.3%) pharmacist interventions were proposed for 357,760 e-prescriptions ordered in the 12 month study period. Of the total number of proposed interventions, 11,381 (95.5%) were accepted by prescribers. The interventions on e-prescriptions were from surgical wards (11.7%) followed by intensive care (5.6%), paediatric (3.5%) and medical specialty wards (2.9%). Anti-infective agents (33.8%) and cardiovascular medicines (27.0%) were among the drugs with the highest rate of interventions. The most common type of intervention was revising the drug regimen (58.4%), especially with anti-infective agents (33.8%). Prescribers in surgical wards showed the highest level of acceptance of pharmacist interventions, which was 97.37%. The presence of ward pharmacists showed a higher number of interventions (6.2 vs. 1.0%, p < 0.001) than wards without pharmacists, as well as a higher percentage of acceptance (96.4 vs. 91.1%, p < 0.001) towards e-prescription intervention. Conclusion: In e-prescribing, errors can be prevented by pharmacists' interventions on e-prescriptions. This helps to prevent medication errors and thus optimise rational pharmacotherapy in patients. The role of ward pharmacists in pharmaceutical care is highly accepted by prescribers.
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