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1.
PLoS One ; 17(9): e0274771, 2022.
Article in English | MEDLINE | ID: mdl-36126036

ABSTRACT

BACKGROUND: Effective knowledge transfer of eLearning objects can hasten the adoption and dissemination of technology in teaching and learning. However, challenges exist which hinder inter-organisational knowledge transfer, particularly across continents. The ACoRD project aimed to transfer knowledge on digital learning development from UK/EU (provider) to Malaysian (receiver) higher education institutions (HEIs). This study explores the challenges encountered during the knowledge transfer process and lessons learned. METHODS: This is a qualitative study involving both the knowledge providers and receivers in focus group discussions (n = 25). Four focus group discussions were conducted in the early (n = 2) and mid-phase (n = 2) of the project by trained qualitative researchers using a topic guide designed to explore experiences and activities representing knowledge transfer in multi-institutional and multi-cultural settings. The interviews were audio-recorded, transcribed verbatim, and checked. The transcripts were analysed using thematic analysis. RESULTS: Five main themes emerged from this qualitative study: mismatched expectations between providers and receivers; acquiring new knowledge beyond the professional "comfort zone"; challenges in cascading newly acquired knowledge to colleagues and management; individual and organisational cultural differences; and disruption of knowledge transfer during the COVID-19 pandemic. CONCLUSION: This study highlights the need to create a conducive platform to facilitate continuous, timely and bi-directional needs assessment and feedback; this should be done in the early phase of the knowledge transfer process. The challenges and strategies identified in this study could guide more effective knowledge transfer between organisations and countries.


Subject(s)
COVID-19 , Computer-Assisted Instruction , COVID-19/epidemiology , Capacity Building , Humans , Knowledge , Pandemics
2.
Adv Pharm Bull ; 12(3): 449-465, 2022 May.
Article in English | MEDLINE | ID: mdl-35935059

ABSTRACT

The development of carbon-based nanomaterials has extensively facilitated new discoveries in various fields. Carbon nanotube-based nanocomposites (CNT-based nanocomposites) have lately recognized as promising biomaterials for a wide range of biomedical applications due to their unique electronic, mechanical, and biological properties. Nanocomposite materials such as silver nanoparticles (AgNPs), polymers, biomolecules, enzymes, and peptides have been reported in many studies, possess a broad range of antibacterial activity when incorporated with carbon nanotubes (CNTs). It is crucial to understand the mechanism which governs the antimicrobial activity of these CNT-based nanocomposite materials, including the decoupling individual and synergistic effects on the cells. In this review, the interaction behavior between microorganisms and different types of CNT-based nanocomposites is summarized to understand the respective antimicrobial performance in different conditions. Besides, the current development stage of CNT-based nanocomposite materials, the technical challenges faced, and the exceptional prospect of implementing potential antimicrobial CNT-based nanocomposite materials are also discussed.

3.
Pharmaceutics ; 14(7)2022 Jul 04.
Article in English | MEDLINE | ID: mdl-35890301

ABSTRACT

The year 2021 marks the 100th anniversary of the momentous discovery of insulin. Through years of research and discovery, insulin has evolved from poorly defined crude extracts of animal pancreas to recombinant human insulin and analogues that can be prescribed and administered with high accuracy and efficacy. However, there are still many challenges ahead in clinical settings, particularly with respect to maintaining optimal glycemic control whilst minimizing the treatment-related side effects of hypoglycemia and weight gain. In this review, the chronology of the development of rapid-acting, short-acting, intermediate-acting, and long-acting insulin analogues, as well as mixtures and concentrated formulations that offer the potential to meet this challenge, are summarized. In addition, we also summarize the latest advancements in insulin delivery methods, along with advancement to clinical trials. This review provides insights on the development of insulin treatment for diabetes mellitus that may be useful for clinicians in meeting the needs of their individual patients. However, it is important to note that as of now, none of the new technologies mentioned have superseded the existing method of subcutaneous administration of insulin.

4.
PLoS One ; 16(6): e0253471, 2021.
Article in English | MEDLINE | ID: mdl-34166432

ABSTRACT

BACKGROUND: Engaging students in the e-learning development process enhances the effective implementation of e-learning, however, students' priority on the topics for e-learning may differ from that of the educators. This study aims to compare the differences between the students and their educators in prioritising the topics in three healthcare curricula for reusable e-learning object (RLO) development. METHOD: A modified Delphi study was conducted among students and educators from University Malaya (UM), Universiti Putra Malaysia (UPM) and Taylor's University (TU) on three undergraduate programmes. In Round 1, participants were asked to select the topics from the respective syllabi to be developed into RLOs. Priority ranking was determined by using frequencies and proportions. The first quartile of the prioritised topics was included in Round 2 survey, which the participants were asked to rate the level of priority of each topic using a 5-point Likert scale. The mean score of the topics was compared between students and educators. RESULT: A total of 43 educators and 377 students participated in this study. For UM and TU Pharmacy, there was a mismatch in the prioritised topics between the students and educators. For UPM, both the educators and students have prioritised the same topics in both rounds. To harmonise the prioritisation of topics between students and educators for UM and TU Pharmacy, the topics with a higher mean score by both the students and educators were prioritised. CONCLUSION: The mismatch in prioritised topics between students and educators uncovered factors that might influence the prioritisation process. This study highlighted the importance of conducting needs assessment at the beginning of eLearning resources development.


Subject(s)
Computer-Assisted Instruction , Delivery of Health Care , Education, Medical , Learning , Students, Medical , Delphi Technique , Female , Humans , Malaysia , Male
5.
Life Sci ; 278: 119658, 2021 Aug 01.
Article in English | MEDLINE | ID: mdl-34048809

ABSTRACT

AIMS: Maslinic acid (MA) is a naturally occurring pentacyclic triterpene known to exert cardioprotective effects. This study aims to investigate the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) for MA-mediated anti-inflammatory effects in atheroma pathogenesis in vitro, including evaluation of tumor necrosis factor-alpha (TNF-α)-induced monocyte recruitment, oxidized low-density lipoprotein (oxLDL)-induced scavenger receptors expression, and nuclear factor-kappa B (NF-ĸB) activity in human umbilical vein endothelial cells (HUVECS) and human acute monocytic leukemia cell line (THP-1) macrophages. MATERIALS AND METHODS: An in vitro monocyte recruitment model utilizing THP-1 and HUVECs was developed to evaluate TNF-α-induced monocyte adhesion and trans-endothelial migration. To study the role of Nrf2 for MA-mediated anti-inflammatory effects, Nrf2 inhibitor ML385 was used as the pharmacological inhibitor. The expression of Nrf2, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 36 (CD36), and scavenger receptor type A (SR-A) in HUVECs and THP-1 macrophages were investigated using RT-qPCR and Western blotting. The NF-κB activity was determined using NF-κB (p65) Transcription Factor Assay Kit. KEY FINDINGS: The results showed opposing effects of MA on Nrf2 expression in HUVECs and THP-1 macrophages. MA suppressed TNF-α-induced Nrf2 expression in HUVECs, but enhanced its expression in THP-1 macrophages. Combined effects of MA and ML385 suppressed MCP-1, VCAM-1, and SR-A expressions. Intriguingly, at the protein level, ML385 selectively inhibited SR-A but enhanced CD36 expression. Meanwhile, ML385 further enhanced MA-mediated inhibition of NF-κB activity in HUVECs. This effect, however, was not observed in THP-1 macrophages. SIGNIFICANCE: MA attenuated foam cell formation by suppressing VCAM-1, MCP-1, and SR-A expression, as well as NF-κB activity, possibly through Nrf2 inhibition. The involvement of Nrf2 for MA-mediated anti-inflammatory effects however differs between HUVECs and macrophages. Future investigations are warranted for a detailed evaluation of the contributing roles of Nrf2 in foam cells formation.


Subject(s)
Anti-Inflammatory Agents/pharmacology , NF-E2-Related Factor 2/metabolism , Plaque, Atherosclerotic/metabolism , Triterpenes/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Human Umbilical Vein Endothelial Cells , Humans , Macrophages/drug effects , Macrophages/metabolism , Macrophages/pathology , Monocytes/drug effects , Monocytes/metabolism , Monocytes/pathology , NF-E2-Related Factor 2/analysis , Plaque, Atherosclerotic/drug therapy , Plaque, Atherosclerotic/pathology , THP-1 Cells , Tumor Necrosis Factor-alpha/analysis
6.
Microbiol Res ; 247: 126722, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33618061

ABSTRACT

The Gram-negative opportunistic pathogen Acinetobacter baumannii has gain notoriety in recent decades, primarily due to its propensity to cause nosocomial infections in critically ill patients. Its global spread, multi-drug resistance features and plethora of virulence factors make it a serious threat to public health worldwide. Though much effort has been expended in uncovering its successes, it continues to confound researchers due to its highly adaptive nature, mutating to meet the needs of a given environment. Its persistence in the clinical setting allows it to be in close proximity to a potential host, where contact can be made facilitating infection and colonization. In this article, we aim to provide a current overview of the bacterial virulence factors, specifically focusing on factors involved in the initial stages of infection, highlighting the role of adaptation facilitated by two-component systems and biofilm formation. Finally, the study of host-pathogen interactions using available animal models, their suitability, notable findings and some perspectives moving forward are also discussed.


Subject(s)
Acinetobacter Infections/microbiology , Acinetobacter baumannii/metabolism , Acinetobacter baumannii/pathogenicity , Biofilms/growth & development , Acinetobacter baumannii/drug effects , Acinetobacter baumannii/genetics , Animals , Cross Infection/microbiology , Disease Models, Animal , Drug Resistance, Multiple, Bacterial/drug effects , Host-Pathogen Interactions , Humans , Sepsis , Virulence Factors/genetics
7.
Chem Res Toxicol ; 34(1): 24-46, 2021 01 18.
Article in English | MEDLINE | ID: mdl-33319996

ABSTRACT

Carbon nanotubes (CNTs) are the most studied allotropic form of carbon. They can be used in various biomedical applications due to their novel physicochemical properties. In particular, the small size of CNTs, with a large surface area per unit volume, has a considerable impact on their toxicity. Despite of the use of CNTs in various applications, toxicity is a big problem that requires more research. In this Review, we discuss the toxicity of CNTs and the associated mechanisms. Physicochemical factors, such as metal impurities, length, size, solubilizing agents, CNTs functionalization, and agglomeration, that may lead to oxidative stress, toxic signaling pathways, and potential ways to control these mechanisms are also discussed. Moreover, with the latest mechanistic evidence described in this Review, we expect to give new insights into CNTs' toxicological effects at the molecular level and provide new clues for the mitigation of harmful effects emerging from exposure to CNTs.


Subject(s)
Nanotubes, Carbon/adverse effects , Animals , Biomedical Research , Humans , Nanotubes, Carbon/chemistry
8.
Materials (Basel) ; 13(7)2020 Apr 03.
Article in English | MEDLINE | ID: mdl-32260216

ABSTRACT

Microorganisms have begun to develop resistance because of inappropriate and extensive use of antibiotics in the hospital setting. Therefore, it seems to be necessary to find a way to tackle these pathogens by developing new and effective antimicrobial agents. Carbon nanotubes (CNTs) have attracted growing attention because of their remarkable mechanical strength, electrical properties, and chemical and thermal stability for their potential applications in the field of biomedical as therapeutic and diagnostic nanotools. However, the impact of carbon nanotubes on microbial growth has not been fully investigated. The primary purpose of this research study is to investigate the antimicrobial activity of CNTs, particularly double-walled and multi-walled nanotubes on representative pathogenic strains such as Gram-positive bacteria Staphylococcus aureus, Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae, and fungal strain Candida albicans. The dispersion ability of CNT types (double-walled and multi-walled) treated with a surfactant such as sodium dodecyl-benzenesulfonate (SDBS) and their impact on the microbial growth inhibition were also examined. A stock concentration 0.2 mg/mL of both double-walled and multi-walled CNTs was prepared homogenized by dispersing in surfactant solution by using probe sonication. UV-vis absorbance, Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) were used for the characterization of CNTs dispersed in the surfactant solution to study the interaction between molecules of surfactant and CNTs. Later, scanning electron microscopy (SEM) was used to investigate how CNTs interact with the microbial cells. The antimicrobial activity was determined by analyzing optical density growth curves and viable cell count. This study revealed that microbial growth inhibited by non-covalently dispersed CNTs was both depend on the concentration and treatment time. In conclusion, the binding of surfactant molecules to the surface of CNTs increases its ability to disperse in aqueous solution. Non-covalent method of CNTs dispersion preserved their structure and increased microbial growth inhibition as a result. Multi-walled CNTs exhibited higher antimicrobial activity compared to double-walled CNTs against selected pathogens.

9.
Folia Microbiol (Praha) ; 65(3): 451-465, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32207097

ABSTRACT

Garlic (Allium sativum L.) is a well-known spice widely utilised for its medicinal properties. There is an extensive record of the many beneficial health effects of garlic which can be traced back to as early as the ancient Egyptian era. One of the most studied properties of garlic is its ability to cure certain ailments caused by infections. In the 1940s, the antimicrobial activities exhibited by garlic were first reported to be due to allicin, a volatile compound extracted from raw garlic. Since then, allicin has been widely investigated for its putative inhibitory activities against a wide range of microorganisms. Allicin has demonstrated a preference for targeting the thiol-containing proteins and/or enzymes in microorganisms. It has also demonstrated the ability to regulate several genes essential for the virulence of microorganisms. Recently, it was reported that allicin may function better in combination with other antimicrobials compared to when used alone. When used in combination with antibiotics or antifungals, allicin enhanced the antimicrobial activities of these substances and improved the antimicrobial efficacy. Hence, it is likely that combination therapy of allicin with additional antimicrobial drug(s) could serve as a viable alternative for combating rising antimicrobial resistance. This review focuses on the antimicrobial activities exhibited by allicin alone as well as in combination with other substances. The mechanisms of action of allicin elucidated by some of the studies are also highlighted in the present review in order to provide a comprehensive overview of this versatile bioactive compound and the mechanistic evidence supporting its potential use in antimicrobial therapy.


Subject(s)
Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Garlic/chemistry , Sulfinic Acids/pharmacology , Sulfinic Acids/therapeutic use , Animals , Disulfides , Drug Synergism , Drug Therapy, Combination , Humans , Plant Extracts/pharmacology , Plant Extracts/therapeutic use
10.
PLoS One ; 11(4): e0153356, 2016.
Article in English | MEDLINE | ID: mdl-27054608

ABSTRACT

Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the ß-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the ß-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that ß-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection.


Subject(s)
Adenocarcinoma/metabolism , Cryptococcus neoformans/physiology , Lung Neoplasms/metabolism , Meningitis, Cryptococcal/metabolism , Metabolomics , Adenocarcinoma/microbiology , Adenocarcinoma/pathology , Gas Chromatography-Mass Spectrometry , Humans , In Vitro Techniques , Lung Neoplasms/microbiology , Lung Neoplasms/pathology , Meningitis, Cryptococcal/microbiology , Meningitis, Cryptococcal/pathology , Tumor Cells, Cultured
11.
Phytomedicine ; 22(5): 517-27, 2015 May 15.
Article in English | MEDLINE | ID: mdl-25981917

ABSTRACT

BACKGROUND: We have previously reported the anti-metastatic effects of 2-methoxy-1,4-naphthoquinone (MNQ) against MDA-MB-231 cell line. PURPOSE: To investigate the molecular mechanism underlying the anti-metastatic effects of MNQ towards MDA-MB-231 cell line via the comparative proteomic approach. STUDY DESIGN/METHODS: Differentially expressed proteins in MNQ-treated MDA-MB-231 cells were identified by using two-dimensional gel electrophoresis coupled with tandem mass spectrometry. Proteins and signalling pathways associated with the identified MNQ-altered proteins were studied by using Western blotting. RESULTS: Significant modulation of MDA-MB-231 cell proteome was observed upon treatment with MNQ in which the expressions of 19 proteins were found to be downregulated whereas another eight were upregulated (>1.5 fold, p < 0.05). The altered proteins were mainly related to cytoskeletal functions and regulations, mRNA processing, protein modifications and oxidative stress response. Notably, two of the downregulated proteins, protein S100-A4 (S100A4) and laminin-binding protein (RPSA) are known to play key roles in driving metastasis and were verified using Western blotting. Further investigation using Western blotting also revealed that MNQ decreased the activations of pro-metastatic ERK1/2 and NF-κB signalling pathways. Moreover, MNQ was shown to stimulate the expression of the metastatic suppressor, E-cadherin. CONCLUSION: This study reports a proposed mechanism by which MNQ exerts its anti-metastatic effects against MDA-MB-231 cell line. The findings from this study offer new insights on the potential of MNQ to be developed as a novel anti-metastatic agent.


Subject(s)
Antineoplastic Agents/pharmacology , Naphthoquinones/pharmacology , Proteome/metabolism , Cell Line, Tumor/drug effects , Humans , Proteomics
12.
Life Sci ; 135: 158-64, 2015 Aug 15.
Article in English | MEDLINE | ID: mdl-25896662

ABSTRACT

AIM: The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells. MAIN METHODS: The growth inhibition potential of MNQ was analyzed using sulforhodamine B assay, flow cytometry cell cycle analysis and Annexin V apoptosis assay. Oxidative stress was determined using 2',7'-dichlorofluorescein diacetate to measure intracellular reactive oxygen species level and comet assay to measure DNA damage. Western blotting was performed to study the activation of mitogen-activated protein kinase signaling pathways. KEY FINDINGS: MNQ induced apoptosis of A549 cells independent of cell cycle arrest, and is mediated by the JNK and p38 MAPK signaling pathways. Further analysis demonstrated that these signaling pathways were stimulated by oxidative DNA damage caused by increased ROS generation in MNQ-treated A549 cells. SIGNIFICANCE: This study is the first to provide an insight into the molecular mechanism of MNQ-induced cytotoxicity of a lung cancer cell, which demonstrates the potential of MNQ as a potential chemotherapeutic drug for lung cancer treatment.


Subject(s)
Adenocarcinoma/enzymology , Apoptosis/drug effects , Cytotoxins/pharmacology , Lung Neoplasms/enzymology , MAP Kinase Kinase 4/metabolism , MAP Kinase Signaling System/drug effects , Naphthoquinones/pharmacology , Neoplasm Proteins/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , DNA Damage , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Oxidation-Reduction/drug effects , Oxidative Stress/drug effects
13.
Toxicol In Vitro ; 28(3): 335-9, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24291160

ABSTRACT

Metastasis contributes to the escalating mortality rate among cancer patients worldwide. The search for novel and more effective anti-metastatic agent is crucial owing to the lack of anticancer drugs that can successfully combat metastasis. Hence, this study aims to examine the effects of 2-Methoxy-1,4-Naphthoquinone (MNQ) towards the metastasis of MDA-MB-231 cells. In invasion assays, the number of cells permeating across a Matrigel barrier was found to be decreased in a dose-dependent manner upon treatment with MNQ (0-7.5 µM). In wound-healing migration assays, MNQ exhibited dose-dependent inhibition of cell migration in which significant reduction in the zone of closure was observed as compared to untreated controls. Furthermore, the proteolytic activity of a pivotal metastatic mediator, matrix metalloproteinase-9 (MMP-9) was also downregulated by MNQ as determined by gelatin zymography. This study reports for the first time, the ability of MNQ to inhibit the invasion and migration characteristics of a highly metastatic MDA-MB-231 cancer cell line.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Matrix Metalloproteinase 9/metabolism , Naphthoquinones/pharmacology , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Movement/drug effects , Collagen/metabolism , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Drug Combinations , Female , Humans , Laminin/metabolism , Naphthoquinones/administration & dosage , Neoplasm Invasiveness , Neoplasm Metastasis , Proteoglycans/metabolism
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