Displaying publications 41 - 60 of 151 in total

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  1. Fulltext Targeting Membrane Lipid a Potential Cancer Cure?
    Tan LT, Chan KG, Pusparajah P, Lee WL, Chuah LH, Khan TM, et al.
    Front Pharmacol, 2017;8:12.
    PMID: 28167913 DOI: 10.3389/fphar.2017.00012
    Cancer mortality and morbidity is projected to increase significantly over the next few decades. Current chemotherapeutic strategies have significant limitations, and there is great interest in seeking novel therapies which are capable of specifically targeting cancer cells. Given that fundamental differences exist between the cellular membranes of healthy cells and tumor cells, novel therapies based on targeting membrane lipids in cancer cells is a promising approach that deserves attention in the field of anticancer drug development. Phosphatidylethanolamine (PE), a lipid membrane component which exists only in the inner leaflet of cell membrane under normal circumstances, has increased surface representation on the outer membrane of tumor cells with disrupted membrane asymmetry. PE thus represents a potential chemotherapeutic target as the higher exposure of PE on the membrane surface of cancer cells. This feature as well as a high degree of expression of PE on endothelial cells in tumor vasculature, makes PE an attractive molecular target for future cancer interventions. There have already been several small molecules and membrane-active peptides identified which bind specifically to the PE molecules on the cancer cell membrane, subsequently inducing membrane disruption leading to cell lysis. This approach opens up a new front in the battle against cancer, and is of particular interest as it may be a strategy that may be prove effective against tumors that respond poorly to current chemotherapeutic agents. We aim to highlight the evidence suggesting that PE is a strong candidate to be explored as a potential molecular target for membrane targeted novel anticancer therapy.
  2. Fulltext Anticancer Activities of Surfactin and Potential Application of Nanotechnology Assisted Surfactin Delivery
    Wu YS, Ngai SC, Goh BH, Chan KG, Lee LH, Chuah LH
    Front Pharmacol, 2017;8:761.
    PMID: 29123482 DOI: 10.3389/fphar.2017.00761
    Surfactin, a cyclic lipopeptide biosurfactant produced by various strains of Bacillus genus, has been shown to induce cytotoxicity against many cancer types, such as Ehrlich ascites, breast and colon cancers, leukemia and hepatoma. Surfactin treatment can inhibit cancer progression by growth inhibition, cell cycle arrest, apoptosis, and metastasis arrest. Owing to the potent effect of surfactin on cancer cells, numerous studies have recently investigated the mechanisms that underlie its anticancer activity. The amphiphilic nature of surfactin allows its easy incorporation nano-formulations, such as polymeric nanoparticles, micelles, microemulsions, liposomes, to name a few. The use of nano-formulations offers the advantage of optimizing surfactin delivery for an improved anticancer therapy. This review focuses on the current knowledge of surfactin properties and biosynthesis; anticancer activity against different cancer models and the underlying mechanisms involved; as well as the potential application of nano-formulations for optimal surfactin delivery.
  3. Fulltext Focused Review: Cytotoxic and Antioxidant Potentials of Mangrove-Derived Streptomyces
    Ser HL, Tan LT, Law JW, Chan KG, Duangjai A, Saokaew S, et al.
    Front Microbiol, 2017;8:2065.
    PMID: 29163380 DOI: 10.3389/fmicb.2017.02065
    Human life expectancy is rapidly increasing with an associated increasing burden of chronic diseases, such as neurodegenerative diseases and cancer. However, there is limited progress in finding effective treatment for these conditions. For this reason, members of the genus Streptomyces have been explored extensively over the past decades as these filamentous bacteria are highly efficient in producing bioactive compounds with human health benefits. Being ubiquitous in nature, streptomycetes can be found in both terrestrial and marine environments. Previously, two Streptomyces strains (MUSC 137T and MUM 256) isolated from mangrove sediments in Peninsular Malaysia demonstrated potent antioxidant and cytotoxic activities against several human cancer cell lines on bioactivity screening. These results illustrate the importance of streptomycetes from underexplored regions aside from the terrestrial ecosystem. Here we provide the insights and significance of Streptomyces species in the search of anticancer and/or chemopreventive agents and highlight the impact of next generation sequencing on drug discovery from the Streptomyces arsenal.
  4. Fulltext Genome sequence of Streptomyces gilvigriseus MUSC 26T isolated from mangrove forest
    Ser HL, Tan WS, Mutalib NA, Yin WF, Chan KG, Goh BH, et al.
    Braz J Microbiol, 2018 02 02;49(2):207-209.
    PMID: 29428207 DOI: 10.1016/j.bjm.2017.04.012
    Streptomycetes remain as one of the important sources for bioactive products. Isolated from the mangrove forest, Streptomyces gilvigriseus MUSC 26T was previously characterised as a novel streptomycete. The high quality draft genome of MUSC 26T contained 5,213,277bp with G+C content of 73.0%. Through genome mining, several gene clusters associated with secondary metabolites production were revealed in the genome of MUSC 26T. These findings call for further investigations into the potential exploitation of the strain for production of pharmaceutically important compounds.
  5. Parents' attitude, awareness and behaviour towards influenza vaccination in Pakistan
    Bukhsh A, Rehman H, Mallhi TH, Ata H, Rehman IU, Lee LH, et al.
    Hum Vaccin Immunother, 2018 04 03;14(4):952-957.
    PMID: 29333939 DOI: 10.1080/21645515.2017.1415686
    National immunization program of Pakistan does not include Influenza vaccines. The low rate of immunization might be attributed to the poor knowledge of influenza vaccination in Pakistan. Current study was aimed to assess the knowledge and attitude of influenza vaccination among parents. A questionnaire-based cross sectional study was conducted among randomly selected parents with at least one child aged >6 months. The responses were recorded against 27 items questionnaire assessing knowledge, perception, attitude and behaviours of parents. Data were analysed by using appropriate statistical methods. A total 532 responses were recorded with male gender preponderance (65%). Most of the parents (61.1%) reported that their children had received or planned to receive all recommended vaccines in Expanded Program on Immunization (EPI) of Pakistan. Only one third of the parents (24.4%) were aware of the availability of influenza vaccines in Pakistan, and very few (6.6%) reported vaccinating their child against influenza. Exploring the parents' attitudes regarding children vaccination, the top motivator was 'immunization is important to keep my children healthy' (relative index = 0.93, p < 0.000). However, substantial number of parents believed that influenza is not a serious disease (18.5%) and vaccines are accompanied by several side effects (24.6%). A positive attitude was reflected among parents who were aware of influenza vaccines in Pakistan. About 35% participants believed that influenza vaccines are not required for healthy children. Current study demonstrated very low vaccination rate against influenza. Awareness and health literacy regarding influenza vaccine is poor among parents. These findings necessitate the need to appropriately structured awareness programs regarding influenza vaccination among parents.
  6. A Systematic Review of the Burden of Multidrug-Resistant Healthcare-Associated Infections Among Intensive Care Unit Patients in Southeast Asia: The Rise of Multidrug-Resistant Acinetobacter baumannii
    Teerawattanapong N, Panich P, Kulpokin D, Na Ranong S, Kongpakwattana K, Saksinanon A, et al.
    Infect Control Hosp Epidemiol, 2018 05;39(5):525-533.
    PMID: 29580299 DOI: 10.1017/ice.2018.58
    OBJECTIVETo summarize the clinical burden (cumulative incidence, prevalence, case fatality rate and length of stay) and economic burden (healthcare cost) of healthcare-associated infections (HAIs) due to multidrug-resistant organisms (MDROs) among patients in intensive care units (ICUs) in Southeast Asia.DESIGNSystematic review.METHODSWe conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, EconLit, and the Cochrane Library databases from their inception through September 30, 2016. Clinical and economic burdens and study quality were assessed for each included study.RESULTSIn total, 41 studies met our inclusion criteria; together, 22,876 ICU patients from 7 Southeast Asian countries were included. The cumulative incidence of HAI caused by A. baumannii (AB) in Southeast Asia is substantially higher than has been reported in other regions, especially carbapenem-resistant AB (CRAB; 64.91%) and multidrug-resistant AB (MDR-AB) (58.51%). Evidence of a dose-response relationship between different degrees of drug resistance and excess mortality due to AB infections was observed. Adjusted odds ratios were 1.23 (95% confidence interval [CI], 0.51-3.00) for MDR-AB, 1.72 (95% CI, 0.77-3.80) for extensively drug-resistant AB (XDR-AB), and 1.82 (95% CI, 0.55-6.00) for pandrug-resistant AB (PDR-AB). There is, however, a paucity of published data on additional length of stay and costs attributable to MDROs.CONCLUSIONSThis review highlights the challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram-negative bacteria are abundant and have a strong impact on society. With our findings, we hope to draw the attention of clinicians and policy makers to the problem of antibiotic resistance and to issue a call for action in the management of MDROs.Infect Control Hosp Epidemiol 2018;39:525-533.
  7. Brief Challenges on Medicinal Plants: An Eye-Opening Look at Ageing-Related Disorders
    Bjørklund G, Dadar M, Martins N, Chirumbolo S, Goh BH, Smetanina K, et al.
    Basic Clin Pharmacol Toxicol, 2018 Jun;122(6):539-558.
    PMID: 29369521 DOI: 10.1111/bcpt.12972
    Several studies have reported that nature-derived antioxidants may prevent free radicals over-production and therefore control the onset and prevent the exacerbation of different kinds of diseases caused by oxidative stress and redox-derived stressors, including ageing, fundamentally by suppressing the oxidative by-products-mediated degradation. Naturally derived antioxidants exert their anti-ageing action via a panoply of signalling systems, many of which engaging reactive oxygen and nitrogen species scavenging, with the Nrf2/Keap1-ARE system and improving the many survival genes and functions (such as the pathway mTOR/Foxo/SIRT1) able to slow cellular senescence. Most of the research in this field has evaluated the regulative effects and even pathways of herbal extracts with antioxidant property in the ageing process, and various age-related disorders such as cardiovascular disease, ischaemia-reperfusion injury, coronary and myocardial circulatory perfusion, peripheral vascular resistance, and even neurodegenerative disorders are prevented plant phytochemicals often via their antioxidant potential. A much more complex ability to interact with survival functions makes these compounds successfully active in preventing ageing-related disorders. This report aimed to discuss in more detail some selected medicinal plants including Allium sativum, Aloe vera, Crataegus spp., Cynara scolymus, Eleutherococcus senticosus, Ginkgo biloba, Hippophae rhamnoides, Panax ginseng, Rosmarinus officinalis, Schizandra chinensis, Vitis vinifera and seaweeds in the prevention of ageing-related pathologies. A systematic overview of the relevant information in the antioxidant function of the many herbal products reviewed here for the control of the ageing process is proposed, to provide a new horizon on the design of anti-ageing herbal medicines.
  8. Fulltext Incidence of methicillin resistant Staphylococcus aureus (MRSA) in burn intensive care unit: a systematic review
    Khan TM, Kok YL, Bukhsh A, Lee LH, Chan KG, Goh BH
    Germs, 2018 Sep;8(3):113-125.
    PMID: 30250830 DOI: 10.18683/germs.2018.1138
    Background: Burn victims admitted in burn intensive care units (ICU) are at a high risk of nosocomial infections generated by methicillin resistant Staphylococcus aureus (MRSA). This systematic review aims to estimate the incidence of MRSA among burn patients admitted to the ICU setting, with an emphasis on the incidence rate and antibiotic resistance profile of the MRSA strains.

    Methods: A systematic literature search was performed in five electronic databases limited to publication dates from 1st January 2000 until 31st August 2017. After screening n=481 articles, n=21 were found to meet the inclusion criteria of this systematic review.

    Results: Results from the meta-analysis revealed that the risk for MRSA isolates in the burn ICU was 55.0% higher (OR 0.55, 95%CI 0.32-0.94). Therefore, timely testing, appropriate hygiene practice and suggested wound care must be practiced while handling such patients.

    Conclusion: Further studies are needed to identify the risk factors of MRSA infections among burn patients and to develop new antimicrobial agents for MRSA infections.

  9. Fulltext Risk factors for Streptococcus suis infection: A systematic review and meta-analysis
    Rayanakorn A, Goh BH, Lee LH, Khan TM, Saokaew S
    Sci Rep, 2018 09 06;8(1):13358.
    PMID: 30190575 DOI: 10.1038/s41598-018-31598-w
    Streptococcus suis (S. suis) is a gram-positive bacterial pathogen in pigs which can cause serious infections in human including meningitis, and septicaemia resulting in serious complications. There were discrepancies between different data and little is known concerning associated risk factors of S. suis. A systematic review and meta-analysis was conducted to investigate on S. suis infection risk factors in human. We searched eight relevant databases using the MeSH terms "Streptococcus suis" OR "Streptococcus suis AND infection" limited in human with no time nor language restriction. Out of 4,999 articles identified, 32 and 3 studies were included for systematic review and meta-analysis respectively with a total of 1,454 Streptococcus suis cases reported. S. suis patients were generally adult males and the elderly. The mean age ranged between 37 to 63 years. Meningitis was the most common clinical manifestation, and deafness was the most common sequelae found among survivors followed by vestibular dysfunction. Infective endocarditis was also noted as among the most common clinical presentations associated with high mortality rate in a few studies. Meta-analyses categorized by type of control groups (community control, and non-S. suis sepsis) were done among 850 participants in 3 studies. The combined odd ratios for studies using community control groups and non-S. Suis sepsis as controls respectively were 4.63 (95% CI 2.94-7.29) and 78.00 (95% CI 10.38-585.87) for raw pork consumption, 4.01 (95% CI 2.61-6.15) and 3.03 (95% CI 1.61-5.68) for exposure to pigs or pork, 11.47, (95% CI 5.68-23.14) and 3.07 (95% CI 1.81-5.18) for pig-related occupation and 3.56 (95% CI 2.18-5.80) and 5.84 (95% CI 2.76-12.36) for male sex. The results were found to be significantly associated with S. suis infection and there was non-significant heterogeneity. History of skin injury and underlying diseases were noted only a small percentage in most studies. Setting up an effective screening protocol and public health interventions would be effective to enhance understanding about the disease.
  10. Fulltext Relaxant effects of Azadirachta indica A. Juss var. siamensis Valeton flower extract on isolated rat ileum contractions and the mechanisms of action
    Duangjai A, Goh BH, Lee LH, Saokaew S
    J Tradit Complement Med, 2018 Oct;8(4):515-520.
    PMID: 30302332 DOI: 10.1016/j.jtcme.2018.01.003
    Azadirachta indica A. Juss var. siamensis Valeton or commonly known as Siamese neem is one of the most well-known plant in traditional Ayurvedic medicine. The aim of the present study was to investigate the relaxant effects of A. indica on isolated rat ileum contractions and its potential underlying mechanisms involved. The isometric contractions of ileum segments were investigated in organ baths for spontaneous activity and response to aqueous extract of Siamese neem flower (SNF). The spasmolytic action of the extract was also assessed on contraction induced by acetylcholine and high potassium. Our findings indicate that cumulative concentrations of SNF aqueous extract induced relaxant effect on spontaneous rat ileum contractions. The extract has also suppressed the cumulative concentration response curve for acetylcholine and pottasium ions-induced contraction. The presence and absence of propranol (antagonist of β-adrenergic receptor) and l-Name (antagonist of nitric oxide synthase) in SNF aqeous extract co-treatment demonstrated no significant different in term of contraction activity when compared to SNF extract treatment alone. The treatment of SNF extract caused a significant inhibition in tissue contraction stimulated by accumulation of calcium ions. Our results showed the relaxant effect of SNF aqueous extract on the isolated rat ileum. In short, the SNF aqueous extract exhibited an inhibitory effect on the spontaneous ileum contactions particularly on the contraction stimulated by acetylcholine and high potassium. The observed effect might acted through the modulation of calcium channels. This findings provide a pharmacological basis for the traditional use of SNF for the treatment of gastrointestinal spasms.
  11. Fulltext Association of diabetes-related self-care activities with glycemic control of patients with type 2 diabetes in Pakistan
    Bukhsh A, Khan TM, Nawaz MS, Ahmed HS, Chan KG, Lee LH, et al.
    Patient Prefer Adherence, 2018;12:2377-2385.
    PMID: 30519003 DOI: 10.2147/PPA.S177314
    Objective: Association of various self-care activities on glycemic control of people with diabetes (PWD) in Pakistan is yet to be explored. The current study aimed to evaluate the association of various diabetes-related self-care activities with glycated hemoglobin (HbA1c) levels and to examine the predictive relationship of patients' demographic variables with their self-care activities.

    Patients and methods: A cross-sectional study was conducted on adult PWD (N=218) who were diagnosed with type 2 diabetes mellitus of at least 1 year duration. Self-care activities were examined by using the Urdu version of Diabetes Self-management Questionnaire. Linear regression analysis was conducted to examine the significant predictors for diabetes-related self-care activities and glycemic control.

    Results: Mean age of the patients was 50.77±13.3 years. Poor glycemic control (HbA1c $7%) was observed in majority of the patients (83%). Linear regression analysis revealed that glucose management (β=-0.44; 95% CI -0.438, -0.209; P<0.001) was the strongest predictor for low levels of patients' HbA1c, followed by dietary control (β=-0.19; 95% CI -0.248, -0.018; P=0.024) and physical activity (β=-0.17; 95% CI -0.165, -0.023; P=0.010), respectively. Linear regression analysis showed that use of oral hypoglycemic agents only (β=-0.218; 95% CI -0.956, -0.200; P=0.003) and higher education level (β=0.204; 95% CI 0.138, 0.777; P=0.005) were significant predictors for higher scores of patients' self-care activities.

    Conclusion: The findings support that PWD having better self-reported self-care activities achieve better glycemic control. Patients' self-care activities should be monitored on a regular basis, especially for those who are at risk of poor glycemic control.
  12. Fulltext Effectiveness of pharmacist-led educational interventions on self-care activities and glycemic control of type 2 diabetes patients: a systematic review and meta-analysis
    Bukhsh A, Tan XY, Chan KG, Lee LH, Goh BH, Khan TM
    Patient Prefer Adherence, 2018;12:2457-2474.
    PMID: 30538430 DOI: 10.2147/PPA.S180256
    Background: Effectiveness of pharmacist-led educational interventions on self-care activities and glycemic control of type 2 diabetes mellitus (T2DM) patients is vague. The purpose of this review is to appraise the effect of pharmacist-led educational interventions on self-care activities and levels of glycated hemoglobin of T2DM patients.

    Methods: Five electronic databases were searched from date of database inception to September 2017. Randomized clinical trials examining the effectiveness of pharmacist-led educational interventions, directed at T2DM patients only, were included for systematic review and meta-analysis. The protocol is available with PROSPERO (CRD42017078854).

    Results: Eleven studies, involving n=1,544 T2DM patients, were included in this systematic review. Meta-analysis demonstrated that pharmacist-led interventions had a significant effect on lowering of the levels of glycated hemoglobin (-0.66; 95% CI [-0.83, -0.50]; I2=58.3%; P=0.008), in comparison to usual care. Self-care activities were assessed by using Summary of Diabetes Self-care Activities tool in eight studies. Overall meta-analysis of self-care activities for included studies demonstrated a significant effect of pharmacist-led interventions on improvement of self-monitoring of blood glucose (1.62; 95% CI [0.92, 2.32]; I2=70.5%; P=0.005), foot care (1.20; 95% CI [0.49, 1.90]; I2=95.0%; P<0.001), and overall diet (1.16; 95% CI [0.38, 1.93]; I2=64.2%; P=0.094).

    Conclusion: The findings of this review demonstrate a significantly positive effect of pharmacist-led educational interventions on HbA1c levels and self-care practices among T2DM patients.
  13. Fulltext Editorial: The Search for Biological Active Agent(s) From Actinobacteria
    Lee LH, Chan KG, Stach J, Wellington EMH, Goh BH
    Front Microbiol, 2018;9:824.
    PMID: 29780365 DOI: 10.3389/fmicb.2018.00824
  14. Efficacy of pharmacist based diabetes educational interventions on clinical outcomes of adults with type 2 diabetes mellitus: a network meta-analysis
    Bukhsh A, Khan TM, Lee SWH, Lee LH, Chan KG, Goh BH
    Front Pharmacol, 2018;9:339.
    PMID: 29692730 DOI: 10.3389/fphar.2018.00339
    Background: Comparative efficacy of different pharmacist based interventions on glycemic control of type 2 diabetes patients is unclear. This review aimed to evaluate and compare the efficacy of different pharmacist based interventions on clinical outcomes of type 2 diabetes patients. Methods: A systematic search was conducted across five databases from date of database inception to September 2017. All randomized clinical trials evaluating the efficacy of pharmacist based interventions on type 2 diabetes patients were included for network meta-analysis (NMA). The protocol is available with PROSPERO (CRD42017078854). Results: A total of 43 studies, involving 6259 type 2 diabetes patients, were included. NMA demonstrated that all interventions significantly lowered glycosylated hemoglobin (HbA1c) levels compared to usual care, but there was no statistical evidence from this study that one intervention was significantly better than the other for reducing HbA1c levels. Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy for reducing HbA1c levels [-0.86, 95% CI -0.983, -0.727; p < 0.001]. Pharmacist based diabetes education plus pharmaceutical care was observed to be statistically significant in lowering levels of systolic blood pressure [-4.94; 95%CI -8.65, -1.23] and triglycerides levels [-0.26, 95%CI -0.51, -0.01], as compared to the interventions which involved diabetes education by pharmacist, and for body mass index (BMI) [-0.57; 95%CI -1.25, -0.12] in comparison to diabetes education by health care team involving pharmacist as member. Conclusion: The findings of this review demonstrate that all interventions had a significantly positive effect on HbA1c, but there was no statistical evidence from this study that one intervention was significantly better than the other for achieving glycemic control.Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy on HbA1c and rest of the clinical outcomes.
  15. Fulltext Antioxidative Potential of a Streptomyces sp. MUM292 Isolated from Mangrove Soil
    Tan LT, Chan KG, Chan CK, Khan TM, Lee LH, Goh BH
    Biomed Res Int, 2018;2018:4823126.
    PMID: 29805975 DOI: 10.1155/2018/4823126
    Mangrove derived microorganisms constitute a rich bioresource for bioprospecting of bioactive natural products. This study explored the antioxidant potentials of Streptomyces bacteria derived from mangrove soil. Based on 16S rRNA phylogenetic analysis, strain MUM292 was identified as the genus Streptomyces. Strain MUM292 showed the highest 16S rRNA gene sequence similarity of 99.54% with S. griseoruber NBRC12873T. Furthermore, strain MUM292 was also characterized and showed phenotypic characteristics consistent with Streptomyces bacteria. Fermentation and extraction were performed to obtain the MUM292 extract containing the secondary metabolites of strain MUM292. The extract displayed promising antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging and also metal-chelating activities. The process of lipid peroxidation in lipid-rich product was also retarded by MUM292 extract and resulted in reduced MDA production. The potential bioactive constituents of MUM292 extract were investigated using GC-MS and preliminary detection showed the presence of pyrazine, pyrrole, cyclic dipeptides, and phenolic compound in MUM292 extract. This work demonstrates that Streptomyces MUM292 can be a potential antioxidant resource for food and pharmaceutical industries.
  16. Fulltext Efficacy and Safety of Cyclosporine in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis
    Rahman FA, Abdullah SS, Manan WZWA, Tan LT, Neoh CF, Ming LC, et al.
    Front Pharmacol, 2018;9:238.
    PMID: 29970999 DOI: 10.3389/fphar.2018.00238
    There are various studies that have addressed the use of Cyclosporine among patients with acute myocardial infarction (AMI). However, to date there is hardly any concise and systematically structured evidence that debate on the efficacy and safety of Cyclosporine in AMI patients. The aim of this review is to systematically summarize the overall evidence from published trials, and to conduct a meta-analysis in order to determine the efficacy and safety of Cyclosporine vs. placebo or control among patients with AMI. All randomized control trial (RCT) published in English language from January 2000 to August 2017 were included for the systematic review and meta-analysis. A total of six RCTs met the inclusion and were hence included in the systematic review and meta-analysis. Based on the performed meta-analysis, no significant difference was found between Cyclosporine and placebo in terms of left ventricular ejection fraction (LVEF) improvement (mean difference 1.88; 95% CI -0.99 to 4.74; P = 0.2), mortality rate (OR 1.01; 95% Cl 0.60 to 1.67, P = 0.98) and recurrent MI occurrence (OR 0.65; 95% Cl 0.29 to 1.45, P = 0.29), with no evidence of heterogeneity, when given to patients with AMI. Cyclosporine also did not significantly lessen the rate of rehospitalisation in AMI patients when compared to placebo (OR 0.91; 95% Cl 0.58 to 1.42, P = 0.68), with moderate heterogeneity (I2 = 46%). There was also no significant improvement in heart failure events between Cyclosporine and placebo in AMI patients (OR 0.63; 95% Cl 0.31 to 1.29, P = 0.21; I2 = 80%). No serious adverse events were reported in Cyclosporine group across all studies suggesting that Cyclosporine is well tolerated when given to patients with AMI. The use of Cyclosporine in this group of patients, however, did not result in better clinical outcomes vs. placebo at improving LVEF, mortality rate, recurrent MI, rehospitalisation and heart failure event.
  17. Fulltext Streptomyces as a Prominent Resource of Future Anti-MRSA Drugs
    Kemung HM, Tan LT, Khan TM, Chan KG, Pusparajah P, Goh BH, et al.
    Front Microbiol, 2018;9:2221.
    PMID: 30319563 DOI: 10.3389/fmicb.2018.02221
    Methicillin-resistant Staphylococcus aureus (MRSA) pose a significant health threat as they tend to cause severe infections in vulnerable populations and are difficult to treat due to a limited range of effective antibiotics and also their ability to form biofilm. These organisms were once limited to hospital acquired infections but are now widely present in the community and even in animals. Furthermore, these organisms are constantly evolving to develop resistance to more antibiotics. This results in a need for new clinically useful antibiotics and one potential source are the Streptomyces which have already been the source of several anti-MRSA drugs including vancomycin. There remain large numbers of Streptomyces potentially undiscovered in underexplored regions such as mangrove, deserts, marine, and freshwater environments as well as endophytes. Organisms from these regions also face significant challenges to survival which often result in the production of novel bioactive compounds, several of which have already shown promise in drug development. We review the various mechanisms of antibiotic resistance in MRSA and all the known compounds isolated from Streptomyces with anti-MRSA activity with a focus on those from underexplored regions. The isolation of the full array of compounds Streptomyces are potentially capable of producing in the laboratory has proven a challenge, we also review techniques that have been used to overcome this obstacle including genetic cluster analysis. Additionally, we review the in vivo work done thus far with promising compounds of Streptomyces origin as well as the animal models that could be used for this work.
  18. Fulltext Resveratrol-Potential Antibacterial Agent against Foodborne Pathogens
    Ma DSL, Tan LT, Chan KG, Yap WH, Pusparajah P, Chuah LH, et al.
    Front Pharmacol, 2018;9:102.
    PMID: 29515440 DOI: 10.3389/fphar.2018.00102
    Bacterial foodborne pathogens are a significant health burden and the recent emergence of pathogenic resistant strains due to the excessive use of antibiotics makes it more difficult to effectively treat infections as a result of contaminated food. Awareness of this impending health crisis has spurred the search for alternative antimicrobials with natural plant antimicrobials being among the more promising candidates as these substances have good acceptability and likely low toxicity levels as they have long been used in traditional medicines. Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring stilbenoid which has been gaining considerable attention in medical field due to its diverse biological activities - it has been reported to exhibit antioxidant, cardioprotective, anti-diabetic, anticancer, and antiaging properties. Given that resveratrol is phytoalexin, with increased synthesis in response to infection by phytopathogens, there has been interest in exploring its antimicrobial activity. This review aims to provide an overview of the published data on the antibacterial activity of resveratrol against foodborne pathogens, its mechanisms of action as well as its possible applications in food packing and processing; in addition we also summarize the current data on its potential synergism with known antibacterials and future research and applications.
  19. The Role of Natural Products in Targeting Cardiovascular Diseases via Nrf2 Pathway: Novel Molecular Mechanisms and Therapeutic Approaches
    Ooi BK, Chan KG, Goh BH, Yap WH
    Front Pharmacol, 2018;9:1308.
    PMID: 30498447 DOI: 10.3389/fphar.2018.01308
    Cardiovascular diseases (CVDs) are closely linked to cellular oxidative stress and inflammation. This may be resulted from the imbalance generation of reactive oxygen species and its role in promoting inflammation, thereby contributing to endothelial dysfunction and cardiovascular complications. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that plays a significant role in regulating expression of antioxidant and cytoprotective enzymes in response to oxidative stress. Natural products have emerged as a potential source of bioactive compounds which have shown to protect against atherogenesis development by activating Nrf2 signaling. This review aims to provide a comprehensive summary of the published data on the function, regulation and activation of Nrf2 as well as the molecular mechanisms of natural products in regulating Nrf2 signaling. The beneficial effects of using natural bioactive compounds as a promising therapeutic approach for the prevention and treatment of CVDs are reviewed.
  20. Fulltext Mangrove derived Streptomyces sp. MUM265 as a potential source of antioxidant and anticolon-cancer agents
    Tan LT, Chan KG, Pusparajah P, Yin WF, Khan TM, Lee LH, et al.
    BMC Microbiol, 2019 02 13;19(1):38.
    PMID: 30760201 DOI: 10.1186/s12866-019-1409-7
    BACKGROUND: Colon cancer is the third most commonly diagnosed cancer worldwide, with a commensurately high mortality rate. The search for novel antioxidants and specific anticancer agents which may inhibit, delay or reverse the development of colon cancer is thus an area of great interest; Streptomyces bacteria have been demonstrated to be a source of such agents.

    RESULTS: The extract from Streptomyces sp. MUM265- a strain which was isolated and identified from Kuala Selangor mangrove forest, Selangor, Malaysia- was analyzed and found to exhibit antioxidant properties as demonstrated via metal-chelating ability as well as superoxide anion, DPPH and ABTS radical scavenging activities. This study also showed that MUM265 extract demonstrated cytotoxicity against colon cancer cells as evidenced by the reduced cell viability of Caco-2 cell line. Treatment with MUM265 extract induced depolarization of mitochondrial membrane potential and accumulation of subG1 cells in cell cycle analysis, suggesting that MUM265 exerted apoptosis-inducing effects on Caco-2 cells.

    CONCLUSION: These findings indicate that mangrove derived Streptomyces sp. MUM265 represents a valuable bioresource of bioactive compounds for the future development of chemopreventive agents, with particular promise suggested for treatment of colon cancer.

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