Displaying publications 1 - 20 of 24 in total

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  1. Benchoula K, Parhar IS, Wong EH
    Arch Biochem Biophys, 2021 Feb 15;698:108743.
    PMID: 33382998 DOI: 10.1016/j.abb.2020.108743
    Hyperglycaemia causes pancreatic β-cells to release insulin that then attaches to a specific expression of receptor isoform and reverses high glucose concentrations. It is well known that insulin is capable of initiating insulin-receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling pathways in target cells; such as liver, adipose tissues, and muscles. However, recent discoveries indicate that many other pathways, such as the Hedgehog (Hh) and growth factor-stimulating Wingless-related integration (Wnt) signaling pathways; are activated in hyperglycaemia as well. Although these two pathways are traditionally thought to have a decisive role in cellular growth and differentiation only, recent reports show that they are involved in regulating cellular homeostasis and energy balance. While insulin-activated IRS/PI3K/PKB pathway cascades are primarily known to reduce glucose production, it was recently discovered to increase the Hh signaling pathway's stability, thereby activating the PI3K/PKB/mammalian target of rapamycin complex 2 (mTORC2) signaling pathway. The Hh signaling pathway not only plays a role in lipid metabolism, insulin sensitivity, inflammatory response, diabetes-related complications, but crosstalks with the Wnt signaling pathway resulting in improved insulin sensitivity and decrease inflammatory response in diabetes.
  2. Wong EH, Subramaniam G, Navaratnam P, Sekaran SD
    Indian J Med Microbiol, 2007 Oct;25(4):391-4.
    PMID: 18087092
    Fluorescent in situ hybridization (FISH) was carried out using two different oligonucleotide probes specific for Pseudomonas spp. and Acinetobacter spp. These probes were tested against different organisms and were found to be highly specific. Sensitivity testing showed that the probes were able to detect as low as 10 3 CFU/mL. In addition, FISH was carried out directly on positive blood culture samples and the detection of microorganisms took less than 2 h. We believe that FISH is a rapid method that can be used as a routine laboratory diagnostic technique for the detection of Acinetobacter spp. and Pseudomonas spp. in clinical samples.
  3. Mea HJ, Yong PVC, Wong EH
    Microbiol Res, 2021 Jun;247:126722.
    PMID: 33618061 DOI: 10.1016/j.micres.2021.126722
    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.
  4. Saleemi MA, Fouladi MH, Yong PVC, Wong EH
    Materials (Basel), 2020 Apr 03;13(7):6-6.
    PMID: 32260216 MyJurnal DOI: 10.3390/ma13071676
    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.
  5. Ahmad B, Serpell CJ, Fong IL, Wong EH
    Front Mol Biosci, 2020;7:76.
    PMID: 32457917 DOI: 10.3389/fmolb.2020.00076
    Obesity is now a widespread disorder, and its prevalence has become a critical concern worldwide, due to its association with common co-morbidities like cancer, cardiovascular diseases and diabetes. Adipose tissue is an endocrine organ and therefore plays a critical role in the survival of an individual, but its dysfunction or excess is directly linked to obesity. The journey from multipotent mesenchymal stem cells to the formation of mature adipocytes is a well-orchestrated program which requires the expression of several genes, their transcriptional factors, and signaling intermediates from numerous pathways. Understanding all the intricacies of adipogenesis is vital if we are to counter the current epidemic of obesity because the limited understanding of these intricacies is the main barrier to the development of potent therapeutic strategies against obesity. In particular, AMP-Activated Protein Kinase (AMPK) plays a crucial role in regulating adipogenesis - it is arguably the central cellular energy regulation protein of the body. Since AMPK promotes the development of brown adipose tissue over that of white adipose tissue, special attention has been given to its role in adipose tissue development in recent years. In this review, we describe the molecular mechanisms involved in adipogenesis, the role of signaling pathways and the substantial role of activated AMPK in the inhibition of adiposity, concluding with observations which will support the development of novel chemotherapies against obesity epidemics.
  6. Idris N, Leong KH, Wong EH, Abdul Rahim N
    J Antibiot (Tokyo), 2023 Dec;76(12):711-719.
    PMID: 37821539 DOI: 10.1038/s41429-023-00659-2
    Polymyxins are last-line antibiotics against multidrug-resistant Klebsiella pneumoniae but using polymyxins alone may not be effective due to emerging resistance. A previous study found that combining polymyxin B with chloramphenicol effectively kills MDR K. pneumoniae, although the bone marrow toxicity of chloramphenicol is concerning. The aim of this study is to assess the antibacterial efficacy and cytotoxicity of polymyxin B when combined with chloramphenicol and its derivatives, namely thiamphenicol and florfenicol (reported to have lesser toxicity compared to chloramphenicol). The antibacterial activity was evaluated with antimicrobial susceptibility testing using broth microdilution and time-kill assays, while the cytotoxic effect on normal bone marrow cell line, HS-5 was evaluated using the MTT assay. All bacterial isolates tested were found to be susceptible to polymyxin B, but resistant to chloramphenicol, thiamphenicol, and florfenicol when used alone. The use of polymyxin B alone showed bacterial regrowth for all isolates at 24 h. The combination of polymyxin B and florfenicol demonstrated additive and synergistic effects against all isolates (≥ 2 log10 cfu ml-1 reduction) at 4 and 24 h, respectively, while the combination of polymyxin B and thiamphenicol resulted in synergistic killing at 24 h against ATCC BAA-2146. Furthermore, the combination of polymyxin B with florfenicol had the lowest cytotoxic effect on the HS-5 cells compared to polymyxin B combination with chloramphenicol and thiamphenicol. Overall, the combination of polymyxin B with florfenicol enhanced bacterial killing against MDR K. pneumoniae and exerted minimal cytotoxic effect on HS-5 cell line.
  7. Nurul Atifah MA, Loo HK, Subramaniam G, Wong EH, Selvi P, Ho SE, et al.
    Malays J Pathol, 2005 Dec;27(2):75-81.
    PMID: 17191389
    Antimicrobial resistance to the extended-spectrum cephalosporins is increasingly reported worldwide. In the local setting, nosocomial infections with multi-resistant Gram-negative bacilli are not uncommon and are a growing concern. However, there is limited data on the carriage rates of such organisms in the local setting. In May 2001, a prospective study was carried out to determine the enteric carriage rates of ceftazidime-resistant Gram negative bacilli (CAZ-R GNB) among residents of nursing homes and from in-patients of the geriatric and adult haematology wards of University Malaya Medical Centre. Ceftazidime-resistant Gram-negative bacilli (CAZ-R GNB) were detected in 25 samples (30%), out of which 6 were from nursing home residents, 5 from geriatric in-patients and 14 from the haematology unit. A total of 28 CAZ-R GNB were isolated and Escherichia coli (10) and Klebsiella pneumoniae (7) were the predominant organisms. Resistance to ceftazidime in E. coli and Klebsiella was mediated by extended-spectrum beta-lactamases (ESBLs). Although the majority of the CAZ-R GNB were from patients in the haematology ward, the six nursing home residents with CAZ-R GNB were enteric carriers of ESBL-producing coliforms. Prior exposure to antibiotics was associated with carriage of ESBL organisms and to a lesser extent, the presence of urinary catheters.
  8. Ahmad B, Friar EP, Vohra MS, Garrett MD, Serpell CJ, Fong IL, et al.
    Phytochemistry, 2020 Dec;180:112513.
    PMID: 33010536 DOI: 10.1016/j.phytochem.2020.112513
    The prevalence of obesity is increasing rapidly globally and has recently reached pandemic proportions. It is a multifactorial disorder linked to a number of non-communicable diseases such as type-2 diabetes, cardiovascular disease, and cancer. Over-nutrition and a sedentary lifestyle are considered the most significant causes of obesity; a healthy lifestyle and behavioural interventions are the most powerful ways to achieve successful weight loss, but to maintain this in the long term can prove difficult for many individuals, without medical intervention. Various pharmacological anti-obesogenic drugs have been tested and marketed in the past and have been moderately successful in the management of obesity, but their adverse effects on human health often outweigh the benefits. Natural products from plants, either in the form of crude extracts or purified phytochemicals, have been shown to have anti-obesogenic properties and are generally considered as nontoxic and cost-effective compared to synthetic alternatives. These plant products combat obesity by targeting the various pathways and/or regulatory functions intricately linked to obesity. Their mechanisms of action include inhibition of pancreatic lipase activities, an increase in energy expenditure, appetite regulation, lipolytic effects, and inhibition of white adipose tissue development. In this review, we discuss the distinct anti-obesogenic properties of recently reported plant extracts and specific bioactive compounds, along with their molecular mechanisms of action. This review will provide a common platform for understanding the different causes of obesity and the possible approaches to using plant products in tackling this worldwide health issue.
  9. Vohra MS, Ahmad B, Serpell CJ, Parhar IS, Wong EH
    Differentiation, 2020 08 23;115:62-84.
    PMID: 32891960 DOI: 10.1016/j.diff.2020.08.003
    Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology.
  10. Chung WY, Zhu Y, Mahamad Maifiah MH, Shivashekaregowda NKH, Wong EH, Abdul Rahim N
    J Antibiot (Tokyo), 2021 02;74(2):95-104.
    PMID: 32901119 DOI: 10.1038/s41429-020-00366-2
    Antimicrobial resistance (AMR) threatens the effective prevention and treatment of a wide range of infections. Governments around the world are beginning to devote effort for innovative treatment development to treat these resistant bacteria. Systems biology methods have been applied extensively to provide valuable insights into metabolic processes at system level. Genome-scale metabolic models serve as platforms for constraint-based computational techniques which aid in novel drug discovery. Tools for automated reconstruction of metabolic models have been developed to support system level metabolic analysis. We discuss features of such software platforms for potential users to best fit their purpose of research. In this work, we focus to review the development of genome-scale metabolic models of Gram-negative pathogens and also metabolic network approach for identification of antimicrobial drugs targets.
  11. Ahmad B, Vohra MS, Saleemi MA, Serpell CJ, Fong IL, Wong EH
    Biochimie, 2021 May;184:26-39.
    PMID: 33548390 DOI: 10.1016/j.biochi.2021.01.015
    Brown and beige adipose tissues are the primary sites for adaptive non-shivering thermogenesis. Although they have been known principally for their thermogenic effects, in recent years, it has emerged that, just like white adipose tissue (WAT), brown and beige adipose tissues also play an important role in the regulation of metabolic health through secretion of various brown adipokines (batokines) in response to various physiological cues. These secreted batokines target distant organs and tissues such as the liver, heart, skeletal muscles, brain, WAT, and perform various local and systemic functions in an autocrine, paracrine, or endocrine manner. Brown and beige adipose tissues are therefore now receiving increasing levels of attention with respect to their effects on various other organs and tissues. Identification of novel secreted factors by these tissues may help in the discovery of drug candidates for the treatment of various metabolic disorders such as obesity, type-2 diabetes, skeletal deformities, cardiovascular diseases, dyslipidemia. In this review, we comprehensively describe the emerging secretory role of brown/beige adipose tissues and the metabolic effects of various brown/beige adipose tissues secreted factors on other organs and tissues in endocrine/paracrine manners, and as well as on brown/beige adipose tissue itself in an autocrine manner. This will provide insights into understanding the potential secretory role of brown/beige adipose tissues in improving metabolic health.
  12. Peremalo T, Madhavan P, Hamzah S, Than L, Wong EH, Nasir MDM, et al.
    J Med Microbiol, 2019 Mar;68(3):346-354.
    PMID: 30724730 DOI: 10.1099/jmm.0.000940
    PURPOSE: Non-albicansCandida species have emerged as fungal pathogens that cause invasive infections, with many of these species displaying resistance to commonly used antifungal agents. This study was confined to studying the characteristics of clinical isolates of the C. rugosa complex and C. pararugosa species.

    METHODOLOGY: Seven isolates of the C. rugosa complex and one isolate of C. pararugosa were obtained from two tertiary referral hospitals in Malaysia. Their antifungal susceptibilities, biofilm, proteinase, phospholipase, esterase and haemolysin activities were characterized. Biofilms were quantified using crystal violet (CV) and tetrazolium (XTT) reduction assays at 1.5, 6, 18, 24, 48 and 72 h.Results/Key findings. The E-test antifungal tests showed that both species have elevated MICs compared to C. albicans and C. tropicalis. The highest biomass was observed in one of the C. rugosa isolates (0.237), followed by C. pararugosa (0.206) at 18 h of incubation. However, the highest bioactivity was observed in the C. rugosa ATCC 10571 strain at 24 h (0.075), followed by C. pararugosa at 48 h (0.048) and the same C. rugosa strain at 24 h (0.046), with P<0.05. All isolates exhibited high proteinase activity (+++) whereas six isolates showed very strong esterase activity (++++). All the isolates were alpha haemolytic producers. None of the isolates exhibited phospholipase activity.

    CONCLUSION: Elevated MICs were shown for the C. rugosa complex and C. pararugosa for commonly used antifungal drugs. Further studies to identify virulence genes involved in the pathogenesis and genes that confer reduced drug susceptibility in these species are proposed.

  13. Saleemi MA, Hosseini Fouladi M, Yong PVC, Chinna K, Palanisamy NK, Wong EH
    Chem Res Toxicol, 2021 01 18;34(1):24-46.
    PMID: 33319996 DOI: 10.1021/acs.chemrestox.0c00172
    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.
  14. Choo S, Chin VK, Wong EH, Madhavan P, Tay ST, Yong PVC, et al.
    Folia Microbiol (Praha), 2020 Jun;65(3):451-465.
    PMID: 32207097 DOI: 10.1007/s12223-020-00786-5
    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.
  15. Qadi WSM, Mediani A, Benchoula K, Wong EH, Misnan NM, Sani NA
    Foods, 2023 May 12;12(10).
    PMID: 37238789 DOI: 10.3390/foods12101971
    Fermentation of milk enhances its nutritional and biological activity through the improvement of the bioavailability of nutrients and the production of bioactive compounds. Coconut milk was fermented with Lactiplantibacillus plantarum ngue16. The aim of this study was to evaluate the effect of fermentation and cold storage for 28 days on physicochemical characteristics, shelf life, and antioxidant and antibacterial activities of coconut milk as well as its proximate and chemical compositions. The pH of fermented milk decreased from 4.26 to 3.92 on the 28th day during cold storage. The viable cell count of lactic acid bacteria (LAB) in fermented coconut milk was significantly increased during fermentation and cold storage period (1 to 14 days), reaching 6.4 × 108 CFU/mL, and then decreased significantly after 14 days to 1.6 × 108 CFU/mL at 28 days. Yeast and molds in fermented coconut milk were only detected on the 21st and 28th days of cold storage, which ranged from 1.7 × 102 to 1.2 × 104 CFU/mL, respectively. However, the growth of coliforms and E. coli was observed on the 14th until the 28th day of cold storage. The fermented coconut milk demonstrated strong antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Cronobacter sakazakii, Bacillus cereus, and Salmonella typhimurium compared to fresh coconut milk. Fermented coconut milk had the greatest 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) values, with 67.1% and 61.961 mmol/g at day 14 of cold storage, respectively. Forty metabolites were detected in fermented and pasteurized coconut milk by proton nuclear magnetic resonance (1H NMR) metabolomics. The principal component analysis (PCA) showed clear difference between the fermented and pasteurized coconut milk as well as the studied cold storage days. The metabolites responsible for this variation were ethanol, valine, GABA, arginine, lactic acid, acetoin, alanine, phenylalanine, acetic acid, methionine, acetone, pyruvate, succinic acid, malic acid, tryptophan, uridine, uracil, and cytosin, which were higher in fermented coconut milk. However, sugars and other identified compounds were higher in fresh coconut milk. The findings of this study show that fermentation of coconut milk with L. plantarum ngue16 had high potential benefits to extending its shelf life and improved biological activities as well as other beneficial nutrients.
  16. Saleemi MA, Ahmad B, Benchoula K, Vohra MS, Mea HJ, Chong PP, et al.
    Infect Genet Evol, 2020 11;85:104583.
    PMID: 33035643 DOI: 10.1016/j.meegid.2020.104583
    The emergence of a new coronavirus, in around late December 2019 which had first been reported in Wuhan, China has now developed into a massive threat to global public health. The World Health Organization (WHO) has named the disease caused by the virus as COVID-19 and the virus which is the culprit was renamed from the initial novel respiratory 2019 coronavirus to SARS-CoV-2. The person-to-person transmission of this virus is ongoing despite drastic public health mitigation measures such as social distancing and movement restrictions implemented in most countries. Understanding the source of such an infectious pathogen is crucial to develop a means of avoiding transmission and further to develop therapeutic drugs and vaccines. To identify the etiological source of a novel human pathogen is a dynamic process that needs comprehensive and extensive scientific validations, such as observed in the Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS), and human immunodeficiency virus (HIV) cases. In this context, this review is devoted to understanding the taxonomic characteristics of SARS-CoV-2 and HIV. Herein, we discuss the emergence and molecular mechanisms of both viral infections. Nevertheless, no vaccine or therapeutic drug is yet to be approved for the treatment of SARS-CoV-2, although it is highly likely that new effective medications that target the virus specifically will take years to establish. Therefore, this review reflects the latest repurpose of existing antiviral therapeutic drug choices available to combat SARS-CoV-2.
  17. Abdul Manap AS, Vijayabalan S, Madhavan P, Chia YY, Arya A, Wong EH, et al.
    Drug Target Insights, 2019;13:1177392819866412.
    PMID: 31391778 DOI: 10.1177/1177392819866412
    Alzheimer disease is a neurodegenerative disease that is signified by cognitive decline, memory loss, and erratic behavior. Till date, no cure for Alzheimer exists and the current Alzheimer medications have limited effectiveness. However, herbal medicines may slow down the disease's progression, which may hopefully reduce the number of cases in the years to come. Numerous studies have been done on characterizing the neuroprotective properties from plants belonging to Scrophulariaceae family, particularly Bacopa monnieri and its polyphenolic compounds known as bacosides. This review presents the findings on bacosides in therapeutic plants and their impact on Alzheimer disease pathology. These reports present data on the clinical, cellular activities, phytochemistry, and biological applications that may be used in new drug treatment for Alzheimer disease.
  18. Ahmad B, Friar EP, Taylor E, Vohra MS, Serpell CJ, Garrett MD, et al.
    Eur J Pharmacol, 2023 Jan 05;938:175445.
    PMID: 36473593 DOI: 10.1016/j.ejphar.2022.175445
    In this study, the anti-obesity effects of 5,7,3',4',5-pentamethoxyflavone (PMF) and 6,2',4'-trimethoxyflavone (TMF) were evaluated through two distinct mechanisms of action: inhibition of crude porcine pancreatic lipase (PL), and inhibition of adipogenesis in 3T3-L1 pre-adipocytes. Both flavones show dose dependent, competitive inhibition of PL activity. Molecular docking studies revealed binding of the flavones to the active site of PL. In 3T3-L1 adipocytes, both flavones reduced the accumulation of lipids and triglycerides. PMF and TMF also lowered the expression of adipogenic and lipogenic genes. They both reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), sterol regulatory element-binding protein 1 (SREBF 1), fatty acid synthase (FASN), adipocyte binding protein 2 (aP2), and leptin gene. In addition, these flavones enhanced adiponectin mRNA expression, increased lipolysis and enhanced the expression of lipolytic genes: adipose triglycerides lipase (ATGL), hormone sensitive lipase (HSL) and monoglycerides lipase (MAGL) in mature 3T3-L1 adipocytes. Overall, PMF was seen to be a more potent inhibitor of both PL activity and adipogenesis versus TMF. These results suggest that PMF and TMF possess anti-obesity activities and can be further evaluated for their anti-obesity effects.
  19. Mohd Noor MNZ, Alauddin AS, Wong YH, Looi CY, Wong EH, Madhavan P, et al.
    Asian Pac J Cancer Prev, 2023 Jan 01;24(1):37-47.
    PMID: 36708550 DOI: 10.31557/APJCP.2023.24.1.37
    BACKGROUND: Cancer remains a challenging target to cure, with present therapeutic methods unable to exhibit restorative outcomes without causing severe negative effects. Molecular hydrogen (H2) has been reported to be a promising adjunctive therapy for cancer treatment, having the capability to induce anti-proliferative, anti-oxidative, pro-apoptotic and anti-tumoural effects. This review summarises the findings from various articles on the mechanism, treatment outcomes, and overall effectiveness of H2 therapy on cancer management.

    METHODS: Using Cochrane, PubMed, and Google Scholar as the search engines, full-text articles in the scope of the study, written in English and within 10 years of publication were selected.

    RESULTS: Out of the 677 articles, 27 articles fulfilled the eligibility criteria, where data was compiled into a table, outlining the general characteristics and findings. Throughout the different forms of H2 administration, study design and types of cancers reported, outcomes were found to be consistent.

    CONCLUSION: From our analysis, H2 plays a promising therapeutic role as an independent therapy as well as an adjuvant in combination therapy, resulting in an overall improvement in survivability, quality of life, blood parameters, and tumour reduction. Although more comprehensive research is needed, given the promising outcomes, H2 is worth considering for use as a complement to current cancer therapy.

  20. Ahmad B, Friar EP, Vohra MS, Khan N, Serpell CJ, Garrett MD, et al.
    Chem Biol Interact, 2023 Jul 01;379:110503.
    PMID: 37084996 DOI: 10.1016/j.cbi.2023.110503
    Hydroxylated polymethoxyflavones (HPMFs) have been shown to possess various anti-disease effects, including against obesity. This study investigates the anti-obesity effects of HPMFs in further detail, aiming to gain understanding of their mechanism of action in this context. The current study demonstrates that two HPMFs; 3'-hydroxy-5,7,4',5'-tetramethoxyflavone (3'OH-TetMF) and 4'-hydroxy-5,7,3',5'-tetramethoxyflavone (4'OH-TetMF) possess anti-obesity effects. They both significantly reduced pancreatic lipase activity in a competitive manner as demonstrated by molecular docking and kinetic studies. In cell studies, it was revealed that both of the HPMFs suppress differentiation of 3T3-L1 mouse embryonic fibroblast cells during the early stages of adipogenesis. They also reduced expression of key adipogenic and lipogenic marker genes, namely peroxisome proliferator-activated receptor-gamma (PPARγ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), adipocyte binding protein 2 (aP2), fatty acid synthase (FASN), and sterol regulatory element-binding protein 1 (SREBF 1). They also enhanced the expression of cell cycle genes, i.e., cyclin D1 (CCND1) and C-Myc, and reduced cyclin A2 expression. When further investigated, it was also observed that these HPMFs accelerate lipid breakdown (lipolysis) and enhance lipolytic genes expression. Moreover, they also reduced the secretion of proteins (adipokines), including pro-inflammatory cytokines, from mature adipocytes. Taken together, this study concludes that these HPMFs have anti-obesity effects, which are worthy of further investigation.
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