MyMedR

Displaying publications 1 - 20 of 28 in total

Abstract:

Sort:

Fulltext Vibrio vulnificus: An Environmental and Clinical Burden

Heng SP, Letchumanan V, Deng CY, Ab Mutalib NS, Khan TM, Chuah LH, et al.

Front Microbiol, 2017;8:997.
PMID: 28620366 DOI: 10.3389/fmicb.2017.00997

Vibrio vulnificus is a Gram negative, rod shaped bacterium that belongs to the family Vibrionaceae. It is a deadly, opportunistic human pathogen which is responsible for the majority of seafood-associated deaths worldwide. V. vulnificus infection can be fatal as it may cause severe wound infections potentially requiring amputation or lead to sepsis in susceptible individuals. Treatment is increasingly challenging as V. vulnificus has begun to develop resistance against certain antibiotics due to their indiscriminate use. This article aims to provide insight into the antibiotic resistance of V. vulnificus in different parts of the world as well as an overall review of its clinical manifestations, treatment, and prevention. Understanding the organism's antibiotic resistance profile is vital in order to select appropriate treatment and initiate appropriate prevention measures to treat and control V. vulnificus infections, which should eventually help lower the mortality rate associated with this pathogen worldwide.
Tocotrienol and cancer metastasis

De Silva L, Chuah LH, Meganathan P, Fu JY

Biofactors, 2016 Mar-Apr;42(2):149-62.
PMID: 26948691 DOI: 10.1002/biof.1259

Tumor metastasis involves some of the most complex and dynamic processes in cancer, often leading to poor quality of life and inevitable death. The search for therapeutic compounds and treatment strategies to prevent and/or manage metastasis is the ultimate challenge to fight cancer. In the past two decades, research focus on vitamin E has had a shift from saturated tocopherols to unsaturated tocotrienols (T3). Despite sharing structural similarities with tocopherols, T3 strive to gain scientific prominence due to their anti-cancer effects. Recent studies have shed some light on the anti-metastatic properties of T3. In this review, the roles of T3 in each step of the metastatic process are discussed. During the invasion process, signaling pathways that regulate the extracellular matrix and tumor cell motility have been reported to be modulated by T3. Although studies on T3 and tumor cell migration are fairly limited, they were shown to play a vital role in the suppression of angiogenesis. Furthermore, the anti-inflammatory effect of T3 could be highly promising in the regulation of tumor microenvironment, which is crucial in supporting tumor growth in distant organs. © 2016 BioFactors, 42(2):149-162, 2016.
The anti-melanogenic properties of Swietenia macrophylla king

Mahendra CK, Ser HL, Abidin SAZ, Khan SU, Pusparajah P, Htar TT, et al.

Biomed Pharmacother, 2023 Apr 15;162:114659.
PMID: 37068335 DOI: 10.1016/j.biopha.2023.114659

Fair flawless skin is the goal for some cultures and the development of irregular skin pigmentation is considered an indication of premature skin aging. Hence, there is a rising demand for skin whitening cosmetics. Thus, this research will be focusing on discovering the anti-pigmentation properties of Swietenia macrophylla seeds. Firstly, the seeds were extracted with ethanol and further fractionate based on their polarity before testing them on zebrafish embryos. The ethanolic extract of the seed demonstrated significant inhibition of both tyrosinase activity and melanin production in the embryos. However, after fractionation, the anti-melanogenic ability was observed to have decreased, signifying that the phytocompounds may be synergistic in nature. Still in the proteomic studies the ethanolic extract and its hexane fraction both induced the downregulation of cathepsin LB and cytoskeletal proteins that have connections to the melanogenic pathway, confirming that S. macrophylla seeds do indeed have anti-pigmentation properties that can be exploited for cosmetic use. Next, limonoids (tetranortriterpenoids found in the seed) were tested for their inhibitory effect against human tyrosinase related protein 1 (TYRP-1) via molecular docking. It was found that limonoids have a stronger binding affinity to TYRP-1 than kojic acid, suggesting that these phytocompounds may have the potential in inhibiting pigmentation. However, this still needs further confirmation before these phytocompounds can be developed into a skin whitening agent. Other assays like ex-vivo or 3D human skin culture can also be used to better study the seeds anti-pigmentation effect on humans.
The TRAIL to cancer therapy: Hindrances and potential solutions

Wong SHM, Kong WY, Fang CM, Loh HS, Chuah LH, Abdullah S, et al.

Crit Rev Oncol Hematol, 2019 Nov;143:81-94.
PMID: 31561055 DOI: 10.1016/j.critrevonc.2019.08.008

Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. Resistance to apoptosis is a hallmark of virtually all malignancies. Despite being a cause of pathological conditions, apoptosis could be a promising target in cancer treatment. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), also known as Apo-2 ligand (Apo2L), is a member of TNF cytokine superfamily. It is a potent anti-cancer agent owing to its specific targeting towards cancerous cells, while sparing normal cells, to induce apoptosis. However, resistance occurs either intrinsically or after multiple treatments which may explain why cancer therapy fails. This review summarizes the apoptotic mechanisms via extrinsic and intrinsic apoptotic pathways, as well as the apoptotic resistance mechanisms. It also reviews the current clinically tested recombinant human TRAIL (rhTRAIL) and TRAIL receptor agonists (TRAs) against TRAIL-Receptors, TRAIL-R1 and TRAIL-R2, in which the outcomes of the clinical trials have not been satisfactory. Finally, this review discusses the current strategies in overcoming resistance to TRAIL-induced apoptosis in pre-clinical and clinical settings.
The Potential of Streptomyces as Biocontrol Agents against the Rice Blast Fungus, Magnaporthe oryzae (Pyricularia oryzae)

Law JW, Ser HL, Khan TM, Chuah LH, Pusparajah P, Chan KG, et al.

Front Microbiol, 2017;8:3.
PMID: 28144236 DOI: 10.3389/fmicb.2017.00003

Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10-30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyces bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae. The ability of various Streptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae. In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents.
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.
Fulltext Revisiting the concept of incretin and enteroendocrine L-cells as type 2 diabetes mellitus treatment

Lok KH, Wareham NJ, Nair RS, How CW, Chuah LH

Pharmacol Res, 2022 Jun;180:106237.
PMID: 35487405 DOI: 10.1016/j.phrs.2022.106237

The significant growth in type 2 diabetes mellitus (T2DM) prevalence strikes a common threat to the healthcare and economic systems globally. Despite the availability of several anti-hyperglycaemic agents in the market, none can offer T2DM remission. These agents include the prominent incretin-based therapy such as glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 inhibitors that are designed primarily to promote GLP-1R activation. Recent interest in various therapeutically useful gastrointestinal hormones in T2DM and obesity has surged with the realisation that enteroendocrine L-cells modulate the different incretins secretion and glucose homeostasis, reflecting the original incretin definition. Targeting L-cells offers promising opportunities to mimic the benefits of bariatric surgery on glucose homeostasis, bodyweight management, and T2DM remission. Revising the fundamental incretin theory is an essential step for therapeutic development in this area. Therefore, the present review explores enteroendocrine L-cell hormone expression, the associated nutrient-sensing mechanisms, and other physiological characteristics. Subsequently, enteroendocrine L-cell line models and the latest L-cell targeted therapies are reviewed critically in this paper. Bariatric surgery, pharmacotherapy and new paradigm of L-cell targeted pharmaceutical formulation are discussed here, offering both clinician and scientist communities a new common interest to push the scientific boundary in T2DM therapy.
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.
Pharmacist-Involved Antiretroviral Stewardship Programs in People Living with HIV/AIDS: A Systematic Review

Ahmed A, Tanveer M, Dujaili JA, Chuah LH, Hashmi FK, Awaisu A

AIDS Patient Care STDS, 2023 Jan;37(1):31-52.
PMID: 36626156 DOI: 10.1089/apc.2022.0192

People living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS; PLWHA) frequently encounter antiretroviral (ARV) therapy-related problems. Clinical pharmacists with specialized training in ARV stewardship play an important role in managing these problems. However, there is a paucity of evidence to clarify the impact of clinical pharmacists' interventions on managing ARV therapy-related problems in PLWHA. Therefore, we aim to systematically review the literature to determine the nature and impact of pharmacists' interventions on managing medication-related problems in PLWHA. The review protocol was registered on International Prospective Register of Systematic Reviews (PROSPERO; CRD42020173078). Relevant records were identified from six electronic bibliographic databases (PubMed, Embase, EBSCOhost, ProQuest, Scopus, and the Cochrane Central Register) from their inception until September 2022. We included all randomized and nonrandomized interventional studies that were published in English. After the abstract and full-text screening, data were extracted from the selected studies, and the quality of the studies was assessed. The electronic database search and citation tracking identified two thousand and three citations. The review included 21 of these studies, involving 2998 PLWHA, published between 2014 and 2022. Pharmacists' interventions, working alone or in a multi-disciplinary team, comprised ARV medication review, management of adverse drug reactions (ADRs), therapeutic drug monitoring, prevention of drug interactions, and provision of drug information to PLWHA or the health care team. The pharmacist-involved interventions significantly reduced incorrect/incomplete ARV regimens, drug interactions, incorrect dosages, duplicate therapy, polypharmacy, administration errors, missing medication, wrong formulation, ADRs, and prescribing errors. Most studies reported that physicians usually accept more than 90% of the pharmacists' recommendations. ARV medication-related problems remain highly prevalent in PLWHA. Pharmacist-led interventions and stewardship significantly reduce ARV therapy-related problems in PLWHA and are widely accepted by physicians. Dedicated pharmacists with specialized training and credentialing in infectious diseases or HIV/AIDS have a great potential to improve health outcomes in PLWHA.
Natural bioactive compounds as a new source of promising G protein-coupled estrogen receptor (GPER) modulators: comprehensive in silico approach

Khan SU, Ahemad N, Chuah LH, Naidu R, Htar TT

J Biomol Struct Dyn, 2020 Oct 15.
PMID: 33054574 DOI: 10.1080/07391102.2020.1830853

Cancer ranks in second place among the cause of death worldwide. Cancer progress in multiple stages of carcinogenesis and metastasis programs through complex pathways. Sex hormones and their receptors are the major factors in promoting cancer progression. Among them, G protein-coupled estrogen receptor-1 (GPER) has shown to mediate cellular signaling pathways and cancer cell proliferation. However, the lack of GPER protein structure limited the search for new modulators. In this study, we curated an extensive database of natural products to discover new potential GPER modulators. We used a combination of virtual screening techniques to generate a homology model of GPER and subsequently used that for the screening of 30,926 natural products from a public database to identify potential active modulators of GPER. The best hits were further screened through the ADMET filter and confirmed by docking analysis. Moreover, molecular dynamics simulations of best hits were also carried out to assess the stability of the ligand-GPER complex. This study predicted several potential GPER modulators with novel scaffolds that could be further investigated and used as the core for the development of novel GPER modulators.Communicated by Ramaswamy H. Sarma.
G protein-coupled estrogen receptor-1: homology modeling approaches and application in screening new GPER-1 modulators

Khan SU, Ahemad N, Chuah LH, Naidu R, Htar TT

J Biomol Struct Dyn, 2020 Nov 08.
PMID: 33164654 DOI: 10.1080/07391102.2020.1844059

G protein-coupled receptors (GPCRs) belong to the largest family of protein targets comprising over 800 members in which at least 500 members are the therapeutic targets. Among the GPCRs, G protein-coupled estrogen receptor-1 (GPER-1) has shown to have the ability in estrogen signaling. As GPER-1 plays a critical role in several physiological responses, GPER-1 has been considered as a potential therapeutic target to treat estrogen-based cancers and other non-communicable diseases. However, the progress in the understanding of GPER-1 structure and function is relatively slow due to the availability of a only a few selective GPER-1 modulators. As with many GPCRs, the X-ray crystal structure of GPER-1 is yet to be resolved and thus has led the researchers to search for new GPER-1 modulators using homology models of GPER-1. In this review, we aim to summarize various approaches used in the generation of GPER-1 homology model and their applications that have resulted in new GPER-1 ligands.
Epigenetics in Metastatic Breast Cancer: Its Regulation and Implications in Diagnosis, Prognosis and Therapeutics

Wu YS, Lee ZY, Chuah LH, Mai CW, Ngai SC

Curr Cancer Drug Targets, 2019;19(2):82-100.
PMID: 29714144 DOI: 10.2174/1568009618666180430130248

Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC are discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed. The combined regimen of epigenetic drugs or with standard chemotherapy drugs enhance the therapeutic effect against MBC. Evidences that epigenetic changes could have implications in diagnosis, prognosis and therapeutics for MBC are also presented. Several genes have been identified as potential epigenetic biomarkers for diagnosis and prognosis, as well as therapeutic targets for MBC. Endeavors in clinical trials of epigenetic drugs against MBC should be continued although limited success has been achieved. Future discovery of epigenetic drugs from natural resources would be an attractive natural treatment regimen for MBC. Further research is warranted in translating research into clinical practice with the ultimate goal of treating MBC by epigenetic therapy in the near future.
Fulltext Editorial: Women in nanomedicine

Chuah LH, Fu JY, Nguyen S, Banciu M, Solanki PR, Ta HT

Front Pharmacol, 2022;13:1122774.
PMID: 36686703 DOI: 10.3389/fphar.2022.1122774
E-cadherin: Its dysregulation in carcinogenesis and clinical implications

Wong SHM, Fang CM, Chuah LH, Leong CO, Ngai SC

Crit Rev Oncol Hematol, 2018 Jan;121:11-22.
PMID: 29279096 DOI: 10.1016/j.critrevonc.2017.11.010

E-cadherin is a transmembrane glycoprotein which connects epithelial cells together at adherens junctions. In normal cells, E-cadherin exerts its tumour suppressing role mainly by sequestering β-catenin from its binding to LEF (Lymphoid enhancer factor)/TCF (T cell factor) which serves the function of transcribing genes of the proliferative Wnt signaling pathway. Despite the ongoing debate on whether the loss of E-cadherin is the cause or effect of epithelial-mesenchymal transition (EMT), E-cadherin functional loss has frequently been associated with poor prognosis and survival in patients of various cancers. The dysregulation of E-cadherin expression that leads to carcinogenesis happens mostly at the epigenetic level but there are cases of genetic alterations as well. E-cadherin expression has been linked to the cellular functions of invasiveness reduction, growth inhibition, apoptosis, cell cycle arrest and differentiation. Studies on various cancers have shown that these different cellular functions are also interdependent. Recent studies have reported a rapid expansion of E-cadherin clinical relevance in various cancers. This review article summarises the multifaceted effect E-cadherin expression has on cellular functions in the context of carcinogenesis as well as its clinical implications in diagnosis, prognosis and therapeutics.
Fulltext Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration

Mahendra CK, Tan LTH, Pusparajah P, Htar TT, Chuah LH, Lee VS, et al.

Oxid Med Cell Longev, 2020;2020:1904178.
PMID: 32855763 DOI: 10.1155/2020/1904178

Retinal pigment epithelial (RPE) cells are an essential part of the human eye because they not only mediate and control the transfer of fluids and solutes but also protect the retina against photooxidative damage and renew photoreceptor cells through phagocytosis. However, their function necessitates cumulative exposure to the sun resulting in UV damage, which may lead to the development of age-related macular degeneration (AMD). Several studies have shown that UVB induces direct DNA damage and oxidative stress in RPE cells by increasing ROS and dysregulating endogenous antioxidants. Activation of different signaling pathways connected to inflammation, cell cycle arrest, and intrinsic apoptosis was reported as well. Besides that, essential functions like phagocytosis, osmoregulation, and water permeability of RPE cells were also affected. Although the melanin within RPE cells can act as a photoprotectant, this photoprotection decreases with age. Nevertheless, the changes in lens epithelium-derived growth factor (LEDGF) and autophagic activity or application of bioactive compounds from natural products can reverse the detrimental effect of UVB. Additionally, in vivo studies on the whole retina demonstrated that UVB irradiation induces gene and protein level dysregulation, indicating cellular stress and aberrations in the chromosome level. Morphological changes like retinal depigmentation and drusen formation were noted as well which is similar to the etiology of AMD, suggesting the connection of UVB damage with AMD. Therefore, future studies, which include mechanism studies via in vitro or in vivo and other potential bioactive compounds, should be pursued for a better understanding of the involvement of UVB in AMD.
Current status in cellular-based therapies for prevention and treatment of COVID-19

Hattab D, Amer MFA, Mohd Gazzali A, Chuah LH, Bakhtiar A

Crit Rev Clin Lab Sci, 2023 Aug;60(5):321-345.
PMID: 36825325 DOI: 10.1080/10408363.2023.2177605

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) outbreaks that resulted in a catastrophic threat to global health, with more than 500 million cases detected and 5.5 million deaths worldwide. Patients with a COVID-19 infection presented with clinical manifestations ranging from asymptomatic to severe symptoms, resulting in acute lung injury, acute respiratory distress syndrome, and even death. Immune dysregulation through delayed innate immune response or impairment of the adaptive immune response is the key contributor to the pathophysiology of COVID-19 and SARS-CoV-2-induced cytokine storm. Symptomatic and supportive therapy is the fundamental strategy in treating COVID-19 infection, including antivirals, steroid-based therapies, and cell-based immunotherapies. Various studies reported substantial effects of immune-based therapies for patients with COVID-19 to modulate the over-activated immune system while simultaneously refining the body's ability to destroy the virus. However, challenges may arise from the complexity of the disease through the genetic variance of the virus itself and patient heterogeneity, causing increased transmissibility and heightened immune system evasion that rapidly change the intervention and prevention measures for SARS-CoV-2. Cell-based therapy, utilizing stem cells, dendritic cells, natural killer cells, and T cells, among others, are being extensively explored as other potential immunological approaches for preventing and treating SARS-CoV-2-affected patients the similar process was effectively proven in SARS-CoV-1 and MERS-CoV infections. This review provides detailed insights into the innate and adaptive immune response-mediated cell-based immunotherapies in COVID-19 patients. The immune response linking towards engineered autologous or allogenic immune cells for either treatment or preventive therapies is subsequently highlighted in an individual study or in combination with several existing treatments. Up-to-date data on completed and ongoing clinical trials of cell-based agents for preventing or treating COVID-19 are also outlined to provide a guide that can help in treatment decisions and future trials.
Curcumin-containing chitosan nanoparticles as a potential mucoadhesive delivery system to the colon

Chuah LH, Billa N, Roberts CJ, Burley JC, Manickam S

Pharm Dev Technol, 2013 May-Jun;18(3):591-9.
PMID: 22149945 DOI: 10.3109/10837450.2011.640688

In the present study, we investigate the mucoadhesive characteristics and release of the anticancer agent curcumin, contained in chitosan nanoparticles (CS-NPs). Such a system has potential therapeutic benefits in the treatment of colon cancer through prolonged retention and delivery. The CS-NPs were ionically gelled with tripolyphosphate (TPP) and registered an isoelectric pH of 6.2 (z-average diameter of 214 nm ± 1.0 nm). pH variations around the isoelectric point caused a reduction in CS-NPs electrical charge which correspondingly increased the z-average due to agglomeration. Curcumin release from CS-NPs was slowest at chitosan to TPP weight ratio of 3:1, with a significant retention (36%) at the end of 6 h. Adsorption isotherms of mucin on CS-NPs fitted both the Freundlich and Langmuir models, suggesting a monolayer-limited adsorption on heterogeneous sites with varied affinities. Encapsulated curcumin exerted an influence on the adsorption of mucin due to H-bonding as well as π-π interactions between the phenolic moieties of curcumin and mucin.
Fulltext Curcumin Nanoformulations for Colorectal Cancer: A Review

Wong KE, Ngai SC, Chan KG, Lee LH, Goh BH, Chuah LH

Front Pharmacol, 2019;10:152.
PMID: 30890933 DOI: 10.3389/fphar.2019.00152

Colorectal cancer (CRC) is the third most prevalent form of cancer, after lung cancer and breast cancer, with the second highest death incidence. Over the years, natural compounds have been explored as an alternative to conventional cancer therapies such as surgery, radiotherapy, and chemotherapy. Curcumin, an active constituent of turmeric has been associated with various health benefits. It has gained much attention as an anticancer agent due to its ability to regulate multiple cell signaling pathways, including NF-κB, STAT3, activated protein-1 (AP-1), epidermal growth response-1 (Egr-1), and p53, which are crucial in cancer development and progression. Nevertheless, the clinical application of curcumin is greatly restricted because of its low water solubility, poor oral absorption, and rapid metabolism. These issues have led to the development of curcumin nanoformulations to overcome the limitations of the compound. Nanotechnology-based delivery systems have been widely used in improving the delivery of poorly-water soluble drugs. Besides, these systems also come with the added benefits of possible cellular targeting and improvement in cellular uptake. An ideal improved formulation should display a greater anticancer activity compared to free curcumin, and at the same time be non-toxic to the normal cells. In this review, we focus on the design and development of various nanoformulations to deliver curcumin for use in CRC such as liposomes, micelles, polymer nanoparticles, nanogels, cyclodextrin complexes, solid lipid nanoparticles (SLN), phytosomes, and gold nanoparticles. We also discuss the current pre-clinical and clinical evidences of curcumin nanoformulations in CRC therapy, analyse the research gap, and address the future direction of this research area.
Fulltext Counteracting the Ramifications of UVB Irradiation and Photoaging with Swietenia macrophylla King Seed

Mahendra CK, Abidin SAZ, Htar TT, Chuah LH, Khan SU, Ming LC, et al.

Molecules, 2021 Apr 01;26(7).
PMID: 33916053 DOI: 10.3390/molecules26072000

In this day and age, the expectation of cosmetic products to effectively slow down skin photoaging is constantly increasing. However, the detrimental effects of UVB on the skin are not easy to tackle as UVB dysregulates a wide range of molecular changes on the cellular level. In our research, irradiated keratinocyte cells not only experienced a compromise in their redox system, but processes from RNA translation to protein synthesis and folding were also affected. Aside from this, proteins involved in various other processes like DNA repair and maintenance, glycolysis, cell growth, proliferation, and migration were affected while the cells approached imminent cell death. Additionally, the collagen degradation pathway was also activated by UVB irradiation through the upregulation of inflammatory and collagen degrading markers. Nevertheless, with the treatment of Swietenia macrophylla (S. macrophylla) seed extract and fractions, the dysregulation of many genes and proteins by UVB was reversed. The reversal effects were particularly promising with the S. macrophylla hexane fraction (SMHF) and S. macrophylla ethyl acetate fraction (SMEAF). SMHF was able to oppose the detrimental effects of UVB in several different processes such as the redox system, DNA repair and maintenance, RNA transcription to translation, protein maintenance and synthesis, cell growth, migration and proliferation, and cell glycolysis, while SMEAF successfully suppressed markers related to skin inflammation, collagen degradation, and cell apoptosis. Thus, in summary, our research not only provided a deeper insight into the molecular changes within irradiated keratinocytes, but also serves as a model platform for future cosmetic research to build upon. Subsequently, both SMHF and SMEAF also displayed potential photoprotective properties that warrant further fractionation and in vivo clinical trials to investigate and obtain potential novel bioactive compounds against photoaging.
Fulltext Cost-Effectiveness of Anti-retroviral Adherence Interventions for People Living with HIV: A Systematic Review of Decision Analytical Models

Ahmed A, Dujaili JA, Chuah LH, Hashmi FK, Le LK, Khanal S, et al.

Appl Health Econ Health Policy, 2023 Sep;21(5):731-750.
PMID: 37389788 DOI: 10.1007/s40258-023-00818-4

BACKGROUND: Although safe and effective anti-retrovirals (ARVs) are readily available, non-adherence to ARVs is highly prevalent among people living with human immunodeficiency virus/acquired immunodeficiency syndrome (PLWHA). Different adherence-improving interventions have been developed and examined through decision analytic model-based health technology assessments. This systematic review aimed to review and appraise the decision analytical economic models developed to assess ARV adherence-improvement interventions.
METHODS: The review protocol was registered on PROSPERO (CRD42022270039), and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Relevant studies were identified through searches in six generic and specialized bibliographic databases, i.e. PubMed, Embase, NHS Economic Evaluation Database, PsycINFO, Health Economic Evaluations Database, tufts CEA registry and EconLit, from their inception to 23 October 2022. The cost-effectiveness of adherence interventions is represented by the incremental cost-effectiveness ratio (ICER). The quality of studies was assessed using the quality of the health economics studies (QHES) instrument. Data were narratively synthesized in the form of tables and texts. Due to the heterogeneity of the data, a permutation matrix was used for quantitative data synthesis rather than a meta-analysis.
RESULTS: Fifteen studies, mostly conducted in North America (8/15 studies), were included in the review. The time horizon ranged from a year to a lifetime. Ten out of 15 studies used a micro-simulation, 4/15 studies employed Markov and 1/15 employed a dynamic model. The most commonly used interventions reported include technology based (5/15), nurse involved (2/15), directly observed therapy (2/15), case manager involved (1/15) and others that involved multi-component interventions (5/15). In 1/15 studies, interventions gained higher quality-adjusted life years (QALYs) with cost savings. The interventions in 14/15 studies were more effective but at a higher cost, and the overall ICER was well below the acceptable threshold mentioned in each study, indicating the interventions could potentially be implemented after careful interpretation. The studies were graded as high quality (13/15) or fair quality (2/15), with some methodological inconsistencies reported.
CONCLUSION: Counselling and smartphone-based interventions are cost-effective, and they have the potential to reduce the chronic adherence problem significantly. The quality of decision models can be improved by addressing inconsistencies in model selection, data inputs incorporated into models and uncertainty assessment methods.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links