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Fulltext Neutrophil-lymphocyte ratios in the prognostication of primary non-metastatic nasopharyngeal carcinoma

Liew KY, Zulkiflee AB

Braz J Otorhinolaryngol, 2017 10 19;84(6):764-771.
PMID: 29128472 DOI: 10.1016/j.bjorl.2017.09.004

INTRODUCTION: Nasopharyngeal carcinoma is a geographically and racially variable disease which has a high incidence in Malaysia. Based on current concepts in tumour related inflammation the inflammatory marker, neutrophil-lymphocyte ratio was tested to find its relationship with prognosis in nasopharyngeal carcinoma.
OBJECTIVE: To investigate the effect of the neutrophil-lymphocyte ratio on prognosis in non-metastatic primary nasopharyngeal carcinoma patients and to further refine the cut off between high and low neutrophil-lymphocyte ratio values.
METHODS: The medical charts of patients with histologically confirmed nasopharyngeal carcinoma from 1st January 2005 until 31st December 2009 were reviewed retrospectively and theneutrophil-lymphocyte ratio was calculated to see if there was any association between their higher values with higher failure rates.
RESULTS: Records of 98 patients (n=98) were retrieved and reviewed. Only neutrophil-lymphocyte ratio (p=0.004) and tumor node metastasis staging (p=0.002) were significantly different between recurrent and non-recurrent groups, with the neutrophil-lymphocyte ratio being independent of tumor node metastasis staging (p=0.007). Treatment failure was significantly higher in the high neutrophil-lymphocyte ratio group (p=0.001). Disease free survival was also significantly higher in this group (p=0.000077).
CONCLUSION: High neutrophil-lymphocyte ratio values are associated with higher rates of recurrence and worse disease free survival in non-metastatic nasopharyngeal carcinoma patients undergoing primary curative treatment.
Endoscopic Transsphenoidal Resection of Craniopharyngioma

Liew KY, Narayanan P, Waran V

J Neurol Surg B Skull Base, 2018 Feb;79(2):S203-S204.
PMID: 29404252 DOI: 10.1055/s-0037-1620243

Objectives To demonstrate, step-by-step, the technique and efficacy of endoscopic transsphenoidal approach in resection of a suprasellar craniopharyngioma. Design The video shows a step-by-step approach to the resection, covering the exposure, access, resection, and confirmation of resection and reconstruction. Setting The surgery was performed in the University of Malaya Medical Centre, a tertiary referral center in the capital of Malaysia. Participants Surgery was performed jointly by Professor Prepageran from the department of otorhinolaryngology and Professor Vicknes Waran from the division of neurosurgery. Both surgeons are from the University of Malaya. Video compilation, editing, and voice narration was done by Dr. Kong Yew Liew. Main Outcome Measures Completeness of resection and avoidance of intra- and postoperative complications. Results Based on intraoperative views and MRI findings, the tumor was completely resected with the patient suffering only transient diabetes insipidus. Conclusion Central suprasellar tumors can be removed completely via an endoscopic transsphenoidal approach with minimal morbidity to the patient. The link to the video can be found at: https://youtu.be/ZNIHfk12cYg .
Pharmacological Properties of 2,4,6-Trihydroxy-3-Geranyl Acetophenone and the Underlying Signaling Pathways: Progress and Prospects

Chan YH, Liew KY, Tan JW, Shaari K, Israf DA, Tham CL

Front Pharmacol, 2021;12:736339.
PMID: 34531753 DOI: 10.3389/fphar.2021.736339

2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) is a bioactive phloroglucinol compound found in Melicope pteleifolia (Champ. ex Benth.) T.G.Hartley, a medicinal plant vernacularly known as "tenggek burung". A variety of phytochemicals have been isolated from different parts of the plant including leaves, stems, and roots by using several extraction methods. Specifically, tHGA, a drug-like compound containing phloroglucinol structural core with acyl and geranyl group, has been identified in the methanolic extract of the young leaves. Due to its high nutritional and medicinal values, tHGA has been extensively studied by using various experimental models. These studies have successfully discovered various interesting pharmacological activities of tHGA such as anti-inflammatory, endothelial and epithelial barrier protective, anti-asthmatic, anti-allergic, and anti-cancer. More in-depth investigations later found that these activities were attributable to the modulatory actions exerted by tHGA on specific molecular targets. Despite these findings, the association between the mechanisms and signaling pathways underlying each pharmacological activity remains largely unknown. Also, little is known about the medicinal potentials of tHGA as a drug lead in the current pharmaceutical industry. Therefore, this mini review aims to summarize and relate the pharmacological activities of tHGA in terms of their respective mechanisms of action and signaling pathways in order to present a perspective into the overall modulatory actions exerted by tHGA. Besides that, this mini review will also pinpoint the unexplored potentials of this compound and provide some valuable insights into the potential applications of tHGA which may serve as a guide for the development of modern medication in the future.
Zerumbone attenuates house dust mite extract-induced epithelial barrier dysfunction in 16HBE14o- cells

Rohhimi W, Tan JW, Liew KY, Jacquet A, Harith HH, Israf DA, et al.

Immunopharmacol Immunotoxicol, 2021 Oct 25.
PMID: 34694946 DOI: 10.1080/08923973.2021.1992633

CONTEXT: The airway epithelial barrier can be disrupted by house dust mite (HDM) allergens leading to allergic airway inflammation. Zerumbone, a natural monocyclic sesquiterpene, was previously found to possess anti-asthmatic effect by modulating Th1/Th2 cytokines. However, the protective role of zerumbone on epithelial barrier function remains to be fully explored.
OBJECTIVE: To investigate the effect of zerumbone on HDM extract-induced airway epithelial barrier dysfunction.
MATERIALS AND METHODS: Human bronchial epithelial cells 16HBE14o- were incubated with 100 μg/mL HDM extract and treated with non-cytotoxic concentrations of zerumbone (6.25 μM, 12.5 μM, and 25 μM) for 24 h. The epithelial junctional integrity and permeability were evaluated through transepithelial electrical resistance (TEER) and fluorescein isothiocynate (FITC)-Dextran permeability assays, respectively. The localization of junctional proteins, occludin and zona occludens (ZO)-1, was studied using immunofluorescence (IF) while the protein expression was measured by western blot.
RESULTS: Zerumbone inhibited changes in junctional integrity (6.25 μM, p ≤ .05; 12.5 μM, p ≤ .001; 25 μM, p ≤ .001) and permeability (6.25 μM, p ≤ .05; 12.5 μM, p ≤ .01; 25 μM, p ≤ .001) triggered by HDM extract in a concentration-dependent manner. This protective effect could be explained by the preservation of occludin (12.5 μM, p ≤ .01 and 25 μM, p ≤ .001) and ZO-1 (12.5 μM, p ≤ .05 and 25 μM, p ≤ .001) localization, rather than the prevention of their cleavage.
DISCUSSION AND CONCLUSION: Zerumbone attenuates HDM extract-induced epithelial barrier dysfunction which supports its potential application for the treatment of inflammation-driven airway diseases such as asthma.
Fulltext Anti-Allergic Properties of Propolis: Evidence From Preclinical and Clinical Studies

Liew KY, Kamise NI, Ong HM, Aw Yong PY, Islam F, Tan JW, et al.

Front Pharmacol, 2021;12:785371.
PMID: 35126124 DOI: 10.3389/fphar.2021.785371

Allergic diseases are a global health burden with increasing prevalence. Side effects of available medications (antihistamines and steroids), lack of patients' perceived effectiveness and high cost of biologic therapies (omalizumab) are challenges to the clinical management of allergic diseases. As allergy symptoms persist for a long time, complementary and alternative medicine (CAM) such as propolis may be considered a potential prophylactic or therapeutic option to avoid long-term medication use. Propolis is a natural resinous substance produced by bees. Although propolis is well known to possess antioxidant, antimicrobial, and anticancer properties, its anti-allergic potential is not fully explored. Several preclinical studies demonstrated the therapeutic effects of propolis extracts against allergic inflammation, asthma, allergic rhinitis, atopic dermatitis, and food allergy, which may be partly attributed to their inhibitory effects on the activation of mast cells and basophils. Clinically, the consumption of propolis as a supplement or an adjunct therapy is safe and attenuates various pathological conditions in asthma. Such an approach may be adopted for atopic dermatitis and allergic rhinitis. Although flavonoids (chrysin, kaempferol, galangin, and pinocembrin) and cinnamic acid derivatives (artepillin C and caffeic acid phenethyl ester) can contribute to the anti-allergic activities, they may not be present in all propolis samples due to variations in the chemical composition. Future studies should relate the anti-allergic activity of propolis with its chemical contents. This mini-review summarizes and discusses existing preclinical and clinical studies reporting the anti-allergic activities of propolis to provide insights into its potential applications in allergic diseases.
Fulltext A Review of Malaysian Herbal Plants and Their Active Constituents with Potential Therapeutic Applications in Sepsis

Liew KY, Hafiz MF, Chong YJ, Harith HH, Israf DA, Tham CL

Evid Based Complement Alternat Med, 2020;2020:8257817.
PMID: 33193799 DOI: 10.1155/2020/8257817

Sepsis refers to organ failure due to uncontrolled body immune responses towards infection. The systemic inflammatory response triggered by pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide (LPS) from Gram-negative bacteria, is accompanied by the release of various proinflammatory mediators that can lead to organ damage. The progression to septic shock is even more life-threatening due to hypotension. Thus, sepsis is a leading cause of death and morbidity globally. However, current therapies are mainly symptomatic treatment and rely on the use of antibiotics. The lack of a specific treatment demands exploration of new drugs. Malaysian herbal plants have a long history of usage for medicinal purposes. A total of 64 Malaysian plants commonly used in the herbal industry have been published in Malaysian Herbal Monograph 2015 and Globinmed website (http://www.globinmed.com/). An extensive bibliographic search in databases such as PubMed, ScienceDirect, and Scopus revealed that seven of these plants have antisepsis properties, as evidenced by the therapeutic effect of their extracts or isolated compounds against sepsis-associated inflammatory responses or conditions in in vitro or/and in vivo studies. These include Andrographis paniculata, Zingiber officinale, Curcuma longa, Piper nigrum, Syzygium aromaticum, Momordica charantia, and Centella asiatica. Among these, Z. officinale is the most widely studied plant and seems to have the highest potential for future therapeutic applications in sepsis. Although both extracts as well as active constituents from these herbal plants have demonstrated potential antisepsis activity, the activity might be primarily contributed by the active constituent(s) from each of these plants, which are andrographolide (A. paniculata), 6-gingerol and zingerone (Z. officinale), curcumin (C. longa), piperine and pellitorine (P. nigrum), biflorin (S. aromaticum), and asiaticoside, asiatic acid, and madecassoside (C. asiatica). These active constituents have shown great antisepsis effects, and further investigations into their clinical therapeutic potential may be worthwhile.
Fulltext Management of Atopic Dermatitis Via Oral and Topical Administration of Herbs in Murine Model: A Systematic Review

Mohd Kasim VNK, Noble SM, Liew KY, Tan JW, Israf DA, Tham CL

Front Pharmacol, 2022;13:785782.
PMID: 35685636 DOI: 10.3389/fphar.2022.785782

Over the past few decades, complementary and alternative medicine (CAM) using herbs, or their active constituents have garnered substantial attention in the management of a chronic and relapsing inflammatory skin disorder called atopic dermatitis (AD), particularly in attenuating disease recurrence and maintaining long-term remission. In Eastern Asian countries including China, Korea and Taiwan, herbal medicine available in both topical and oral preparation plays a significant role in treating skin diseases like AD as they possibly confer high anti-inflammatory properties and immunomodulatory functions. Conventional murine models of AD have been employed in drug discovery to provide scientific evidence for conclusive and specific pharmacological effects elicited by the use of traditional herbs and their active constituents. Coupled with the goal to develop safe and effective novel therapeutic agents for AD, this systematic review consists of a summary of 103 articles on both orally and topically administered herbs and their active constituents in the murine model, whereby articles were screened and selected via a specialized framework known as PICO (Population, Intervention, Comparator and Outcome). The objectives of this review paper were to identify the efficacy of oral and topical administered herbs along with their active constituents in alleviating AD and the underlying mechanism of actions, as well as the animal models and choice of inducer agents used in these studies. The main outcome on the efficacy of the majority of the herbs and their active constituents illustrated suppression of Th2 response as well as improvements in the severity of AD lesions, suppression of Immunoglobulin E (IgE) concentration and mast cell infiltration. The majority of these studies used BALB/c mice followed by NC/Nga mice (commonly used gender-male; commonly used age group - 6-8 weeks). The most used agent in inducing AD was 2, 4-Dinitrochlorobenzene (DNCB), and the average induction period for both oral and topical administered herbs and their active constituents in AD experiments lasted between 3 and 4 weeks. In light of these findings, this review paper could potentially assist researchers in exploring the potential candidate herbs and their active constituents using murine model for the amelioration of AD.
Efficacy of Mobiderm® Bandage in Compression Therapy for Venous Ulcers: A Prospective Case Series

Nair HKR, Lew X, Liew KY, Kamis SA, Nik Kub NMH, Zakaria AM, et al.

Int J Low Extrem Wounds, 2023 Dec;22(4):759-766.
PMID: 34806457 DOI: 10.1177/15347346211058273

Background: Venous leg ulcers severely affect patients' quality of life due to its high morbidity and recurrent nature. Currently, compression therapy is the first-line treatment for venous leg ulcers. Aim: This study sought to evaluate the efficacy of the Mobiderm® technology developed by Thuasne in a prospective case series of venous leg ulcers. Methods: Nine patients (N = 9) with venous leg ulcers were enrolled into this case series. Mobiderm® bandage was applied on to the affected limbs of the patients in the multi-component bandages system. The bandages were changed as frequent as the patients had their wound dressing for their standard treatment in a 12-week duration. Wound size and calf circumference were measured at week 0 and week 12. Paired sample t-test was used to compare the mean values of wound size and calf circumference pre- and post-treatment. Results: Reductions in wound size and calf circumference were observed in all nine patients (100%). Five patients were evaluable at week 12. The wound sizes significantly reduced by 27.2% to 53.2% (p = 0.02), and the calf circumferences significantly reduced by 3.2% to 26.0% (p = 0.02) after 12 weeks (N = 5). Safety was unremarkable, with no occurrence of treatment-emergent-related adverse event. Conclusion: Mobiderm® bandage was reported to be effective in promoting wound healing and reducing swelling, suggesting it to be integrated in the compression therapy for the management of venous leg ulcers.
A synthetic curcumin-like diarylpentanoid analog inhibits rhinovirus infection in H1 hela cells via multiple antiviral mechanisms

Liew KY, Chee HY, Abas F, Leong SW, Harith HH, Israf DA, et al.

Daru, 2024 Dec;32(2):729-744.
PMID: 39395148 DOI: 10.1007/s40199-024-00542-x

BACKGROUND: Rhinovirus (RV) infection is a major cause of common colds and asthma exacerbations, with no antiviral drug available. Curcumin exhibits broad-spectrum antiviral activities, but its therapeutic effect is limited by a poor pharmacokinetics profile. Curcumin-like diarylpentanoid analogs, particularly 2-benzoyl-6-(3,4-dihydroxybenzylidene)cyclohexen-1-ol (BDHBC) and 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), have better solubility and stability compared to curcumin.
OBJECTIVES: Therefore, this study aims to evaluate and compare the antiviral effects of curcumin, BDHBC, and DHHPD in an in vitro model of RV infection.
METHODS: The inhibitory effects on RV-16 infection in H1 HeLa cells were assessed using cytopathic effect (CPE) reduction assay, virus yield reduction assay, RT-qPCR, and Western blot. Antiviral effects in different modes of treatment (pre-, co-, and post-treatment) were also compared. Additionally, intercellular adhesion molecule 1 (ICAM-1) expression, RV binding, and infectivity were measured with Western blot, flow cytometry, and virucidal assay, respectively.
RESULTS: When used as a post-treatment, BDHBC (EC50: 4.19 µM; SI: 8.32) demonstrated stronger antiviral potential on RV-16 compared to DHHPD (EC50: 18.24 µM; SI: 1.82) and curcumin (less than 50% inhibition). BDHBC also showed the strongest inhibitory effect on RV-induced CPE, virus yield, vRNA, and viral proteins (P1, VP0, and VP2). Furthermore, BDHBC pre-treatment has a prophylactic effect against RV infection, which was attributed to reduced basal expression of ICAM-1. However, it did not affect virus binding, but exerted virucidal activity on RV-16, contributing to its antiviral effect during co-treatment.
CONCLUSION: BDHBC exhibits multiple antiviral mechanisms against RV infection and thus could be a potential antiviral agent for RV.