Displaying publications 1 - 20 of 22 in total

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  1. Tulbah AS, Lee WH
    Pharmaceuticals (Basel), 2021 Oct 19;14(10).
    PMID: 34681283 DOI: 10.3390/ph14101059
    The rise of coronavirus (COVID-19) cases worldwide has driven the need to discover and develop novel therapeutics with superior efficacy to treat this disease. This study aims to develop an innovative aerosolized nano-formulation of favipiravir (FPV) as an anti-viral agent against coronavirus infection. The local delivery of FPV nanoparticles (NPs) via nebulization ensures that the drug can reach the site of infection, the lungs. Solid lipid NPs of favipiravir (FPV-SLNs) were formulated utilizing the hot-evaporation method. The physicochemical formulation properties were evaluated using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The aerosol formulation performance was evaluated using an Andersen Cascade Impactor (ACI) at a flow rate of 15 L/min. The FPV-SLN formulation's in vitro anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was also evaluated using the SARS-CoV-2 pathogen (hCoV-19/Egypt/NRC-3/2020 isolate). The FPV-SLNs' morphology was defined utilizing transmission electron microscopy, showing an irregular shape. By means of FPV-SLNs' nebulization, a fine particle fraction of 60.2 ± 1.7% was produced with 60.2 ± 1.7%, and this finding suggests that FPV-SLNs were appropriate for inhalation drug delivery with a particle size of 537.6 ± 55.72 nm. Importantly, the FPV-SLNs showed anti-viral activity against SARS-CoV-2 with CC50 and IC50 values of 449.6 and 29.9 µg/mL, respectively. This study suggests that inhaled solid lipid NPs of favipiravir could potentially be used against coronavirus.
  2. Aye LM, Lee WH
    PMID: 38572261 DOI: 10.1017/gmh.2024.23
    BACKGROUND: In Malaysia, a nationwide movement control order (MCO), implemented to curb the COVID-19 spread, impacted on the lives of the working population which could impair sleep quality.

    OBJECTIVE: This study aims to find the sleep quality status and its association with the socioeconomic, employment and lifestyle factors of working adults during the MCO period.

    METHODS: A cross-sectional study was conducted among 500 eligible working adults. Data were collected using a structured questionnaire consisting of the Pittsburg Sleep Quality Index.

    RESULTS: The proportion of poor sleep quality is found to be 59.4%. Analysis shows that the use of electronic devices before sleep (OR = 2.33, 95% CI = 1.02-5.35, p-value = 0.046), increased amount of workload (OR = 0.45, p-value = 0.005), decreased in amount of workload (OR = 0.48, p-value = 0.003) and distracted while working (OR = 0.57, p-value = 0.014) are the factors significantly associated with and are predictors of poor sleep quality.

    CONCLUSION: During crisis, there is a need for public health interventions for the working population to adopt a healthy lifestyle. Employers are recommended to support employees' well-being and to provide a healthy workplace during challenging times. Policy recommendations are also made to implement flexible working arrangements, workload management, workplace mental health support and legal protections on reasonable working hours, rest breaks and time off during crises.

  3. Lee WH, Rohanizadeh R, Loo CY
    Colloids Surf B Biointerfaces, 2021 Oct;206:111938.
    PMID: 34198233 DOI: 10.1016/j.colsurfb.2021.111938
    This study developed a novel bioactive bone substitute (hydroxyapatite, HA) with improved anti-biofilm activity by functionalizing with curcumin (anti-biofilm compound) which provide sufficient flux of curcumin concentration for 14 days. The released curcumin acts to inhibit biofilm formation and control the number of viable planktonic cells simultaneously. To prepare curcumin-functionalized HA, different concentrations of curcumin (up to 3% w/v) were added simultaneously during the precipitation process of HA. The highest loading (50 mg/g HA) of curcumin onto HA was achieved with 2% w/v of curcumin. Physicochemical characterizations of curcumin-functionalized HA composites revealed that curcumin was successfully incorporated onto HA. Curcumin was sustainably released over 14 days, while higher curcumin release was observed in acidic condition (pH 4.4) compared to physiological (pH 7.4). The cytotoxicity assays revealed that no significant difference on bone cells growth on curcumin-functionalized HA and non-functionalized HA. Curcumin-functionalized HA was effective to inhibit bacterial cell attachment and subsequent biofilm maturation stages. The anti-biofilm effect was stronger against Staphylococcus aureus compared to Pseudomonas aeruginosa. The curcumin-functionalized HA composite significantly delayed the maturation of S. aureus compared to non-functionalized HA in which microcolonies of cells only begin to appear at 96 h. Up to 3.0 log reduction in colony forming unit (CFU)/mL of planktonic cells was noted at 24 h of incubation for both microorganisms. Thus, in this study we have suggested that curcumin loaded HA could be an alternative antimicrobial agent to control the risk of infections in post-surgical implants.
  4. Tan KL, Lee WH, Kim JW
    Eur Arch Otorhinolaryngol, 2017 Jan;274(1):223-229.
    PMID: 27423641 DOI: 10.1007/s00405-016-4201-4
    The skull base attachment of the second lamella and suprabullar pneumatization are likely to be consistent landmarks if they are systematically classified. This study aimed to classify the pneumatization pattern according to the second lamella skull base attachment. A total of 202 computed tomography sides of 101 patients who underwent endoscopic sinus surgery were studied. Suprabullar pneumatization was defined as air cells present above the ethmoid bulla between the second and third lamellae. Its pattern was classified according to the air cell number and location as in the frontal cell classification. Type 0 suprabullar pneumatization was defined as no air cells between the ethmoid bulla and skull base; type 1, as a single suprabullar cell; and type 2, as multiple suprabullar cells above the ethmoid bulla. In type 3 pneumatization, the second lamella extended into the frontal sinus forming a frontal bullar cell. Type 2 was the most prevalent (40.1 %), followed by types 1, 3, and 0 (24.3, 23.3, and 12.4 %, respectively). The distance between the second lamella and anterior ethmoid artery was 8.93, 8.30, 8.50, and 11.25 mm in types 0, 1, 2, and 3 pneumatization, respectively. No patients had intraoperative injuries in the anterior ethmoid artery or lateral lamella. The second lamella skull base attachment and suprabullar pneumatization pattern could be systematically classified and be a consistent landmark to identify the frontal sinus opening.
  5. Lee WH, Loo CY, Rohanizadeh R
    Mater Sci Eng C Mater Biol Appl, 2019 Jun;99:929-939.
    PMID: 30889767 DOI: 10.1016/j.msec.2019.02.030
    This study has evaluated the effect of functionalizing surface charges of hydroxyapatite on the modulation of loading and release of curcumin nanoparticles. The increase in loading and release of curcumin nanoparticles indirectly translates to enhanced anti-cancer effect. Owing to the hydrophobic characteristics of curcumin which have resulted in low bioavailability in cancer cells, the engineering curcumin into nanoparticles is therefore a viable solution to overcomes its limitation. In order to maintain a sustained release profile of curcumin nanoparticles, curcumin nanoparticles were loaded (Cur-NPs) onto hydroxyapatite (HA) via physical adsorption. To regulate the adsorption capacity of Cur-NPs onto HA, we functionalized HA with different carboxylic acids (lactic acid, tartaric acid and citric acid). The presence of carboxylic groups on HA significantly affected the binding and the release profile of Cur-NPs. The effects of Cur-NPs loaded HA were evaluated on breast cancer cell line (MCF-7), which included cell proliferation, cellular uptake of Cur-NPs, apoptosis and cell cycle analysis. The results showed that carboxylic acid-functionalized HA demonstrated higher anti-proliferating activity and time dependent cytoplasmic uptake of Cur-NPs in MCF-7 cells compared to unmodified HA. In addition, Cur-NPs loaded on functionalized HA induced higher apoptosis and cell cycle arrest in MCF-7 cells compared to unmodified HA. The present study indicates that the delivery of Cur-NPs to breast cancer using carboxylic acid-functionalized HA carrier could improve their anti-cancer activities.
  6. Loo CY, Lee WH, Zhou QT
    Pharm Res, 2023 May;40(5):1015-1036.
    PMID: 37186073 DOI: 10.1007/s11095-023-03520-1
    With the rapid outbreak of respiratory viral infections, various biological (e.g. vaccines, peptides, recombinant proteins, antibodies and genes) and antiviral agents (e.g. ribavirin, palivizumab and valaciclovir) have been successfully developed for the treatment of respiratory virus infections such as influenza, respiratory syncytial virus and SARS-CoV-2 infections. These therapeutics are conventionally delivered via oral, intramuscular or injection route and are associated with several adverse events due to systemic toxicity. The inherent in vivo instability of biological therapeutics may hinder them from being administered without proper formulations. Therefore, we have witnessed a boom in nanotechnology coupled with a needle-free administration approach such as the inhalation route for the delivery of complex therapeutics to treat respiratory infections. This review discussed the recent advances in the inhalation strategies of nanoformulations that target virus respiratory infections.
  7. Lee WH, Loo CY, Nomura CT, Sudesh K
    Bioresour Technol, 2008 Oct;99(15):6844-51.
    PMID: 18325764 DOI: 10.1016/j.biortech.2008.01.051
    The combination of plant oils and 3-hydroxyvalerate (3HV) precursors were evaluated for the biosynthesis of polyhydroxyalkanoate (PHA) copolymers containing 3HV monomers by Cupriavidus necator H16. Among various mixtures of plant oils and 3HV-precursors, the mixture of palm kernel oil and sodium propionate was suitable for the biosynthesis of high concentration of PHA (6.8gL(-1)) containing 7mol% of 3HV. The 3HV monomer composition can be regulated in the range of 0-23mol% by changing culture parameters such as the initial pH, and the nitrogen source and its concentration. PHA copolymers with high weight-average molecular weights (Mw) ranging from 1,400,000 to 3,100,000Da were successfully produced from mixtures of plant oils and 3HV-precursors. The mixture of plant oils and sodium propionate resulted in PHA copolymers with higher M(w) compared to the mixture of plant oils and sodium valerate. DSC analysis on the PHA containing 3HV monomers showed the presence of two distinct melting temperature (Tm), which indicated that the PHA synthesized might be a blend of P(3HB) and P(3HB-co-3HV). Sodium propionate appears to be the better precursor of 3HV than sodium valerate.
  8. Loo CY, Lee WH, Tsuge T, Doi Y, Sudesh K
    Biotechnol Lett, 2005 Sep;27(18):1405-10.
    PMID: 16215858
    Palm kernel oil, palm olein, crude palm oil and palm acid oil were used for the synthesis of poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(3HB-co-3HHx)] by a mutant strain of Wautersia eutropha (formerly Ralstonia eutropha) harboring the Aeromonas caviae polyhydroxyalkanoate (PHA) synthase gene. Palm kernel oil was an excellent carbon source for the production of cell biomass and P(3HB-co-3HHx). About 87% (w/w) of the cell dry weight as P(3HB-co-3HHx) was obtained using 5 g palm kernel oil/l. Gravimetric and microscopic analyses further confirmed the high PHA content in the recombinant cells. The molar fraction of 3HHx remained constant at 5 mol % regardless of the type and concentration of palm oil products used. The small amount of 3HHx units was confirmed by 13C NMR analysis. The number average molecular weight (M(n)) of the PHA copolymer produced from the various palm oil products ranged from 27 0000 to 46 0000 Da. The polydispersity was in the range of 2.6-3.9.
  9. Lee WH, Lai CW, Hamid SBA
    Materials (Basel), 2015 Aug 28;8(9):5702-5714.
    PMID: 28793530 DOI: 10.3390/ma8095270
    WO₃-decorated TiO₂ nanotube arrays were successfully synthesized using an in situ anodization method in ethylene glycol electrolyte with dissolved H₂O₂ and ammonium fluoride in amounts ranging from 0 to 0.5 wt %. Anodization was carried out at a voltage of 40 V for a duration of 60 min. By using the less stable tungsten as the cathode material instead of the conventionally used platinum electrode, tungsten will form dissolved ions (W(6+)) in the electrolyte which will then move toward the titanium foil and form a coherent deposit on the titanium foil. The fluoride ion content was controlled to determine the optimum chemical dissolution rate of TiO₂ during anodization to produce a uniform nanotubular structure of TiO₂ film. Nanotube arrays were then characterized using FESEM, EDAX, XRD, as well as Raman spectroscopy. Based on the FESEM images obtained, nanotube arrays with an average pore diameter of up to 65 nm and a length of 1.8 µm were produced. The tungsten element in the samples was confirmed by EDAX results which showed varying tungsten content from 0.22 to 2.30 at%. XRD and Raman results showed the anatase phase of TiO₂ after calcination at 400 °C for 4 h in air atmosphere. The mercury removal efficiency of the nanotube arrays was investigated by photoirradiating samples dipped in mercury chloride solution with TUV (Tube ultraviolet) 96W UV-B Germicidal light. The nanotubes with the highest aspect ratio (15.9) and geometric surface area factor (92.0) exhibited the best mercury removal performance due to a larger active surface area, which enables more Hg(2+) to adsorb onto the catalyst surface to undergo reduction to Hg⁰. The incorporation of WO₃ species onto TiO₂ nanotubes also improved the mercury removal performance due to improved charge separation and decreased charge carrier recombination because of the charge transfer from the conduction band of TiO₂ to the conduction band of WO₃.
  10. Lee WH, Loo CY, Leong CR, Young PM, Traini D, Rohanizadeh R
    Expert Opin Drug Deliv, 2017 08;14(8):937-957.
    PMID: 27759437 DOI: 10.1080/17425247.2017.1247804
    INTRODUCTION: The effectiveness of conventional cancer chemotherapy is hampered by the occurrence of multidrug resistance (MDR) in tumor cells. Although many studies have reported the development of novel MDR chemotherapeutic agents, clinical success is lacking owing to the high associated toxicity. Nanoparticle-based delivery of chemotherapeutic drugs has emerged as alternative approach to treat MDR cancers via exploitation of leaky vasculature in the tumor microenvironment. Accordingly, functionalization of nanoparticles with target specific ligands can be employed to achieve significant improvements in the treatment of MDR cancer. Areas covered: This review focuses on the recent advances in the functionalization of nanocarriers with specific ligands, including antibodies, transferrin, folate, and peptides to overcome MDR cancer. The limitations of effective ligand-functionalized nanoparticles as well as therapeutic successes in ligand targeting are covered in the review. Expert opinion: Targeting MDR tumors with ligand-functionalized nanoparticles is a promising approach to improve the treatment of cancer. With this approach, higher drug concentrations at targeted sites would be achieved with lower dosage frequencies and reduced side effects in comparison to existing formulations of chemotherapeutic drugs. However, potential toxicities and immunological responses to ligands should be carefully reviewed for viable options in for future MDR cancer treatment.
  11. Sulaiman E, Alarami N, Wong YI, Lee WH, Al-Haddad A
    Dent Med Probl, 2018 10 18;55(3):275-279.
    PMID: 30328305 DOI: 10.17219/dmp/94656
    BACKGROUND: There is no sufficient literature on the effect of post location on endodontically treated premolar teeth with 2 roots.

    OBJECTIVES: The aim of the study was to evaluate the effect of fiber post location on fracture resistance and failure mode of endodontically treated premolars with 2 roots.

    MATERIAL AND METHODS: Fifty extracted maxillary first premolars with 2 roots were divided randomly into 5 groups. Group 1 was comprised of sound teeth, which received only metal crowns (control). Teeth from groups 2, 3, 4, and 5 were decoronated 2 mm above the cementoenamel junction (CEJ) and were endodontically treated. No post was placed in group 2 teeth. Teeth from groups 3, 4 and 5 were given a fiber post placed in the buccal canal, palatal canal, and both buccal and palatal canals, respectively. All teeth in groups 2, 3, 4, and 5 were built up with composite and full coverage metal crowns. A compressive static load was applied at an angle of 25° to the crowns with a crosshead speed of 0.5 mm/min, until fracture.

    RESULTS: One-way analysis of variance (ANOVA) showed significant differences among the groups (p = 0.002). A post hoc test showed significantly lower fracture resistance of group 4 compared to group 5 (p = 0.011). Furthermore, group 2 had significantly less fracture resistance compared to group 1 (p = 0.021) and group 5 (p = 0.002). According to Fisher's exact test, different post locations are non-significantly associated with fracture mode (p = 0.256).

    CONCLUSIONS: Fiber post location has a significant effect on fracture resistance of severely damaged, endodontically treated maxillary premolars with 2 roots. However, post placement in the palatal root is preferred, as it maintains the restorability of the tooth.

  12. Lee WH, Loo CY, Ghadiri M, Leong CR, Young PM, Traini D
    Adv Drug Deliv Rev, 2018 08;133:107-130.
    PMID: 30189271 DOI: 10.1016/j.addr.2018.08.012
    Lung cancer is a highly invasive and prevalent disease with ineffective first-line treatment and remains the leading cause of cancer death in men and women. Despite the improvements in diagnosis and therapy, the prognosis and outcome of lung cancer patients is still poor. This could be associated with the lack of effective first-line oncology drugs, formation of resistant tumors and non-optimal administration route. Therefore, the repurposing of existing drugs currently used for different indications and the introduction of a different method of drug administration could be investigated as an alternative to improve lung cancer therapy. This review describes the rationale and development of repositioning of drugs for lung cancer treatment with emphasis on inhalation. The review includes the current progress of repurposing non-cancer drugs, as well as current chemotherapeutics for lung malignancies via inhalation. Several potential non-cancer drugs such as statins, itraconazole and clarithromycin, that have demonstrated preclinical anti-cancer activity, are also presented. Furthermore, the potential challenges and limitations that might hamper the clinical translation of repurposed oncology drugs are described.
  13. Loo CY, Lee WH, Lauretani G, Scalia S, Cipolla D, Traini D, et al.
    Pharm Res, 2018 Feb 07;35(3):50.
    PMID: 29417313 DOI: 10.1007/s11095-018-2350-4
    PURPOSE: The failure of chronic therapy with antibiotics to clear persistent respiratory infection is the key morbidity and mortality factor for patients with chronic lung diseases, primarily due to the presence of biofilm in the lungs. It is hypothesised that carbon sources, such as mannitol, could stimulate the metabolic activity of persister cells within biofilms and restore their susceptibility to antibiotics. The aims of the current study are to: (1) establish a representative in vitro model of Pseudomonas aeruginosa biofilm lung infection, and (2) investigate the effects of nebulised mannitol on antibiotic efficacy, focusing on ciprofloxacin, in the eradication of biofilm.

    METHOD: Air interface biofilm was cultured onto Snapwell inserts incorporated into a modified pharmacopeia deposition apparatus, the Anderson Cascade Impactor (ACI). Three different formulations including mannitol only, ciprofloxacin only and combined ciprofloxacin and mannitol were nebulised onto the P. aeruginosa biofilm using the modified ACI. Antibacterial effectiveness was evaluated using colony-forming units counts, biofilm penetration and scanning electron microscopy.

    RESULTS: Nebulised mannitol promotes the dispersion of bacteria from the biofilm and demonstrated a synergistic enhancement of the antibacterial efficacy of ciprofloxacin compared to delivery of antibiotic alone.

    CONCLUSIONS: The combination of ciprofloxacin and mannitol may provide an important new strategy to improve antibiotic therapy for the treatment of chronic lung infections. Furthermore, the development of a representative lung model of bacterial biofilm could potentially be used as a platform for future new antimicrobial pre-clinical screening.

  14. Dash S, Kamath MG, Sharma K, Lee WH, Ponusamy T, Pathmaseelan K, et al.
    MyJurnal
    Introduction: Sleep deprivation is a concern in young adults and the use of mobile phone is very common in this population. This study aimed to measure and correlate the sleep quality, pattern of sleep and problematic mobile phone use in young medical students. Methods: A cross-sectional study was conducted using the Pittsburgh Sleep Quality Index (PSQI), Problematic Mobile Phone Use Scale (PMPUS) and Morningness-Eveningness Questionnaire (MEQ) among medical students in a Malaysian medical college. Correlation among the variables was done using bi-variate analysis followed by Pearson correlation coefficient and 2-tailed significance. A level for p  0.05 was con- sidered as statistically significant. Results: We found significant positive correlation between poor sleep quality and total problematic mobile phone use as well as its sub dimensions, namely deprivation, adverse outcomes and control disorder. PSQI score showed significant negative correlation with different patterns of MEQ like moderate evening, late sleepers, moderate morning and early risers. Positive correlation of the PSQI with sub dimension of PMPUS re- flects unhealthy dependency on mobile phone in this population. Conclusion: Our study revealed that the unhealthy use of mobile phone adversely affected sleep quality in the cohort of young medical students. It is thus important for medical schools to formulate policies and create educational programs vis-a-vis sleep health and to increase aware- ness regarding controlled mobile phone usage.
    Study site: Indian campus of a Malaysian-Indian University
  15. Prakash P, Lee WH, Loo CY, Wong HSJ, Parumasivam T
    Nanomaterials (Basel), 2022 Jan 05;12(1).
    PMID: 35010124 DOI: 10.3390/nano12010175
    Polyhydroxyalkanoates (PHAs) are natural polymers produced under specific conditions by certain organisms, primarily bacteria, as a source of energy. These up-and-coming bioplastics are an undeniable asset in enhancing the effectiveness of drug delivery systems, which demand characteristics like non-immunogenicity, a sustained and controlled drug release, targeted delivery, as well as a high drug loading capacity. Given their biocompatibility, biodegradability, modifiability, and compatibility with hydrophobic drugs, PHAs often provide a superior alternative to free drug therapy or treatments using other polymeric nanocarriers. The many formulation methods of existing PHA nanocarriers, such as emulsion solvent evaporation, nanoprecipitation, dialysis, and in situ polymerization, are explained in this review. Due to their flexibility that allows for a vessel tailormade to its intended application, PHA nanocarriers have found their place in diverse therapy options like anticancer and anti-infective treatments, which are among the applications of PHA nanocarriers discussed in this article. Despite their many positive attributes, the advancement of PHA nanocarriers to clinical trials of drug delivery applications has been stunted due to the polymers' natural hydrophobicity, controversial production materials, and high production costs, among others. These challenges are explored in this review, alongside their existing solutions and alternatives.
  16. Kwan MK, Chiu CK, Hasan MS, Tan SH, Loh LH, Yeo KS, et al.
    Spine (Phila Pa 1976), 2019 03 15;44(6):E348-E356.
    PMID: 30130336 DOI: 10.1097/BRS.0000000000002848
    STUDY DESIGN: Retrospective study.

    OBJECTIVE: To evaluate the perioperative outcome of dual attending surgeon strategy for severe adolescent idiopathic scoliosis (AIS) patients with Cobb angle more than or equal to 90°.

    SUMMARY OF BACKGROUND DATA: The overall complication rate for AIS remains significant and is higher in severe scoliosis. Various operative strategies had been reported for severe scoliosis. However the role of dual attending surgeon strategy in improving the perioperative outcome in severe scoliosis has not been investigated.

    METHODS: The patients were stratified into two groups, Cobb angles 90° to 100° (Group 1) and more than 100° (Group 2). Demographic, intraoperative, preoperative, and postoperative day 2 data were collected. The main outcome measures were intraoperative blood loss, use of allogeneic blood transfusion, operative time, duration of hospital stay postsurgery, and documentation of any perioperative complications.

    RESULTS: Eighty-five patients were recruited. The mean age for the whole cohort was 16.2 ± 5.2 years old. The mean age of Group 1 was 16.7 ± 5.7 and Group 2 was 15.6 ± 4.8 years old. The majority of the patients in both groups were Lenke 2 curves with the average Cobb angle of 93.9 ± 3.0° in Group 1 and 114.2 ± 10.2° in Group 2. The average operative time was 198.5 ± 47.5 minutes with an average blood loss of 1699.5 ± 939.3 mL. The allogeneic blood transfusion rate was 17.6%. The average length of stay postoperation was 71.6 ± 22.5 hours. When comparing the patients between Group 1 and Group 2, the operating time, total blood loss, allogeneic transfusion rate showed significant intergroup differences. Five complications were documented (one intraoperative seizure, one massive blood loss, one intraoperative loss of somatosensory evoked potential (SSEP) signal, and two superficial wound breakdown).

    CONCLUSION: Dual attending surgeon strategy in severe AIS more than or equal to 90° demonstrated an average operative time of 199 minutes, intraoperative blood loss of 1.7 L, postoperative hospital stay of 71.6 hours, and a complication rate of 5.9% (5/85 patients). Curves with Cobb angle more than 100° lead to longer operating time, greater blood loss, and allogeneic transfusion rate.

    LEVEL OF EVIDENCE: 4.

  17. Zhu J, Lee WH, Yip KC, Wu Z, Wu J, Leaw CP, et al.
    Sci Total Environ, 2023 May 10;872:162236.
    PMID: 36791857 DOI: 10.1016/j.scitotenv.2023.162236
    The dinoflagellates Gambierdiscus and Fukuyoa can produce Ciguatoxins (CTXs) and Maitotoxins (MTXs) that lead to ciguatera poisoning (CP). The CP hotspots, however, do not directly relate to the occurrence of the ciguatoxic Gambierdiscus and Fukuyoa. Species-wide investigations often showed no association between CTX level and the molecular identity of the dinoflagellates. In the Pacific region, Kiribati is known as a CP hotspot, while Malaysia has only three CP outbreaks reported thus far. Although ciguatoxic strains of Gambierdiscus were isolated from both Kiribati and Malaysia, no solid evidence on the contribution of ciguatoxic strains to the incidence of CP outbreak was recorded. The present study aims to investigate the regional differences in CP risks through region-specific toxicological assessment of Gambierdiscus and Fukuyoa. A total of 19 strains of Gambierdiscus and a strain of Fukuyoa were analyzed by cytotoxicity assay of the neuro-2a cell line, hemolytic assay of fish erythrocytes, and high-resolution mass spectrometry. Gambierdiscus from both Kiribati and Malaysia showed detectable ciguatoxicity; however, the Kiribati strains were more hemolytic. Putative 44-methylgambierone was identified as part of the contributors to the hemolytic activity, and other unknown hydrophilic toxins produced can be potentially linked to higher CP incidence in Kiribati.
  18. Lee ZY, Lee WH, Lim JS, Ali AAA, Loo JSE, Wibowo A, et al.
    Life Sci, 2024 Sep 01;352:122868.
    PMID: 38936604 DOI: 10.1016/j.lfs.2024.122868
    Membrane trafficking within the Golgi apparatus plays a pivotal role in the intracellular transportation of lipids and proteins. Dysregulation of this process can give rise to various pathological manifestations, including cancer. Exploiting Golgi defects, cancer cells capitalise on aberrant membrane trafficking to facilitate signal transduction, proliferation, invasion, immune modulation, angiogenesis, and metastasis. Despite the identification of several molecular signalling pathways associated with Golgi abnormalities, there remains a lack of approved drugs specifically targeting cancer cells through the manipulation of the Golgi apparatus. In the initial section of this comprehensive review, the focus is directed towards delineating the abnormal Golgi genes and proteins implicated in carcinogenesis. Subsequently, a thorough examination is conducted on the impact of these variations on Golgi function, encompassing aspects such as vesicular trafficking, glycosylation, autophagy, oxidative mechanisms, and pH alterations. Lastly, the review provides a current update on promising Golgi apparatus-targeted inhibitors undergoing preclinical and/or clinical trials, offering insights into their potential as therapeutic interventions. Significantly more effort is required to advance these potential inhibitors to benefit patients in clinical settings.
  19. Ong MZ, Kimberly SA, Lee WH, Ling M, Lee M, Tan KW, et al.
    Curr Pharm Biotechnol, 2024;25(11):1377-1393.
    PMID: 39034731 DOI: 10.2174/0113892010257212231001082741
    CAR T-cell therapy is a promising approach for cancer treatment, utilizing a patient's own T-cells (autologous cell) or T-cells from a healthy donor (allogeneic cell) to target and destroy cancer cells. Over the last decade, significant advancements have been made in this field, including the development of novel CAR constructs, improved understanding of biology and mechanisms of action, and expanded clinical applications for treating a wider range of cancers. In this review, we provide an overview of the steps involved in the production of CAR T-cells and their mechanism of action. We also introduce different CAR T-cell therapies available, including their implementation, dosage, administration, treatment cost, efficacy, and resistance. Common side effects of CAR T-cell therapy are also discussed. The CAR T-cell products highlighted in this review are FDA-approved products, which include Kymriah® (tisagenlecleucel), Tecartus® (brexucabtagene autoleucel), Abecma® (Idecabtagene vicleucel), Breyanzi® (lisocabtagene maraleucel), and Yescarta® (axicabtagene ciloleucel). In conclusion, CAR T-cell therapy has made tremendous progress over the past decade and has the potential to revolutionize cancer treatment. This review paper provides insights into the progress, challenges, and future directions of CAR T-cell therapy, offering valuable information for researchers, clinicians, and patients.
  20. Dai X, Mak YL, Lu CK, Mei HH, Wu JJ, Lee WH, et al.
    Harmful Algae, 2017 07;67:107-118.
    PMID: 28755713 DOI: 10.1016/j.hal.2017.07.002
    Recent molecular phylogenetic studies of Gambierdiscus species flagged several new species and genotypes, thus leading to revitalizing its systematics. The inter-relationships of clades revealed by the primary sequence information of nuclear ribosomal genes (rDNA), however, can sometimes be equivocal, and therefore, in this study, the taxonomic status of a ribotype, Gambierdiscus sp. type 6, was evaluated using specimens collected from the original locality, Marakei Island, Republic of Kiribati; and specimens found in Rawa Island, Peninsular Malaysia, were further used for comparison. Morphologically, the ribotype cells resembled G. scabrosus, G. belizeanus, G. balechii, G. cheloniae and G. lapillus in thecal ornamentation, where the thecal surfaces are reticulate-foveated, but differed from G. scabrosus by its hatchet-shaped Plate 2', and G. belizeanus by the asymmetrical Plate 3'. To identify the phylogenetic relationship of this ribotype, a large dataset of the large subunit (LSU) and small subunit (SSU) rDNAs were compiled, and performed comprehensive analyses, using Bayesian-inference, maximum-parsimony, and maximum-likelihood, for the latter two incorporating the sequence-structure information of the SSU rDNA. Both the LSU and SSU rDNA phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between Gambierdiscus sp. type 6 and G. balechii was monophyletic. As a result, the taxonomic status of Gambierdiscus sp. type 6 was revised, and assigned as Gambierdiscus balechii. Toxicity analysis using neuroblastoma N2A assay confirmed that the Central Pacific strains were toxic, ranging from 1.1 to 19.9 fg P-CTX-1 eq cell-1, but no toxicity was detected in a Western Pacific strain. This suggested that the species might be one of the species contributing to the high incidence rate of ciguatera fish poisoning in Marakei Island.
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