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  1. Tiong TJ, Low LE, Teoh HJ, Chin JK, Manickam S
    Ultrason Sonochem, 2015 Nov;27:165-70.
    PMID: 26186833 DOI: 10.1016/j.ultsonch.2015.04.033
    Ultrasonic VialTweeter is used for the sonication of small volume samples. It contains a titanium block with 8 holes for vial insertion, to be used simultaneously for batch operation. In this investigation, the ultrasonic and sonochemical performance of ultrasonic VialTweeter has been evaluated at its different positions. Experimental results using calorimetry, ultrasonic capillary effect, sonochemiluminescence and degradation of Rhodamine B showed that the sonochemical activity differs greatly at different positions along the VialTweeter, with positions 3 and 4 showing the maximum efficiency whereas the positions 1 and 2 being the least effective positions. These results were further verified by acoustic pressure simulation, confirming that certain locations in the VialTweeter may not perform in the same way as others due to the variation in acoustic pressure at different locations.
  2. Low LE, Tan LT, Goh BH, Tey BT, Ong BH, Tang SY
    Int J Biol Macromol, 2019 Apr 15;127:76-84.
    PMID: 30639596 DOI: 10.1016/j.ijbiomac.2019.01.037
    Stimuli-responsive drug release and controlled delivery play crucial roles in enhancing the therapeutic efficacy and lowering over-dosage induced side effects. In this paper, we report magnetically-triggered drug release and in-vitro anti-colon cancer efficacy of Fe3O4@cellulose nanocrystal (MCNC)-stabilized Pickering emulsions containing curcumin (CUR). The loading efficiency of CUR in the micron-sized (≈7 μm) MCNC-stabilized Pickering emulsions (MCNC-PE) template was found to be 99.35%. The drug release profiles showed that the exposure of MCNC-PE to external magnetic field (EMF) (0.7 T) stimulated the release of bioactive from MCNC-PE achieving 53.30 ± 5.08% of the initial loading over a 4-day period. The MTT assay demonstrated that the CUR-loaded MCNC-PE can effectively inhibits the human colon cancer cells growth down to 18% in the presence of EMF. The formulation also resulted in 2-fold reduction on the volume of the 3-D multicellular spheroids of HCT116 as compared to the control sample. The MCNC particle was found to be non-toxic to brine shrimp up to a concentration of 100 μg/mL. Our findings suggested that the palm-based MCNC-PE could be a promising yet effective colloidal drug delivery system for magnetic-triggered release of bioactive and therapeutics.
  3. Low LE, Tey BT, Ong BH, Chan ES, Tang SY
    Carbohydr Polym, 2017 Jan 02;155:391-399.
    PMID: 27702526 DOI: 10.1016/j.carbpol.2016.08.091
    We studied the formation of palm olein-in-water (O/W) Pickering emulsion stabilized by Fe3O4-cellulose nanocrystals (MCNC) nanocomposites obtained by ultrasound assisted in-situ co-precipitation method. The synthesized MCNC nanocomposites successfully stabilized Pickering emulsion with dual responses. The magnetic tests revealed a direct-relation between attractability of MCNC-stabilized Pickering emulsions and the emulsion droplet diameter. The Pickering emulsions were stable under pH ranging from 3 to 6. The stability substantially reduced around pH 8-10, and regained slowly when approaching pH 13. From microscopic and mastersizer analysis, monodisperse emulsion droplets were noticed at pH 3-6, and 13, while polydisperse emulsion were obtained at pH 8-12. The Pickering emulsions prepared at pH 6 are stable up to 14 days, while Pickering emulsions at pH 8 experienced coalescence. In this study, the dual stimuli-responsive Pickering emulsion stabilized by MCNC may hold potentials for biomedical and drug delivery as new generation of smart nanotherapeutic carrier.
  4. Low LE, Siva SP, Ho YK, Chan ES, Tey BT
    Adv Colloid Interface Sci, 2020 Mar;277:102117.
    PMID: 32035999 DOI: 10.1016/j.cis.2020.102117
    Recently, there have been increasing demand for the application of Pickering emulsions in various industries due to its combined advantage in terms of cost, quality and sustainability. This review aims to provide a complete overview of the available methodology for the physical characterization of emulsions that are stabilized by solid particles (known as Pickering emulsion). Current approaches and techniques for the analysis of the formation and properties of the Pickering emulsion were outlined along with the expected results of these methods on the emulsions. Besides, the application of modelling techniques has also been elaborated for the effective characterization of Pickering emulsions. Additionally, approaches to assess the stability of Pickering emulsions against physical deformation such as coalescence and gravitational separation were reviewed. Potential future developments of these characterization techniques were also briefly discussed. This review can act as a guide to researchers to better understand the standard procedures of Pickering emulsion assessment and the advanced methods available to date to study these emulsions, down to the minute details.
  5. Low LE, Wu J, Lee J, Tey BT, Goh BH, Gao J, et al.
    J Control Release, 2020 Aug 10;324:69-103.
    PMID: 32423874 DOI: 10.1016/j.jconrel.2020.05.014
    The recent designs of dynamic nanoassemblies exploiting the tumor-targeting properties have received increasing attention for tumor imaging and therapy due to their tumor-specific delivery and enhanced antitumor efficacy. However, these designs are mainly focused on the macroscopic tumor therapeutic effect, while the nano-bio interactions in the tumor microenvironment (TME) remain poorly understood. This review aims to provide an overview of the development of tumor-responsive nanoassemblies towards the imaging, therapy and TME modulation in the tumor site. The tumor biology leading to TME formation and the potential TME properties for the practicable design of tumor-targeting nanoassemblies has been outlined. Furthermore, the various approaches for TME modification and the realization via dynamic nanoassemblies for enhanced tumor therapy were reviewed. Lastly, the prospects of these methods were briefly discussed. These strategies may inspire the development of new combinational cancer therapeutics.
  6. Wang Q, Liang Z, Li F, Lee J, Low LE, Ling D
    Exploration (Beijing), 2021 Oct;1(2):20210009.
    PMID: 37323214 DOI: 10.1002/EXP.20210009
    Contrast agents can improve the sensitivity and resolution of magnetic resonance imaging (MRI) by accelerating the relaxation times of surrounding water protons. The MRI performances of contrast agents are closely related to their structural characteristics, including size, shape, surface modification, and so on. Recently, dynamically switchable MRI contrast agents that can undergo structural changes and imaging functional activations upon reaching the disease microenvironment have been developed for high performance MRI. This perspective highlights the ingenious design, controllable structural transformation, and tunable imaging property of dynamic MRI contrast agents. Additionally, the current challenges of the dynamic MRI contrast agents for medical diagnosis are discussed. Furthermore, the future integration of high-resolution ultra-high field MRI technology and cutting-edge dynamic MRI contrast agents for non-invasive histopathological level accurate detection of microscopic lesions are commented.
  7. Kuppusamy G, Kong CK, Segaran GC, Tarmalingam E, Herriman M, Ismail MF, et al.
    Biology (Basel), 2020 Sep 05;9(9).
    PMID: 32899563 DOI: 10.3390/biology9090274
    Black soldier fly (BSF) larva is an attractive animal feed replacer due to its noticeable nutritional content. However, the conventional rearing method often resulted in BSF with undesirably high heavy metal residues that are harmful to animals. In this work, putrefied Sesbania grandiflora (S. Grandiflora) leaves were employed as feed to rear BSF larvae. The resultant BSF prepupae were found to contain 43.5% protein and 16.7% fat, reflecting a comparable protein content and a 2-fold reduction in crude fat than those reared using conventional kitchen waste. Moreover, high quantities of arginine (25.4 g/kg dry matter basis (DM)), carnitine (32.9 g/kg DM), and short-chain fatty acids, including lauric (40.00%), palmitic (19.20%), and oleic (12.10%) acids, have also been noticed in the BSF prepupae. Furthermore, the BSF larvae have been recorded with 0.185 mg/kg chromium, 0.380 mg/kg selenium, and mercury below the detection limit, which is far lower than those reared using conventional kitchen and agricultural wastes (≈1.7 mg/kg chromium, 1.2 mg/kg selenium, and 0.2 mg/kg mercury). Overall, the study shows that the nutritional quality of BSF prepupae is extensively improved when using S. Grandiflora as their feed. The resultant BSF prepupae may serve as an alternative feed for animal rearing.
  8. Kong CK, Low LE, Siew WS, Yap WH, Khaw KY, Ming LC, et al.
    Front Pharmacol, 2020;11:552453.
    PMID: 33679383 DOI: 10.3389/fphar.2020.552453
    Snowdrop is an iconic early spring flowering plant of the genus Galanthus (Amaryllidaceae). Galanthus species (Galanthus spp.) are economically important plants as ornaments. Galanthus spp has gained significance scientific and commercial interest due to the discovery of Galanthamine as symptomatic treatment drug for Alzhiermer disease. This review aims to discuss the bioactivities of Galanthus spp including anticholinesterase, antimicrobial, antioxidant and anticancer potential of the extracts and chemical constituents of Galanthus spp. This review highlights that Galanthus spp. as the exciting sources for drug discovery and nutraceutical development.
  9. Low LE, Wang Q, Chen Y, Lin P, Yang S, Gong L, et al.
    Nanoscale, 2021 Jun 17;13(23):10197-10238.
    PMID: 34027535 DOI: 10.1039/d1nr02127c
    Neurodegenerative disorder is an illness involving neural dysfunction/death attributed to complex pathological processes, which eventually lead to the mortality of the host. It is generally recognized through features such as mitochondrial dysfunction, protein aggregation, oxidative stress, metal ions dyshomeostasis, membrane potential change, neuroinflammation and neurotransmitter impairment. The aforementioned neuronal dysregulations result in the formation of a complex neurodegenerative microenvironment (NME), and may interact with each other, hindering the performance of therapeutics for neurodegenerative disease (ND). Recently, smart nanoassemblies prepared from functional nanoparticles, which possess the ability to interfere with different NME factors, have shown great promise to enhance the diagnostic and therapeutic efficacy of NDs. Herein, this review highlights the recent advances of stimuli-responsive nanoassemblies that can effectively combat the NME for the management of ND. The first section outlined the NME properties and their interrelations that are exploitable for nanoscale targeting. The discussion is then extended to the controlled assembly of functional nanoparticles for the construction of stimuli-responsive nanoassemblies. Further, the applications of stimuli-responsive nanoassemblies for the enhanced diagnosis and therapy of ND are introduced. Finally, perspectives on the future development of NME-tailored nanomedicines are given.
  10. Low LE, Wong SK, Tang SY, Chew CL, De Silva HA, Lee JMV, et al.
    Ultrason Sonochem, 2019 Jun;54:121-128.
    PMID: 30827901 DOI: 10.1016/j.ultsonch.2019.02.008
    The current work proposed an alternative ultrasound (US) technology, namely the high-intensity ultrasonic tubular reactor (HUTR) for preparing Pickering emulsions. Using the non-toxic and environmentally friendly cellulose nanocrystal (CNC) as a solid stabilizer, Pickering emulsions were produced using the HUTR and the results showed that Pickering emulsions as small as 1.5 µm can be produced using HUTR at the US power and sonication time of 300 W and 15 min respectively. Additionally, the sizes of Pickering emulsion obtained are found to remain the same upon 30 days of storage. The performance of HUTR in emulsion preparation is compared to conventional US horn system at the same US power. It was observed that the use of HUTR allowed generation of Pickering emulsion that is significantly smaller (around 7.40 μm) and with better droplet size distribution (Coefficient of variation, CV = 31%) as compared to those prepared with US horn method (12.75 µm, CV = 36%). This is owing to the better distribution of cavitation activity in the treatment chamber of HUTR as compared to those in the horn, according to the sonochemiluminescence (SCL) study. From the 30-days storage stability analysis, the CNC-PE prepared using HUTR was found to more stable against droplet coalescence in comparison to those prepared using US horn. Our findings suggested that the HUTR possessed superior Pickering emulsification capacity when compared to conventional US horn. Further work will be necessary to evaluate the feasibility of such intensifying tubular reactor technology for larger scale emulsification and other process intensification applications.
  11. Shin Low S, Nong Lim C, Yew M, Siong Chai W, Low LE, Manickam S, et al.
    Ultrason Sonochem, 2021 Dec;80:105805.
    PMID: 34706321 DOI: 10.1016/j.ultsonch.2021.105805
    Recent advances in ultrasound (US) have shown its great potential in biomedical applications as diagnostic and therapeutic tools. The coupling of US-assisted drug delivery systems with nanobiomaterials possessing tailor-made functions has been shown to remove the limitations of conventional drug delivery systems. The low-frequency US has significantly enhanced the targeted drug delivery effect and efficacy, reducing limitations posed by conventional treatments such as a limited therapeutic window. The acoustic cavitation effect induced by the US-mediated microbubbles (MBs) has been reported to replace drugs in certain acute diseases such as ischemic stroke. This review briefly discusses the US principles, with particular attention to the recent advancements in drug delivery applications. Furthermore, US-assisted drug delivery coupled with nanobiomaterials to treat different diseases (cancer, neurodegenerative disease, diabetes, thrombosis, and COVID-19) are discussed in detail. Finally, this review covers the future perspectives and challenges on the applications of US-mediated nanobiomaterials.
  12. Low SS, Yew M, Lim CN, Chai WS, Low LE, Manickam S, et al.
    Ultrason Sonochem, 2022 Jan;82:105887.
    PMID: 34954629 DOI: 10.1016/j.ultsonch.2021.105887
    Ultrasound (US) demonstrates remarkable potential in synthesising nanomaterials, particularly nanobiomaterials targeted towards biomedical applications. This review briefly introduces existing top-down and bottom-up approaches for nanomaterials synthesis and their corresponding synthesis mechanisms, followed by the expounding of US-driven nanomaterials synthesis. Subsequently, the pros and cons of sono-nanotechnology and its advances in the synthesis of nanobiomaterials are drawn based on recent works. US-synthesised nanobiomaterials have improved properties and performance over conventional synthesis methods and most essentially eliminate the need for harsh and expensive chemicals. The sonoproduction of different classes and types of nanobiomaterials such as metal and superparamagnetic nanoparticles (NPs), lipid- and carbohydrate-based NPs, protein microspheres, microgels and other nanocomposites are broadly categorised based on the physical and/or chemical effects induced by US. This review ends on a good note and recognises US-driven synthesis as a pragmatic solution to satisfy the growing demand for nanobiomaterials, nonetheless some technical challenges are highlighted.
  13. 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.
  14. Tan PX, Thiyagarasaiyar K, Tan CY, Jeon YJ, Nadzir MSM, Wu YJ, et al.
    Mar Drugs, 2021 May 30;19(6).
    PMID: 34070821 DOI: 10.3390/md19060317
    Air pollution has recently become a subject of increasing concern in many parts of the world. The World Health Organization (WHO) estimated that nearly 4.2 million early deaths are due to exposure to fine particles in polluted air, which causes multiple respiratory diseases. Algae, as a natural product, can be an alternative treatment due to potential biofunctional properties and advantages. This systematic review aims to summarize and evaluate the evidence of metabolites derived from algae as potential anti-inflammatory agents against respiratory disorders induced by atmospheric particulate matter (PM). Databases such as Scopus, Web of Science, and PubMed were systematically searched for relevant published full articles from 2016 to 2020. The main key search terms were limited to "algae", "anti-inflammation", and "air pollutant". The search activity resulted in the retrieval of a total of 36 publications. Nine publications are eligible for inclusion in this systematic review. A total of four brown algae (Ecklonia cava, Ishige okamurae, Sargassum binderi and Sargassum horneri) with phytosterol, polysaccharides and polyphenols were reported in the nine studies. The review sheds light on the pathways of particulate matter travelling into respiratory systems and causing inflammation, and on the mechanisms of actions of algae in inhibiting inflammation. Limitations and future directions are also discussed. More research is needed to investigate the potential of algae as anti-inflammatory agents against PM in in vivo and in vitro experimental models, as well as clinically.
  15. Mahendra CK, Tan LTH, Lee WL, Yap WH, Pusparajah P, Low LE, et al.
    Front Pharmacol, 2020;11:366.
    PMID: 32372949 DOI: 10.3389/fphar.2020.00366
    Angelicin, a member of the furocoumarin group, is related to psoralen which is well known for its effectiveness in phototherapy. The furocoumarins as a group have been studied since the 1950s but only recently has angelicin begun to come into its own as the subject of several biological studies. Angelicin has demonstrated anti-cancer properties against multiple cell lines, exerting effects via both the intrinsic and extrinsic apoptotic pathways, and also demonstrated an ability to inhibit tubulin polymerization to a higher degree than psoralen. Besides that, angelicin too demonstrated anti-inflammatory activity in inflammatory-related respiratory and neurodegenerative ailments via the activation of NF-κB pathway. Angelicin also showed pro-osteogenesis and pro-chondrogenic effects on osteoblasts and pre-chondrocytes respectively. The elevated expression of pro-osteogenic and chondrogenic markers and activation of TGF-β/BMP, Wnt/β-catenin pathway confirms the positive effect of angelicin bone remodeling. Angelicin also increased the expression of estrogen receptor alpha (ERα) in osteogenesis. Other bioactivities, such as anti-viral and erythroid differentiating properties of angelicin, were also reported by several researchers with the latter even displaying an even greater aptitude as compared to the commonly prescribed drug, hydroxyurea, which is currently on the market. Apart from that, recently, a new application for angelicin against periodontitis had been studied, where reduction of bone loss was indirectly caused by its anti-microbial properties. All in all, angelicin appears to be a promising compound for further studies especially on its mechanism and application in therapies for a multitude of common and debilitating ailments such as sickle cell anaemia, osteoporosis, cancer, and neurodegeneration. Future research on the drug delivery of angelicin in cancer, inflammation and erythroid differentiation models would aid in improving the bioproperties of angelicin and efficacy of delivery to the targeted site. More in-depth studies of angelicin on bone remodeling, the pro-osteogenic effect of angelicin in various bone disease models and the anti-viral implications of angelicin in periodontitis should be researched. Finally, studies on the binding of angelicin toward regulatory genes, transcription factors, and receptors can be done through experimental research supplemented with molecular docking and molecular dynamics simulation.
  16. Ting NC, Yaakub Z, Kamaruddin K, Mayes S, Massawe F, Sambanthamurthi R, et al.
    BMC Genomics, 2016;17(1):289.
    PMID: 27079197 DOI: 10.1186/s12864-016-2607-4
    The commercial oil palm (Elaeis guineensis Jacq.) produces a mesocarp oil (commonly called 'palm oil') with approximately equal proportions of saturated and unsaturated fatty acids (FAs). An increase in unsaturated FAs content or iodine value (IV) as a measure of the degree of unsaturation would help to open up new markets for the oil. One way to manipulate the fatty acid composition (FAC) in palm oil is through introgression of favourable alleles from the American oil palm, E. oleifera, which has a more unsaturated oil.
  17. Low LE, Kong CK, Yap WH, Siva SP, Gan SH, Siew WS, et al.
    Chem Biol Interact, 2023 Dec 01;386:110750.
    PMID: 37839513 DOI: 10.1016/j.cbi.2023.110750
    Hydroxychloroquine (HCQ) is a unique class of medications that has been widely utilized for the treatment of cancer. HCQ plays a dichotomous role by inhibiting autophagy induced by the tumor microenvironment (TME). Preclinical studies support the use of HCQ for anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they sensitize tumor cells to drugs, potentiating the therapeutic activity. However, clinical evidence has suggested poor outcomes for HCQ due to various obstacles, including non-specific distribution, low aqueous solubility and low bioavailability at target sites, transport across tissue barriers, and retinal toxicity. These issues are addressable via the integration of HCQ with nanotechnology to produce HCQ-conjugated nanomedicines. This review aims to discuss the pharmacodynamic, pharmacokinetic and antitumor properties of HCQ. Furthermore, the antitumor performance of the nanoformulated HCQ is also reviewed thoroughly, aiming to serve as a guide for the HCQ-based enhanced treatment of cancers. The nanoencapsulation or nanoconjugation of HCQ with nanoassemblies appears to be a promising method for reducing the toxicity and improving the antitumor efficacy of HCQ.
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