41 results on '"Lai, Kok-Song"'
Search Results
2. miRNA in Ischemic Heart Disease and Its Potential as Biomarkers: A Comprehensive Review.
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Kong, Amanda Shen-Yee, Lai, Kok-Song, Lim, Swee-Hua Erin, Sivalingam, Sivakumar, Loh, Jiun-Yan, and Maran, Sathiya
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MYOCARDIAL ischemia , *CORONARY disease , *MICRORNA , *BIOMARKERS - Abstract
Ischemic heart disease (IHD) constitutes the leading global cause of mortality and morbidity. Although significant progress has been achieved in the diagnosis, treatment, and prognosis of IHD, more robust diagnostic biomarkers and therapeutic interventions are still needed to circumvent the increasing incidence of IHD. MicroRNAs (miRNAs) are critical regulators of cardiovascular function and are involved in various facets of cardiovascular biology. While the knowledge of the role of miRNAs in IHD as diagnostic biomarkers has improved, research emphasis on how miRNAs can be effectively used for diagnosis and prognosis of IHD is crucial. This review provides an overview of the biology, therapeutic and diagnostic potential, as well as the caveats of using miRNAs in IHD based on existing research. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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3. RNA-Seq analysis revealed genes associated with UV-induced cell necrosis through MAPK/TNF-α pathways in human dermal fibroblast cells as an inducer of premature photoaging.
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Alafiatayo, Akinola Adekoya, Lai, Kok-Song, Ahmad, Syahida, Mahmood, Maziah, and Shaharuddin, Noor Azmi
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T helper cells , *TUMOR necrosis factors , *SOLAR ultraviolet radiation , *APOPTOSIS , *NECROSIS , *GENES , *ULTRAVIOLET radiation - Abstract
Exposing the skin to solar UV radiation induces cascades of signaling pathways and biological alterations such as redox imbalance, suppression of antioxidant genes and programmed cell death. Therefore, the aim of this study was to use RNA-Seq to unravel the effects of UV radiation on Normal Human Adult Fibroblast cells (NHDF). Cells were exposed to UV (20 mJ/cm2 for 3 mins) and incubated for 24 h. Total mRNA from the cells generated libraries of 72,080,648 and 40,750,939 raw reads from UV-treated and control cells respectively. Of the differentially expressed genes (DEGs) produced 2,007 were up-regulated and 2,791 were down-regulated (fold change ≥2, p < 0.05). The expression of 4 genes was validated with RT-qPCR. Chemokine signaling pathways in cancer were significantly activated and antioxidant genes were down-regulated. This study applied Next Generation Sequencing technology to reveal the genes and pathways involved in UV-induced human dermal fibroblast cells necrosis. • The key genes related to UV-induced cell necrosis were investigated by RNA-Seq. • A total of 2007 genes were up-regulated and 2791 down-regulated. • Antioxidant defence genes were greatly suppressed in UV irradiated cells. • Chemokine – signalling and pathways in cancer were activated as a response to UV treatment. [ABSTRACT FROM AUTHOR]
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- 2020
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4. Phytochemical Evaluation, Embryotoxicity, and Teratogenic Effects of Curcuma longa Extract on Zebrafish (Danio rerio).
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Alafiatayo, Akinola Adekoya, Lai, Kok-Song, Syahida, Ahmad, Mahmood, Maziah, and Shaharuddin, Noor Azmi
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ANIMAL experimentation , *DOSE-effect relationship in pharmacology , *FISHES , *FLAVONOIDS , *HERBAL medicine , *HIGH performance liquid chromatography , *INSECT larvae , *PLANT roots , *TERATOGENIC agents , *TOXICITY testing , *TRADITIONAL medicine , *PHYTOCHEMICALS , *PLANT extracts , *EMBRYOS , *TREATMENT effectiveness , *DESCRIPTIVE statistics , *EVALUATION - Abstract
Curcuma longa L. is a rhizome plant often used as traditional medicinal preparations in Southeast Asia. The dried powder is commonly known as cure-all herbal medicine with a wider spectrum of pharmaceutical activities. In spite of the widely reported therapeutic applications of C. longa, research on its safety and teratogenic effects on zebrafish embryos and larvae is still limited. Hence, this research aimed to assess the toxicity of C. longa extract on zebrafish. Using a reflux flask, methanol extract of C. longa was extracted and the identification and quantification of total flavonoids were carried out with HPLC. Twelve fertilized embryos were selected to test the embryotoxicity and teratogenicity at different concentration points. The embryos were exposed to the extract in the E3M medium while the control was only exposed to E3M and different developmental endpoints were recorded with the therapeutic index calculated using the ratio of LC50/EC50. C. longa extract was detected to be highly rich in flavonoids with catechin, epicatechin, and naringenin as the 3 most abundant with concentrations of 3,531.34, 688.70, and 523.83μg/mL, respectively. The toxicity effects were discovered to be dose-dependent at dosage above 62.50μg/mL, while, at 125.0μg/mL, mortality of embryos was observed and physical body deformities of larvae were recorded among the hatched embryos at higher concentrations. Teratogenic effect of the extract was severe at higher concentrations producing physical body deformities such as kink tail, bend trunk, and enlarged yolk sac edema. Finally, the therapeutic index (TI) values calculated were approximately the same for different concentration points tested. Overall, the result revealed that plants having therapeutic potential could also pose threats when consumed at higher doses especially on the embryos. Therefore, detailed toxicity analysis should be carried out on medicinal plants to ascertain their safety on the embryos and its development. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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5. Efficient regeneration and Agrobacterium-mediated transformation protocol for recalcitrant indica rice (Oryza sativa L.).
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Wong Kiing Fook, Clement, Lai Kok Song, Wong Mui Yun, and Mahmood, Maziah
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TRANSGENIC rice , *AGROBACTERIUM , *RICE varieties , *RICE microbiology ,RICE genetics - Abstract
Rice shoot apices have been selected as the potential explant for genetic transformation since lesser time for regeneration and lower incidence of somaclonal variants were reported as compared to embryogenic callus. Utilizing this explant, efficient regeneration and Agrobacterium transformation protocol have been developed for the recalcitrant Malaysian indica rice, MR219. In this study, 4 mg/L of KIN was selected as the suitable cytokinin for multiple shoot formation as compared to TDZ and BAP. KIN was able to produce relatively high number of shoots as well as producing good quality shoots with the highest total chlorophyll content, and moderately high total soluble sugar content. In-vitro shoots were successfully acclimatized in glasshouse without signs of infertility. The optimization of the Agrobacterium-mediated protocol revealed that Agrobacterium supervirulent strain EHA101, shoot apices derived from 4 days old seedlings, excised wounded explants, 30 minutes of bacterial immersion time and 72 hours (3 days) of co-cultivation gave the highest percentage of plant transiently expressing two reporter genes -- GFP and GUS. After 30 days of hygromycin selection and PCR verification of the putative transformants, the transformation efficiency was reported to be 5.83%. The established regeneration system and transformation protocol for MR219 rice shoot apices will serve as an essential fundamental platform for the production of transgenic rice with superior traits. [ABSTRACT FROM AUTHOR]
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- 2015
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6. Post-Transcriptional Regulatory Crosstalk between MicroRNAs and Canonical TGF-β/BMP Signalling Cascades on Osteoblast Lineage: A Comprehensive Review.
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Loh, Hui-Yi, Norman, Brendan P., Lai, Kok-Song, Cheng, Wan-Hee, Nik Abd. Rahman, Nik Mohd Afizan, Mohamed Alitheen, Noorjahan Banu, and Osman, Mohd Azuraidi
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WNT signal transduction , *RUNX proteins , *MESSENGER RNA , *MICRORNA , *BONE growth , *RNA regulation - Abstract
MicroRNAs (miRNAs) are a family of small, single-stranded, and non-protein coding RNAs about 19 to 22 nucleotides in length, that have been reported to have important roles in the control of bone development. MiRNAs have a strong influence on osteoblast differentiation through stages of lineage commitment and maturation, as well as via controlling the activities of osteogenic signal transduction pathways. Generally, miRNAs may modulate cell stemness, proliferation, differentiation, and apoptosis by binding the 3′-untranslated regions (3′-UTRs) of the target genes, which then can subsequently undergo messenger RNA (mRNA) degradation or protein translational repression. MiRNAs manage the gene expression in osteogenic differentiation by regulating multiple signalling cascades and essential transcription factors, including the transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP), Wingless/Int-1(Wnt)/β-catenin, Notch, and Hedgehog signalling pathways; the Runt-related transcription factor 2 (RUNX2); and osterix (Osx). This shows that miRNAs are essential in regulating diverse osteoblast cell functions. TGF-βs and BMPs transduce signals and exert diverse functions in osteoblastogenesis, skeletal development and bone formation, bone homeostasis, and diseases. Herein, we highlighted the current state of in vitro and in vivo research describing miRNA regulation on the canonical TGF-β/BMP signalling, their effects on osteoblast linage, and understand their mechanism of action for the development of possible therapeutics. In this review, particular attention and comprehensive database searches are focused on related works published between the years 2000 to 2022, using the resources from PubMed, Google Scholar, Scopus, and Web of Science. [ABSTRACT FROM AUTHOR]
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- 2023
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7. In-silico identification of deleterious non-synonymous SNPs of TBX1 gene: Functional and structural impact towards 22q11.2DS.
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Almakhari, Maitha, Chen, Yan, Kong, Amanda Shen-Yee, Moradigaravand, Danesh, Lai, Kok-Song, Lim, Swee-Hua Erin, Loh, Jiun-Yan, and Maran, Sathiya
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DIGEORGE syndrome , *SINGLE nucleotide polymorphisms , *PROTEIN stability , *POST-translational modification , *PROTEIN-protein interactions - Abstract
The TBX1 gene plays a critical role in the development of 22q11.2 deletion syndrome (22q11.2DS), a complex genetic disorder associated with various phenotypic manifestations. In this study, we performed in-silico analysis to identify potentially deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TBX1 gene and evaluate their functional and structural impact on 22q11.2DS. A comprehensive analysis pipeline involving multiple computational tools was employed to predict the pathogenicity of nsSNPs. This study assessed protein stability and explored potential alterations in protein-protein interactions. The results revealed the rs751339103(C>A), rs780800634(G>A), rs1936727304(T>C), rs1223320618(G>A), rs1248532217(T>C), rs1294927055 (C>T), rs1331240435 (A>G, rs1601289406 (A>C), rs1936726164 (G>A), and rs911796187(G>A) with a high-risk potential for affecting protein function and stability. These nsSNPs were further analyzed for their impact on post-translational modifications and structural characteristics, indicating their potential disruption of molecular pathways associated with TBX1 and its interacting partners. These findings provide a foundation for further experimental studies and elucidation of potential therapeutic targets and personalized treatment approaches for individuals affected by 22q11.2DS. [ABSTRACT FROM AUTHOR]
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- 2024
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8. Crude Oil Yield and Properties of Rice Bran Oil from Different Varieties as Affected by Extraction Conditions Using Soxhterm Method.
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Daud, Nurul Shafinas Mohd, Zaidel, Dayang Norulfairuz Abang, Lai, Kok Song, Khairuddin, Nozieana, Jusoh, Yanti Maslina Mohd, and Muhamad, Ida Idayu
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PETROLEUM production , *RICE oil , *SOLVENTS - Abstract
The current study was employed to investigate the effect of solvent type, extraction time and bran ratio on the rice bran oil (RBO) properties from three varieties of rice bran namely Bario, lowland and upland rice. RBO was extracted by using soxtherm extraction method using methanol solvent at different extraction time (3, 4 and 5 h) and bran ratio (10, 20 and 30 g). Free fatty acid (FFA), total phenolic content (TPC) and antioxidant properties were assessed. Solvent that has low polarity exhibited the attraction of polar component of oil with the highest yield by ethanol (16.16%), followed by methanol (15.38%). FFA contents occurred higher in lowland types of rice bran in all types of solvents at P<0.05
with ethanol (12.73%), methanol (11.96%) and hexane (11.13%), while the total phenolic content and antioxidant properties were influenced by the types of rice bran and solvents used for extracting components out of the bran. The highest phenolic content in the crude oil was extracted using ethanol in lowland (0.509 mg/ml), and the lowest was extracted by hexane in Bario (0.061 mg/ml). The highest antioxidant activity was observed in RBO extracted using methanol of lowland (73.74%) and RBO extracted using ethanol of upland (73.65%), while the lowest were observed in RBO extracted using hexane. The different types of solvent have the significant impact on the crude oil yield and properties of crude oil extracted. [ABSTRACT FROM AUTHOR] - Published
- 2018
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9. Aflatoxin Contamination: An Overview on Health Issues, Detection and Management Strategies.
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Alameri, Meera Mohamed, Kong, Amanda Shen-Yee, Aljaafari, Mariam Nasser, Ali, Hajer Al, Eid, Khadija, Sallagi, Maryam Al, Cheng, Wan-Hee, Abushelaibi, Aisha, Lim, Swee-Hua Erin, Loh, Jiun-Yan, and Lai, Kok-Song
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AFLATOXINS , *POISONS , *SORGHUM , *ASPERGILLUS parasiticus , *MILK contamination , *PUBLIC health , *ASPERGILLUS flavus ,CORN disease & pest control - Abstract
Aflatoxins (AFs) represent one of the main mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus, with the most prevalent and lethal subtypes being AFB1, AFB2, AFG1, and AFG2. AFs are responsible for causing significant public health issues and economic concerns that affect consumers and farmers globally. Chronic exposure to AFs has been linked to liver cancer, oxidative stress, and fetal growth abnormalities among other health-related risks. Although there are various technologies, such as physical, chemical, and biological controls that have been employed to alleviate the toxic effects of AF, there is still no clearly elucidated universal method available to reduce AF levels in food and feed; the only mitigation is early detection of the toxin in the management of AF contamination. Numerous detection methods, including cultures, molecular techniques, immunochemical, electrochemical immunosensor, chromatographic, and spectroscopic means, are used to determine AF contamination in agricultural products. Recent research has shown that incorporating crops with higher resistance, such as sorghum, into animal feed can reduce the risk of AF contamination in milk and cheese. This review provides a current overview of the health-related risks of chronic dietary AF exposure, recent detection techniques, and management strategies to guide future researchers in developing better detection and management strategies for this toxin. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Promoter Cis-Element Analyses Reveal the Function of αVPE in Drought Stress Response of Arabidopsis.
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Tang, Chu-Nie, Wan Abdullah, Wan Muhamad Asrul Nizam, Wee, Chien-Yeong, Balia Yusof, Zetty Norhana, Yap, Wai-Sum, Cheng, Wan-Hee, Baharum, Nadiya Akmal, Ong-Abdullah, Janna, Loh, Jiun-Yan, and Lai, Kok-Song
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GENE expression profiling , *APOPTOSIS , *DROUGHTS , *DROUGHT tolerance , *PHOTOSYNTHETIC pigments , *ARABIDOPSIS , *ARABIDOPSIS thaliana - Abstract
Simple Summary: Vacuolar processing enzyme (VPE) is a cysteine protease responsible for vacuolar proteins' maturation and regulation of programmed cell death in plants. Among four isoforms of Arabidopsis thaliana VPEs, only the functions of βVPE, γVPE, and δVPE were determined. Hence, to investigate the possible function of αVPE, promoter analysis, co-expression network, gene expression profiling, and loss of function studies were performed. Repetitive drought-related cis-elements such as ABRE, MBS, MYC, and MYB were successfully identified with the aid of PlantCARE and PLACE databases. Similarly, the co-expression network also revealed that genes interacting with αVPE were involved in drought-regulation-related function. In addition, A. thaliana under drought treatment recorded an upregulation of αVPE expression (2.7-fold). Loss of function study through αvpe knockout mutants showed that αvpe mutants remained viable with 22% higher water retention as compared with wild-type after drought treatment. Biochemical analyses recorded a 47% reduction in proline activity, 70% decrease in sucrose content, and 39% lower MDA content, but 50% increased photosynthetic pigments in αvpe mutants. Altogether, our study provided important proof and a foundation for understanding the involvement of αVPE in modulating drought tolerance in A. thaliana. Vacuolar processing enzyme (VPE) is a cysteine protease responsible for vacuolar proteins' maturation and regulation of programmed cell death (PCD). Four isoforms of Arabidopsis thaliana VPEs were identified previously, but only the functions of βVPE, γVPE, and δVPE were determined. The specific function of a gene is linked to the cis-acting elements in the promoter region. A promoter analysis found repetitive drought-related cis-elements in αVPE, which highlight its potential involvement in drought regulation in A. thaliana. The further co-expression network portraying genes interacting with αVPE substantiated its drought-regulation-related function. Expression of αVPE was upregulated after drought treatment in A. thaliana. To confirm the role of αVPE, a loss of function study revealed that αVPE knockout mutants remained green compared with WT after drought treatment. The mutants had reduced proline activity, decreased sucrose content, and lower MDA content, but increased photosynthetic pigments, indicating that αVPE negatively regulates drought tolerance in A. thaliana. Taken together, our findings serve as important evidence of the involvement of αVPE in modulating drought tolerance in A. thaliana. [ABSTRACT FROM AUTHOR]
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- 2023
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11. λ-Carrageenan promotes plant growth in banana via enhancement of cellular metabolism, nutrient uptake, and cellular homeostasis.
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Thye, Kah-Lok, Wan Abdullah, Wan Muhamad Asrul Nizam, Balia Yusof, Zetty Norhana, Wee, Chien-Yeong, Ong-Abdullah, Janna, Loh, Jiun-Yan, Cheng, Wan-Hee, Lamasudin, Dhilia Udie, and Lai, Kok-Song
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BANANAS , *NUTRIENT uptake , *HOMEOSTASIS , *PLANT growth , *MARINE algae as food , *METABOLITES , *PROTEIN synthesis - Abstract
Banana (Musa acuminata) is an important fruit crop and source of income for various countries, including Malaysia. To date, current agrochemical practice has become a disputable issue due to its detrimental effect on the environment. λ-carrageenan, a natural polysaccharide extracted from edible red seaweed, has been claimed to be a potential plant growth stimulator. Hence, the present study investigates the effects of λ-carrageenan on plant growth using Musa acuminata cv. Berangan (AAA). Vegetative growth such as plant height, root length, pseudostem diameter, and fresh weight was improved significantly in λ-carrageenan-treated banana plants at an optimum concentration of 750 ppm. Enhancement of root structure was also observed in optimum λ-carrageenan treatment, facilitating nutrients uptake in banana plants. Further biochemical assays and gene expression analysis revealed that the increment in growth performance was consistent with the increase of chlorophyll content, protein content, and phenolic content, suggesting that λ-carrageenan increases photosynthesis rate, protein biosynthesis, and secondary metabolites biosynthesis which eventually stimulate growth. Besides, λ-carrageenan at optimum concentration also increased catalase and peroxidase activities, which led to a significant reduction in hydrogen peroxide and malondialdehyde, maintaining cellular homeostasis in banana plants. Altogether, λ-carrageenan at optimum concentration improves the growth of banana plants via inducing metabolic processes, enhancing nutrient uptake, and regulation of cell homeostasis. Further investigations are needed to evaluate the effectiveness of λ-carrageenan on banana plants under field conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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12. Identification of NRAS Diagnostic Biomarkers and Drug Targets for Endometrial Cancer—An Integrated in Silico Approach.
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Alessandro, Larsen, Low, Kat-Jun Eric, Abushelaibi, Aisha, Lim, Swee-Hua Erin, Cheng, Wan-Hee, Chang, Sook-keng, Lai, Kok-Song, Sum, Yap Wai, and Maran, Sathiya
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ENDOMETRIAL cancer , *RAS oncogenes , *DRUG target , *GENETIC regulation , *BIOMARKERS , *FORCEPS - Abstract
The diagnosis of endometrial cancer involves sequential, invasive tests to assess the thickness of the endometrium by a transvaginal ultrasound scan. In 6–33% of cases, endometrial biopsy results in inadequate tissue for a conclusive pathological diagnosis and 6% of postmenopausal women with non-diagnostic specimens are later discovered to have severe endometrial lesions. Thus, identifying diagnostic biomarkers could offer a non-invasive diagnosis for community or home-based triage of symptomatic or asymptomatic women. Herein, this study identified high-risk pathogenic nsSNPs in the NRAS gene. The nsSNPs of NRAS were retrieved from the NCBI database. PROVEAN, SIFT, PolyPhen-2, SNPs&GO, PhD-SNP and PANTHER were used to predict the pathogenicity of the nsSNPs. Eleven nsSNPs were identified as "damaging", and further stability analysis using I-Mutant 2.0 and MutPred 2 indicated eight nsSNPs to cause decreased stability (DDG scores < −0.5). Post-translational modification and protein–protein interactions (PPI) analysis showed putative phosphorylation sites. The PPI network indicated a GFR-MAPK signalling pathway with higher node degrees that were further evaluated for drug targets. The P34L, G12C and Y64D showed significantly lower binding affinity towards GTP than wild-type. Furthermore, the Kaplan–Meier bioinformatics analyses indicated that the NRAS gene deregulation affected the overall survival rate of patients with endometrial cancer, leading to prognostic significance. Findings from this could be considered novel diagnostic and therapeutic markers. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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13. CD36-Fatty Acid-Mediated Metastasis via the Bidirectional Interactions of Cancer Cells and Macrophages.
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Zaidi, Noorzaileen Eileena, Shazali, Nur Aima Hafiza, Leow, Thean-Chor, Osman, Mohd Azuraidi, Ibrahim, Kamariah, Cheng, Wan-Hee, Lai, Kok-Song, and Nik Abd Rahman, Nik Mohd Afizan
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TUMOR-infiltrating immune cells , *CANCER cells , *TUMOR microenvironment , *MACROPHAGES , *METASTASIS , *CELL receptors - Abstract
Tumour heterogeneity refers to the complexity of cell subpopulations coexisting within the tumour microenvironment (TME), such as proliferating tumour cells, tumour stromal cells and infiltrating immune cells. The bidirectional interactions between cancer and the surrounding microenvironment mark the tumour survival and promotion functions, which allow the cancer cells to become invasive and initiate the metastatic cascade. Importantly, these interactions have been closely associated with metabolic reprogramming, which can modulate the differentiation and functions of immune cells and thus initiate the antitumour response. The purpose of this report is to review the CD36 receptor, a prominent cell receptor in metabolic activity specifically in fatty acid (FA) uptake, for the metabolic symbiosis of cancer–macrophage. In this review, we provide an update on metabolic communication between tumour cells and macrophages, as well as how the immunometabolism indirectly orchestrates the tumour metastasis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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14. Biochemical Composition and Biological Activities of Date Palm (Phoenix dactylifera L.) Seeds: A Review.
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Alkhoori, Maryam Abdulraheem, Kong, Amanda Shen-Yee, Aljaafari, Mariam Nasser, Abushelaibi, Aisha, Erin Lim, Swee-Hua, Cheng, Wan-Hee, Chong, Chou-Min, and Lai, Kok-Song
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DATE palm , *CROPS , *DATES (Fruit) , *FRUIT processing , *WASTE products , *DIETARY fiber - Abstract
Date palm (Phoenix dactylifera L.) is an essential agricultural crop in most Middle Eastern countries, and its fruit, known as dates, is consumed by millions of people. Date seeds, a by-product of the date fruit processing industry, are a waste product used as food for domestic farm animals. Date seeds contain abundant sources of carbohydrates, oil, dietary fiber, and protein; they also contain bioactive phenolic compounds that may possess potential biological properties. In addition, its rich chemical composition makes date seeds suitable for use in food product formulation, cosmetics, and medicinal supplements. This review aims to provide a discourse on the nutritional value of date seeds. The latest data on the cytotoxicity of date seed compounds against cancer cell lines, its ability to combat diabetes, antioxidant potential, antimicrobial effect, and anti-inflammatory activity will be provided, considering its potential to be a nutritional therapeutic agent for chronic diseases. Application of date seeds in the form of powder and oil will also be discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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15. Predicting Deleterious Non-Synonymous Single Nucleotide Polymorphisms (nsSNPs) of HRAS Gene and In Silico Evaluation of Their Structural and Functional Consequences towards Diagnosis and Prognosis of Cancer.
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Chai, Chuan-Yu, Maran, Sathiya, Thew, Hin-Yee, Tan, Yong-Chiang, Rahman, Nik Mohd Afizan Nik Abd, Cheng, Wan-Hee, Lai, Kok-Song, Loh, Jiun-Yan, and Yap, Wai-Sum
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RAS oncogenes , *SINGLE nucleotide polymorphisms , *GENETIC regulation , *CANCER prognosis , *CANCER diagnosis , *MACHINE learning - Abstract
Simple Summary: The HRAS gene has been reported to cause cancer, and identifying alleles that could potentially predispose one to cancer could lead to early diagnosis and better prognosis. Here for the first time, we conducted a machine-learning approach to identify high-risk predictive alleles of the HRAS gene. Our study reported alleles that may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer. The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein–protein interactions. Functional and structural analysis was employed in analyzing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein–protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as "pathogenic" or "harmful". Stability analysis predicted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227, and rs121917759 as unstable. Protein–protein interaction analysis revealed that HRAS has a hub connecting three clusters consisting of 11 proteins, and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan–Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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16. MgrB Mutations and Altered Cell Permeability in Colistin Resistance in Klebsiella pneumoniae.
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Yap, Polly Soo-Xi, Cheng, Wan-Hee, Chang, Sook-Keng, Lim, Swee-Hua Erin, and Lai, Kok-Song
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COLISTIN , *KLEBSIELLA pneumoniae , *CELL permeability , *BACTERIAL cell walls , *POLYMYXIN , *PLASMIDS - Abstract
There has been a resurgence in the clinical use of polymyxin antibiotics such as colistin due to the limited treatment options for infections caused by carbapenem-resistant Enterobacterales (CRE). However, this last-resort antibiotic is currently confronted with challenges which include the emergence of chromosomal and plasmid-borne colistin resistance. Colistin resistance in Klebsiella pneumoniae is commonly caused by the mutations in the chromosomal gene mgrB. MgrB spans the inner membrane and negatively regulates PhoP phosphorylation, which is essential for bacterial outer membrane lipid biosynthesis. The present review intends to draw attention to the role of mgrB chromosomal mutations in membrane permeability in K. pneumoniae that confer colistin resistance. With growing concern regarding the global emergence of colistin resistance, deciphering physical changes of the resistant membrane mediated by mgrB inactivation may provide new insights for the discovery of novel antimicrobials that are highly effective at membrane penetration, in addition to finding out how this can help in alleviating the resistance situation. [ABSTRACT FROM AUTHOR]
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- 2022
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17. A Metal-Containing NP Approach to Treat Methicillin-Resistant Staphylococcus aureus (MRSA): Prospects and Challenges.
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Yeo, Wendy Wai Yeng, Maran, Sathiya, Kong, Amanda Shen-Yee, Cheng, Wan-Hee, Lim, Swee-Hua Erin, Loh, Jiun-Yan, and Lai, Kok-Song
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METHICILLIN-resistant staphylococcus aureus , *METAL nanoparticles , *MULTIDRUG resistance , *ANTIBACTERIAL agents - Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of pneumonia in humans, and it is associated with high morbidity and mortality rates, especially in immunocompromised patients. Its high rate of multidrug resistance led to an exploration of novel antimicrobials. Metal nanoparticles have shown potent antibacterial activity, thus instigating their application in MRSA. This review summarizes current insights of Metal-Containing NPs in treating MRSA. This review also provides an in-depth appraisal of opportunities and challenges in utilizing metal-NPs to treat MRSA. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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18. Host–Bacterial Interactions: Outcomes of Antimicrobial Peptide Applications.
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Alkatheri, Asma Hussain, Yap, Polly Soo-Xi, Abushelaibi, Aisha, Lai, Kok-Song, Cheng, Wan-Hee, and Lim, Swee-Hua Erin
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- 2022
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19. In-Silico Analysis of Deleterious SNPs of FGF4 Gene and Their Impacts on Protein Structure, Function and Bladder Cancer Prognosis.
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Lim, Ee Chen, Lim, Shu Wen, Tan, Kenneth JunKai, Sathiya, Maran, Cheng, Wan Hee, Lai, Kok-Song, Loh, Jiun-Yan, and Yap, Wai-Sum
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BLADDER cancer , *PROTEIN structure , *FIBROBLAST growth factors , *CANCER prognosis , *GENETIC regulation , *URODYNAMICS - Abstract
Dysregulation of fibroblast growth factors is linked to the pathogenesis of bladder cancer. The role of FGF1 and FGF3 is evident in bladder cancer; however, the role of FGF4 is vague. Despite being reported that FGF4 interacts with FGF1 and FGF3 in MAPK pathways, its pathogenesis and mechanism of action are yet to be elucidated. Therefore, this study aimed to elucidate pathogenic nsSNPs and their role in the prognosis of bladder cancer by employing in-silico analysis. The nsSNPs of FGF4 were retrieved from the NCBI database. Different in silico tools, PROVEAN, SIFT, PolyPhen-2, SNPs&GO, and PhD-SNP, were used for predicting the pathogenicity of the nsSNPs. Twenty-seven nsSNPs were identified as "damaging", and further stability analysis using I-Mutant 2.0 and MUPro indicated 22 nsSNPs to cause decreased stability (DDG scores < −0.5). Conservation analysis predicted that Q97K, G106V, N164S, and N167S were highly conserved and exposed. Biophysical characterisation indicated these nsSNPs were not tolerated, and protein-protein interaction analysis showed their involvement in the GFR-MAPK signalling pathway. Furthermore, Kaplan Meier bioinformatics analyses indicated that the FGF4 gene deregulation affected the overall survival rate of patients with bladder cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of FGF4 may serve as potential targets for diagnoses and therapeutic interventions focusing on bladder cancer. [ABSTRACT FROM AUTHOR]
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- 2022
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20. Contribution of Aldehydes and Their Derivatives to Antimicrobial and Immunomodulatory Activities.
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Aljaafari, Mariam Nasser, Alkhoori, Maryam Abdulraheem, Hag-Ali, Mohammed, Cheng, Wan-Hee, Lim, Swee-Hua-Erin, Loh, Jiun-Yan, and Lai, Kok-Song
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ALDEHYDE derivatives , *ANTI-infective agents , *ESSENTIAL oils , *METABOLITES , *PLANT extracts , *CATHELICIDINS - Abstract
Essential oils (EOs) are intricate combinations of evaporative compounds produced by aromatic plants and extracted by distillation or expression. EOs are natural secondary metabolites derived from plants and have been found to be useful in food and nutraceutical manufacturing, perfumery and cosmetics; they have also been found to alleviate the phenomenon of antimicrobial resistance (AMR) in addition to functioning as antibacterial and antifungal agents, balancing menstrual cycles and being efficacious as an immune system booster. Several main aldehyde constituents can be found in different types of EOs, and thus, aldehydes and their derivatives will be the main focus of this study with regard to their antimicrobial, antioxidative, anti-inflammatory and immunomodulatory effects. This brief study also explores the activity of aldehydes and their derivatives against pathogenic bacteria for future use in the clinical setting. [ABSTRACT FROM AUTHOR]
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- 2022
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21. Functional and structural analysis of non-synonymous single nucleotide polymorphisms (nsSNPs) in the MYB oncoproteins associated with human cancer.
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Lim, Shu Wen, Tan, Kennet JunKai, Azuraidi, Osman Mohd, Sathiya, Maran, Lim, Ee Chen, Lai, Kok Song, Yap, Wai-Sum, and Afizan, Nik Abd Rahman Nik Mohd
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SINGLE nucleotide polymorphisms , *POST-translational modification , *FUNCTIONAL analysis , *PHARMACOGENOMICS , *DNA-binding proteins , *PROTEIN analysis , *PROTEIN stability - Abstract
MYB proteins are highly conserved DNA-binding domains (DBD) and mutations in MYB oncoproteins have been reported to cause aberrant and augmented cancer progression. Identification of MYB molecular biomarkers predictive of cancer progression can be used for improving cancer management. To address this, a biomarker discovery pipeline was employed in investigating deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in predicting damaging and potential alterations on the properties of proteins. The nsSNP of the MYB family; MYB, MYBL1, and MYBL2 was extracted from the NCBI database. Five in silico tools (PROVEAN, SIFT, PolyPhen-2, SNPs&GO and PhD-SNP) were utilized to investigate the outcomes of nsSNPs. A total of 45 nsSNPs were predicted as high-risk and damaging, and were subjected to PMut and I-Mutant 2.0 for protein stability analysis. This resulted in 32 nsSNPs with decreased stability with a DDG score lower than − 0.5, indicating damaging effect. G111S, N183S, G122S, and S178C located within the helix-turn-helix (HTH) domain were predicted to be conserved, further posttranslational modifications and 3-D protein analysis indicated these nsSNPs to shift DNA-binding specificity of the protein thus altering the protein function. Findings from this study would help in the field of pharmacogenomic and cancer therapy towards better intervention and management of cancer. [ABSTRACT FROM AUTHOR]
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- 2021
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22. Antimicrobial activity and mode of action of 1,8-cineol against carbapenemase-producing Klebsiella pneumoniae.
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Moo, Chew-Li, Osman, Mohd Azuraidi, Yang, Shun-Kai, Yap, Wai-Sum, Ismail, Saila, Lim, Swee-Hua-Erin, Chong, Chou-Min, and Lai, Kok-Song
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KLEBSIELLA pneumoniae , *BACTERIAL cell membranes , *CELL death , *SCANNING transmission electron microscopy , *ESSENTIAL oils , *SURFACE charges , *REACTIVE oxygen species - Abstract
Antimicrobial resistance remains one of the most challenging issues that threatens the health of people around the world. Plant-derived natural compounds have received considerable attention for their potential role to mitigate antibiotic resistance. This study was carried out to assess the antimicrobial activity and mode of action of a monoterpene, 1,8-cineol (CN) against carbapenemase-producing Klebsiella pneumoniae (KPC-KP). Results showed that resazurin microplate assay and time-kill analysis revealed bactericidal effects of CN at 28.83 mg/mL. Zeta potential showed that CN increased the surface charge of bacteria and an increase of outer membrane permeability was also detected. CN was able to cause leakage of proteins and nucleic acids in KPC-KP cells upon exposure to CN and ethidium bromide influx/efflux experiment showed the uptake of ethidium bromide into the cell; this was attributed to membrane damage. CN was also found to induce oxidative stress in CN-treated KPC-KP cells through generation of reactive oxygen species which initiated lipid peroxidation and thus damaging the bacterial cell membrane. Scanning and transmission electron microscopies further confirmed the disruption of bacterial cell membrane and loss of intracellular materials. In this study, we demonstrated that CN induced oxidative stress and membrane damage resulting in KPC-KP cell death. [ABSTRACT FROM AUTHOR]
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- 2021
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23. Kinetic studies and homology modeling of a dual-substrate linalool/nerolidol synthase from Plectranthus amboinicus.
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Ashaari, Nur Suhanawati, Ab. Rahim, Mohd Hairul, Sabri, Suriana, Lai, Kok Song, Song, Adelene Ai-Lian, Abdul Rahim, Raha, and Ong Abdullah, Janna
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LINALOOL , *HOMOLOGY (Biochemistry) , *PLECTRANTHUS , *BIOSYNTHESIS , *PYROPHOSPHATES - Abstract
Linalool and nerolidol are terpene alcohols that occur naturally in many aromatic plants and are commonly used in food and cosmetic industries as flavors and fragrances. In plants, linalool and nerolidol are biosynthesized as a result of respective linalool synthase and nerolidol synthase, or a single linalool/nerolidol synthase. In our previous work, we have isolated a linalool/nerolidol synthase (designated as PamTps1) from a local herbal plant, Plectranthus amboinicus, and successfully demonstrated the production of linalool and nerolidol in an Escherichia coli system. In this work, the biochemical properties of PamTps1 were analyzed, and its 3D homology model with the docking positions of its substrates, geranyl pyrophosphate (C10) and farnesyl pyrophosphate (C15) in the active site were constructed. PamTps1 exhibited the highest enzymatic activity at an optimal pH and temperature of 6.5 and 30 °C, respectively, and in the presence of 20 mM magnesium as a cofactor. The Michaelis–Menten constant (Km) and catalytic efficiency (kcat/Km) values of 16.72 ± 1.32 µM and 9.57 × 10–3 µM−1 s−1, respectively, showed that PamTps1 had a higher binding affinity and specificity for GPP instead of FPP as expected for a monoterpene synthase. The PamTps1 exhibits feature of a class I terpene synthase fold that made up of α-helices architecture with N-terminal domain and catalytic C-terminal domain. Nine aromatic residues (W268, Y272, Y299, F371, Y378, Y379, F447, Y517 and Y523) outlined the hydrophobic walls of the active site cavity, whilst residues from the RRx8W motif, RxR motif, H-α1 and J-K loops formed the active site lid that shielded the highly reactive carbocationic intermediates from the solvents. The dual substrates use by PamTps1 was hypothesized to be possible due to the architecture and residues lining the catalytic site that can accommodate larger substrate (FPP) as demonstrated by the protein modelling and docking analysis. This model serves as a first glimpse into the structural insights of the PamTps1 catalytic active site as a multi-substrate linalool/nerolidol synthase. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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24. Sodium lignosulfonate improves shoot growth of Oryza sativa via enhancement of photosynthetic activity and reduced accumulation of reactive oxygen species.
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Kok, Andrew De-Xian, Wan Abdullah, Wan Muhamad Asrul Nizam, Tang, Chu-Nie, Low, Lee-Yoon, Yuswan, Mohd Hafis, Ong-Abdullah, Janna, Tan, Ngai-Paing, and Lai, Kok-Song
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LIGNOSULFONATES , *PLANT shoots , *RICE , *PHOTOSYNTHESIS , *REACTIVE oxygen species - Abstract
Lignosulfonate (LS) is a by-product obtained during sulfite pulping process and is commonly used as a growth enhancer in plant growth. However, the underlying growth promoting mechanism of LS on shoot growth remains largely unknown. Hence, this study was undertaken to determine the potential application of eco-friendly ion-chelated LS complex [sodium LS (NaLS) and calcium LS (CaLS)] to enhance recalcitrant indica rice MR 219 shoot growth and to elucidate its underlying growth promoting mechanisms. In this study, the shoot apex of MR 219 rice was grown on Murashige and Skoog medium supplemented with different ion chelated LS complex (NaLS and CaLS) at 100, 200, 300 and 400 mg/L The NaLS was shown to be a better shoot growth enhancer as compared to CaLS, with optimum concentration of 300 mg/L. Subsequent comparative proteomic analysis revealed an increase of photosynthesis-related proteins [photosystem II (PSII) CP43 reaction center protein, photosystem I (PSI) iron-sulfur center, PSII CP47 reaction center protein, PSII protein D1], ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), carbohydrate metabolism-related proteins (glyceraldehyde-3-phosphate dehydrogenase 3, fructose-bisphosphate aldolase) and stress regulator proteins (peptide methionine sulfoxide reductase A4, delta-1-pyrroline-5-carboxylate synthase 1) abundance in NaLS-treated rice as compared to the control (MSO). Consistent with proteins detected, a significant increase in biochemical analyses involved in photosynthetic activities, carbohydrate metabolism and protein biosynthesis such as total chlorophyll, rubisco activity, total sugar and total protein contents were observed in NaLS-treated rice. This implies that NaLS plays a role in empowering photosynthesis activities that led to plant growth enhancement. In addition, the increased in abundance of stress regulator proteins were consistent with low levels of peroxidase activity, malondialdehyde content and phenylalanine ammonia lyase activity observed in NaLS-treated rice. These results suggest that NaLS plays a role in modulating cellular homeostasis to provide a conducive cellular environment for plant growth. Taken together, NaLS improved shoot growth of recalcitrant MR 219 rice by upregulation of photosynthetic activities and reduction of ROS accumulation leading to better plant growth. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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25. The Missing Piece: Recent Approaches Investigating the Antimicrobial Mode of Action of Essential Oils.
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Yang, Shun-Kai, Tan, Ngai-Paing, Chong, Chun-Wie, Abushelaibi, Aisha, Lim, Swee-Hua-Erin, and Lai, Kok-Song
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METABOLITES , *ESSENTIAL oils , *PLANT metabolites , *DRUG resistance in bacteria , *ANTIMICROBIAL polymers , *MEDICAL care costs , *DEATH rate - Abstract
Antibiotic resistance is a major global health issue that has seen alarming rates of increase in all parts of the world over the past two decades. The surge in antibiotic resistance has resulted in longer hospital stays, higher medical costs, and elevated mortality rates. Constant attempts have been made to discover newer and more effective antimicrobials to reduce the severity of antibiotic resistance. Plant secondary metabolites, such as essential oils, have been the major focus due to their complexity and bioactive nature. However, the underlying mechanism of their antimicrobial effect remains largely unknown. Understanding the antimicrobial mode of action of essential oils is crucial in developing potential strategies for the use of essential oils in a clinical setting. Recent advances in genomics and proteomics have enhanced our understanding of the antimicrobial mode of action of essential oils. We might well be at the dawn of completing a mystery on how essential oils carry out their antimicrobial activities. Therefore, an overview of essential oils with regard to their antimicrobial activities and mode of action is discussed in this review. Recent approaches used in identifying the antimicrobial mode of action of essential oils, specifically from the perspective of genomics and proteomics, are also synthesized. Based on the information gathered from this review, we offer recommendations for future strategies and prospects for the study of essential oils and their function as antimicrobials. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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26. Calcium lignosulfonate improves proliferation of recalcitrant indica rice callus via modulation of auxin biosynthesis and enhancement of nutrient absorption.
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Wan Abdullah, Wan Muhamad Asrul Nizam, Tan, Ngai-Paing, Low, Lee-Yoon, Loh, Jiun-Yan, Wee, Chien-Yeong, Md Taib, Azney Zuhaily, Ong-Abdullah, Janna, and Lai, Kok-Song
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CALLUS , *CALCIUM ions , *BIOSYNTHESIS , *ROOT formation , *POTASSIUM ions , *AUXIN , *FRACTURE healing - Abstract
Lignosulfonate (LS) is a commonly used to promote plant growth. However, the underlying growth promoting responses of LS in plant remain unknown. Therefore, this study was undertaken to elucidate the underlying growth promoting mechanisms of LS, specifically calcium lignosulfonate (CaLS). Addition of 100 mg/L CaLS in phytohormone-free media enhanced recalcitrant indica rice cv. MR219 callus proliferation rate and adventitious root formation. Both, auxin related genes (OsNIT1 , OsTAA1 and OsYUC1) and tryptophan biosynthesis proteins were upregulated in CaLS-treated calli which corroborated with increased of endogenous auxin content. Moreover, increment of OsWOX11 gene on CaLS-treated calli implying that the raised of endogenous auxin was utilized as a cue to enhance adventitious root development. Besides, CaLS-treated calli showed higher nutrient ions content with major increment in calcium and potassium ions. Consistently, increased of potassium protein kinases genes (OsAKT1 , OsHAK5 , OsCBL , OsCIPK23 and OsCamk1) were also recorded. In CaLS treated calli, the significant increase of calcium ion was observed starting from week one while potassium ion only recorded significant increase on week two onwards, suggesting that increment of potassium ion might be dependent on the calcium ion content in the plant cell. Additionally, reduced callus blackening was also coherent with downregulation of ROS scavenging protein and reduced H 2 O 2 content in CaLS-treated calli suggesting the role of CaLS in mediating cellular homeostasis via prevention of oxidative burst in the cell. Taken together, CaLS successfully improved MR219 callus proliferation and root formation by increasing endogenous auxin synthesis, enhancing nutrients uptake and regulating cellular homeostasis. • CaLS stimulates root formation in rice callus via regulation of auxin biosynthesis. • Enhancement of nutrient uptake was observed in CaLS-treated rice calli. • CaLS improves cellular homeostasis level and enhances callus proliferation rate. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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27. Screening of 22q11.2DS Using Multiplex Ligation-Dependent Probe Amplification as an Alternative Diagnostic Method.
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Maran, Sathiya, Faten, Siti Aisyah, Lim, Swee-Hua Erin, Lai, Kok-Song, Ibrahim, Wan Pauzi Wan, Ankathil, Ravindran, Gan, Siew Hua, and Tan, Huay Lin
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CONGENITAL heart disease , *MOLECULAR diagnosis , *FLUORESCENCE in situ hybridization , *GENETIC testing , *DISEASE incidence , *22Q11 deletion syndrome - Abstract
Background. The 22q11.2 deletion syndrome (22q11.2DS) is the most common form of deletion disorder in humans. Low copy repeats flanking the 22q11.2 region confers a substrate for nonallelic homologous recombination (NAHR) events leading to rearrangements which have been reported to be associated with highly variable and expansive phenotypes. The 22q11.2DS is reported as the most common genetic cause of congenital heart defects (CHDs). Methods. A total of 42 patients with congenital heart defects, as confirmed by echocardiography, were recruited. Genetic molecular analysis using a fluorescence in situ hybridization (FISH) technique was conducted as part of routine 22q11.2DS screening, followed by multiplex ligation-dependent probe amplification (MLPA), which serves as a confirmatory test. Results. Two of the 42 CHD cases (4.76%) indicated the presence of 22q11.2DS, and interestingly, both cases have conotruncal heart defects. In terms of concordance of techniques used, MLPA is superior since it can detect deletions within the 22q11.2 locus and outside of the typically deleted region (TDR) as well as duplications. Conclusion. The incidence of 22q11.2DS among patients with CHD in the east coast of Malaysia is 0.047. MLPA is a scalable and affordable alternative molecular diagnostic method in the screening of 22q11.2DS and can be routinely applied for the diagnosis of deletion syndromes. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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28. The Regulatory Role of MicroRNAs in Breast Cancer.
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Loh, Hui-Yi, Norman, Brendan P., Lai, Kok-Song, Rahman, Nik Mohd Afizan Nik Abd., Alitheen, Noorjahan Banu Mohamed, and Osman, Mohd Azuraidi
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BREAST cancer , *MESSENGER RNA , *NON-coding RNA , *CANCER cell proliferation , *CANCER relapse , *REGULATOR genes - Abstract
MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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29. Functional characterization of a new terpene synthase from Plectranthus amboinicus.
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Ashaari, Nur Suhanawati, Ab. Rahim, Mohd Hairul, Sabri, Suriana, Lai, Kok Song, Song, Adelene Ai-Lian, Abdul Rahim, Raha, Wan Abdullah, Wan Muhamad Asrul Nizam, and Ong Abdullah, Janna
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PLECTRANTHUS , *AMINO acid sequence , *MOLECULAR weights , *HERBAL medicine , *TERPENES , *SYNTHASES , *LAMIACEAE , *THYMES - Abstract
Plectranthus amboinicus (Lour.) Spreng is an aromatic medicinal herb known for its therapeutic and nutritional properties attributed by the presence of monoterpene and sesquiterpene compounds. Up until now, research on terpenoid biosynthesis has focused on a few mint species with economic importance such as thyme and oregano, yet the terpene synthases responsible for monoterpene production in P. amboinicus have not been described. Here we report the isolation, heterologous expression and functional characterization of a terpene synthase involved in P. amboinicus terpenoid biosynthesis. A putative monoterpene synthase gene (PamTps1) from P. amboinicus was isolated with an open reading frame of 1797 bp encoding a predicted protein of 598 amino acids with molecular weight of 69.6 kDa. PamTps1 shares 60–70% amino acid sequence similarity with other known terpene synthases of Lamiaceae. The in vitro enzymatic activity of PamTps1 demonstrated the conversion of geranyl pyrophosphate and farnesyl pyrophosphate exclusively into linalool and nerolidol, respectively, and thus PamTps1 was classified as a linalool/nerolidol synthase. In vivo activity of PamTps1 in a recombinant Escherichia coli strain revealed production of linalool and nerolidol which correlated with its in vitro activity. This outcome validated the multi-substrate usage of this enzyme in producing linalool and nerolidol both in in vivo and in vitro systems. The transcript level of PamTps1 was prominent in the leaf during daytime as compared to the stem. Gas chromatography-mass spectrometry (GC-MS) and quantitative real-time PCR analyses showed that maximal linalool level was released during the daytime and lower at night following a diurnal circadian pattern which correlated with the PamTps1 expression pattern. The PamTps1 cloned herein provides a molecular basis for the terpenoid biosynthesis in this local herb that could be exploited for valuable production using metabolic engineering in both microbial and plant systems. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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30. Transcriptomic analysis of multi-drug resistant Escherichia coli K-12 strain in response to Lavandula angustifolia essential oil.
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Lai, Pey-Jiun, Ng, Ee-Von, Yang, Shun-Kai, Moo, Chew-Li, Low, Wai Yee, Yap, Polly Soo-Xi, Lim, Swee-Hua Erin, and Lai, Kok-Song
- Subjects
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ESCHERICHIA coli , *LAVENDERS , *MICROBIAL metabolism , *METABOLIC regulation , *MICROBIAL genes - Abstract
To better understand the synergistic antibacterial activity between piperacillin and Lavandula angustifolia essential oil (LEO) against multidrug-resistant Escherichia coli, we performed microarray transcriptomic analysis of LEO when used alone and in combination with piperacillin against the non-treated control. In total, 90 genes were differentially expressed after the combination of LEO and piperacillin treatment. Among the up-regulated genes, nfsB, nemA, fruA, nfsB, nemA are known to control microbial metabolism and nitrotoluene degradation, which were observed only in the LEO–piperacillin combinatory treatment. Four candidate genes from the microarray result, srIA, srID, waaR and nfsB, were validated by qRT-PCR as these genes showed differential expression consistently in the two methods. Biochemical pathway analysis showed that there was upregulation of genes involved in several biological processes including fructose and mannose metabolism, phosphotransferase system (PTS), lipopolysaccharide biosynthesis and nitrotoluene degradation. Genes involved in microbial metabolism in diverse environments were found both up- and down-regulated in LEO–piperacillin combinatory treatment. Our study provides new information concerning the transcriptional changes that occur during the LEO and piperacillin interaction against the multidrug-resistant bacteria and contributes to unravel the mechanisms underlying this synergism. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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31. Mutations in the tail domain of MYH3 contributes to atrial septal defect.
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Maran, Sathiya, Ee, Robson, Faten, Siti Aisyah, Sy Bing, Choi, Khaw, Kooi Yeong, Erin Lim, Swee-Hua, Lai, Kok-Song, Wan Ibrahim, Wan Pauzi, Mohd Zain, Mohd Rizal, Chan, Kok Gan, Gan, Siew Hua, and Tan, Huay Lin
- Subjects
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ATRIAL septal defects , *CONGENITAL heart disease , *TAILS , *PATHOLOGY - Abstract
Atrial septal defect (ASD) is one of the most common congenital heart defects diagnosed in children. Sarcomeric genes has been attributed to ASD and knockdown of MYH3 functionally homologues gene in chick models indicated abnormal atrial septal development. Here, we report for the first time, a case-control study investigating the role of MYH3 among non-syndromic ASD patients in contributing to septal development. Four amplicons which will amplifies the 40 kb MYH3 were designed and amplified using long range-PCR. The amplicons were then sequenced using indexed paired-end libraries on the MiSeq platform. The STREGA guidelines were applied for planning and reporting. The non-synonymous c. 3574G>A (p.Ala1192Thr) [p = 0.001, OR = 2.30 (1.36–3.87)] located within the tail domain indicated a highly conserved protein region. The mutant model of c. 3574G>A (p.Ala1192Thr) showed high root mean square deviation (RMSD) values compared to the wild model. To our knowledge, this is the first study to provide compelling evidence on the pathogenesis of MYH3 variants towards ASD hence, suggesting the crucial role of non-synonymous variants in the tail domain of MYH3 towards atrial septal development. It is hoped that this gene can be used as panel for diagnosis of ASD in future. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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32. Protein expression patterns in hek-Blue™ - Cells treated with Clinacanthus nutans extracts.
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Yang, Shun-Kai, Leo, Teik-Kee, Mai, Chun-Wai, Chin, Swee-Yee, Lamasudin, Dhilia, Lim, Swee-Hua-Erin, Tan, Ngai-Paing, and Lai, Kok-Song
- Subjects
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REACTIVE oxygen species , *PROTEIN expression , *SODIUM dodecyl sulfate , *GEL electrophoresis , *EXTRACTS - Abstract
Background: Clinacanthus nutans (CN) is a small shrub native to tropical Asia known for their anti-oxidant, anti-inflammation, anti-cancer, and anti-viral activities. Objectives: This study aimed to investigate the effect of CN extract on human embryonic kidney cell line (HEK-Blue™-4) in a proteomic perspective. Materials and Methods: Comparative proteomic profiling through two-dimensional sodium dodecyl sulfate gel electrophoresis was performed on HEK-Blue™-4 treated with CN leaf polar extract. Results: We successfully identified seven upregulated proteins, of which five promoted the growth of the HEK-Blue™-4 cells. Interestingly, a potent antioxidant enzyme which neutralizes reactive oxygen or nitrogen species, peroxiredoxin-1 was also upregulated in HEK-Blue™-4 cell lines after treatment with CN leaf polar extract. Conclusion: CN leaf polar extract promotes the growth of HEK-Blue™-4 cells and induced the expression of peroxiredoxin-1, which protects the cells from reactive oxygen species during the inflammation process. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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33. Growth promoting effects of Pluronic F-68 on callus proliferation of recalcitrant rice cultivar.
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Kok, Andrew De-Xian, Wan Abdullah, Wan Muhamad Asrul Nizam, Tan, Ngai-Paing, Ong-Abdullah, Janna, Sekeli, Rogayah, Wee, Chien-Yeong, and Lai, Kok-Song
- Subjects
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CALLUS , *AMINO acid metabolism , *ROOT formation , *HYDROGEN peroxide , *PLANT growth - Abstract
This study was undertaken to evaluate growth-promoting effects of Pluronic F-68 (PF-68) on recalcitrant MR 219 rice callus. Our study shows that calli grown on Murashige and Skoog medium supplemented with 0.04% PF-68 significantly increased callus proliferation by 58.80% (fresh weight) and 23.98% (dry weight) while root formation from callus was enhanced by 28.57%. Enhanced callus proliferation was supported by biochemical analysis, whereby highest amount of soluble sugar (1.77 mg/mL) and protein (0.17 mg/mL) contents were recorded in calli grown on 0.04% PF-68. Furthermore, enhanced expression of sucrose synthase (2.65-folds) and NADH-dependent glutamate synthase (1.86-folds) genes in calli grown on 0.04% PF-68 also correlates with enhanced callus proliferation. In contrast, high concentration of PF-68 (0.10%) recorded highest amount of phenolic (0.74 mg/mL), flavonoid (0.08 mg/mL), and hydrogen peroxide content (0.06 mg/mL) as compared to other treatment groups indicates activation of plant defence mechanism towards stress. Similarly, high expression of 4-coumarate:CoA ligase 3 (1.28-folds), chalcone-flavonone isomerase (1.65-folds) and ascorbate peroxidase (1.61-folds) genes were observed in calli grown on 0.10% PF-68 further supports increasing stress caused by the high concentration of PF-68. Taken together, our study revealed that optimum concentration of PF-68 could improve recalcitrant rice callus proliferation via enhanced sugar metabolism and amino acid biosynthesis which are crucial towards plant growth and development. However, at high concentration, PF-68 induces stress in plant which enhance the production of secondary metabolite to maintain cellular homeostasis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
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34. Disruption of KPC-producing Klebsiella pneumoniae membrane via induction of oxidative stress by cinnamon bark (Cinnamomum verum J. Presl) essential oil.
- Author
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Yang, Shun-Kai, Yusoff, Khatijah, Ajat, Mokrish, Thomas, Warren, Abushelaibi, Aisha, Akseer, Riaz, Lim, Swee-Hua Erin, and Lai, Kok-Song
- Subjects
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ESSENTIAL oils , *CINNAMON tree , *OXIDATIVE stress , *KLEBSIELLA pneumoniae , *DNA mismatch repair , *BACTERIAL cell walls - Abstract
Klebsiella pneumoniae (KP) remains the most prevalent nosocomial pathogen and carries the carbapenemase (KPC) gene which confers resistance towards carbapenem. Thus, it is necessary to discover novel antimicrobials to address the issue of antimicrobial resistance in such pathogens. Natural products such as essential oils are a promising source due to their complex composition. Essential oils have been shown to be effective against pathogens, but the overall mechanisms have yet to be fully explained. Understanding the molecular mechanisms of essential oil towards KPC-KP cells would provide a deeper understanding of their potential use in clinical settings. Therefore, we aimed to investigate the mode of action of essential oil against KPC-KP cells from a proteomic perspective by comparing the overall proteome profile of KPC-KP cells treated with cinnamon bark (Cinnamomum verum J. Presl) essential oil (CBO) at their sub-inhibitory concentration of 0.08% (v/v). A total of 384 proteins were successfully identified from the non-treated cells, whereas only 242 proteins were identified from the CBO-treated cells. Proteins were then categorized based on their biological processes, cellular components and molecular function prior to pathway analysis. Pathway analysis showed that CBO induced oxidative stress in the KPC-KP cells as indicated by the abundance of oxidative stress regulator proteins such as glycyl radical cofactor, catalase peroxidase and DNA mismatch repair protein. Oxidative stress is likely to oxidize and disrupt the bacterial membrane as shown by the loss of major membrane proteins. Several genes selected for qRT-PCR analysis validated the proteomic profile and were congruent with the proteomic abundance profiles. In conclusion, KPC-KP cells exposed to CBO undergo oxidative stress that eventually disrupts the bacterial membrane possibly via interaction with the phospholipid bilayer. Interestingly, several pathways involved in the bacterial membrane repair system were also affected by oxidative stress, contributing to the loss of cells viability. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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35. Epigenetic of DNA Methylation Patterns in Lowland and Upland Malaysian Rice Cultivars under Induced Drought and Salinity.
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Yap, Wai Sum, Yeo, Yang Lin, Lai, Kok Song, and Wee, Chien Yeong
- Subjects
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EPIGENETICS , *DNA methylation , *RICE varieties , *EFFECT of drought on plants , *EFFECT of salt on plants - Published
- 2016
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36. Nutraceuticals: Transformation of Conventional Foods into Health Promoters/Disease Preventers and Safety Considerations.
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AlAli, Mudhi, Alqubaisy, Maream, Aljaafari, Mariam Nasser, AlAli, Asma Obaid, Baqais, Laila, Molouki, Aidin, Abushelaibi, Aisha, Lai, Kok-Song, Lim, Swee-Hua Erin, Tesoriere, Luisa, and Pak, Sokcheon
- Subjects
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INFECTION prevention , *CARDIOVASCULAR system , *CANCER prevention - Abstract
Nutraceuticals are essential food constituents that provide nutritional benefits as well as medicinal effects. The benefits of these foods are due to the presence of active compounds such as carotenoids, collagen hydrolysate, and dietary fibers. Nutraceuticals have been found to positively affect cardiovascular and immune system health and have a role in infection and cancer prevention. Nutraceuticals can be categorized into different classes based on their nature and mode of action. In this review, different classifications of nutraceuticals and their potential therapeutic activity, such as anti-cancer, antioxidant, anti-inflammatory and anti-lipid activity in disease will be reviewed. Moreover, the different mechanisms of action of these products, applications, and safety upon consumers including current trends and future prospect of nutraceuticals will be included. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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37. An Overview of the Potential Therapeutic Applications of Essential Oils.
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Aljaafari, Mariam Nasser, AlAli, Asma Obaid, Baqais, Laila, Alqubaisy, Maream, AlAli, Mudhi, Molouki, Aidin, Ong-Abdullah, Janna, Abushelaibi, Aisha, Lai, Kok-Song, Lim, Swee-Hua Erin, and Tullio, Vivian
- Subjects
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LAVENDERS , *PLANT products , *NATURAL products , *ESSENTIAL oils , *MEMBRANE permeability (Biology) , *PSEUDOPOTENTIAL method , *DRUG resistance in microorganisms - Abstract
The emergence of antimicrobial resistance (AMR) has urged researchers to explore therapeutic alternatives, one of which includes the use of natural plant products such as essential oils (EO). In fact, EO obtained from clove, oregano, thymus, cinnamon bark, rosemary, eucalyptus, and lavender have been shown to present significant inhibitory effects on bacteria, fungi, and viruses; many studies have been done to measure EO efficacy against microorganisms. The strategy of combinatory effects via conventional and non-conventional methods revealed that the combined effects of EO–EO or EO–antibiotic exhibit enhanced efficacy. This paper aims to review the antimicrobial effects of EO, modes of EO action (membrane disruption, efflux inhibition, increase membrane permeability, and decrease in intracellular ATP), and their compounds' potential as effective agents against bacteria, fungi, and viruses. It is hoped that the integration of EO applications in this work can be used to consider EO for future clinical applications. [ABSTRACT FROM AUTHOR]
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- 2021
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38. Application, monitoring and adverse effects in pesticide use: The importance of reinforcement of Good Agricultural Practices (GAPs).
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Leong, Wye-Hong, Teh, Shu-Yi, Hossain, Mohammad Moshaddeque, Nadarajaw, Thiyagar, Zabidi-Hussin, Zabidi, Chin, Swee-Yee, Lai, Kok-Song, and Lim, Swee-Hua Erin
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PESTICIDE residues in food , *PESTICIDE pollution , *PESTICIDES , *CAPILLARY electrophoresis , *PEST control , *CHEMICAL sample preparation - Abstract
This review intends to integrate the relevant information that is related to pesticide applications in food commodities and will cover three main sections. The first section encompasses some of the guidelines that have been implemented on management of pesticide application worldwide, such as the establishment of a value called Maximum Residue Level (MRL) through the application of Good Agricultural Practices (GAPs) into daily agricultural activities. A brief overview of the methods adopted in quantification of these trace residues in different food samples will also be covered. Briefly, pesticide analysis is usually performed in two stages: sample preparation and analytical instrumentation. Some of the preparation methods such as QuEChERs still remain as the technique of choice for most of the analytical scientists. In terms of the instrumentation such as the gas chromatography-mass spectrophotometry (GC-MS) and high performance-liquid chromatography (HPLC), these are still widely used, in spite of new inventions that are more sustainable and efficient such as the capillary electrophoresis (CE). Finally, the third section emphasizes on how pesticides can affect our health significantly whereby different types of pesticides result in different adverse health implications, despite its application benefits in agriculture in controlling pests. To date, there are limited reviews on pesticide usage in many agricultural-based nations; for the purpose of this review, Malaysia is selected to better illustrate pesticide regulations and implementation of policies. Finally, the review aims to provide an insight on how implementation of GAP and food safety assurance are inter-related and with this established correlation, to identify further measures for improvement to enable reinforcement of optimised agricultural practices specifically in these countries. • MRLs and a few other parameters have been established to ascertain the safe value of pesticide residues in food commodities. • Different examples of technologies in pesticide quantification are discussed. • Preserving the agriculture sustainability of a nation can be achieved by implementing relevant regulations and policies with regard to GAPs. • The application of pesticide in agriculture-based countries especially Malaysia has a significant impact on the economic development of the nation but unfortunately, poses great harm to human health in various aspects. [ABSTRACT FROM AUTHOR]
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- 2020
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39. Middle Eastern Plant Extracts: An Alternative to Modern Medicine Problems.
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Varijakzhan, Disha, Chong, Chou-Min, Abushelaibi, Aisha, Lai, Kok-Song, and Lim, Swee-Hua Erin
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PLANT extracts , *ALTERNATIVE medicine , *OPUNTIA ficus-indica , *DRUG resistance in microorganisms , *HERBACEOUS plants , *DATE palm - Abstract
Middle Eastern countries are primarily known for their dry sand deserts; however, they have a wider physiographic range which includes upland plateau and mountain ranges. The Middle East is home to various types of plants, such as Phoenix dactylifera (date palm tree), Scrophularia striata (herbaceous plants), and Opuntia ficus-indica (cactus). These plants have been found to have various types of bioactivities, such as antimicrobial activities against both bacteria and fungi, in addition to exhibiting anti-inflammatory effects and anti-cancer characteristics which can be utilized in the clinical setting for treatment. Due to limited reviews focusing on plant extracts from the Middle East, we aim to provide a discourse on plants from this region which have various bioactivities and to provide information on the compounds that can be identified from these plants. This is to enhance our understanding to improve modern medicine problems such as antimicrobial resistance and to find an alternative cure for cancer. It is hoped that the collation of information from this review will enable an assessment of the direct role of Middle Eastern plants in providing therapeutic options to address the predicaments in the medical field. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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40. Terpene Derivatives as a Potential Agent against Antimicrobial Resistance (AMR) Pathogens.
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Mahizan, Nik Amirah, Yang, Shun-Kai, Moo, Chew-Li, Song, Adelene Ai-Lian, Chong, Chou-Min, Chong, Chun-Wie, Abushelaibi, Aisha, Lim, Swee-Hua Erin, Lai, Kok-Song, and Avato, Pinarosa
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METABOLITES , *ESSENTIAL oils , *TERPENES , *PATHOGENIC bacteria , *ANTI-infective agents , *PATHOGENIC microorganisms - Abstract
The evolution of antimicrobial resistance (AMR) in pathogens has prompted extensive research to find alternative therapeutics. Plants rich with natural secondary metabolites are one of the go-to reservoirs for discovery of potential resources to alleviate this problem. Terpenes and their derivatives comprising of hydrocarbons, are usually found in essential oils (EOs). They have been reported to have potent antimicrobial activity, exhibiting bacteriostatic and bactericidal effects against tested pathogens. This brief review discusses the activity of terpenes and derivatives against pathogenic bacteria, describing the potential of the activity against AMR followed by the possible mechanism exerted by each terpene class. Finally, ongoing research and possible improvisation to the usage of terpenes and terpenoids in therapeutic practice against AMR are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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41. Proteome of rice roots treated with exogenous proline.
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Teh, Chui-Yao, Ho, Chai-Ling, Shaharuddin, Noor Azmi, Lai, Kok-Song, and Mahmood, Maziah
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ROOT (Botany) proteins , *RICE , *PROLINE , *ROOT growth , *PROTEOMICS , *GLUTATHIONE reductase , *GLUTATHIONE peroxidase - Abstract
Proteomic analysis was conducted to identify the rice root proteins induced by exogenous proline and their involvement in root growth. Proteins were extracted from the root tissues grown under two conditions, T1 (control) and T2 (10 mM proline), and profiled by two-dimensional polyacrylamide gel electrophoresis. Seventeen of 30 differentially expressed proteins were identified by mass spectrometry. Proline-treated rice roots showed up-regulation and down-regulation of nine and eight proteins, respectively, when compared to those in the control. Among the differentially expressed proteins, the down-regulation of glutathione reductase and peroxidase could be involved in the regulation of cellular hydrogen peroxide and reactive oxygen species levels that modulate the root cell wall structure. Differentially expressed proteins identified as pathogenesis-related proteins might be related to stress adaptive mechanisms in response to exogenous proline treatment. In addition, differentially expressed protein identified as the fructose-bisphosphate aldolases and cytochrome c oxidase might be associated with energy metabolism, which is needed during root developmental process. This is the first attempt to study the changes in rice root proteome treated with proline. The acquired information could open new avenues for further functional studies on the involvement of proline in modulating root development and its relation to stress adaptation of plants. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
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