Displaying publications 1 - 20 of 76 in total

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  1. Tan ML, Lim LE
    Drug Chem Toxicol, 2015;38(3):241-53.
    PMID: 25156015 DOI: 10.3109/01480545.2014.947504
    Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.
  2. Tan ML, Hamid SBS
    J Cancer Prev, 2021 Mar 30;26(1):1-17.
    PMID: 33842401 DOI: 10.15430/JCP.2021.26.1.1
    Patients with cancer are prone to several debilitating side effects including fatigue, insomnia, depression and cognitive disturbances. Beetroot (Beta vulgaris L.) as a health promoting functional food may be potentially beneficial in cancer. As a source of polyphenols, flavonoids, dietary nitrates and other useful nutrients, beetroot supplementation may provide a holistic means to prevent cancer and manage undesired effects associated with chemotherapy. The main aim of this narrative review is to discuss beetroot's nutrient composition, current studies on its potential utility in chemoprevention and cancer-related fatigue or treatment-related side effects such as cardiotoxicity. This review aims to provide the current status of knowledge and to identify the related research gaps in this area. The flavonoids and polyphenolic components present in abundance in beetroot support its significant antioxidant and anti-inflammatory capacities. Most in vitro and in vivo studies have shown promising results; however, the molecular mechanisms underlying chemopreventive and chemoprotective effects of beetroot have not been completely elucidated. Although recent clinical trials have shown that beetroot supplementation improves human performance, translational studies on beetroot and its functional benefits in managing fatigue or other symptoms in patients with cancer are still lacking.
  3. Tan HK, Moad AI, Tan ML
    Asian Pac J Cancer Prev, 2014;15(16):6463-75.
    PMID: 25169472
    The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.
  4. Tan ML, Lentaris G, Amaratunga Aj G
    Nanoscale Res Lett, 2012;7(1):467.
    PMID: 22901374
    The performance of a semiconducting carbon nanotube (CNT) is assessed and tabulated for parameters against those of a metal-oxide-semiconductor field-effect transistor (MOSFET). Both CNT and MOSFET models considered agree well with the trends in the available experimental data. The results obtained show that nanotubes can significantly reduce the drain-induced barrier lowering effect and subthreshold swing in silicon channel replacement while sustaining smaller channel area at higher current density. Performance metrics of both devices such as current drive strength, current on-off ratio (Ion/Ioff), energy-delay product, and power-delay product for logic gates, namely NAND and NOR, are presented. Design rules used for carbon nanotube field-effect transistors (CNTFETs) are compatible with the 45-nm MOSFET technology. The parasitics associated with interconnects are also incorporated in the model. Interconnects can affect the propagation delay in a CNTFET. Smaller length interconnects result in higher cutoff frequency.
  5. Mundada P, Tan ML, Soh AW
    Med J Malaysia, 2015 Aug;70(4):256-8.
    PMID: 26358025
    Although it is common to have extra-hepatic metastasis of hepatocellular carcinoma (HCC) at the time of presentation, it is extremely rare to have extra-hepatic metastatic HCC without a detectable primary in the liver. We report a unique case in which a patient presented with bilateral large adrenal masses which were subsequently proven to be metastases from HCC. However, there was no tumour seen in the liver on imaging.
  6. Tan HK, Muhammad TST, Tan ML
    Toxicol Appl Pharmacol, 2016 06 01;300:55-69.
    PMID: 27049118 DOI: 10.1016/j.taap.2016.03.017
    14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the mechanistic toxicology properties of 14-DDA in T-47D cells were further investigated. 14-DDA is found to induce the formation of endoplasmic reticulum (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the breast carcinoma cells. It stimulated an increase in cytosolic calcium concentration and caused a collapse in mitochondrial membrane potential in these cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress and autophagy is dependent on this transcription factor. Collectively, it is possible that GADD45A/p38 MAPK/DDIT3 pathway is involved in the 14-DDA-induced ER-stress-mediated autophagy in T-47D cells.
  7. Chong YM, Kaur G, Tan ML
    J Asian Nat Prod Res, 2019 Aug;21(8):754-771.
    PMID: 30606060 DOI: 10.1080/10286020.2018.1520704
    Andrographolide, a major bioactive compound isolated from Andrographis paniculata (Burm. F.) Nees, was evaluated for its effects on the hOAT1 membrane transporter. Substrate determination and inhibition of hOAT1-mediated uptake transport assay was carried out using recombinant CHO-hOAT1 cells. The results showed that the uptake ratio of andrographolide was less than 2.0 at all concentrations tested, indicating that andrographolide is not a hOAT1 substrate. Andrographolide has no significant effects on the p-aminohippuric acid uptake and on the mRNA and protein expression of hOAT1. In conclusion, andrographolide may not pose a drug-herb interaction risk related to hOAT1.
  8. Tan ML, Ho JJ, Teh KH
    Cochrane Database Syst Rev, 2016 Sep 28;9:CD009398.
    PMID: 27678554 DOI: 10.1002/14651858.CD009398.pub3
    BACKGROUND: About 5% of school children have a specific learning disorder, defined as unexpected failure to acquire adequate abilities in reading, writing or mathematics that is not a result of reduced intellectual ability, inadequate teaching or social deprivation. Of these events, 80% are reading disorders. Polyunsaturated fatty acids (PUFAs), in particular, omega-3 and omega-6 fatty acids, which normally are abundant in the brain and in the retina, are important for learning. Some children with specific learning disorders have been found to be deficient in these PUFAs, and it is argued that supplementation of PUFAs may help these children improve their learning abilities.

    OBJECTIVES: 1. To assess effects on learning outcomes of supplementation of polyunsaturated fatty acids (PUFAs) for children with specific learning disorders.2. To determine whether adverse effects of supplementation of PUFAs are reported in these children.

    SEARCH METHODS: In November 2015, we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, 10 other databases and two trials registers. We also searched the reference lists of relevant articles.

    SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-RCTs comparing PUFAs with placebo or no treatment in children younger than 18 years with specific learning disabilities, as diagnosed in accordance with the fifth (or earlier) edition of theDiagnostic and Statistical Manual of Mental Disorders (DSM-5), or the 10th (or earlier) revision of the International Classification of Diseases (ICD-10) or equivalent criteria. We included children with coexisting developmental disorders such as attention deficit hyperactivity disorder (ADHD) or autism.

    DATA COLLECTION AND ANALYSIS: Two review authors (MLT and KHT) independently screened the titles and abstracts of articles identified by the search and eliminated all studies that did not meet the inclusion criteria. We contacted study authors to ask for missing information and clarification, when needed. We used the GRADE approach to assess the quality of evidence.

    MAIN RESULTS: Two small studies involving 116 children, mainly boys between 10 and 18 years of age, met the inclusion criteria. One study was conducted in a school setting, the other at a specialised clinic. Both studies used three months of a combination of omega-3 and omega-6 supplements as the intervention compared with placebo. Although both studies had generally low risk of bias, we judged the risk of reporting bias as unclear in one study, and as high in the other study. In addition, one of the studies was funded by industry and reported active company involvement in the study.None of the studies reported data on the primary outcomes of reading, writing, spelling and mathematics scores, as assessed by standardised tests.Evidence of low quality indicates that supplementation of PUFAs did not increase the risk of gastrointestinal disturbances (risk ratio 1.43, 95% confidence interval 0.25 to 8.15; two studies, 116 children). Investigators reported no other adverse effects.Both studies reported attention deficit hyperactivity disorder (ADHD)-related behaviour outcomes. We were unable to combine the results in a meta-analysis because one study reported findings as a continuous outcome, and the other as a dichotomous outcome. No other secondary outcomes were reported.We excluded one study because it used a cointervention (carnosine), and five other studies because they did not provide a robust diagnosis of a specific learning disorder. We identified one ongoing study and found three studies awaiting classification.

    AUTHORS' CONCLUSIONS: Evidence is insufficient to permit any conclusions about the effect of PUFAs on the learning abilities of children with specific learning disorders. Well-designed RCTs with clearly defined populations of children with specific learning disorders who have been diagnosed by standardised diagnostic criteria are needed.

  9. Alkoudmani RM, Ooi GS, Tan ML
    PMID: 37327997 DOI: 10.1016/j.japh.2023.06.007
    BACKGROUND: The world is moving fast towards digital transformation as we live in the artificial intelligence (AI) era. The COVID-19 pandemic accelerates this movement. Chatbots were used successfully to help researchers collect data for research purposes.

    OBJECTIVE: To implement a chatbot on the Facebook® platform to establish connections with healthcare professionals who had subscribed to the chatbot, provide medical and pharmaceutical educational content, and collect data for online pharmacy research projects. Facebook® was chosen because it has billions of daily active users which offers a massive potential audience for research projects.

    PRACTICE DESCRIPTION: The chatbot was successfully implemented on the Facebook® platform following three consecutive steps. Firstly, the ChatPion script was installed on the Pharmind website to establish the chatbot system. Secondly, the PharmindBot application was developed on Facebook®. Finally, the PharmindBot app was integrated with the chatbot system.

    PRACTICE INNOVATION: The chatbot responds automatically to public comments and sends subscribers private responses using artificial intelligence. The chatbot collected quantitative and qualitative data with minimal costs.

    EVALUATION METHODS: The chatbot's auto-reply function was tested using a post published on a specific page on Facebook®. Testers were asked to leave pre-defined keywords to test its functionality. The chatbot's ability to collect and save data was tested by asking testers to fill out an online survey within Facebook Messenger® for quantitative data and answer pre-defined questions for qualitative data.

    RESULTS: The chatbot was tested on 1000 subscribers who interacted with it. Almost all testers (n = 990, 99%) obtained a successful private reply from the chatbot after sending a pre-defined keyword. Also, the chatbot replied privately to almost all public comments (n = 985, 98.5%) which helped to increase the organic reach and to establish a connection with the chatbot subscribers. No missing data was found when the chatbot was used to collect quantitative and qualitative data.

    CONCLUSIONS: The chatbot reached thousands of healthcare professionals and provided them with automated responses. At a low cost, the chatbot was able to gather both qualitative and quantitative data without relying on Facebook® ads to reach the intended audience. The data collection was efficient and effective. Using chatbots by pharmacy and medical researchers will help do more feasible online studies using AI to advance healthcare research.

  10. Tan ML, Abrams SA, Osborn DA
    Cochrane Database Syst Rev, 2020 Dec 11;12(12):CD013046.
    PMID: 33305822 DOI: 10.1002/14651858.CD013046.pub2
    BACKGROUND: Vitamin D deficiency is common worldwide, contributing to nutritional rickets and osteomalacia which have a major impact on health, growth, and development of infants, children and adolescents. Vitamin D levels are low in breast milk and exclusively breastfed infants are at risk of vitamin D insufficiency or deficiency.

    OBJECTIVES: To determine the effect of vitamin D supplementation given to infants, or lactating mothers, on vitamin D deficiency, bone density and growth in healthy term breastfed infants.

    SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to 29 May 2020 supplemented by searches of clinical trials databases, conference proceedings, and citations.

    SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs in breastfeeding mother-infant pairs comparing vitamin D supplementation given to infants or lactating mothers compared to placebo or no intervention, or sunlight, or that compare vitamin D supplementation of infants to supplementation of mothers.

    DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We used the GRADE approach to assess the certainty of evidence.

    MAIN RESULTS: We included 19 studies with 2837 mother-infant pairs assessing vitamin D given to infants (nine studies), to lactating mothers (eight studies), and to infants versus lactating mothers (six studies). No studies compared vitamin D given to infants versus periods of infant sun exposure. Vitamin D supplementation given to infants: vitamin D at 400 IU/day may increase 25-OH vitamin D levels (MD 22.63 nmol/L, 95% CI 17.05 to 28.21; participants = 334; studies = 6; low-certainty) and may reduce the incidence of vitamin D insufficiency (25-OH vitamin D < 50 nmol/L) (RR 0.57, 95% CI 0.41 to 0.80; participants = 274; studies = 4; low-certainty). However, there was insufficient evidence to determine if vitamin D given to the infant reduces the risk of vitamin D deficiency (25-OH vitamin D < 30 nmol/L) up till six months of age (RR 0.41, 95% CI 0.16 to 1.05; participants = 122; studies = 2), affects bone mineral content (BMC), or the incidence of biochemical or radiological rickets (all very-low certainty). We are uncertain about adverse effects including hypercalcaemia. There were no studies of higher doses of infant vitamin D (> 400 IU/day) compared to placebo. Vitamin D supplementation given to lactating mothers: vitamin D supplementation given to lactating mothers may increase infant 25-OH vitamin D levels (MD 24.60 nmol/L, 95% CI 21.59 to 27.60; participants = 597; studies = 7; low-certainty), may reduce the incidences of vitamin D insufficiency (RR 0.47, 95% CI 0.39 to 0.57; participants = 512; studies = 5; low-certainty), vitamin D deficiency (RR 0.15, 95% CI 0.09 to 0.24; participants = 512; studies = 5; low-certainty) and biochemical rickets (RR 0.06, 95% CI 0.01 to 0.44; participants = 229; studies = 2; low-certainty). The two studies that reported biochemical rickets used maternal dosages of oral D3 60,000 IU/day for 10 days and oral D3 60,000 IU postpartum and at 6, 10, and 14 weeks. However, infant BMC was not reported and there was insufficient evidence to determine if maternal supplementation has an effect on radiological rickets (RR 0.76, 95% CI 0.18 to 3.31; participants = 536; studies = 3; very low-certainty). All studies of maternal supplementation enrolled populations at high risk of vitamin D deficiency. We are uncertain of the effects of maternal supplementation on infant growth and adverse effects including hypercalcaemia. Vitamin D supplementation given to infants compared with supplementation given to lactating mothers: infant vitamin D supplementation compared to lactating mother supplementation may increase infant 25-OH vitamin D levels (MD 14.35 nmol/L, 95% CI 9.64 to 19.06; participants = 269; studies = 4; low-certainty). Infant vitamin D supplementation may reduce the incidence of vitamin D insufficiency (RR 0.61, 95% CI 0.40 to 0.94; participants = 334; studies = 4) and may reduce vitamin D deficiency (RR 0.35, 95% CI 0.17 to 0.72; participants = 334; studies = 4) but the evidence is very uncertain. Infant BMC and radiological rickets were not reported and there was insufficient evidence to determine if maternal supplementation has an effect on infant biochemical rickets. All studies enrolled patient populations at high risk of vitamin D deficiency. Studies compared an infant dose of vitamin D 400 IU/day with varying maternal vitamin D doses from 400 IU/day to > 4000 IU/day. We are uncertain about adverse effects including hypercalcaemia.

    AUTHORS' CONCLUSIONS: For breastfed infants, vitamin D supplementation 400 IU/day for up to six months increases 25-OH vitamin D levels and reduces vitamin D insufficiency, but there was insufficient evidence to assess its effect on vitamin D deficiency and bone health. For higher-risk infants who are breastfeeding, maternal vitamin D supplementation reduces vitamin D insufficiency and vitamin D deficiency, but there was insufficient evidence to determine an effect on bone health. In populations at higher risk of vitamin D deficiency, vitamin D supplementation of infants led to greater increases in infant 25-OH vitamin D levels, reductions in vitamin D insufficiency and vitamin D deficiency compared to supplementation of lactating mothers. However, the evidence is very uncertain for markers of bone health. Maternal higher dose supplementation (≥ 4000 IU/day) produced similar infant 25-OH vitamin D levels as infant supplementation of 400 IU/day. The certainty of evidence was graded as low to very low for all outcomes.

  11. Ooi KL, Muhammad TS, Tan ML, Sulaiman SF
    J Ethnopharmacol, 2011 Jun 1;135(3):685-95.
    PMID: 21497647 DOI: 10.1016/j.jep.2011.04.001
    The decoction of the whole plant of Elephantopus mollis Kunth. is traditionally consumed to treat various free radical-mediated diseases including cancer and diabetes.
  12. Moad AI, Tan ML, Kaur G, Mabruk M
    Asian Pac J Cancer Prev, 2012;13(12):6239-44.
    PMID: 23464438
    BACKGROUND: The basal cell carcinoma (BCC) is the most common non-melanoma skin cancer (NMSK). BCC might develop because of the faulty cell cycle arrest. P15INK4b is a tumor suppressor gene, involved in cell cycle arrest and inactivated in most human cancers. The role of p15INK4b protein expression in the genesis of BCC is as yet unknown. In a previous study we showed the absence of p15INK4b expression in the majority of tissue microarray cores of cutaneous squamous cell carcinoma (SCCs), another type of non-melanoma skin cancer, indicating that p15INK4b could possibly be involved in the pathogenesis of cutaneous SCC. The aim of this study was to investigate p15INK4b protein expression in BCCs.

    MATERIALS AND METHOD: Protein expression of p15INK4b in 35 cases of BCC tissue arrays and 19 cases of normal human skin tissue was studied using an immunohistochemical approach.

    RESULTS: The expression of p15INK4b was not significantly different in the BCC cases as compared with normal human skin (p=0.356; p>0.05). In addition, there were no significant relationship between clinicopathologic variables of patients (age and sex) and p15INK4b protein expression.

    CONCLUSIONS: Our finding may indicate that p15INK4b protein expression does not play a role in the genesis of BCC.

  13. Tan ML, Muhammad TS, Najimudin N, Sulaiman SF
    J Ethnopharmacol, 2005 Jan 15;96(3):375-83.
    PMID: 15619555
    Epipremnum pinnatum (L.) Engl. hexane extract produced a significant growth inhibition against T-47D breast carcinoma cells and analysis of cell death mechanisms indicated that the extract elicited a non-apoptotic programmed cell death. T-47D cells exposed to the extract at EC(50) concentration (72 h) for 24 h failed to demonstrate typical DNA fragmentation associated with apoptosis, as carried out using a modified TUNEL assay. In addition, acute exposure to the extract produced an insignificant regulation of caspase-3 and p53 mRNA expression but increased in the c-myc mRNA expression. Ultrastructural analysis using transmission electron microscope demonstrated distinct vacuolated cells, which strongly indicated a Type II non-apoptotic cell death although the changes in chromatin were also detected. The presence of non-apoptotic programmed cell death was then reconfirmed with annexin-V and propidium iodide staining. These findings suggested that up-regulation of c-myc mRNA expression may have contributed to the growth arrest and Type II non-apoptotic programmed cell death in the Epipremnum pinnatum (L.) Engl. hexane extract-treated T-47D cells.
  14. Tan HK, Tengku Muhammad TS, Tan ML
    Data Brief, 2016 Jun;7:1506-10.
    PMID: 27182548 DOI: 10.1016/j.dib.2016.04.046
    The data presented in this article are related to the research article entitled "14-deoxy-11,12-didehydroandrographolide induces DDIT3-dependent endoplasmic reticulum stress-mediated autophagy in T-47D breast carcinoma cells", which the mechanistic toxicology properties of 14-deoxy-11,12-didehydroandrographolide (14-DDA) were investigated (Tan et al., 2016 [1]). This article describes the derivation of cytotoxic parameters of 14-DDA, cell viability data after double transfection and DDIT3 silencing in T-47D cells.
  15. Brindha K, Paul R, Walter J, Tan ML, Singh MK
    Environ Geochem Health, 2020 Nov;42(11):3819-3839.
    PMID: 32601907 DOI: 10.1007/s10653-020-00637-9
    Monitoring the groundwater chemical composition and identifying the presence of pollutants is an integral part of any comprehensive groundwater management strategy. The present study was conducted in a part of West Tripura, northeast India, to investigate the presence and sources of trace metals in groundwater and the risk to human health due to direct ingestion of groundwater. Samples were collected from 68 locations twice a year from 2016 to 2018. Mixed Ca-Mg-HCO3, Ca-Cl and Ca-Mg-Cl were the main groundwater types. Hydrogeochemical methods showed groundwater mineralization due to (1) carbonate dissolution, (2) silicate weathering, (3) cation exchange processes and (4) anthropogenic sources. Occurrence of faecal coliforms increased in groundwater after monsoons. Nitrate and microbial contamination from wastewater infiltration were apparent. Iron, manganese, lead, cadmium and arsenic were above the drinking water limits prescribed by the Bureau of Indian Standards. Water quality index indicated 1.5% had poor, 8.7% had marginal, 16.2% had fair, 66.2% had good and 7.4% had excellent water quality. Correlation and principal component analysis reiterated the sources of major ions and trace metals identified from hydrogeochemical methods. Human exposure assessment suggests health risk due to high iron in groundwater. The presence of unsafe levels of trace metals in groundwater requires proper treatment measures before domestic use.
  16. Tan ML, Parkinson EK, Yap LF, Paterson IC
    Sci Rep, 2021 01 12;11(1):584.
    PMID: 33436723 DOI: 10.1038/s41598-020-79789-8
    Many of the characteristics ascribed to cancer-associated fibroblasts (CAFs) are shared by activated, autophagic and senescent fibroblasts. Whilst most oral squamous cell carcinomas (OSCCs) are genetically unstable (GU-OSCC), genetically stable variants (GS-OSCC) have been described and, notably, CAF activation (myofibroblast differentiation) and senescence are characteristics particularly associated with GU-OSCCs. However, it is not known whether autophagy is disrupted in these cells or whether autophagy regulates the development of the myofibroblast and senescent phenotypes. In this study, we show that senescent CAFs from GU-OSCCs contained more autophagosomes than normal human oral fibroblasts (NHOFs) and CAFs from GS-OSCCs possibly due to autophagic impairment. Further, we show that deregulation of autophagy in normal fibroblasts, either by inhibition with autophagy inhibitor, SAR405, or activation with TGF-β1, induced fibroblast activation and senescence: In response to TGF-β1, autophagy was induced prior to the development of the activated and senescent phenotypes. Lastly, we show that both SAR405- and TGF-β1-treated NHOFs enhance OSCC cell migration but only TGF-β1-treated cells increase OSCC invasion through Matrigel, indicating that TGF-β1 has additional effects that are independent of fibroblast activation/senescence. These results suggest a functional role for autophagy in the development of myofibroblast and CAF phenotypes.
  17. Ooi KL, Zakaria R, Tan ML, Sulaiman SF
    J Ethnopharmacol, 2021 Oct 05;278:114294.
    PMID: 34090914 DOI: 10.1016/j.jep.2021.114294
    ETHNOPHARMACOLOGICAL RELEVANCE: Anti-hyperuricemic plant parts that were selected for this study, are traditionally used to treat gout in Malaysia. Caffeic acid (a hydroxycinnamic acid), apigenin (a flavone), myricetin, quercetin and kaempferol (flavonols), were reported to act as potent xanthine oxidase inhibitors. These compounds can be found in some of the selected ethnomedicinal plants. However, there is still lack of published research works on the quantification of these inhibitors from these urate-lowering phytotherapies.

    AIMS OF THE STUDY: The compounds were quantified from 21 hydrolyzed extracts of the phytotherapies for gout. The activity-content contributions of the compounds to the potent extracts were determined.

    MATERIALS AND METHODS: The anti-hyperuricemic activities of the extracts and the compounds were determined using a xanthine oxidase inhibitory assay. Ultra-Performance Liquid Chromatography (UPLC) coupled with Photodiode Array Detector (PDA) was used to quantify the compounds in the extracts.

    RESULTS: The results revealed higher activity of the hydrolyzed extracts. The hydrolyzed extract of the flower bud of Syzygium aromaticum Merr. & L.M.Perry exhibited the highest activity (EC50 = 39.58 ± 0.10 μg/mL) due to the highest content of myricetin (42,297.55 ± 159.47 μg/g). The activity-content contribution of myricetin was 7.69%. Due to the highest activity of apigenin (EC50 = 3.27 ± 0.09 μg/mL), the highest contribution of this flavone (29.96%) to the hydrolyzed extract of Orthosiphon aristatus (Blume) Miq. was observed.

    CONCLUSION: The results revealed different contents and activities of xanthine oxidase inhibitors in the hydrolyzed extracts of anti-hyperuricemic plants can play a major role to influence the activity.

  18. Moad AI, Muhammad TS, Oon CE, Tan ML
    Cell Biochem Biophys, 2013 Jul;66(3):567-87.
    PMID: 23300026 DOI: 10.1007/s12013-012-9504-5
    Autophagy is an evolutionarily conserved lysosomal degradation pathway and plays a critical role in the homeostatic process of recycling proteins and organelles. Functional relationships have been described between apoptosis and autophagy. Perturbations in the apoptotic machinery have been reported to induce autophagic cell deaths. Inhibition of autophagy in cancer cells has resulted in cell deaths that manifested hallmarks of apoptosis. However, the molecular relationships and the circumstances of which molecular pathways dictate the choice between apoptosis and autophagy are currently unknown. This study aims to identify specific gene expression of rapamycin-induced autophagy and the effects of rapamycin when the autophagy process is inhibited. In this study, we have demonstrated that rapamycin is capable of inducing autophagy in T-47D breast carcinoma cells. However, when the autophagy process was inhibited by 3-MA, the effects of rapamycin became apoptotic. The Phlda1 gene was found to be up-regulated in both autophagy and apoptosis and silencing this gene was found to reduce both activities, strongly suggests that Phlda1 mediates and positively regulates both autophagy and apoptosis pathways.
  19. Tan ML, Gassman PW, Liang J, Haywood JM
    Sci Total Environ, 2021 Nov 15;795:148915.
    PMID: 34328938 DOI: 10.1016/j.scitotenv.2021.148915
    Alternative climate products, such as gauge-based gridded data, ground-based weather radar, satellite precipitation and climate reanalysis products, are being increasingly applied for hydrological modelling. This review aims to summarize the studies that have evaluated alternative climate products within Soil and Water Assessment Tool (SWAT) applications and to propose future research directions, primarily for modelers who wish to study limited gauge, ungauged or transnational river basins. A total of 126 articles have been identified since 2004, the majority of which have been published within the last five years. About 58% of the studies were conducted in Asia, mostly in China and India, while another 14% were reported for United States studies. CFSR and TRMM are the most popular applied products in SWAT modelling, followed by PERSIANN, CMADS, APHRODITE, CHIRPS and NEXRAD. Generally, the performance of climate products is region-dependent; e.g., CFSR typically performs well in the United States and South America, but performs more poorly for Asia, Africa and mountainous basin conditions, as compared to other products. In contrast, the CMADS, TRMM, APRHODITE and NEXRAD have shown the strongest capability for supporting SWAT modelling in these regions. However, most of the evaluated products contain only precipitation input; therefore, merging reliable precipitation with CFSR-temperature is recommended for hydro-climatic modelling. Future research directions include: (1) examination of optimal combinations; e.g. CHIRPS-precipitation and CFSR-temperature, for simulating streamflow in different types of river basins; (2) development of a standardized validation scheme which incorporates the commonly accepted products, statistical approaches and temperature variables; (3) further evaluation of existing climate data products to accurately capture extreme events, pattern and indices as well as WGEN statistics; (4) improvement of climate data in terms of averaging approach, bias correction and additional factors or indices integration; and (5) bias correction of CMIP6 climate projections using the optimal climate data combinations.
  20. Abduraman MA, Azizan NA, Teoh SH, Tan ML
    Obes Res Clin Pract, 2020 12 25;15(1):10-18.
    PMID: 33371997 DOI: 10.1016/j.orcp.2020.12.001
    Obesity is a serious chronic disease and a public health concern in both developing and developed countries. Managing obesity has been a great challenge for both health care professionals and patients alike. Among the various diet programs aimed at promoting weight loss, the ketogenic diet, a diet high in fat and low in carbohydrates, has been at the forefront recently and its mechanism in weight loss is much debated. Activation of Sirtuin 1 or SIRT1 is able to circumvent various diseases, including metabolic syndrome and obesity and is thought to be a potentially reliable treatment target for both of them. Augmentation of SIRT1 may be carried out using dietary means such as nicotinamide adenine dinucleotide (NAD) supplementation and/or ketogenic diet. Although ketogenic diet may augment SIRT1 activation in people affected by obesity, recent studies have indicated that the relationship between SIRT1 and ketogenesis is unpredictable. The exact circumstances and mechanisms of SIRT1, NAD and ketogenesis in the clinical setting as an intervention tool in managing obesity remained uncertain. Although several recent literatures have documented significant weight-loss following ketogenic diet interventions, there were limitations with regards to duration of trial, choice and the number of trial subjects. Studies investigating the safety of ketogenic diet in the long term, beyond 46 weeks and related mechanism and pathways are still lacking and the sustainability of this diet remains to be determined. This review explores the recent progress on ketogenic diet and its relationships with SIRT1 as a tool in managing obesity and relevant clinical implications.
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