Displaying publications 41 - 60 of 162 in total

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  1. Teoh SL, Letchumanan V, Lee LH
    Front Psychol, 2021;12:633319.
    PMID: 33716901 DOI: 10.3389/fpsyg.2021.633319
    Objective: Mindfulness-based intervention (MBI) has been proposed to alleviate loneliness and improve social connectedness. Several randomized controlled trials (RCTs) have been conducted to evaluate the effectiveness of MBI. This study aimed to critically evaluate and determine the effectiveness and safety of MBI in alleviating the feeling of loneliness. Methods: We searched Medline, Embase, PsycInfo, Cochrane CENTRAL, and AMED for publications from inception to May 2020. We included RCTs with human subjects who were enrolled in MBI with loneliness as an outcome. The quality of evidence was assessed using Cochrane's Risk of Bias (ROB) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A random-effects model was used for meta-analysis. Results: Out of 92 articles identified, eight studies involving 815 participants were included in this study. Most (7/8) trials conducted a minimum of 8 weeks of MBI. Most of the trials (5/8) used UCLA-Loneliness Scale. A pooled analysis combining three trials and compared with wait-list showed significant improvement in loneliness score reduction using the UCLA-R scale with MD of -6.33 [95% confidence interval (CI): -9.39, -3.26]. Subgroup analysis with only two Cognitively-Based Compassion Training (CBCT) trials also showed similar MD of -6.05 (95% CI: -9.53, 2.58). The overall quality of evidence (GRADE) was low. Conclusions: Mindfulness intervention with an average length of 8-week duration significantly improved the population's loneliness level with no mental health issue. However, this evidence had a low GRADE level.
  2. Ser HL, Letchumanan V, Goh BH, Wong SH, Lee LH
    Front Microbiol, 2021;12:519836.
    PMID: 34054740 DOI: 10.3389/fmicb.2021.519836
    Fecal microbiome transplant (FMT) has gained popularity over the past few years, given its success in treating several gastrointestinal diseases. At the same time, microbial populations in the gut have been shown to have more physiological effects than we expected as "habitants" of the gut. The imbalance in the gut microbiome or dysbiosis, particularly when there are excessive harmful pathogens, can trigger not just infections but can also result in the development of common diseases, such as cancer and cardiometabolic diseases. By using FMT technology, the dysbiosis of the gut microbiome in patients can be resolved by administering fecal materials from a healthy donor. The current review summarizes the history and current uses of FMT before suggesting potential ideas for its high-quality application in clinical settings.
  3. Law JW, Law LN, Letchumanan V, Tan LT, Wong SH, Chan KG, et al.
    Molecules, 2020 Nov 17;25(22).
    PMID: 33212836 DOI: 10.3390/molecules25225365
    Worldwide cancer incidence and mortality have always been a concern to the community. The cancer mortality rate has generally declined over the years; however, there is still an increased mortality rate in poorer countries that receives considerable attention from healthcare professionals. This suggested the importance of the prompt detection, effective treatment, and prevention strategies. The genus Streptomyces has been documented as a prolific producer of biologically active secondary metabolites. Streptomycetes from mangrove environments attract researchers' attention due to their ability to synthesize diverse, interesting bioactive metabolites. The present review highlights research on mangrove-derived streptomycetes and the production of anticancer-related compounds from these microorganisms. Research studies conducted between 2008 and 2019, specifically mentioning the isolation of streptomycetes from mangrove areas and described the successful purification of compound(s) or generation of crude extracts with cytotoxic activity against human cancer cell lines, were compiled in this review. It is anticipated that there will be an increase in prospects for mangrove-derived streptomycetes as one of the natural resources for the isolation of chemotherapeutic agents.
  4. Lee JK, Hern Tan LT, Ramadas A, Ab Mutalib NS, Lee LH
    PMID: 32977611 DOI: 10.3390/ijerph17196963
    The mortality rate of very preterm infants with birth weight <1500 g is as high as 15%. The survivors till discharge have a high incidence of significant morbidity, which includes necrotising enterocolitis (NEC), early-onset neonatal sepsis (EONS) and late-onset neonatal sepsis (LONS). More than 25% of preterm births are associated with microbial invasion of amniotic cavity. The preterm gut microbiome subsequently undergoes an early disruption before achieving bacterial maturation. It is postulated that bacterial gut colonisation at birth and postnatal intestinal dysbacteriosis precede the development of NEC and LONS in very preterm infants. In fact, bacterial colonization patterns in preterm infants greatly differ from term infants due to maternal chorioamnionitis, gestational age, delivery method, feeding type, antibiotic exposure and the environment factor in neonatal intensive care unit (NICU). In this regard, this review provides an overview on the gut bacteria in preterm neonates' meconium and stool. More than 50% of preterm meconium contains bacteria and the proportion increases with lower gestational age. Researchers revealed that the gut bacterial diversity is reduced in preterm infants at risk for LONS and NEC. Nevertheless, the association between gut dysbacteriosis and NEC is inconclusive with regards to relative bacteria abundance and between-sample beta diversity indices. With most studies show a disruption of the Proteobacteria and Firmicutes preceding the NEC. Hence, this review sheds light on whether gut bacteria at birth either alone or in combination with postnatal gut dysbacteriosis are associated with mortality and the morbidity of LONS and NEC in very preterm infants.
  5. Chew SS, Tan LT, Law JW, Pusparajah P, Goh BH, Ab Mutalib NS, et al.
    Cancers (Basel), 2020 Aug 13;12(8).
    PMID: 32823729 DOI: 10.3390/cancers12082272
    Colorectal cancer (CRC) is a global public health issue which poses a substantial humanistic and economic burden on patients, healthcare systems and society. In recent years, intestinal dysbiosis has been suggested to be involved in the pathogenesis of CRC, with specific pathogens exhibiting oncogenic potentials such as Fusobacterium nucleatum, Escherichia coli and enterotoxigenic Bacteroides fragilis having been found to contribute to CRC development. More recently, it has been shown that initiation of CRC development by these microorganisms requires the formation of biofilms. Gut microbial biofilm forms in the inner colonic mucus layer and is composed of polymicrobial communities. Biofilm results in the redistribution of colonic epithelial cell E-cadherin, increases permeability of the gut and causes a loss of function of the intestinal barrier, all of which enhance intestinal dysbiosis. This literature review aims to compile the various strategies that target these pathogenic biofilms and could potentially play a role in the prevention of CRC. We explore the potential use of natural products, silver nanoparticles, upconverting nanoparticles, thiosalicylate complexes, anti-rheumatic agent (Auranofin), probiotics and quorum-sensing inhibitors as strategies to hinder colon carcinogenesis via targeting colon-associated biofilms.
  6. Mangzira Kemung H, Tan LT, Chan KG, Ser HL, Law JW, Lee LH, et al.
    Molecules, 2020 Aug 03;25(15).
    PMID: 32756432 DOI: 10.3390/molecules25153545
    There is an urgent need to search for new antibiotics to counter the growing number of antibiotic-resistant bacterial strains, one of which is methicillin-resistant Staphylococcus aureus (MRSA). Herein, we report a Streptomyces sp. strain MUSC 125 from mangrove soil in Malaysia which was identified using 16S rRNA phylogenetic and phenotypic analysis. The methanolic extract of strain MUSC 125 showed anti-MRSA, anti-biofilm and antioxidant activities. Strain MUSC 125 was further screened for the presence of secondary metabolite biosynthetic genes. Our results indicated that both polyketide synthase (pks) gene clusters, pksI and pksII, were detected in strain MUSC 125 by PCR amplification. In addition, gas chromatography-mass spectroscopy (GC-MS) detected the presence of different chemicals in the methanolic extract. Based on the GC-MS analysis, eight known compounds were detected suggesting their contribution towards the anti-MRSA and anti-biofilm activities observed. Overall, the study bolsters the potential of strain MUSC 125 as a promising source of anti-MRSA and antibiofilm compounds and warrants further investigation.
  7. Johnson D, Letchumanan V, Thurairajasingam S, Lee LH
    Nutrients, 2020 Jul 03;12(7).
    PMID: 32635373 DOI: 10.3390/nu12071983
    The study of human microbiota and health has emerged as one of the ubiquitous research pursuits in recent decades which certainly warrants the attention of both researchers and clinicians. Many health conditions have been linked to the gut microbiota which is the largest reservoir of microbes in the human body. Autism spectrum disorder (ASD) is one of the neurodevelopmental disorders which has been extensively explored in relation to gut microbiome. The utilization of microbial knowledge promises a more integrative perspective in understanding this disorder, albeit being an emerging field in research. More interestingly, oral and vaginal microbiomes, indicating possible maternal influence, have equally drawn the attention of researchers to study their potential roles in the etiopathology of ASD. Therefore, this review attempts to integrate the knowledge of microbiome and its significance in relation to ASD including the hypothetical aetiology of ASD and its commonly associated comorbidities. The microbiota-based interventions including diet, prebiotics, probiotics, antibiotics, and faecal microbial transplant (FMT) have also been explored in relation to ASD. Of these, diet and probiotics are seemingly promising breakthrough interventions in the context of ASD for lesser known side effects, feasibility and easier administration, although more studies are needed to ascertain the actual clinical efficacy of these interventions. The existing knowledge and research gaps call for a more expanded and resolute research efforts in establishing the relationship between autism and microbiomes.
  8. Sun S, Tan LT, Fang YL, Jin ZJ, Zhou L, Goh BH, et al.
    Mol Plant Microbe Interact, 2020 Mar;33(3):488-498.
    PMID: 31710580 DOI: 10.1094/MPMI-09-19-0264-R
    Phenazine-1-carboxylic acid (PCA) is the primary active component in the newly registered, commercial biopesticide Shenqinmycin and is produced during fermentation by the engineered rhizobacterium strain Pseudomonas PA1201. Both phz1 and phz2 gene clusters contribute to PCA biosynthesis. In this study, we evaluated the role of OxyR in the regulation of PCA biosynthesis in PA1201. We first showed a functional link between oxyR expression and PCA biosynthesis. Deletion of oxyR and overexpression of oxyR both increase PCA biosynthesis. The molecular mechanisms underlying OxyR regulation of PCA production were investigated using several approaches. OxyR acts divergently in phz1 and phz2. Overexpression of oxyR activated the expression of phz1 and phz1-dependent PCA production. However, overexpression of oxyR had little effect on phz2-dependent PCA biosynthesis, while deletion of oxyR promoted phz2-dependent PCA production and exerted a negative effect on phz2 expression. Further, OxyR directly bound to the phz2 promoter region. In addition, the regulation of PCA biosynthesis by OxyR was associated with quorum sensing (QS) systems. Overexpression of OxyR positively regulated pqs QS system. Finally, transcriptomic analysis and subsequent genetic analysis revealed the small RNA phrS plays a key role in OxyR-dependent PCA accumulation. Specifically, OxyR directly binds to the phrS promoter region to positively regulate phrS expression wherein PhrS regulates the PCA positive regulator MvfR in order to control PCA biosynthesis.
  9. Baharudin R, Tieng FYF, Lee LH, Ab Mutalib NS
    Cancers (Basel), 2020 Feb 14;12(2).
    PMID: 32074995 DOI: 10.3390/cancers12020445
    Secreted frizzled-related protein 1 (SFRP1) is a gene that belongs to the secreted glycoprotein SFRP family. SFRP1 has been classified as a tumor suppressor gene due to the loss of expression in various human cancers, which is mainly attributed by epigenetic inactivation via DNA methylation or transcriptional silencing by microRNAs. Epigenetic silencing of SFRP1 may cause dysregulation of cell proliferation, migration, and invasion, which lead to cancer cells formation, disease progression, poor prognosis, and treatment resistance. Hence, restoration of SFRP1 expression via demethylating drugs or over-expression experiments opens the possibility for new cancer therapy approach. While the role of SFRP1 as a tumor suppressor gene is well-established, some studies also reported the possible oncogenic properties of SFRP1 in cancers. In this review, we discussed in great detail the dual roles of SFRP1 in cancers-as tumor suppressor and tumor promoter. The epigenetic regulation of SFRP1 expression will also be underscored with additional emphasis on the potentials of SFRP1 in modulating responses toward chemotherapeutic and epigenetic-modifying drugs, which may encourage the development of novel drugs for cancer treatment. We also present findings from clinical trials and patents involving SFRP1 to illustrate its clinical utility, extensiveness of each research area, and progression toward commercialization. Lastly, this review provides directions for future research to advance SFRP1 as a promising cancer biomarker.
  10. Rehman IU, Lai PS, Kun LS, Lee LH, Chan KG, Khan TM
    Ther Apher Dial, 2020 Feb;24(1):17-25.
    PMID: 31152625 DOI: 10.1111/1744-9987.12862
    CKD-associated pruritus is one of the common symptoms in patients undergoing dialysis, thus contributing to the diminished and compromised quality of life. This study aimed to explore the association between the CKD-associated pruritus on quality of life of patients undergoing hemodialysis in Malaysia. A cross-sectional multicenter study, carried out from February to September 2017 at tertiary care settings in Kuala Lumpur, Malaysia. Patients aged 18 years and above, undergoing hemodialysis, understanding Malay language and willing to participate were included. The CKD-associated pruritus was assessed by using Malay 5D-itch scale and Malay FANLTC questionaiare. To determine the factors associated with pruritus and quality of life, multivariate logistic regression analysis was used having P value < 0.05 as statistically significant. Among n = 334 recruited patients with a response rate of 100%, 59.6% were males and total of 61.3% were having CKD-associated pruritus. The results showed a statistically significant weak negative correlation between CKD-associated pruritus and quality of life. Multivariate linear regression revealed none of these factors were found to be associated with pruritus; however, CKD-associated prurtius was found to be associated with quality of life score. CKD-associated pruritus is have a negative impact on the patient's quality of life including physical, social, mental/emotional, and functional well-being. Despite the high prevalence and negative impact of CKD-associated pruritus on quality of life, it is disregarded by most health care professionals. It is thus pertinent to monitor the potential risk factors and consider providing timely treatment implications for CKD-associated pruritus in hemodialysis patients, in order to improve their quality of life.
  11. Law JW, Ser HL, Ab Mutalib NS, Saokaew S, Duangjai A, Khan TM, et al.
    Sci Rep, 2020 Jan 10;10(1):319.
    PMID: 31924829 DOI: 10.1038/s41598-019-55964-4
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  12. Wang S, Liu F, Tan KS, Ser HL, Tan LT, Lee LH, et al.
    J Cell Mol Med, 2020 01;24(1):722-736.
    PMID: 31680470 DOI: 10.1111/jcmm.14780
    Evidence demonstrates that M1 macrophage polarization promotes inflammatory disease. Here, we discovered that (R)-salbutamol, a β2 receptor agonist, inhibits and reprograms the cellular metabolism of RAW264.7 macrophages. (R)-salbutamol significantly inhibited LPS-induced M1 macrophage polarization and downregulated expressions of typical M1 macrophage cytokines, including monocyte chemotactic protein-1 (MCP-1), interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α). Also, (R)-salbutamol significantly decreased the production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and reactive oxygen species (ROS), while increasing the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. In contrast, (S)-salbutamol increased the production of NO and ROS. Bioenergetic profiles showed that (R)-salbutamol significantly reduced aerobic glycolysis and enhanced mitochondrial respiration. Untargeted metabolomics analysis demonstrated that (R)-salbutamol modulated metabolic pathways, of which three metabolic pathways, namely, (a) phenylalanine metabolism, (b) the pentose phosphate pathway and (c) glycerophospholipid metabolism were the most noticeably impacted pathways. The effects of (R)-salbutamol on M1 polarization were inhibited by a specific β2 receptor antagonist, ICI-118551. These findings demonstrated that (R)-salbutamol inhibits the M1 phenotype by downregulating aerobic glycolysis and glycerophospholipid metabolism, which may propose (R)-salbutamol as the major pharmacologically active component of racemic salbutamol for the treatment of inflammatory diseases and highlight the medicinal value of (R)-salbutamol.
  13. Kemung HM, Tan LT, Chan KG, Ser HL, Law JW, Lee LH, et al.
    Biomed Res Int, 2020;2020:6402607.
    PMID: 32258133 DOI: 10.1155/2020/6402607
    The mangrove ecosystem of Malaysia remains yet to be fully explored for potential microbes that produce biologically active metabolites. In the present study, a mangrove-derived Streptomyces sp. strain MUSC 14 previously isolated from the state of Pahang, Malaysia Peninsula, was studied for its potential in producing antioxidant metabolites. The identity of Streptomyces sp. strain MUSC14 was consistent with the genotypic and phenotypic characteristics of the Streptomyces genus. The antioxidant potential of Streptomyces sp. strain MUSC 14 was determined through screening of its methanolic extract against sets of antioxidant assays. The results were indicative of Streptomyces sp. strain MUSC 14 displaying strong antioxidant activity against ABTS, DPPH free radicals and metal chelating activity of 62.71 ± 3.30%, 24.71 ± 2.22%, and 55.82 ± 2.35%, respectively. The result of ferric reducing activity measured in terms of dose was equivalent to 2.35-2.45 μg of positive control ascorbic acid. Furthermore, there was a high correlation between the total phenolic content and the antioxidant activities with r = 0.979, r = 0.858, and r = 0.983 representing ABTS, DPPH, and metal chelation, respectively. Overall, the present study suggests that Streptomyces sp. strain MUSC 14 from mangrove forest soil has potential to produce antioxidant metabolites that can be further exploited for therapeutic application.
  14. Rayanakorn A, Ser HL, Pusparajah P, Chan KG, Goh BH, Khan TM, et al.
    PLoS One, 2020;15(5):e0232947.
    PMID: 32469959 DOI: 10.1371/journal.pone.0232947
    OBJECTIVE: To compare relative efficacy of different antibiotic therapies either with or without the addition of corticosteroids among adult patients with acute bacterial meningitis on all-cause mortality, neurological complications and any hearing loss.

    METHODS: We searched nine databases from inception to 8 February 2018 for randomized controlled trials evaluating pharmacological interventions and clinical outcomes in adult bacterial meningitis. An updated search from 9 February to 9 March 2020 was performed, and no new studies met the inclusion criteria. Study quality was assessed using the revised Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development and Evaluation system was used for quality of evidences evaluation. Meta-analyses were conducted to estimate the risk ratio with 95% confidence interval for both direct and indirect comparisons on the primary outcomes of all-cause mortality, neurologic sequelae and any hearing loss. The study was registered in PROSPERO (CRD42018108062).

    RESULTS: Nine RCTs were included in systematic review, involving 1,002 participants with a mean age ranging between 25.3 to 50.56 years. Six RCTs were finally included in the network-meta analysis. No significant difference between treatment was noted in meta-analysis. Network meta-analysis suggests that corticosteroids in combination with antibiotic therapy was more effective in reducing the risk of any hearing loss compared to mono antibiotic therapy (RR 0.64; 95%CI, 0.45 to 0.91, 4 RCTs, moderate certainty of evidence). Numerical lower risk of mortality and neurological complications was also shown for adjunctive corticosteroids in combination with antibiotic therapy versus mono antibiotic therapy (RR 0.65; 95%CI, 0.42 to 1.02, 6 RCTs, moderate certainty of evidence; RR 0.75; 95%CI, 0.47 to 1.18, 6 RCTs, moderate certainty of evidence). No differences were noted in the adverse events between different therapies. The overall certainty of evidence was moderate to very low for all primary outcomes examined.

    CONCLUSIONS: Results of this study suggest that corticosteroids therapy in combination with antibiotic is more effective than mono antibiotic therapy in reducing the risk of any hearing loss in adult patients with acute bacterial meningitis. More well-design RCTs to investigate relative effective treatments in acute bacterial meningitis particularly in adult population should be mandated to aid clinicians in treatment recommendations.

  15. Zhong M, Lin B, Pathak JL, Gao H, Young AJ, Wang X, et al.
    Front Med (Lausanne), 2020;7:580796.
    PMID: 33363183 DOI: 10.3389/fmed.2020.580796
    Background: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that mainly transfers from human to human via respiratory and gastrointestinal routes. The S-glycoprotein in the virus is the key factor for the entry of SARS-CoV-2 into the cell, which contains two functional domains: S1 is an angiotensin-converting enzyme 2 (ACE2) receptor binding domain, and S2 is necessary for fusion of the coronavirus and cell membranes. Moreover, it has been reported that ACE2 is likely to be the receptor for SARS-CoV-2. In addition, mRNA level expression of Furin enzyme and ACE2 receptor had been reported in airway epithelia, cardiac tissue, and enteric canals. However, the expression patterns of ACE2 and Furin in different cell types of oral tissues are still unclear. Methods: In order to investigate the potential infective channel of the new coronavirus via the oropharyngeal cavity, we analyze the expression of ACE2 and Furin in human oral mucosa using the public single-cell sequence datasets. Furthermore, immunohistochemistry was performed in mucosal tissue from different oral anatomical sites to confirm the expression of ACE2 and Furin at the protein level. Results: The bioinformatics results indicated the differential expression of ACE2 and Furin on epithelial cells from different oral anatomical sites. Immunohistochemistry results revealed that both the ACE2-positive and Furin-positive cells in the target tissues were mainly positioned in the epithelial layers, partly expressed in fibroblasts, further confirming the bioinformatics results. Conclusions: Based on these findings, we speculated that SARS-CoV-2 could invade oral mucosal cells through two possible routes: binding to the ACE2 receptor and fusion with cell membrane activated by Furin protease. Our results indicated that oral mucosa tissues are susceptible to SARS-CoV-2 that could facilitate COVID-19 infection via respiratory and fecal-oral routes.
  16. Tieng FYF, Baharudin R, Abu N, Mohd Yunos RI, Lee LH, Ab Mutalib NS
    Front Pharmacol, 2020;11:135.
    PMID: 32174835 DOI: 10.3389/fphar.2020.00135
    Colorectal cancer (CRC) is among the most common cancer worldwide, a challenge for research, and a model for studying the molecular mechanisms involved in its development. Previously, bulk transcriptomics analyses were utilized to classify CRC based on its distinct molecular and clinicopathological features for prognosis and diagnosis of patients. The introduction of single-cell transcriptomics completely turned the table by enabling the examination of the expression levels of individual cancer cell within a single tumor. In this review, we highlighted the importance of these single-cell transcriptomics analyses as well as suggesting circulating tumor cells (CTCs) as the main focus of single-cell RNA sequencing. Characterization of these cells might reveal the intratumoral heterogeneity present in CRC while providing critical insights into cancer metastasis. To summarize, we believed the analysis of gene expression patterns of CTC from CRC at single-cell resolution holds the potential to provide key information for identification of prognostic and diagnostic markers as well as the development of precise and personalized cancer treatment.
  17. Mahendra CK, Tan LTH, Lee WL, Yap WH, Pusparajah P, Low LE, et al.
    Front Pharmacol, 2020;11:366.
    PMID: 32372949 DOI: 10.3389/fphar.2020.00366
    Angelicin, a member of the furocoumarin group, is related to psoralen which is well known for its effectiveness in phototherapy. The furocoumarins as a group have been studied since the 1950s but only recently has angelicin begun to come into its own as the subject of several biological studies. Angelicin has demonstrated anti-cancer properties against multiple cell lines, exerting effects via both the intrinsic and extrinsic apoptotic pathways, and also demonstrated an ability to inhibit tubulin polymerization to a higher degree than psoralen. Besides that, angelicin too demonstrated anti-inflammatory activity in inflammatory-related respiratory and neurodegenerative ailments via the activation of NF-κB pathway. Angelicin also showed pro-osteogenesis and pro-chondrogenic effects on osteoblasts and pre-chondrocytes respectively. The elevated expression of pro-osteogenic and chondrogenic markers and activation of TGF-β/BMP, Wnt/β-catenin pathway confirms the positive effect of angelicin bone remodeling. Angelicin also increased the expression of estrogen receptor alpha (ERα) in osteogenesis. Other bioactivities, such as anti-viral and erythroid differentiating properties of angelicin, were also reported by several researchers with the latter even displaying an even greater aptitude as compared to the commonly prescribed drug, hydroxyurea, which is currently on the market. Apart from that, recently, a new application for angelicin against periodontitis had been studied, where reduction of bone loss was indirectly caused by its anti-microbial properties. All in all, angelicin appears to be a promising compound for further studies especially on its mechanism and application in therapies for a multitude of common and debilitating ailments such as sickle cell anaemia, osteoporosis, cancer, and neurodegeneration. Future research on the drug delivery of angelicin in cancer, inflammation and erythroid differentiation models would aid in improving the bioproperties of angelicin and efficacy of delivery to the targeted site. More in-depth studies of angelicin on bone remodeling, the pro-osteogenic effect of angelicin in various bone disease models and the anti-viral implications of angelicin in periodontitis should be researched. Finally, studies on the binding of angelicin toward regulatory genes, transcription factors, and receptors can be done through experimental research supplemented with molecular docking and molecular dynamics simulation.
  18. Rayanakorn A, Katip W, Goh BH, Oberdorfer P, Lee LH
    PLoS One, 2020;15(2):e0228488.
    PMID: 32017787 DOI: 10.1371/journal.pone.0228488
    BACKGROUND: Streptococcus suis (S.suis) is an emerging zoonosis disease with a high prevalence in Southeast Asia. There are over 1,500 cases reported globally in which majority of cases are from Thailand followed by Vietnam. The disease leads to meningitis in human with sensorineural hearing loss (SNHL) as the most common complication suffered by the patients. Early diagnosis and treatment is important to prevent severe neurological complication. In this study, we aim to develop an easy-to-use risk score to promote early diagnosis and detection of S.suis in patients who potentially develop hearing loss.

    METHODS: Data from a retrospective review of 13-year S.suis patient records in a tertiary hospital in Chiang Mai, Northern, Thailand was obtained. Univariate and multivariate logistic regressions were employed to develop a predictive model. The clinical risk score was constructed from the coefficients of significant predictors. Area under the receiver operator characteristic curve (AuROC) was identified to verify the model discriminative performance. Bootstrap technique with 1000-fold bootstrapping was used for internal validation.

    KEY RESULTS: Among 133 patients, the incidence of hearing loss was 31.6% (n = 42). Significant predictors for S. suis hearing loss were meningitis, raw pork consumption, and vertigo. The predictive score ranged from 0-4 and correctly classified 81.95% patients as being at risk of S.suis hearing loss. The model showed good power of prediction (AuROC: 0.859; 95%CI 0.785-0.933) and calibration (AuROC: 0.860; 95%CI 0.716-0.953).

    CONCLUSIONS: To our best knowledge, this is the first risk scoring system development for S.suis hearing loss. We identified meningitis, raw pork consumption and vertigo as the main risk factors of S.suis hearing loss. Future studies are needed to optimize the developed scoring system and investigate its external validity before recommendation for use in clinical practice.

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