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World Journal of Gastroenterology 2014年第20期20卷 5962-5972页

作者： Weiqi Tan Yang Li Seng-Gee lim Theresa MC Tan Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Singapore S117597 Singapore Department of Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore S117597 Singapore

MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational *** polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in *** has two other paralogs in the human genome,the miR-106b-25 cluster and the miR-106a-363 ***,the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families,namely the miR-17,the miR-92,the miR-18and the miR-19 ***-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular *** of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C *** targets of these microRNAs have been identified,and these targets are involved in tumor growth,cell survival and *** this review,we first describe the regulation of these clusters by c-Myc and E2F1,and how the members of these clusters inturn regulate E2F1 expression forming an auto-regulatory *** addition,the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.

关键词： miR-106b-25 cluster miR-17-92 cluster Hepatocellular carcinoma Liver cirrhosis MicroRNAs

Genomic,transcriptomic,and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites

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Journal of Integrative Plant Biology 2023年第6期65卷 1442-1466页

作者： Irene Julca Daniela Mutwil-Anderwald Vaishnervi Manoj Zahra Khan Soak Kuan Lai Lay K.Yang Ing T.Beh Jerzy Dziekan Yoon P.lim Shen K.lim Yee W.Low Yuen I.Lam Seth Tjia Yuguang Mu Qiao W.Tan Przemyslaw Nuc Le M.Choo Gillian Khew loo Shining Antony Kam James P.Tam Zbynek Bozdech Maximilian Schmidt Bjoern Usadel Yoganathan Kanagasundaram Saleh Alseekh Alisdair Fernie Hoi Y.Li Marek Mutwil School of Biological Sciences Nanyang Technological UniversitySingapore 639798Singapore Shared Analytics Singapore Institute of Food and Biotechnology Innovation(SIFBI)Agency for ScienceTechnology and Research(A*STAR)Singapore 138671Singapore Department of Biochemistry National University of SingaporeSingapore 117596Singapore Singapore Botanic Gardens Singapore 259569Singapore Department of Gene Expression Faculty of BiologyInstitute of Molecular Biology and BiotechnologyAdam Mickiewicz UniversityPoznan 61-614Poland IBG-4 Bioinformatics Forschungszentrum JülichJülich 52428Germany Max-Planck-Institut für Molekulare Pflanzenphysiologie Potsdam-Golm 14476Germany Center of Plant Systems Biology and Biotechnology Plovdiv 4000Bulgaria

Plants accumulate a vast array of secondary metabolites,which constitute a natural resource for *** corymbosa belongs to the Rubiaceae family,and has been used in traditional medicine to treat different diseases,including ***,the active metabolites of the plant,their biosynthetic pathway and mode of action in cancer are *** fill these gaps,we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression,metabolic profiles,and anti-cancer *** results show that *** extracts are active against breast cancer cell lines and that ursolic acid is responsible for this ***,we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic ***,we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay(CETSA)and reverse ***,these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group,while the mode of action of ursolic acid will allow us to further develop this valuable compound.

关键词： genome medicinal metabolomics mode of action transcriptome

Escitalopram-induced liver injury: A case report and review of literature

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World Journal of Hepatology 2019年第10期11卷 719-724页

作者： Qin Xiang Ng Christl Suet Kwan Yong Wayren Loke wee Song Yeo Alex Yu Sen Soh Institute of Mental Health Buangkok Green Medical ParkSingapore 539747Singapore MOH Holdings Pte Ltd Singapore 099253Singapore National University Hospital National University Health SystemSingapore 119074Singapore Yong loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore

BACKGROUND Depression is a growing public health problem that affects over 350 million people globally and accounts for approximately 7.5%of healthy years lost due to ***,one of the first-line medications for the treatment of depression,is a selective serotonin reuptake inhibitor and one of the most commonly prescribed antidepressant medications *** thought to be generally safe and with minimal drug-drug interactions,we herein present an unusual case of cholestatic liver injury,likely secondary to escitalopram *** SUMMARY A 56-year-old Chinese lady presented with fever and cholestatic liver injury two weeks after initiation of escitalopram for the treatment of psychotic *** examination was *** investigations,including a computed tomography scan of the abdomen and pelvis and tests for hepatitis A,B and C and for autoimmune liver disease were ***,a diagnosis of escitalopram-induced liver injury was *** stopping escitalopram,repeat liver function tests showed downtrending liver enzymes with eventual normalization of serum aspartate aminotransferase and alanine aminotransferase one-week *** Clinicians should be aware of the possibility of escitalopram-induced liver injury when initiating depressed patients on antidepressant *** requires extra vigilance as most patients may remain *** of liver function tests could be considered after initiation of antidepressant treatment,especially in patients with pre-existing liver disease.

关键词： Depression Antidepressant Escitalopram Liver injury Drug-induced Druginduced liver injury

Is there an association between Helicobacter pylori infection and irritable bowel syndrome? A meta-analysis

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World Journal of Gastroenterology 2019年第37期25卷 5702-5710页

作者： Qin Xiang Ng Nadine Xinhui Foo Wayren Loke Yun Qing Koh Vanessa Jing Min Seah Alex Yu Sen Soh wee Song Yeo Medicine MOH Holdings Pte LtdSingapore 099253Singapore General and Community Psychiatry Institute of Mental HealthSingapore 117597Singapore Department of General Medicine Tan Tock Seng Hospital11 Jalan Tan Tock SengSingapore 308433Singapore Department of Gastroenterology and Hepatology National University HospitalNational University Health SystemSingapore 119074Singapore Yong loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore

BACKGROUND Irritable bowel syndrome(IBS)is a prevalent and debilitating gastrointestinal *** has reported persistent,low-grade mucosal inflammation and significant overlaps between patients with IBS and those with dyspepsia,suggesting a possible pathogenic role of Helicobacter pylori(***)in *** study therefore aimed to provide the first systematic review and meta-analysis on the association between *** infection and *** To investigate the association between *** infection and *** Using the keywords“*** OR Helicobacter OR Helicobacter pylori OR infection”AND“irritable bowel syndrome OR IBS”,a preliminary search of PubMed,Medline,Embase,Cochrane Database of Systematic Reviews,Web of Science,Google Scholar and WanFang databases yielded 2924 papers published in English between 1 January 1960 and 1 June *** were also made to search grey *** A total of 13 clinical studies were systematically reviewed and nine studies were included in the final ***-effects meta-analysis found a slight increased likelihood of *** infection in patients with IBS,albeit this was not statistically significant(pooled odds ratio 1.47,95%confidence interval:0.90-2.40,P=0.123).It must also be acknowledged that all of the available studies reported only crude odd *** eradication therapy also does not appear to improve IBS *** publication bias was not observed in the funnel plot,there was a high degree of heterogeneity amongst the studies included in the meta-analysis(I2=87.38%).CONCLUSION Overall,current evidence does not support an association between IBS and *** *** rigorous and detailed studies with larger sample sizes and after *** eradication therapy are warranted.

关键词： Irritable bowel syndrome Functional Helicobacter pylori Infection Metaanalysis

Deciphering lipid dysregulation in ALS:from mechanisms to translational medicine

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Translational Neurodegeneration 2022年第1期11卷 192-218页

作者： Ira Agrawal Yong Shan lim Shi-Yan Ng Shuo-Chien Ling Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeTahir Foundation BuildingMD116-03-H12 Science Drive 2Singapore 117549Singapore Healthy Longevity Translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Institute of Molecular and Cell Biology A*STAR Research EntitiesSingaporeSingapore Program in Neuroscience and Behavior Disorders Duke-National University of Singapore Medical SchoolSingaporeSingapore.

Lipids,defined by low solubility in water and high solubility in nonpolar solvents,can be classified into fatty acids,glycerolipids,glycerophospholipids,sphingolipids,and *** not only regulate integrity and fluidity of biologi-cal membranes,but also serve as energy storage and bioactive molecules for *** mutations in SPTLC1(serine palmitoyltransferase long chain subunit 1)gene within the lipogenic pathway have been identified in amyo-trophic lateral sclerosis(ALS),a paralytic and fatal motor neuron ***,lipid dysmetabolism within the central nervous system and circulation is associated with ***,we aim to delineate the diverse roles of different lipid classes and understand how lipid dysmetabolism may contribute to ALS *** the different lipids,accumulation of ceramides,arachidonic acid,and lysophosphatidylcholine is commonly emerging as detri-mental to motor *** end with exploring the potential ALS therapeutics by reducing these toxic lipids.

关键词： Amyotrophic lateral sclerosis Sphingolipids Triglycerides Phospholipids Cholesterol esters Fatty acids Ceramides Arachidonic acid Lysophosphatidylcholine Eicosanoids

Novel mechanism of drug resistance to proteasome inhibitors in multiple myeloma

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World Journal of Clinical Oncology 2019年第9期10卷 303-306页

作者： Jianbiao Zhou wee-Joo Chng Cancer Science Institute of Singapore National University of SingaporeCentre for Translational MedicineSingapore 117599Singapore Department of Medicine Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119074Singapore Department of Hematology-Oncology National University Cancer InstituteNUHSSingapore 119228Singapore

Multiple myeloma(MM) is a cancer caused by uncontrolled proliferation of antibody-secreting plasma cells in bone marrow, which represents the second most common hematological malignancy. MM is a highly heterogeneous disease and can be classified into a spectrum of subgroups based on their molecular and cytogenetic abnormalities. In the past decade, novel therapies, especially, the first-in-class proteasome inhibitor bortezomib, have been revolutionary for the treatment of MM patients. Despite these remarkable achievements, myeloma remains incurable with a high frequency of patients suffering from a relapse, due to drug resistance. Mutation in the proteasome β5-subunit(PSMB5) was found in a bortezomib-resistant cell line generated via long-term coculture with increasing concentrations of bortezomib in 2008, but their actual implication in drug resistance in the clinic has not been reported until recently. A recent study discovered four resistance-inducing PSMB5 mutations from a relapsed MM patient receiving prolonged bortezomib treatment. Analysis of the dynamic clonal evolution revealed that two subclones existed at the onset of disease, while the other two subclones were induced. Protein structural modeling and functional assays demonstrated that all four mutations impaired the binding of bortezomib to the 20 S proteasome, conferring different degrees of resistance. The authors further demonstrated two potential approaches to overcome drug resistance by using combination therapy for targeting proteolysis machinery independent of the 20 S proteasome.

关键词： Multiple myeloma Proteasome inhibitor Bortezomib Proteasome β5-subunit Drug resistance Clonal evolution Combination therapy

NF-κB promotes the stem-like properties of leukemia cells by activation of LIN28B

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World Journal of Stem Cells 2018年第4期10卷 34-42页

作者： Jianbiao Zhou Jing-Yuan Chooi Ying Qing Ching Jessie Yiying Quah Sabrina Hui-Min Toh Yvonne Ng Tuan Zea Tan wee-Joo Chng Cancer Science Institute of Singapore National University of Singapore Department of Medicine Yong Loo Lin School of MedicineNational University of Singapore Department of Hematology-Oncology National University Cancer Institute

AIM To examine whether nuclear factor kappa B(NF-κB) activity regulates LIN28 B expression and their roles in leukemia stem cell(LSC)-like properties. METHODS We used pharmacological inhibitor and cell viability assays to examine the relation between NF-κB and LIN28 B. Western blot and q RT-PCR was employed to determine their protein and m RNA levels. Luciferase reporter was constructed and applied to explore the transcriptional regulation of LIN28 B. We manipulated LIN28 B level in acute myeloid leukemia(AML) cells and investigated LSC-like properties with colony forming and serial replating assays. RESULTS This study revealed the relationship between NF-κB and LIN28 B in AML cells through drug inhibition and overexpression experiments. Notably,inhibition of NF-κB by pharmacological inhibitors reduced LIN28 B expression and decreased cell proliferation. We demonstrated that NF-κB binds to the-819 to-811 region of LIN28 B promoter,and transcriptionally regulates LIN28 B expression. LIN28 B protein was significantly elevated in NFκB1 transfected cells compared to vector control. Importantly,ectopic expression of LIN28 B partially rescued the self-renewal capacity impaired by pharmacological inhibition of NF-κB activity. CONCLUSION These results uncover a regulatory signaling,NF-κB/LIN28 B,which plays a pivotal role in leukemia stem cell-like properties and it could serve as a promising intervening target for effective treatment of AML disease.

关键词： Nuclear factor kappa B LIN28B Leukemia stem cell Acute myeloid leukemia

Clinical utility of Epstein-Barr virus DNA and other liquid biopsy markers in nasopharyngeal carcinoma

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Cancer Communications 2020年第11期40卷 564-585页

作者： Rong Tan Sean Kean Ann Phua Yoke lim Soong Lynette Lin Ean Oon Kian Sing Chan Sasidharan Swarnalatha Lucky Jamie Mong Min Han Tan Chwee Ming lim Yong loo Lin School of Medicine National University of SingaporeSingapore 117599Singapore Department of Radiation Oncology National Cancer CenterSingapore 169608Singapore Department of Molecular Pathology Singapore General HospitalSingapore 169608Singapore Institute of Bioengineering and Nanotechnology Singapore 138669Singapore Department of Otorhinolaryngology-Head and Neck Surgery Singapore General HospitalSingapore 169608Singapore Lucence Diagnostics Singapore 159552Singapore Surgery Academic Clinical Programme Duke-NUS Graduate Medical SchoolSingapore 169857Singapore

Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor ubiquitously associated with the Epstein-Barr virus(EBV),which is highly prevalent in South China,Southeast Asia,and North *** being a highly radio-sensitive and treatable cancer,a majority of NPC patients are diagnosed in their advanced stage,and locoregional and distant relapses following definitive treatment contribute largely to cancer-specific mortality among these *** that EBV-driven NPC is the predominant variant seen in endemic regions,various EBV detection methods have been developed and are utilized in screening,prognostication,and post-treatment surveillance of NPC *** the Immunoglobulin A(IgA)serology assay is the most extensively studied EBV detection method,the detection of plasma EBV DNA released during replication or cellular apoptosis has shown superior outcomes in endemic population screening,prognostication,and detection of distant ***,there is emerging evidence on the use of circulating tumor cells,microRNAs,DNA hypermethylation,and combination assays in various clinical ***,this paper provides a comprehensive overview of the relevant studies using various EBV detection techniques in the management of ***,the recent advances,clinical evidence,and challenges associated with the clinical application of EBV liquid biopsies in population screening,prognostication,and surveillance of NPC are presented.

关键词： circulating tumor cells EBV DNA Epstein-Barr virus microRNA nasopharyngeal carcinoma prognosis screening serology surveillance

Unusual phenomenon-“polyp”arising from a diverticulum:A case report

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World Journal of Clinical Cases 2023年第13期11卷 3070-3075页

作者： Jacqueline Jin Li Liew Wei Shyann lim Frederick H Koh Yong loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore Colorectal Service Department of General SurgerySengkang General HospitalSingapore 544886Singapore

BACKGROUND Sealed perforation of colonic diverticulum is a common clinical condition and may be differentiated from an underlying malignant perforation using interval *** present an uncommon colonoscopy finding of a healed diverticular perforation,mimicking a polyp,6 wk post-diverticulitis-something that has not been reported in *** aim to shed light on the likely process that resulted in the trompe l'oeil after *** also introduces the possibility of more targeted colonic resection in the event of a similar *** SUMMARY A middle-aged Chinese female presented with a 3-d history of non-colicky left iliac fossa *** was associated with fever(Tmax 37.6℃),non-bloody diarrhoea and non-bloody,non-bilious *** had a history of Type 2 diabetes mellitus,well controlled on *** was noted on the left iliac fossa region with no guarding or *** white cell count(11.45×10^(9)/L)and C-reactive protein levels(213.9 mg/L)were *** tomography imaging of the abdomen revealed pericolonic fat stranding and extraluminal air pockets fluid density with peritoneal thickening at the sigmoid colon,likely representing a sealed *** weeks after the episode,she underwent a follow-up *** exophytic polypoid lesion closely associated with a diverticulum was seen in the sigmoid *** lesion was easily“pinched”off without much effort using endoscopic forceps and sent for histology which revealed granulation tissue suggesting a healed diverticular *** Granulation tissue associated with healed diverticular perforations resemble *** around these sites may allow for future targeted colonic resections.

关键词： Diverticulitis Colonoscopy Colonic polyps Colorectal cancer Diverticular perforation Case report