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Journal of Science in Sport and Exercise 2023年第1期5卷 16-24页

作者： Marcus Lee Jericho Wee Nick Dobbin Quintin Roman Gabriel Choong Sport Science National Youth Sports InstituteSingaporeSingapore Department of Health Professions Manchester Metropolitan UniversityManchesterUK Human Potential Translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Performance Pathway National Youth Sports InstituteSingaporeSingapore

Purpose This study examined the effects of tournament load on neuromuscular function,perceived wellness and coach rat-ings of performance across two 6-day netball *** Thirty-nine female youth netballers(age=14.6±0.5 years,stature=165.9±4.7 cm,body mass=56.5±7.2 kg)were categorised as HIGH(10-11 matches,n=20)or LOW(6 matches,n=19)tournament *** load,jump height,perceived wellness and coach ratings of performance were monitored *** HIGH tournament load resulted in greater reductions in jump height on match-day 4(-8.3%,±5.6%)when compared to *** tournament load resulted in greater reductions in perceived soreness(-0.9,±1.1 AU)and overall wellness(-2.6,±2.3 AU)on match-day 3,and a greater reduction in perceived sleep(-0.9,±1.1 AU)on match-day *** tournament load was negatively associated with sleep quality and coach ratings of performance(effect size correlation=-0.34 to-0.47)when compared to *** Our results indicate that a higher tournament load resulted in greater increases in neuromuscular fatigue,reduced perceived wellness,and lower ratings of *** should consider pre-tournament preparation and monitoring strategies to minimise the physiological disturbances during an intensified tournament.

关键词： Netball Monitoring Post-match fatigue Youth tournament Tournament structure

Calcaneal osteochondroma masquerading as plantar fasciitis: An approach to plantar heel pain-A case report and literature review

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World Journal of Orthopedics 2019年第9期10卷 339-347页

作者： Don Koh Yvonne Goh Nicholas Yeo Department of Orthopaedic Surgery Singapore General HospitalSingapore 169856Singapore nus yong loo lin school of medicine NUHS Tower BlockSingapore 119228Singapore

BACKGROUND Heel pain is a common orthopaedic complaint,and if left untreated can be a source of chronic *** diagnosis can be challenging,owing to the complex anatomy and multiple pain generators present in the *** aim to share our clinical experience managing an unusual case of chronic heel pain secondary to *** SUMMARY A 41-year-old obese male who works as a porter presented with a long-standing history of left plantar heel *** was assessed to have point tenderness over the plantar insertion of the calcaneus as well as a positive Silfverski?ld *** was treated for plantar fasciitis and tight gastrocnemius but failed conservative therapies as well as surgical *** resonance imaging revealed the presence of a pedunculated bony protrusion over the plantar aspect of the *** decision was made for excision of the osteochondroma,and the patient has been pain-free *** Osteochondromas are rarely symptomatic in skeletally mature *** most are benign with a very low risk of malignant transformation,surgical excision can yield excellent results and significant pain relief in symptomatic patients.

关键词： Chronic heel pain Recalcitrant heel pain Osteochondroma Diagnostic challenge Case report

Precision medicine in inflammatory bowel disease:Individualizing the use of biologics and small molecule therapies

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World Journal of Gastroenterology 2023年第10期29卷 1539-1550页

作者： Eric Cheah James Guoxian Huang Department of Gastroenterology and Clinical Nutrition The Royal Children's Hospital MelbourneParkvilleVIC 3052Australia Department of Paediatrics Khoo Teck Puat-National University Children's Medical InstituteNational University Health SystemSingapore 119228Singapore Department of Paediatrics Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore

The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of *** introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted *** do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of *** who fail to respond to anti-TNF agents typically have a poorer response rate to second-line *** is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic *** introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory *** review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.

关键词： Precision medicine Therapeutic ceiling Inflammatory bowel disease Biologics Small molecules

Design,challenges,and the potential of transcriptomics to understand social behavior

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Current Zoology 2020年第3期66卷 321-330页

作者： Wen Kin LIM Ajay S.MATHURU Science Division Yale-NUS College12 College Avenue W estSingapore Institute of Molecular and Cell Biology(IMCB) 61 Biopolis DriveSingapore Department of Physiology Yong Loo Lin School of Medicine(YLL)National University of SingaporeSingapore

Rapid advances in Ribonucleic Acid sequencing(or RNA-seq)technology for analyzing entire transcriptomes of desired tissue samples,or even of single cells at scale,have revolutionized biology in the past *** accessibility and falling costs are making it possible to address many problems in biology that were once considered intractable,including the study of various social ***-seq is opening new avenues to understand long-standing questions on the molecular basis of behavioral plasticity and individual variation in the expression of a *** whole transcriptomes are examined,it has become possible to make unbiased discoveries of underlying mechanisms with little or no necessity to predict genes involved in ***,researchers need to be aware of technical limitations and have to make specific decisions when applying RNA-seq to study social ***,we provide a perspective on the applications of RNA-seq and experimental design considerations for behavioral scientists who are unfamiliar with the technology but are considering using it in their research.

关键词： behavioral variability behavioral plasticity neurotranscriptomics RNA-seq social behaviors

Themis regulates metabolic signaling and effector functions in CD4^(+) T cells by controlling NFAT nuclear translocation

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Cellular & Molecular Immunology 2021年第9期18卷 2249-2261页

作者： Mukul Prasad Joanna Brzostek Namrata Gautam Renu Balyan Vasily Rybakin Nicholas R.J.Gascoigne Translational Immunology Programme Yong Loo Lin School of MedicineNational University of Singapore5 Science Drive 2Singapore 117545Singapore Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University of Singapore5 Science Drive 2Singapore 117545Singapore H.Lee Moffitt Cancer Center and Research Institute TampaFLUSA Torque Therapeutics CambridgeMAUSA

Themis is a T cell lineage-specific molecule that is involved in TCR signal *** effects of germline Themis deletion on peripheral CD4^(+)T cell function have not been described *** this study,we found that Themis-deficient CD4^(+)T cells had poor proliferative responses,reduced cytokine production in vitro and weaker inflammatory potential,as measured by their ability to cause colitis in *** T cells are quiescent,whereas activated T cells have high metabolic *** of these metabolic demands depends upon nutrient availability and upregulation of nutrient intake channels after efficient TCR signal transduction,which leads to metabolic reprogramming in T *** tested whether defects in effector functions were caused by impaired metabolic shifts in Themis-deficient CD4^(+)T cells due to inefficient TCR signal transduction,in turn caused by the lack of *** found that upon TCR stimulation,Themis-deficient CD4^(+)T cells were unable to upregulate the expression of insulin receptor(IR),glucose transporter(GLUT1),the neutral amino acid transporter CD98 and the mTOR pathway,as measured by c-Myc and pS6 *** analysis of activated Themis-deficient CD4^(+)T cells showed more oxidative phosphorylation(OXPHOS)than aerobic glycolysis,indicating defective metabolic ***,we found reduced NFAT translocation in Themis-deficient CD4^(+)T cells upon TCR *** previously reported ChIP-seq and RNA-seq data,we found that NFAT nuclear translocation controls IR gene ***,our results describe an internal circuit between TCR signal transduction,NFAT nuclear translocation,and metabolic signaling in CD4^(+)T cells.

关键词： Immunometabolism NFAT nuclear translocation Insulin receptor mTOR Mitochondria

Evaluation of antiviral activities of Houttuynia cordata ***,quercetin,quercetrin and cinanserin on murine coronavirus and dengue virus infection

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Asian Pacific Journal of Tropical medicine 2016年第1期9卷 1-7页

作者： K.H.Chiow M.C.Phoon Thomas Putti Benny K.H.Tan Vincent T.Chow Department of Microbiology Department of Pathologyand Department of PharmacologyYong Loo Lin School of MedicineNational University Health SystemNational University of Singapore

Objective:To evaluate the in vitro activities of the ethyl acetate(EA) fraction of Houttuynia cordata(***) Thunb.(Saururaceae) and three of its constituent flavonoids(*** and rutin) against murine coronavirus and dengue virus(DENV).Methods:The antiviral activities of various concentrations of the EA fraction of *** and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus(MHV) and DENV type 2(DENV-2).Cinanserin hydrochloride was also tested against *** EA fraction of *** was tested for acute oral toxicity in C57BL/6 ***:The EA fraction of *** inhibited viral infectivity up to 6 *** hydrochloride was able to inhibit MHV for only 2 *** 50%inhibitory concentrations(IC_(50)) of the EA fraction of *** added before the viral adsorption stage were 0.98 μg/mL for MHV and 7.50 μg/mL for DENV-2with absence of *** mice fed with the EA fraction up to 2 000 mg/kg did not induce any signs of acute toxicity,with normal histological features of major *** flavonoids exhibited comparatively weaker antiviral activity,notably quercetin which could inhibit both MHV and *** was followed by quercitrin which could inhibit DENV-2but not MHV,whereas rutin did not exert any inhibitory effect on either *** quercetin was combined with quercitrin,enhancement of anti-DENV-2 activity and reduced cytotoxicity were ***,the synergistic efficacy of the flavonoid combination was still less than that of the EA ***:The compounds in *** contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in *** has much potential for the development of antiviral agents against coronavirus and dengue infections.

关键词： Houttuynia cordata Murine coronavirus Dengue virus Quercetin Quercetrin Cinanserin

Antioxidant effect of a novel synthetic hydrogen sulfide releasing Danshensu derivative and its clinical implications

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中国药理学与毒理学杂志 2018年第4期32卷 273-274页

作者： Jin-song BIAN Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore 117600 PR Singapore

Oxidative stress induces apoptosis of many cells and arrest of their *** Danshensu(DSS) and hydrogen sulfide(H_2S) produce significant antioxidant effect in various *** this study,we synthesized SDSS,a new H_2S-releasing compound derived from DSS,and studied its antioxidant effect in an H_2O_2-induced MC3T3-E1 osteoblastic cell injury *** first characterized the H_2S releasing property of SDSS in both in vivo and in vitro *** chromatogram showed that intravenous injection of SDSS in adult rats released ADT-OH,a well proved H_2S sustained-release moiety,within several minutes in the rat *** an H_2S selective fluorescent probe,we further confirmed that SDSS released H_2S in MC3T3-E1 osteoblastic *** studies revealed that SDSS had no significant toxic effect but produced protective effects against H_2O_2-induced MC3T3-E1 cell *** also reversed the arrest of cell differentiation caused by H_2O_2 *** was caused by the stimulatory effect of SDSS on bone sialo protein,runt-related transcription factor-2,collagen expression,alkaline phosphatase activity,and bone nodule *** studies revealed that SDSS reversed the reduced superoxide dismutase activity and glutathione content,and the increased ROS production in H_2O_2 treated *** addition,SDSS significantly attenuated H_2O_2-induced activation of p38-,ERK1/2-,and *** also stimulated phosphatidylinositol 3-kinase/Akt signaling *** of this pathway attenuated the cytoprotective effect of *** also observed the effect of SDSS on aspirin-induced gastric injury and found that SDSS protected against aspirin-induced gastric *** conclusion,SDSS protects cells against H_2O_2-induced apoptosis by suppressing oxidative stress.

关键词：细胞凋亡丹神素治疗方法临床分析

Safety evaluation of nanodiamond-doxorubicin complexes in a Naïve Beagle canine model using hematologic,histological,and urine analysis

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Nano Research 2022年第4期15卷 3356-3366页

作者： Liping Wang Wenqiong Su Khan Zara Ahmad Xin Wang Ting Zhang Youyi Yu Edward Kai-Hua Chow Dean Ho Xianting Ding State Key Laboratory of Oncogenes and Related Genes Institute for Personalized MedicineSchool of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200030China Cancer Science Institute of Singapore Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore The N.1 Institute for Health(N.1) National University of SingaporeSingapore 117456Singapore The Institute for Digital medicine(WisDM) National University of SingaporeSingapore 117456Singapore Department of Pharmacology National University of SingaporeSingapore 117597Singapore Department of Biomedical Engineering National University of SingaporeSingapore 117583Singapore

While doxorubicin(DOX)is one of the most common chemotherapeutic drugs for treating cancer,use of DOX must be managed carefully due to dose-related ***(ND)drug delivery system conjugated with DOX(NDX)has been reported to enhance treatment efficacy and attenuate toxicity in murine cancer *** addition,extensive biocompatibility studies indicate that NDs seem to be well tolerated in non-human *** the clinical translation of NDX,it is necessary to verify the safety of ND in large *** of nanomedicine drug safety for large animal are not commonly reported,and this work represents a key milestone in bridging earlier advances towards clinical ***,NDs’safety as a drug-delivery platform was evaluated in Naïve Beagle *** study is performed with DOX,ND,and NDX in a dual-gender animal model using intravenous(IV)injection and hepatic portal vein(HPV)injection *** dogs are monitored for their health phenotype changes in continuous 5 *** and urine obtained are for clinical pathology *** results indicate that ND drug delivery platform significantly relieves DOX toxicity for Naïve Beagle dog *** study provides guidance for the pre-clinical safety assessment of NDX therapy at large animal level.

关键词： nanomedicine doxorubicin nanodiamonds safety biodistribution

Valproic acid as a micro RNA modulator to promote neurite outgrowth

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Neural Regeneration Research 2016年第10期11卷 1564-1565页

作者： Hirotaka Oikawa Judy C.G.Sng Neuroepigenetics Laboratory Singapore Institute for Clinical Sciences Agency for Science and Technology (A*STAR) Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore

Valproic acid （VPA） has been a first-choice drug for clinical treatment of epilepsy and manic disorder. For decades, its phar- macological action was believed to act on inhibition of gam- ma-aminobutyric acid （GABA） transaminase, in turn, increas- ing GABA in inhibitory synapses. However, in recent years, VPA has been investigated on other therapeutic actions. Those investigations demonstrate that VPA shows neuroprotective ef- fects by promoting neurogenesis, neuronal differentiation, and neuroregeneration （Foti et al., 2013）.

关键词： VPA RNA Valproic acid as a micro RNA modulator to promote neurite outgrowth acid

Rabs and axonal regeneration

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Neural Regeneration Research 2019年第4期14卷 566-569页

作者： Cheryl Qian Ying yong Bor Luen Tang Department of Biochemistry Yong Loo Lin School of Medicine National University Health System National University of Singapore Graduate school for Integrative Sciences and Engineering National University of Singapore

Membrane trafficking processes are presumably vital for axonal regeneration after injury, but mechanistic understanding in this regard has been sparse. A recent loss-of-function screen had been carried out for factors important for axonal regeneration by cultured cortical neurons and the results suggested that the activity of a number of Rab GTPases might act to restrict axonal regeneration. A loss of Rab27b, in particular, is shown to enhance axonal regeneration in vitro, as well as in C. elegans and mouse central nervous system injury models in vivo. Possible mechanisms underlying this new finding, which has important academic and translational implication, are discussed.

关键词： Arf Rab Rab27b axon regeneration axonal transport cortical neurons central nervous system injury membrane trafficking Myosin-V