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Orthogonal assays for the identification of inhibitors of the single-stranded nucleic acid binding protein YB-1

Acta Pharmaceutica Sinica B 2019年第5期9卷 997-1007页

作者： Alexander J.Trevarton Yan Zhou Dehua Yang Gordon W.Rewcastle Jack U.Flanagan Antony Braithwaite Peter R.Shepherd Cristin G.Print Ming-Wei Wang Annette Lasham Department of molecular Medicine and Pathology University of AucklandAucklandNew Zealand The National Center for Drug Screening and the CAS Key laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai201203China Auckland Cancer Society Research Centre AucklandNew Zealand Maurice Wilkins Centre for molecular biodiscovery University of AucklandAucklandNew Zealand Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedinNew Zealand Maurice Wilkins Centre for molecular biodiscovery University of OtagoDunedinNew Zealand School of Pharmacy Fudan UniversityShanghai201203China

We have previously shown that high expression of the nucleic acid binding factor YB-1 is strongly associated with poor prognosis in a variety of cancer types. The 3-dimensional protein structure of YB-1 has yet to be determined and its role in transcriptional regulation remains elusive. Drug targeting of transcription factors is often thought to be difficult and there are very few published high-throughput screening approaches. YB-1 predominantly binds to single-stranded nucleic acids, adding further difficulty to drug discovery. Therefore, we have developed two novel screening assays to detect compounds that interfere with the transcriptional activation properties of YB-1, both of which may be generalizable to screen for inhibitors of other nucleic acid binding molecules. The first approach is a cell-based luciferase reporter gene assay that measures the level of activation of a fragment of the E2 F1 promoter by YB-1. The second approach is a novel application of the Alpha Screen system, to detect interference of YB-1 interaction with a single-stranded DNA binding site. These complementary assays examine YB-1 binding to two discrete nucleic acid sequences using two different luminescent signal outputs and were employed sequentially to screen 7360 small molecule compounds leading to the identification of three putative YB-1 inhibitors.

关键词： Cancer YB-1 Luciferase Alpha Screen Transcription factor Single-stranded DNA

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Effect of different intensities of physical activity on cardiometabolic markers and vascular and cardiac function in adult rats fed with a high-fat high-carbohydrate diet

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Journal of Sport and Health Science 2018年第1期7卷 109-119页

作者： Romeo B.Batacan Jr Mitch J.Duncan Vincent J.Dalbo Geraldine L.Buitrago Andrew S.Fenning School of Medical and Applied Sciences Central Queensland University Centre for Physical Activity Studies Central Queensland University School of Medicine & Public Health Priority Research Centre for Physical Activity and Nutrition Faculty of Health and MedicineThe University of Newcastle University Drive Clinical Biochemistry laboratory Central Queensland University Centre for biodiscovery and molecular Development of Therapeutics Australian Institute of Tropical Health and MedicineJames Cook University

Background: Physical activity(PA) and diet are 2 lifestyle factors that affect cardiometabolic risk. However, data on how a high-fat highcarbohydrate(HFHC) diet influences the effect of different intensities of PA on cardiometabolic health and cardiovascular function in a controlled setting are yet to be fully established. This study investigated the effect of sedentary behavior, light-intensity training(LIT), and high-intensity interval training(HIIT) on cardiometabolic markers and vascular and cardiac function in HFHC-fed adult ***: Twelve-week-old Wistar rats were randomly allocated to 4 groups(12 rats/group): control(CTL), sedentary(SED), LIT, and *** indices, glucose and lipid control, inflammatory and oxidative stress markers, vascular reactivity, and cardiac electrophysiology of the experimental groups were examined after 12 weeks of HFHC-diet feeding and PA ***: The SED group had slower cardiac conduction(p = 0.0426) and greater thoracic aortic contractile responses(p < 0.05) compared with the CTL group. The LIT group showed improved cardiac conduction compared with the SED group(p = 0.0003), and the HIIT group showed decreased mesenteric artery contractile responses compared with all other groups and improved endothelium-dependent mesenteric artery relaxation compared with the LIT group(both p < 0.05). The LIT and HIIT groups had lower visceral(p = 0.0057 for LIT, p = 0.0120 for HIIT)and epididymal fat(p < 0.0001 for LIT, p = 0.0002 for HIIT) compared with the CTL ***: LIT induced positive adaptations on fat accumulation and cardiac conduction, and HIIT induced a positive effect on fat accumulation,mesenteric artery contraction, and endothelium-dependent relaxation. No other differences were observed between groups. These findings suggest that few positive health effects can be achieved through LIT and HIIT when consuming a chronic and sustained HFHC diet.

关键词： High-intensity interval training Inflammation Light-intensity training Metabolic syndrome Oxidative stress Sedentary behavior Western diet

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Differential diagnosis of gallstones by using hypericin as a fluorescent optical imaging agent

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World Journal of Gastroenterology 2016年第29期22卷 6690-6705页

作者： Marlein Miranda Cona Ye-Wei Liu Antoine Hubert Ting Yin Yuan-Bo Feng Peter de Witte Etienne Waelkens Yan-Sheng Jiang Jian Zhang Stefaan Mulier Qian Xia Gang Huang Raymond Oyen Yi-Cheng Ni Department of Imaging and Pathology Faculty of Medicine Biomedical Sciences Group University HospitalsKU Leuven Department of Cellular and molecular Medicine Biomedical Sciences GroupKU Leuven molecular biodiscovery laboratory Faculty of Pharmaceutical Sciences Biomedical Sciences GroupKU Leuven laboratory of Translational Medicine Jiangsu Province Academy of Traditional Chinese Medicine Department of Nuclear Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University

AIM: To explore the feasibility of using hypericin as an optical imaging probe with affinity for cholesterol for differential fluorescent detection of human ***: Cholesterol, mixed and pigment stones from cholecystectomy patients were incubated with hypericin or solvent. After 72 h, the stones were analysed for fluorescence(365 nm) and treated with 2-propanol/dimethyl sulfoxide for high performance liquid chromatography(HPLC) analysis. Rats with virtual gallbladder containing human cholesterol, mixed or pigment gallstones(VGHG) received 5 mg/kg hypericin or solvent and VGHG rats with cholesterol stones were given different hypericin doses(5-15 mg/kg). Twelve hours later, the stones were analysed at 365 nm. Biliary excretion and metabolites of hypericin were assessed in common bile duct(CBD) cannulated rats for 9 h using fluorospectrometry, HPLC and matrixassisted laser desorption/ionization-time-of-flight mass spectrometry(MALDI-TOF MS).RESULTS: Homogeneous high fluorescence was seen on cholesterol stones either pre-incubated with hypericin or extracted from VGHG rats receiving hypericin. Mixed stones showed a dotted fluorescent pattern, whereas pigment and solvent-treated ones lacked fluorescence. HPLC showed 7.68, 6.65 and 0.08 × 10^(-3) M of cholesterol in extracts from cholesterol, mixed, and pigment gallstones, respectively. Hypericin accounted for 2.0, 0.5 and 0.2 × 10-6 M in that order. On cholesterol stones from VGHG rats receiving different hypericin doses, a positive correlation was observed between dose and fluorescence. In the bile from CBD-cannulated rats, fluorescence represented 20% of the injected dose with two peaks in 9 h. HPLC analysis revealed that hypericin conjugates reached 60% of the peak area. By MALDI-TOF MS, hypericinglucuronide was detected. CONCLUSION: This study proves the potential use of hypericin for differential fluorescent detection of human gallstones regarding their chemical composition.

关键词： Differential detection Fluorescence Human gallstones Hypericin Rat model of cholelithiasis

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Genomic scanning enabling discovery of a new antibacterial bicyclic carbamate-containing alkaloid

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Synthetic and Systems Biotechnology 2021年第1期6卷 12-19页

作者： Qing Fang Linrui Wu Caroline Urwald Morgane Mugat Shan Wang Kwaku Kyeremeh Carol Philips Samantha Law d Yongjun Zhou Hai Deng Marine biodiscovery Centre Department of ChemistryUniversity of AberdeenMeston WalkAberdeenAB243UEScotlandUK ENSAIA 2 avenue de la forêt de Haye54505 vandoeuvre lès NancyFrance Department of Chemistry University of GhanaP.O.Box LG56Legon-AccraGhana NCIMB Ltd Ferguson BuildingCraibstone EstateBucksburnAberdeenAB219YAScotlandUK Research Centre for Marine Drugs State Key Laboratory of Oncogenes and Related GenesDepartment of PharmacyRen Ji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai200127China

Non-ribosomal peptides are a group of structurally diverse natural products with various important therapeutic and agrochemical *** pyrrolizidine alkaloids(PAs),containing a scaffold of two fused five-membered ring system with a nitrogen atom at the bridgehead,have been found to originate from a multidomain non-ribosomal peptide synthetase to generate indolizidine intermediates,followed by multistep oxidation,catalysed by single Bayer-Villiger(BV)enzymes,to yield PA *** bacterial PAs are rare in natural product inventory,bioinformatics analysis suggested that the biosynthetic gene clusters(BGCs)that are likely to be responsible for the production of PA-like metabolites are widely distributed in bacterial ***,most of the strains containing PA-like BGCs are not deposited in the public domain,therefore preventing further assessment of the chemical spaces of this group of bioactive ***,we report a genomic scanning strategy to assess the potential of PA metabolites production in our culture collection without prior knowledge of genome *** the strains tested,we found fifteen contain the key BV enzymes that are likely to be involved in the last step of PA ring *** one-strain-many-compound(OSMAC)method,supported by a combination of HR-MS,NMR,SMART 2.0 technology,and GNPS analysis,allowed identification and characterization of a new[5+7]heterobicyclic carbamate,legoncarbamate,together with five known PAs,bohemamine derivatives,from Streptomyces ***37,a Ghanaian soil *** absolute stereochemistry of legoncarbamate was determined by comparison of measured and calculated ECD *** displays antibacterial activity against *** ATCC 25922 with an MIC value of 3.1μg/***,a biosynthetic model of legoncarbamate and other bohemamines was proposed based on the knowledge we have gained so far.

关键词： Genomic scanning Bayer villiger monooxygenase Carbamate alkaloids Pyrrolizidine alkaloids Non-ribosomal peptide synthetases

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Rational design of hydrogels for immunomodulation

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Regenerative Biomaterials 2022年第1期9卷 979-1000页

作者： Wenhuan Bu Yuanhao Wu Amir M.Ghaemmaghami Hongchen Sun Alvaro Mata Liaoning Provincial Key laboratory of Oral Diseases School of StomatologyChina Medical UniversityNo.117Nanjing North StreetHeping DistrictShenyang 110001China Department of Dental Materials School of StomatologyChina Medical UniversityNo.117Nanjing North StreetHeping DistrictShenyang 110001China Department of Center laboratory School of StomatologyChina Medical UniversityNo.117Nanjing North StreetHeping DistrictShenyang 110001China School of Pharmacy University of NottinghamUniversity ParkNottingham NG72RDUK biodiscovery Institute University of NottinghamUniversity ParkNottingham NG72RDUK Division of Immunology School of Life SciencesUniversity of NottinghamUniversity ParkNottingham NG72RDUK Terasaki Institute for Biomedical Innovation 1018 Westwood BlvdLos AngelesCA 90024USA Department of Chemical and Environmental Engineering University of NottinghamUniversity ParkNottingham NG72RDUK

The immune system protects organisms against endogenous and exogenous harm and plays a key role in tissue development,repair and *** immunomodulatory biologics exhibit limitations including degradation by enzymes,short half-life and lack of targeting *** or binding these biologics within biomaterials is an effective way to address these *** are promising immunomodulatory materials because of their prominent biocompatibility,tuneability and ***,to take advantage of these opportunities and optimize material performance,it is important to more specifically elucidate,and leverage on,how hydrogels affect and control the immune ***,we summarize how key physical and chemical properties of hydrogels affect the immune *** first provide an overview of underlying steps of the host immune response upon exposure to ***,we discuss recent advances in immunomodulatory strategies where hydrogels play a key role through(i)physical properties including dimensionality,stiffness,porosity and topography;(ii)chemical properties including wettability,electric property and molecular presentation;and(iii)the delivery of bioactive molecules via chemical or physical ***,this review aims to build a conceptual and practical toolkit for the design of immune-instructive hydrogels capable of modulating the host immune response.

关键词： hydrogels immunomodulation physical properties chemical properties

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HLA-G and single nucleotide polymorphism(SNP)associations with cancer in African populations:Implications in personal medicine

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Genes & Diseases 2022年第5期9卷 1220-1233页

作者： Ismael Chatita Adolf Amany Almars Nazima Dharsee Teddy Mselle Gokce Akan Irene Jeremiah Nguma Abdolrahman S.Nateri Fatmahan Atalar Mbeya College of Health and Allied Sciences University of Dar es SalaamMbeyaP.O Box 608Tanzania Cancer Genetics&Stem Cell Group BioDiscovery InstituteDivision of Cancer and Stem CellsSchool of MedicineUniversity of NottinghamNottinghamNG72UHUK Ocean Road Cancer Institute Department of OncologyDar es SalaamP.O Box 3592Tanzania Muhimbili University of Health and Allied Sciences MUHAS Genetic LaboratoryDepartment of BiochemistryDar es SalaamP.O Box 65001Tanzania Clinical Oncology Department Mbeya Zonal Referral Hospital(MZRH)Mbeya P.O Box 419Tanzania Child Health Institute Department of Rare DiseasesIstanbul UniversityIstanbul 34093Turkey

The immune system plays an important role in protecting the body against *** cancer immunoediting,the immune system can recognize and keep checking the tumor cells by down-expression of some self-molecules or by increasing expression of some novel ***,the microenvironment created in the course of cancer development hampers the immune ability to recognize and destroy the transforming *** Leukocyte Antigen G(HLA-G)is emerging as immune checkpoint molecule produced more by cancer cells to weaken the immune response against ***-G is a non-classical HLA class I molecule which is normally expressed in immune privileged tissues as a soluble or membrane-bound ***-G locus is highly polymorphic in the non-coding 3′untranslated region(UTR)and in the 5′upstream regulatory region(5′URR).HLA-G expression is controlled by polymorphisms located in these regions,and several association studies between these polymorphic sites and disease predisposition,response to therapy,and/or HLA-G protein expression have been *** polymorphisms are demonstrated to modulate its expression and this is increasingly finding more significance in cancer *** review focuses on the relevance of the HLA-G gene and its polymorphisms in cancer *** highlight population genetics of HLA-G as evidence to espouse the need and importance of exploring potential utility of HLA-G in cancer diagnosis,prognosis and immunotherapy in the currently understudied African population.

关键词： African population Cancer HLA-G Immune system checkpoints MHC Single nucleotide polymorphism

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MEP pathway products allosterically promote monomerization of deoxy-D-xylulose-5-phosphate synthase to feedback-regulate their supply

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Plant Communications 2023年第3期4卷 171-182页

作者： supply Xueni Di David Ortega-Alarcon Ramu Kakumanu Javier Iglesias-Fernandez Lucia Diaz Edward E.K.Baidoo Adrian Velazquez-Campoy Manuel Rodríguez-Concepción Jordi Perez-Gil Institute for Plant molecular and Cell Biology(IBMCP) CSIC-Universitat Politècnica de València46022 ValenciaSpain 2Centre for Research in Agricultural Genomics(CRAG)CSIC-IRTA-UAB-UBCampus UAB Bellaterra08193 BarcelonaSpain 3Institute for Biocomputation and Physics of Complex Systems(BIFI)Joint Unit GBsC-CSIC-BIFIUniversidad de Zaragoza50009 ZaragozaSpain 4Departamento de Bioquímica y Biología Molecular y CelularUniversidad de Zaragoza50009 ZaragozaSpain 5Joint BioEnergy Institute5885 Hollis StreetEmeryvilleCA 94608USA 6Biological Systems and Engineering DivisionLawrence Berkeley National LaboratoryBerkeleyCA 94720USA 7Nostrum Biodiscovery SL08029 BarcelonaSpain 8Instituto de Investigación Sanitaria de Aragón(IIS Aragon)50009 ZaragozaSpain 9Centro de Investigación Biomédica en Red en elÁrea Temática de Enfermedades Hepáticas y Digestivas(CIBERehd)28029 MadridSpain

Isoprenoids are a very large and diverse family of metabolites required by all living *** isoprenoids derive fromthe double-bond isomers isopentenyl diphosphate(IPP)and dimethylallyl diphosphate(DMAPP),which are produced by the methylerythritol 4-phosphate(MEP)pathway in bacteria and plant *** has been reported that IPP and DMAPP feedback-regulate the activity of deoxyxylulose 5-phosphate synthase(DXS),a dimeric enzyme that catalyzes the main flux-controlling step of the MEP *** we provide experimental insights *** titration calorimetry and dynamic light scattering approaches showed that IPP and DMAPP can allosterically bind to DXS in vitro,causing a size *** silico ligand binding site analysis and docking calculations identified a potential allosteric site in the contact region between the two monomers of the active DXS *** of IPP and DMAPP contents in vivo followed by immunoblot analyses confirmed that high IPP/DMAPP levels resulted in monomerization and eventual aggregation of the enzyme in bacterial and plant *** of the enzymatically active dimeric conformation allows a fast and reversible reduction of DXS activity in response to a sudden increase or decrease in IPP/DMAPP supply,whereas aggregation and subsequent removal of monomers that would otherwise be available for dimerization appears to be a more drastic response in the case of persistent IPP/DMAPP overabundance(e.g.,by a blockage in their conversion to downstream isoprenoids).Our results represent an important step toward understanding the regulation of the MEP pathway and rational design of biotechnological endeavors aimed at increasing isoprenoid contents in microbial and plant systems.

关键词： isoprenoids DXS feedback regulation allosteric monomerization

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An online resource for marine fungi

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Fungal Diversity 2019年第3期96卷 347-433页

作者： E.B.Gareth Jones Ka-Lai Pang Mohamed A.Abdel-Wahab Bettina Scholz Kevin D.Hyde Teun Boekhout Rainer Ebel Mostafa E.Rateb Linda Henderson Jariya Sakayaroj Satinee Suetrong Monika C.Dayarathne Vinit Kumar Seshagiri Raghukumar K.R.Sridhar Ali H.A.Bahkali Frank H.Gleason Chada Norphanphoun Deptartment of Botany and Microbiology College of ScienceKing Saud UniversityP.O Box 2455Riyadh 11451Kingdom of Saudi Arabia Hampshire UK Institute of Marine Biology and Centre of Excellence for the Oceans Taiwan Ocean University2 Pei-Ning RoadKeelung 20224TaiwanChina Department of Botany and Microbiology Faculty of ScienceSohag UniversitySohag 82524Egypt BioPol ehf Marine BiotechnologyEinbuastig 2545 SkagastrondIceland Center of Excellence in Fungal Diversity Mae Fah Luang University 333 M.1 ThasudMuang Chiang RaiChiang Rai 57100Thailand Westerdijk Fungal Biodiversity Institute Uppsalalaan 8UtrechtThe Netherlands Institute of Biodiversity and Ecological Dynamics(IBED) University of AmsterdamAmsterdamThe Netherlands Department of Chemistry Marine Biodiscovery CentreUniversity of AberdeenAberdeen AB243UEUK School of Computing Engineering&Physical SciencesUniversity of the West of ScotlandPaisley PA12BEUK School of Life and Environmental Sciences University of SydneyMacleay Building A12SydneyNSW 2006Australia School of Science Walailak University222 ThaiburiThasala DistrictNakhon Si Thammarat 80161Thailand Fungal Biodiversity laboratory(BFBD) National Center for Genetic Engineering and Biotechnology(BIOTEC)113 Thailand Science ParkPhaholyothin RoadKhlong NuengKhlong LuangPathum Thani 12120Thailand Tamra' 313(Plot No.162)Vainguinnim ValleyDona PaulaGoa 403004India Department of Biosciences Mangalore UniversityMangaloreKarnatakaIndia School of Life and Environmental Sciences University of SydneySydneyNSW 2006Australia Department of Entomology and Plant Pathology Faculty of AgricultureChiang Mai UniversityHuay Keaw RoadSuthepMuang DistrictChiang Mai 50200Thailand

Index Fungorum,Species Fungorum and MycoBank are the key fungal nomenclature and taxonomic databases that can be sourced to find taxonomic details concerning fungi,while DNA sequence data can be sourced from the NCBI,EBI and UNITE *** and ecological data on freshwater fungi can be accessed on http://***/,while http://***/provides a comprehensive list of names of marine organisms,including information on their *** websites however have little information on marine fungi and their ecology,beside articles that deal with marine fungi,especially those published in the nineteenth and early twentieth centuries may not be accessible to those working in third world *** address this problem,a new website *** was set up and is introduced in this *** website provides a search facility to genera of marine fungi,full species descriptions,key to species and illustrations,an up to date classification of all recorded marine fungi which includes all fungal groups(Ascomycota,Basidiomycota,Blastocladiomycota,Chytridiomycota,Mucoromycota and fungus-like organisms ***),and listing recent ***,1257 species are listed in the marine fungi website(***),in 539 genera,74 orders,168 families,20 classes and five phyla,with new taxa continuing to be *** website has curators with specialist mycological expertise who help to provide update data on the classification of marine *** article also reviews knowledge of marine fungi covering a wide range of topics:their higher classification,ecology and world distribution,role in energy transfer in the oceans,origin and new chemical *** updated classification of marine fungi is also *** would like to invite all mycologists to contribute to this innovative website.

关键词： Fungal classification marine fungi website High-throughput sequencing techniques Fungal diversity Origin of marine fungi

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