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Disco.ery of a novel small inhibitor R J19 targeting to human Hsp90

Nuclear Science and Techniques 2017年第10期28卷 71-78页

作者： Hui-Ling Cao Kai-Kai Lyu Bin Liu Jian Li Jian-Hua He Shaanxi Key Laboratory of Ischemic Cardiovascular Disease Institute of Basic and Translational MedicineXi'an MedicalUniversityXi'an 710021China University of Chinese Academy of Sciences Beijing 100049China Key Laboratory of Protein Modification and Tumor HubeiPolytechnic University School of MedicineHuangshi 435003China Shanghai Institute of Applied Physics Chinese Academy ofSciencesShanghai 201204China biotech and Biomedicine Science co.Ltd. Shenyang 110000China Department of Molecular and Cellular Biochemistry Collegeof MedicineUniversity of KentuckyLexingtonKY 40508USA

Heat shock protein 90(Hsp90) can promote growth and proliferation of cancer cells by helping in folding, co.formational maturation, and activation of various client proteins. Therefore, Hsp90 has been paid more attention to as an anticancer drug target. Reported Hsp90 inhibitors have several limitations such as poor solubility, limited bioavailability, and hepatotoxicity. Here, a novel small inhibitor RJ19 has been designed using fragment-based drug disco.ery and synthesized. Additionally, a crystal structure of Hsp90 N-RJ19 was determined by X-ray diffraction(resolution limit, 2.0 A, PDB co.e 4 L90). The crystal structure of Hsp90 N-RJ19 was analyzed in detail and co.pared with that of native Hsp90 N, Hsp90 N-ATP, and Hsp90 N-GDM,respectively. It was indicated that RJ19 interacted with Hsp90~N at the ATP-binding pocket, which suggests that RJ19 may replace nucleotides to bind with Hsp90~N to result in chaperone function failure of Hsp90. RJ19, therefore, has emerged as a promising anticancer lead co.pound. Rearrangement and displacement of L2 Loop in Hsp90~N-RJ 19 play a key role in the function failure, which also makes the pocket wider and longer facilitating structure modification of RJ19 later. The co.plex crystal structure and interaction between RJ19 and Hsp90~N provide a rational basis for the design and optimization of novel anticancer drugs.

关键词：热休克蛋白90 HSP90 抑制剂晶体结构 X射线衍射法抗癌药物 Hsp90 生物利用度

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An enhanced method for nucleic acid detection with CRISPR-Cas12a using phosphorothioate modified primers and optimized gold-nanopaticle strip

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Bioactive Materials 2021年第12期6卷 4580-4590页

作者： Jiaojiao Gong Lijuan Kan Xiuming Zhang Ying He Jiaqiang Pan Liping Zhao Qianyun Li Menghao Liu Jie Tian Sili Lin Zhouyu Lu Liang Xue Chaojun Wang Guanghui Tang Yaneng biotech Co.LtdFosun PharmaShenzhen 518100China Department of Urology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Laboratory Medicine Luohu District People’s HospitalShenzhen 518001China Department of Laboratory Medicine The Eighth Affiliated HospitalSun Yat-sen UniversityShenzhen 518033China Department of Laboratory Medicine Nanning First People’s HospitalNanning 530022China Department of Neurology Hwa Mei HospitalUniversity of Chinese Academy of SciencesNingbo 315010China Nanobiological Medicine Center Key Lab of Fuel Cell Technology of Guangdong ProvinceSchool of Chemistry and Chemical EngineeringSouth China University of TechnologyGuangzhou 510641China

CRISPR-Cas12a system has been shown promising for nucleic acid diagnostics due to its rapid,portable and accurate ***,cleavage of the amplico.s and primers by the cis-and trans-activity of Cas12a hinders the attempts to integrate the amplification and detection into a single *** phosphorothioate modification of primers,we realized onepot detection with high sensitivity using plasmids of SARS-co.-2,HPV16 and *** also identified the activated Cas12a has a much higher affinity to C nucleotide-rich reporter than *** applying such reporters,the reaction time required for a lateral-flow readout was significantly ***,to improve the specificity of the strip-based assay,we created a novel reporter and,when co.bined with a customized gold-nanopaticle strip,the readout was greatly enhanced owing to the elimination of the nonspecific *** established system,termed Targeting DNA by Cas12a-based Eye Sight Testing in an Onepot Reaction(TESTOR),was validated using clinical cervical scrape samples for human papillomaviruses(HPVs)*** system represents a general approach to integrating the nucleic acid amplification and detection into a single reaction in CRISPR-Cas systems,highlighting its potential as a rapid,portable and accurate detection platform of nucleic acids.

关键词： CRISPR-Cas12a Onepot Visual detection

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Rat cardiomyocyte H9c2(2-1)-based sulforhodamine B assay as a promising in vitro method to assess the biological co.ponent of effluent toxicity

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Journal of Environmental Sciences 2020年第10期32卷 163-170页

作者： Elsa T Rodrigues Susana F Nascimento Maria Joao Moreno Paulo J Oliveira Miguel A Pardal University of co.mbra Centre for Functional EcologyDepartment of Life SciencesCalcada Martim de FreitasCoimbra 3000-456Portugal University of co.mbra Coimbra Chemistry CenterDepartment of ChemistryCoimbra 3004-535Portugal Centre for Neuroscience and Cell Biology Uniuersity of CoimbraUC BiotechBiocant ParkCantanhede 3060-197Portugal

The treatment of wastewaters is crucial to maintain the eco.ogical status of receiving waters,and thereby guarantee the protection of aquatic life and human *** quality evaluation is co.ventionally based on physico.hemical parameters,but increasing attention has been paid to integrate physico.hemical and biological ***,the regulatory use of fish in biological testing methods has been subject to various ethical and co.t co.cerns,and in vitro cell-based assays have thus beco.e an important topic of ***,the present study intends:(a) to evaluate the efficiency of two different sample pre-co.centration techniques (lyophilisation and solid phase extraction) to assess the toxicity of municipal effluents on rat cardiomyoblast H9c2(2-1) cells,and (b) maximizing the use of the effluent sample co.lected,to estimate the environmental co.dition of the receiving *** gathered results demonstrate that the H9c2(2-1) sulforhodamine B-based assay is an appropriate in vitro method to assess biological effluent toxicity,and the best results were attained by lyophilising the sample as *** to its response,the H9c2(2-1) cell line might be a possible alternative in vitro model for fish lethal testing to assess the toxicity of municipal *** physico.hemical status of the sample suggests a high potential for eutrophication,and iron exceeded the permissible level for wastewater discharge,possibly due to the addition of ferric chloride for wastewater *** general,the levels of carbamazepine and sulfamethoxazole are higher than those reported for other co.ntries,and both surpassed the aquatic protective values for long-term exposure.

关键词： Municipal wastewater treatment plant effluent Lyophilisation Solid phase extraction Cell-based assays H9c2(2-1)cell line SRB assay

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Study on the Quality Evaluation of Steamed Bread and the Physical and Chemical Properties of Wheat

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Agricultural biotechnology 2021年第2期10卷 125-127页

作者： Fenglan ZHANG Chengmei WANG De LI Shandong China Quality Inspection co. LtdJining 272000China Kaisai(Jinxiang)biotech co. Ltd.Jinxiang 272200China

In this study,the different physical and chemical properties of wheat were studied,and on this basis,and the quality of steamed bread made was *** analyzed the co.relation between the evaluation indexes of steamed bread and the basic physical and chemical indexes of wheat,and investigated important factors that affect the evaluation indexes of steamed bread,including flour extraction rate,protein co.tent,amylose co.tent,protein,added amount of yeast,fermentation time and other *** to the study results,it was shown that different factors had different effect on steamed bread quality,with both positive co.relation and negative co.relation.

关键词： Steamed bread quality evaluation Wheat physical and chemical properties co.relation analysis

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Clinical Effect of Dendrobium officinale Kimura et Migo from Longhushan on Treatment of Type 2 Diabetes

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Medicinal Plant 2017年第6期8卷 60-62页

作者： Jun WU Guoxing WANG Huanghui ZHUANG Zhitian MAO Tianming LI Wei LI Huiqin WU Yujiang co.nty Hospital of Traditional Chinese Medicine Yingtan Tianyuan Xianhu biotech co. Ltd

[Objectives] To observe and co.pare the clinical effect and safety of Dendrobium officinale Kimura et Migo from Longhushan on treatment of type 2 diabetes. [Methods] 90 patients with type 2 diabetes were randomly divided into group A,group B and co.trol group by randomized co.trol method. Group A adopted D. officinale Kimura et Migo and metformin hydrochloride; group B adopted D. officinale Kimura et Migo; the co.trol group adopted metformin hydrochloride. The fasting plasma gluco.e( FPG) of 3 groups was measured before the treatment and 2 weeks,4 weeks,6 weeks,8 weeks,10 weeks,and 12 weeks after the treatment,Hb A1 c was measured and diabetes symptom grade sco.e was co.nted before the treatment and 12 weeks after treatment,observation indicators and clinical effect of 3 groups of patients were co.pared. [Results] The fasting plasma gluco.e level in group A was lower than that in other 2 groups,the difference was statistically significant( P co.trol group( P >0. 05); Hb A1 c of group A for 12 weeks after treatment was lower than that of other 2 groups,the difference was statistically significant( P co.trol group( P > 0. 05); the difference in diabetes symptom grade sco.e of group A was greater than that in other 2 groups,the difference was statistically significant( P co.trol group( P > 0. 05). [co.clusions]D. officinale Kimura et Migo from Longhushan can effectively reduce the fasting plasma gluco.e level and Hb A1 c of type 2 diabetic patients and effectively improve the symptoms of patients; clinical application of D. officinale Kimura et Migo has equivalent effect with metformin hydrochloride,and co.bination of D. officinale Kimura et Migo with metformin hydrochloride has better effect th

关键词： Type 2 diabetes Dendrobium officinale Kimura et Migo Longhushan Metformin hydrochloride

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Development of Streptomyces sp. FR-008 as an emerging chassis

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Synthetic and Systems biotechnology 2016年第3期1卷 207-214页

作者： Qian Liu Liping Xiao Yuanjie Zhou Kunhua Deng Gaoyi Tan Yichao Han Xinhua Liu Zixin Deng Tiangang Liu State Key Laboratory of Microbial Metabolism and School of Life Science&biotechnology Shanghai Jiao Tong UniversityShanghai 200240China Key Laboratory of co.binatorial Biosynthesis and Drug Disco.ery Ministry of EducationWuhan University School of Pharmaceutical SciencesWuhan 430071China Hubei Engineering Laboratory for Synthetic Microbiology Wuhan Institute of BiotechnologyWuhan 430075China J1 biotech Co.Ltd.Wuhan 430075China

Microbial-derived natural products are important in both the pharmaceutical industry and academic *** the metabolic potential of original producer especially Streptomyces is often limited by slow growth rate,co.plicated cultivation profile,and unfeasible genetic manipulation,so exploring a Streptomyces as a super industrial chassis is valuable and *** ***-008 is a fast-growing microorganism and can also produce a co.siderable amount of macrolide candicidin via modular polyketide *** this study,we evaluated Streptomyces ***-008 as a potential industrial-production ***,PacBio sequencing and transcriptome analyses indicated that the Streptomyces ***-008 genome size is 7.26 Mb,which represents one of the smallest of currently sequenced Streptomyces *** addition,we simplified the co.jugation procedure without heat-shock and pre-germination treatments but with high co.jugation efficiency,suggesting it is inherently capable of accepting heterologous *** addition,a series of promoters selected from literatures was assessed based on GusA activity in Streptomyces *** with the co.mon used promoter ermE*-p,the strength of these promoters co.prise a library with a co.stitutive range of 60e860%,thus providing the useful regulatory elements for future genetic engineering *** order to minimum the genome,we also target deleted three endogenous polyketide synthase(PKS)gene clusters to generate a mutant ***3 is thus an“updated”version of Streptomyces ***-008,producing fewer seco.dary metabolites profiles than Streptomyces *** believe this work co.ld facilitate further development of Streptomyces ***-008 for use in biotechnological applications.

关键词： smallest urgent germination

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Therapeutic Characterization of ^(131)I-Labeled Humanized Anti-B7-H3 Antibodies for Radioimmunotherapy for Glioblastoma

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Engineering 2023年第11期30卷 190-202页

作者： Fengqing Fu Meng Zheng Shandong Zhao Yan Wang Minzhou Huang Hanqing Chen Ziyi Huang Kaijie Zhang Liyan Miao Xueguang Zhang Jiangsu Institute of Clinical Immunology the First Affiliated Hospital of Soochow UniversitySuzhou 215000China State Key Laboratory of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China Department of Clinical Pharmaco.ogy the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Suzhou Bright Scistar Antibody biotech.co. Ltd.Suzhou 215152China Institute for Interdisciplinary Drug Research and Translational Sciences College of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China Department of Hematology the First Affiliated Hospital of Soochow UniversitySuzhou 215000China

B7 homolog 3(B7-H3)has attracted much attention in glioblastoma(GBM)radioimmunotherapy(RIT)due to its abnormally high expression on tumor *** this study,we report that two specific humanized anti-human B7-H3 antibodies(hu4G4 and hu4H12)derived from mouse anti-human B7-H3 antibodies that were generated by co.puter-aided design and exclusively reco.nize membrane expression of B7-H3 by human glioma cells,Hu4G4 and hu4H12 were radiolabeled with^(89)Zr for RIT antibody ***-positron emission tomography(PET)imaging,biodistribution and pharmaco.inetic(PK)analyses of^(89)Zr-labeled antibodies were performed in U87-xenografted models.^(125)I labelling of the antibodies for single-photon emission co.puted tomography(SPECT)imaging was also used to investigate the biological behavior of the antibodies in *** rthermore,the pharmaco.ynamic(PD)of the^(131)Ilabeled antibodies were evaluated in U87-xenografted mice and GL261 Red-FLuc-B7-H3 in situ glioma tumor ***-PET imaging and biodistribution analysis with a gamma co.nter showed that^(89)Zr-deferoxamine(DFO)-hu4G4 had higher tumor targeting performance with lower liver uptake than^(89)Zr-DFO-(hu4H12,immunoglobulin G(IgG)).The biodistribution results of^(125)I-SPECT imaging were similar to those of^(89)Zr-PET imaging,though the biodistribution in long bone joints and the thyroid *** PD analysis results indicated that^(131)I-hu4G4 had an excellent therapeutic effect and high safety with no apparent ***,^(131)I-hu4G4 improved the tumor vasculature in tissues with higher expression of co.lagen typeⅣand platelet-derived growth factor receptorβ(PDGFR-β)co.pared with co.trol treatment,as determined by immunofluorescence(IF),which co.tributed to inhibiting tumor *** together,our data indicate that hu4G4 exhibits good tumor targeting and specificity,achieves low nonspecific co.centrations in normal tissues,and has acceptable PK characteristics.^(131)I-hu4G4 also exerts effect

关键词： B7-H3 Radioimmunotherapy Glioblastoma Pharmaco.inetics Pharmaco.ynamics

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Identification of functional tumor necrosis factor-alpha promoter variants associated with Helico.acter pylori infection in the Sudanese population: co.putational approach

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World Journal of Gastroenterology 2022年第2期28卷 242-262页

作者： Abeer Babiker Idris Alaa B Idris Manal A Gumaa Mohammed Babiker Idris Amanda Elgoraish Mohamed Mansour Dalia Allam Bashir MO Arbab Nazar Beirag El-Amin M Ibrahim Mohamed A Hassan Department of Agricultural Science and Technology Institute of Natural and Applied SciencesErciyes UniversityKayseri 38039Turkey Department of Medical Microbiology Faculty of Medical Laboratory SciencesUniversity of KhartoumKhartoum 11111Sudan Department of Neurosurgery Ribat University HospitalKhartoum 11111Sudan BioMérieux Clinical and Application Advisor Al-Jeel Medical Co.Riyadh 11422Saudi Arabia Department of Epidemiology Tropical Medicine Research InstituteKhartoum 11111Sudan Department of Gastroenterology Ibn Sina Specialized HospitalKhartoum 11111Sudan Department of Gastroenterology Modern Medical CentreKhartoum 11111Sudan Biosciences College of HealthMedicine and Life SciencesBrunel UniversityLondon UB83PHUxbridgeUnited Kingdom Department of Translation Bioinformatics Detavax BiotechKayseri 38350Turkey

BACKGROUND Helico.acter pylori(***)is a ubiquitous bacterium that affects nearly half of the world’s population with a high morbidity and mortality *** within the tumor necrosis factor-alpha(TNF-A)promoter region are co.sidered a possible genetic basis for this *** To functionally characterize the genetic variations in the TNF-A 5’-region(-584 to+107)of Sudanese patients infected with *** using in silico.*** An observational study was carried out in major public and private hospitals in Khartoum state.A total of 122 gastric biopsies were taken from patients who had been referred for *** DNA was *** of the TNF-A-1030 polymorphism was performed using PCR with co.fronting two-pair primer to investigate its association with the susceptibility to *** infection in the Sudanese ***,Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5’-region(-584 to+107)of TNF-A in ***-infected *** analyses were used to predict whether these mutations would alter transcription factor binding sites or co.posite regulatory elements in this region.A co.parative profiling analysis was co.ducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible ***,a multivariate logistic regression model was co.structed to estimate odds ratios and their 95%co.fidence intervals for the association between TNF-A-1030,sociodemographic characteristics and *** *** were statistically significant if PA,-76)was located at the in silico.predicted promoter region(-146 to+10),and it was predicted to alter transcription factor b

关键词： 5’-region Promoter TNF-A Helico.acter pylori In silico.analysis Sudan

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The molecular determinants governing the immunogenicity of Japanese encephalitis live attenuated vaccines

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Signal Transduction and Targeted Therapy 2017年第1期2卷 251-257页

作者： Yuhua Li Yin Fu Xinyu Liu Huiqiang Yang Yongxin Yu Lili Jia Xuguang Li Aaron Farnsworth Junzhi Wang National Institutes for Food and Drug co.trol BeijingChina State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan UniversityCollaborative Innovation Center for Biotherapy Department of Viral Vaccine Chengdu Institute of Biological Products Co.LtdChina National Biotech GroupChengduChina Centre for Vaccine Evaluation Biologics and Genetic Therapies DirectorateHealth Canada.

In the co.rse of isolating the attenuated Japanese encephalitis vaccine SA14-14-2,two attenuated strains SA14-9-7 and SA14-5-3 were also obtained that elicited low antibody responses in humans(o10%and 62%,respectively)and exerted much weaker immune protection in animal challenge ***,the reason for these differences remains *** order to understand why SA14-14-2 is superior to SA14-9-7 and SA14-5-3,we employed a reverse genetics method to identify the key mutations in the virus genome that determine the immunogenicity of live attenuated Japanese encephalitis *** first sequenced the full genomic sequences of SA14-9-7 and SA14-5-3 and found mutations that changed four amino-acid base pairs when co.pared to the envelope gene of *** mutated the genome of SA14-14-2 to generate these mutations both singly(E-177,E-264,E-279 and E-315)and in co.bination(E-177/264,E-279/315 and E-177/264/279/315)and tested these mutants along with parental strains SA14-14-2,SA14-9-7 and SA14-5-3 for their immunogenicity in *** mice were immunized with SA14-9-7 and SA14-5-3,lower levels of neutralizing antibodies were generated co.pared with the immune response to ***,SA14-5-3 was more immunogenic than SA14-9-7,which replicated the results previously seen in *** mutations E-177,E-264,E-279 and E-315 diminished the immunogenicity of SA14-14-2 with E-264 and E-315,co.tributing the most to this *** mutant rJEV(E-177/E-264/E-279/E-315)co.taining all four point mutations exhibited the lowest immunogenicity with a seroco.version rate of 0 at an inoculation dose of 103 PFU(plaque-forming unit).We have identified the key amino acids in the envelope protein that acco.nt for the superior immunogenicity of SA14-14-2.

关键词： Japanese governing envelope

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Therapeutic effect of secretome from TNF-αstimulated mesenchymal stem cells in an experimental model of co.neal limbal stem cell deficiency

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International Journal of Ophthalmology(English edition) 2021年第2期14卷 179-185页

作者： Guo-Hu Di Xia Qi Jing Xu Chao-Qun Yu Qi-Long Cao Zhi-Jun Xing Zhi-Chao Li School of Basic Medicine Qingdao UniversityQingdao266071Shandong ProvinceChina Shandong Eye Institute Qingdao266071Shandong ProvinceChina Qingdao Haier biotech co.Ltd. Qingdao266071Shandong ProvinceChina Qingdao Hospital of Traditional Chinese Medicine(Qingdao Hiser Hospital) Qingdao266033Shandong ProvinceChina Department of Gyneco.ogy and Obstetrics Qingdao Municipal HospitalQingdao UniversityQingdao266033Shandong ProvinceChina

AIM:To explore the secretome efficacy in tumor necrosis factor(TNF)-αstimulated mouse mesenchymal stem cells(MSCs)in a murine model of co.neal limbal alkali ***:co.neal limbal stem cell deficiency(LSCD)was created in the eyes of male C57 *** co.ditioned medium from TNF-αstimulated MSCs(MSC-CMT)was applied topically for 4 wk,with basal medium and co.ditioned medium from MSCs as *** opacification,co.neal inflammatory response,and co.neal neovascularization(NV)were *** epithelial cell apoptosis,co.neal co.junctivation,and inflammatory cell infiltration were assessed with TUNEL staining,CK3 and Muc-5 AC immunostaining,and CD11 b immunofluorescence staining,*** effect of TSG-6 was further evaluated by knockdown with short hairpin RNA(sh RNA).RESULTS:co.pared to the co.trols,topical administration of MSC-CMT significantly ameliorated the clinical symptoms of alkali-induced LSCD,with restrained co.neal NV,reduced co.neal epithelial cell apoptosis,and inhibition of co.neal *** addition,MSC-CMT treatment significantly reduced CD11 b+inflammatory cell infiltration,and inhibited the expression of pro-inflammatory cytokines(IL-1β,TNF-αand IL-6).Furthermore,the promotion of co.neal epithelial reco.struction by MSC-CMT was largely abolished by TSG-6 ***:Our study provides evidence that MSCCMT enhances the alleviation of co.neal alkali injuries,partially through TSG-6-mediated anti-inflammatory protective ***-CMT may serve as a potential strategy for treating co.neal disorders.

关键词： MSC-CMT limbal stem cell deficiency TSG-6

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