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Preparation of kakkatin derivatives and their anti-tumor activity

World Journal of Clinical Oncology 2024年第8期15卷 1078-1091页

作者： Yu-Ying Jiang Hui-Hua Dong Wen-Ting Zhou Jia-Zi Luo Xian Wei Yan-Qiang Huang Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina Collaborative Innovation center for Guangxi Ethnic Medicine The School of Chemistry and Pharmaceutical SciencesYoujiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina research center for the Prevention and Treatment of Drug Resistant Microbial Infecting Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina

BACKGROUND Modern pharmacological studies have confirmed that plant-derived compounds from Puerariae flos(PF)has significant biological activities against liver damage,tumors and *** is an isoflavone polyphenolic compound isolated from PF ***,the effect of kakkatin and its derivatives on anti-tumor has not been well *** To design and synthesize a kakkatin derivative[6-(hept-6-yn-1-yloxy)-3-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one(HK)]to explore its anti-tumor biological *** Hept-6-yn-1-yl ethanesulfonate was introduced to replace hydrogen at the hydroxyl position of kakkatin phenol,and the derivative of kakkatin was prepared;the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to detect cell viability,a clone formation assay was adopted to detect cell proliferation,apoptosis,necrosis,and cell cycles were analyzed by Annexin V/propidium iodide staining and flow *** migration and invasion ability were evaluated by cell scratch assay and transwell *** potential mechanism of HK on hepatocellular carcinoma(HCC)SMMC-7721 cells was explored through network pharmacology and molecular docking,and finally real-time PCR assays was used to verify the potential targets and evaluate the biological activity of *** Compared with kakkatin,the modified HK did not significantly increase the inhibitory activity of gastric cancer MGC803 cells,but the inhibitory activity of HCC SMMC-7721 cells was increased by about 30 times,with an IC50 value of 2.5μM,and the tumor inhibition effect was better than cisplatin,which could significantly inhibit the cloning,invasion and metastasis of HCC SMMC-7721 cells,and induce apoptosis and G2/M cycle *** mechanism of action is mainly related to the upregulation of PDE3B and NFKB1 target proteins in the cAMP *** HK have a significant inhibitory effect on HCC SMMC-7721 cells,and the targets of their action may be PDE3B and NFKB1 prote

关键词： Kakkatin Derivative Hepatocellular carcinoma Anti-tumor Biological activity

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Conventional Breeding and molecular Markers for Blast Disease Resistance in Rice (Oryza sativa L.)

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Phyton-International Journal of Experimental Botany 2023年第3期92卷 725-746页

作者： Adel A.Rezk Mohamed M.El-Malky Hossam S.El-Beltagi Mohammed Al-daej Kotb AAttia Agricultural Biotechnology Department College of Agricultural and Food ScienceKing Faisal UniversityAl-Ahsa31982Saudi Arabia Plant Pathology research Institute Agriculture Research CenterGiza12619Egypt Rice research and Training center SakhaField Crops Research InstituteAgricultural Research CenterKafr El-Sheikh33717Egypt Biochemistry Department Faculty of AgricultureCairo UniversityGiza12613Egypt center of Excellence in Biotechnology research King Saud UniversityRiyadh11451Saudi Arabia Rice Biotechnology Laboratory Rice Research DepartmentField Crops Research InstituteARCKafr EL-Sheikh33717Egypt

Monogenic lines,which carried 23 genes for blast resistance were tested and used donors to transfer resistance genes by crossing *** results under blast nursery revealed that 9 genes from 23 genes were susceptible to highly susceptible under the three locations(Sakha,Gemmeza,and Zarzoura in Egypt);Pia,Pik,Pik-p,Piz-t,Pita,Pi b,Pi,Pi 19 and Pi ***,the genes Pii,Pik-s,Pik-h,Pi z,Piz-5,Pi sh,Pi 3,Pi 1,Pi 5,Pi 7,Pi 9,Pi 12,Pikm and Pita-2 were highly resistant at the same *** analysis confirmed the results,which divided into two groups;the first one included all the susceptible genes,while the second one included the resistance *** the greenhouse test,the reaction pattern of five races produced 100%resistance under artificial inoculation with eight genes showing complete resistance to all *** completely resistant genes:Pii,Pik-s,Piz,Piz-5(=bi2)(t),Pita(=Pi4)(t),Pita,Pi b and Pi1 as well as clustering analysis confirmed the *** the F1 crosses,the results showed all the 25 crosses were resistant for leaf blast disease under field ***,the results in F2 population showed seven crosses with segregation ratio of 15(R):1(S),two cross gave segregated ratio of 3 R:1 S and one gave 13:*** the identification of blast resistance genes in the parental lines,the marker K3959,linked to Pik-s gene and the variety IRBLKS-F5 carry this gene,which was from the monogenic *** results showed that four genotypes;Sakha 105,Sakha 103,Sakha 106 and IRBLKS-F5 were carrying Pik-s gene,while was absent in the Sakha 101,Sakha 104,IRBL5-M,IRBL9-W,IRBLTACP1 and IRBL9-W(R)*** for Pi 5 gene,the results showed that it was present in Sakha 103 and Sakha 104 varieties and absent in the rest of the *** addition,Pita-Pita-2 gene was found in the three Egyptian genotypes(Sakha 105,Sakha 101 and Sakha 104)plus IRBLTACP1 *** F2 generation,six populations were used to study the inheritance of blast resistance and s

关键词： Biotechnology tools clustering analysis monogenic lines resistance genes breeding Oryza sativa L.

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Redesigned Duplex RT-qPCR for the Detection of GI and GII Human Noroviruses

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Engineering 2020年第4期6卷 442-448页

作者： Danlei Liu Zilei Zhang Qingping Wu Peng Tian Haoran Geng Ting Xu Dapeng Wang Department of Food Science and Technology School of Agriculture and BiologyShanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of Applied microbiology Southern China&Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application&Guangdong Open Laboratory of Applied microbiology&Guangdong Institute of microbiology Guangzhou 510070China Produce Safety and microbiology research Unit Western Regional Research CenterAgricultural Research ServiceUnited States Department of AgricultureAlbanyCA 94706USA

Human noroviruses(HuNoVs)are major foodborne pathogens that cause nonbacterial acute gastroenteritis *** the tissue-culture system for HuNoVs is not mature enough for routine detection of the virus,detection is mainly dependent on molecular approaches such as reverse transcription polymerase chain reaction(RT-PCR)and reverse transcription quantitative real-time polymerase chain reaction(RTqPCR).The widely used primers and probes for RT-qPCR were established in the early *** HuNoVs are highly variant viruses,viral genome mutations result in previously designed primers and/or probes that were perfectly matched working less efficiently over *** this study,a new duplex RT-qPCR(ND-RT-qPCR)was designed for the detection of genogroup Ⅰ(GⅠ)and genogroup Ⅱ(GⅡ)HuNoVs based on an analysis of viral sequences added in the database after *** long transcribed viral RNAs,the results demonstrate that the sensitivity of ND-RT-qPCR is as low as one genomic copy for both GⅠ and GⅡ *** performance of ND-RT-qPCR was further evaluated by a comparison with the commonly used Kageyama primer/probe sets for RT-qPCR(Kageyama RT-qPCR)for 23 HuNoV-positive clinical *** five GⅠ samples were registered as positive by ND-RT-qPCR,whereas only two samples were registered as positive by Kageyama *** 18 GⅡ samples were registered as positive by ND-RT-qPCR,while 17 samples were registered as positive by Kageyama *** sensitivity reflected by the quantification cycle(Cq)value was lower in ND-RT-qPCR than in Kageyama *** data suggest that ND-RT-qPCR could be a good fit for the detection of current strains of HuNoVs.

关键词： Human noroviruses RT-qPCR Redesign Primer Probe Detection

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Co-Inheritance of Beta &Delta-Globin Gene (HbYialousa) Mutations in an Iranian <i>β</i>-Thalassemia Carrier

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International Journal of Clinical Medicine 2012年第7期3卷 633-636页

作者： Atefeh Valaei Farnaz Eghbalpour Zahra Kainimoghaddam Fatemeh Bayat Maryam Taghavi Basmanj Morteza Karimipoor Sirous Zeinali Kawsar Human Genetics research center Tehran Iran molecular Medicine Department Biotechnology Research Center Pasteur Institute of Iran Tehran Iran

Introduction: Beta-thalassemia is characterized by absence or reduced synthesis of the β-globin. Carriers of β-thalas- semia, typically have microcytic hypochromic anemia and elevated hemoglobin HbA2 and normal HbF level. On the other hand carriers of severe alpha-thalassemia also have similar CBC parameters to that of β-thalassemia with normal HbA2 level. Co-presence of mutations in the β-globin and delta-globin genes (point mutations or deletions) usually give normal HbA2 and elevated HbF level. We report a β-thal carrier with normal level of HbA2 and increased level of HbF who had a point mutation in CD39 on the beta-globin gene and a point mutation in CD27 on the δ-globin gene named Hb-Yialousa. Materials & Methods: An individual with low hematological indices, normal HbA2 and elevated HbF was referred to our center as routine premarital screening program. Mutations in the β-globin and δ-globin genes were screened using ARMS and sequencing methods. Results: The mutation in β- and δ-globin genes were identified as CD39 and CD27 (HbYialousa) respectively. No point mutation or deletion in α-globin gene was identified. Discussion: We showed that normal HBA2 with elevated HbF level is due to co-inheritance of delta-globin gene mutation with mutation in the β-globin gene. When screening for β-thalassemia, one has to either rule out presence of α-globin gene mutation of mutation in the delta-globin gene.

关键词： δ-Globin Gene β-Thalassemia HbYialousa β-Globin Gene CD39

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molecular docking-aided AIEgen design: concept, synthesis and applications

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Science China Chemistry 2024年第8期67卷 2614-2628页

作者： Jian-Qing Zhang Xiao-Yu Xu Fu-Sheng Liu Shu-Qiang Cao Yu-Xin Gui Yi-Wen Su Xiao-Yu He Ji-Yuan Liang You-Quan Zou Department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of EducationWuhan UniversityWuhan 430071China Tai Kang center for Life and Medical Sciences Wuhan UniversityWuhan 430071China Department of Hepatobiliary Pancreatic SurgeryZhongnan Hospital of Wuhan UniversityWuhan 430071China

Aggregate-induced emission luminogens(AIEgens) have been widely used in biological imaging, chemical sensing, and disease treatments. The rational design and construction of AIEgens have received considerable research interests during the last few years. Herein, molecular docking-aided AIEgen design has been reasonably proposed and AIEgen TBQZY with excellent ~1O_(2) generation ability has been synthesized. The newly developed TBQZY could efficiently kill S. epidermidis and methicillinresistant S. epidermidis(MRSE) by tightly binding to bacteria and triggering the accumulation of ~1O_(2) in bacteria. TBQZY specifically regulated the immune system and polarized macrophages from M1 to M2 to accelerate the elimination of biofilm in vivo. In addition, healing acceleration was observed in chronic wounds treated with TBQZY, and side effects were ***, TBQZY had extraordinary potential for combating drug-resistant bacteria in the clinical setting. This research not only provided new concepts for the design of AIEgens, but also shed some lights on the discovery of drugs against drug-resistant bacteria.

关键词： AIEgen molecular docking drug-resistant bacteria biofilm chronic wounds healing

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A Pseudopaline Fluorescent Probe for the Selective Detection of Pseudomonas aeruginosa

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CCS Chemistry 2021年第9期3卷 2405-2417页

作者： Tianhu Zhao Jian Zhang Xiaowan Han Jun Yang Xin Wang Maarten Vercruysse Hai-Yu Hu Xiaoguang Lei Beijing National Laboratory for molecular Sciences Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationDepartment of Chemical BiologyCollege of Chemistry and Molecular EngineeringSynthetic and Functional Biomolecules CenterPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871 State Key Laboratory of Bioactive Substances and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050 Roche Pharma research&Early Development(pRED) Roche Innovation Center Basel4070 Basel

The rise of resistance to all known antibiotics is a global *** addition to novel treatment options,there is an urgent need to develop rapid,specific,sensitive,and reliable diagnostic methods to detect pathogenic bacteria in clinical samples and reduce the overuse and misuse ***,a metallophore produced by the human pathogen Pseudomonas aeruginosa,transports divalent metal ions via a dedicated active transport system,making it an ideal carrier for a second functional moiety.

关键词： bacterial detection Pseudomonas aeruginosa metallophore fluorescent probe Gram-negative bacteria

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Glycosylation and an amino acid insertion in the head of hemagglutinin independently affect the antigenic properties of H5N1 avian influenza viruses

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Science China(Life Sciences) 2019年第1期62卷 76-83页

作者： Chunyang Gu Xianying Zeng Yangming Song Yanbing Li Liling Liu Yoshihiro Kawaoka Dongming Zhao Hualan Chen State Key Laboratory of Veterinary Biotechnology Harbin Veterinary Research Institute Chinese Academy of Agricultural Sciences Division of Virology Department of Microbiology and Immunology Institute of Medical Science University of Tokyo

Antigenic drift forces us to frequently update influenza vaccines; however, the genetic basis for antigenic variation remains largely unknown. In this study, we used clade 7.2 H5 viruses as models to explore the molecular determinants of influenza virus antigenic variation. We generated eight monoclonal antibodies(MAbs) targeted to the hemagglutinin(HA) protein of the index virus A/chicken/Shanxi/2/2006 and found that two representative antigenically drifted clade 7.2 viruses did not react with six of the eight MAbs. The E131 N mutation and insertion of leucine at position 134 in the HA protein of the antigenically drifted strains eliminated the reactivity of the virus with the MAbs. We also found that the amino acid N131 in the H5 HA protein is glycosylated. Our results provide experimental evidence that glycosylation and an amino acid insertion or deletion in HA influence antigenic variation.

关键词： Influenza virus H5N1 antigenic variation genetic basis

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Reduced graphene oxide membrane as supporting film for high-resolution cryo-EM

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Biophysics Reports 2021年第3期7卷 227-238页

作者： Nan Liu Liming Zheng Jie Xu Jia Wang Cuixia Hu Jun Lan Xing Zhang Jincan Zhang Kui Xu Hang Cheng Zi Yang Xin Gao Xinquan Wang Hailin Peng Yanan Chen Hong-Wei Wang Ministry of Education Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologySchool of Life SciencesTsinghua University Tsinghua-Peking Joint center for Life Sciences Tsinghua University center for Nanochemistry Beijing Science and Engineering Center for NanocarbonsBeijing National Laboratory for Molecular SciencesCollege of Chemistry and Molecular EngineeringPeking University Joint Graduate Program of Peking-Tsinghua-NIBS School of Life SciencesTsinghua University Beijing Frontier research center for Biological Structures Tsinghua University Academy for Advanced Interdisciplinary Studies Peking University School of Materials Science and Engineering Tianjin University

Although single-particle cryogenic electron microscopy(cryo-EM) has been applied extensively for elucidating many crucial biological mechanisms at the molecular level, this technique still faces critical challenges, the major one of which is to prepare the high-quality cryo-EM specimen. Aiming to achieve a more reproducible and efficient cryo-EM specimen preparation, novel supporting films including graphene-based two-dimensional materials have been explored in recent years. Here we report a robust and simple method to fabricate EM grids coated with single-or few-layer reduced graphene oxide(RGO) membrane in large batch for high-resolution cryo-EM structural determination. The RGO membrane has decreased interlayer space and enhanced electrical conductivity in comparison to regular graphene oxide(GO) membrane. Moreover, we found that the RGO supporting film exhibited nice particle-absorption ability, thus avoiding the air–water interface problem. More importantly, we found that the RGO supporting film is particularly useful in cryo-EM reconstruction of sub-100-k Da biomolecules at near-atomic resolution, as exemplified by the study of RBD-ACE2 complex and other small protein molecules. We envision that the RGO membranes can be used as a robust graphene-based supporting film in cryo-EM specimen preparation.

关键词： Reduced graphene oxide Cryo-EM 3D reconstruction Air–water interface

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Antagonism of estrogen-mediated cell proliferation by raloxifene in prevention of ageing-related prostatic hyperplasia

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Asian Journal of Andrology 2010年第5期12卷 735-743页

作者： Rui Yang Yu-Xia Ma Lin-Feng Chen Ying Zhou Zhan-Po Yang Yan Zhu Xiao-Ling Du Jian-Dang Shi Hong-Shun Ma Ju Zhang Bioactive Materials Key Lab of Ministry of Education Department of Biochemistry and Molecular Biology College of Life Sciences Nankai University Tianjin 300071 China Dana Farber Cancer Institute Harvard Medical School Boston MA 02445 USA Department of Urology Tianjin First Central Hospital Tianjin 300192 China molecular Cardiology research Institute Tufts Medical Center Tufts University School of Medicine Boston MA 02111 USA

Estrogen has important roles in the initiation and development of benign prostatic hyperplasia （BPH）. Regulators of the estrogen receptor （ER） are tissue- and cell-specific. We evaluated the effect of estrogen antagonist, raloxifene （Ral）, on the prevention and treatment of BPH by investigating its effect on the proliferation of two different prostate cell lines： a stromal cell line, WPMY-1, and a benign prostatic hyperplasia epithelial cell line, BPH-1. We additionally evaluated its effect on prostatic hyperplasia induced by estrogen and androgen in a rat model. The effect of Ral on the prevention of prostatic hyperplasia was analyzed by haematoxylin and eosin staining and quantitative immunohistochemistry （IHC） for proliferating cell nuclear antigen and α-smooth muscle actin. In vitro and in vivo, tamoxifen （Tam）, another anti-estrogen drug, and finasteride （Fin）, a drug for the clinical treatment of BPH, served as efficacy controls. The in vitro data showed that neither Ral nor Tam alone affected the proliferation of WPMY-1 and BPH-1, but both antagonized the effect of oestradiol in promoting the proliferation of the two cells. Results from the IHC staining of the rat prostates indicated that, similar to Tam and Fin, Ral inhibited the proliferation of stromal cells in vivo. Interestingly, in contrast to Tam, both Ral and Fin inhibited the proliferation of epithelial cells. Furthemore, Ral treatment much strongly decreased the number of prostatic acini and the surrounding layers of smooth muscle cells than Fin （P 〈 0.05）. Our data showed for the first time that Ral may have a role in the response of the rat prostate to selective ER modulators.

关键词： estrogen prostatic hyperplasia raloxifene rats

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Fusobacterium nucleatum promotes colon cancer progression by changing the mucosal microbiota and colon transcriptome in a mouse model

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World Journal of Gastroenterology 2022年第18期28卷 1981-1995页

作者： Na Wu Yu-Qing Feng Na Lyu Di Wang Wei-Dong Yu Yong-Fei Hu Department of Central Laboratory&Institute of Clinical molecular Biology Peking University People’s HospitalBeijing 100044China State Key Laboratory of Animal Nutrition College of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China CAS Key Laboratory of Pathogenic microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

BACKGROUND Fusobacterium nucleatum(***)has long been known to cause opportunistic infections and has recently been implicated in colorectal cancer(CRC),which has attracted broad ***,the mechanism by which it is involved in CRC development is not fully *** To explore its potential causative role in CRC development,we evaluated the colon pathology,mucosa barrier,colon microbiota and host transcriptome profile after *** infection in an azoxymethane/dextran sulfate sodium salt(AOM/DSS)mouse *** Three groups of mice were compared to reveal the differences,i.e.,the control,AOM/DSS-induced CRC and AOM/DSS-FUSO infection *** Both the AOM/DSS and AOM/DSS-FUSO groups exhibited a significantly reduced body weight and increased tumor numbers than the control group,and AOM/DSS mice with *** infection showed the highest tumor formation ratio among the three ***,the colon pathology was the most serious in the AOM/DSS-FUSO *** found that the structure of the colon microbiota changed considerably after *** infection;striking differences in mucosal microbial population patterns were observed between the AOM/DSS-FUSO and AOM/DSS groups,and inflammation-inducing bacteria were enriched in the mucosal microbiota in the AOM/DSS-FUSO *** comparing intestinal transcriptomics data from AOM vs AOM/DSSFUSO mice,we showed that transcriptional activity was strongly affected by dysbiosis of the gut *** most microbiota-sensitive genes were oncogenes in the intestine,and the cyclic adenosine monophosphate signaling pathway,neuroactive ligand–receptor interaction,PPAR signaling pathway,retinol metabolism,mineral absorption and drug metabolism were highly enriched in the AOM/DSS-FUSO ***,we showed that microbial dysbiosis driven by *** infection enriched eight taxa belonging to Proteobacteria,which correlates with increased expression of oncogenic *** Our

关键词： Fusobacterium nucleatum Mucosal microbiota Transcriptome Colorectal cancer Inflammation-inducing bacteria

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