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nucleic acids and analogs for bone regeneration

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Bone Research 2018年第4期6卷 331-339页

作者： Yuxin Zhang Wenjuan Ma Yuxi Zhan Chenchen Mao Xiaoru Shao Xueping Xie Xiawei Wei Yunfeng Lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Diseases Department of Oral Surgery West China Hospital of Stomatology Sichuan University Lab of Aging Research and Nanotoxicology State Key Laboratory of Biotherapy West China Hospital Sichuan University

With the incidence of different bone diseases increasing, effective therapies are needed that coordinate a combination of various technologies and biological materials. Bone tissue engineering has also been considered as a promising strategy to repair various bone defects. Therefore, different biological materials that can promote stem cell proliferation, migration, and osteoblastic differentiation to accelerate bone tissue regeneration and repair have also become the focus of research in multiple fields. Stem cell therapy, biomaterial scaffolds, and biological growth factors have shown potential for bone tissue engineering; however, off-target effects and cytotoxicity have limited their clinical use. The application of nucleic acids(deoxyribonucleic acid or ribonucleic acid)and nucleic acid analogs(peptide nucleic acids or locked nucleic acids), which are designed based on foreign genes or with special structures, can be taken up by target cells to exert different effects such as modulating protein expression, replacing a missing gene, or targeting specific gens or proteins. Due to some drawbacks, nucleic acids and nucleic acid analogs are combined with various delivery systems to exert enhanced effects, but current studies of these molecules have not yet satisfied clinical requirements. In-depth studies of nucleic acid or nucleic acid analog delivery systems have been performed, with a particular focus on bone tissue regeneration and repair. In this review, we mainly introduce delivery systems for nucleic acids and nucleic acid analogs and their applications in bone repair and regeneration. At the same time, the application of conventional scaffold materials for the delivery of nucleic acids and nucleic acid analogs is also discussed.

关键词： nucleic regeneration defects

Multi?targeted Antisense Oligonucleotide Delivery by a Framework nucleic Acid for Inhibiting Biofilm Formation and Virulence

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Nano-Micro Letters 2020年第6期12卷 113-125页

作者： Yuxin Zhang Xueping Xie Wenjuan Ma Yuxi Zhan Chenchen Mao Xiaoru Shao Yunfeng Lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041People’s Republic of China

Biofilm formation is responsible for numerous chronic infections and represents a serious health *** and the extracellular polysaccharides(EPS)cause biofilms to become adherent,toxic,resistant to antibiotics,and ultimately difficult to *** of EPS synthesis can prevent the formation of bacterial biofilms,reduce their robustness,and promote ***,we have developed a framework nucleic acid delivery system with a tetrahedral *** can easily access bacterial cells and functions by delivering antisense oligonucleotides that target specific *** designed antisense oligonucleotide sequences with multiple targets based on conserved regions of the VicK protein-binding *** delivered to bacterial cells,they significantly decreased EPS synthesis and biofilm *** to existing approaches,this system is highly efficacious because it simultaneously reduces the expression of all targeted genes(gtfBCD,gbpB,ftf).We demonstrate a novel nucleic acid-based nanomaterial with multi-targeted inhibition that has great potential for the treatment of chronic infections caused by biofilms.

关键词： Biofilm Framework nucleic acid Multi-targeting Antisense oligonucleotide Delivery system

Solidifying framework nucleic acids

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Science China Chemistry 2018年第12期61卷 1481-1482页

作者： Yuliang Zhao Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety Excellence Center for Nanosciences Chinese Academy of SciencesNational Center for Nanosciences and Technology of China

Living organisms have developed their unique strategies during the natural evolution for building hard tissues with minerals,including silica,calcium carbonate,calcium phosphate,and ferric oxide [1].Such biomineralized materials generally have complex hierarchical structures with excellent mechanical *** bioinspired approaches have led to the creation of well-defined synthetic structural materials ranging from micro to macro scales,the rational design of discrete biomimetic structures at the nanoscale remains a grand challenge.

关键词： Solidifying framework nucleic acids

Analytical methods for locating modifications in nucleic acids

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Chinese Chemical Letters 2019年第9期30卷 1618-1626页

作者： Chubo Qi Jianghui Ding Bifeng Yuan Yuqi Feng Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education) Department of Chemistry Wuhan University Wuhan 430072 China Hubei Cancer Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430079 China

In addition to the canonical nucleobases, a variety of chemical modifications have been identified presence in nucleic acids. These modifications have been demonstrated to involve in regulating the spatiotemporal expression of genes. Up to date, over 150 types of chemical modifications have been found existence in nucleic acids. Understanding the functional roles of modifications relies on deciphering the location information of modifications in nucleic acids. Analytical methods for studying nucleic acid modifications have greatly advanced in the last decade. To locate the modifications in nucleic acids, various mass spectrometry (MS)-based analytical strategies have been established. Recent progress in next-generation sequencing (NGS) in conjugation with immunoprecipitation, chemical reaction, enzyme-mediated mutation, or nanomaterials offer genome-wide or transcriptome-wide mapping of modifications, which greatly revolutionize the field of epigenetic modifications. Herein, we reviewed and summarized the established methods and the breakthrough of the techniques for locating modifications in nucleic acids. In addition, we discussed the principles, applications, advantages and drawbacks of these methods. We believe that with the rapid advancement of techniques and methods,the functions of nucleic acid modifications will be fully understood in the future.

关键词： nucleic acid modification Location Mapping Mass spectrometry Sequencing Nanomaterial

Resonance Rayleigh scattering study of the interaction of bleomycinA_5 with nucleic acids and its analytical application

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Science China Chemistry 2007年第5期50卷 629-637页

作者： LIU JiangTao1,2, LIU ZhongFang1 & LIU ShaoPu1 1 School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China 2 Department of Chemistry, Fuling Normal University, Chongqing 408000, China School of Chemistry and Chemical Engineering Southwest UniversityChongqing400715China Department of Chemistry Fuling Normal UniversityChongqing 408000China

The interaction of bleomycinA5 with nucleic acids has been investigated byusing resonance Rayleigh scattering (RRS),molecular absorption and fluorescence *** resultshows that in near pH 2.2 buffer medium and absence of any metal ions,nucleic acids are capable ofbinding with bleomycinA5 (BLMA5) to form complexes which can remarkably enhance the RRS intensityand result in batho-chromic and hyperchromic molecular absorption of nucleic acids and fluorescencequenching of *** RRS spectral characteristics for the binding products of bleomycinA5with various DNA and RNA are similar,and the maximum RRS peaks are at 301 nm for ctDNA and sDNA,370nm for hsDNA,310 nm for RNAtypeVI and RNAtypelll,*** increments of RRS intensity aregreatly different in which DNA enhances greatly and RNA enhances *** this work,the optimumconditions of the interaction and some influencing factors have been *** reactionmechanism and a binding model for the interaction of BLMA5 with the nucleic acids are ***,a highly sensitive,simple and rapid new method for the determination of DNA has *** detection limits (3 sigma) are 5.7 ng/mL for ctDNA,7.4 ng/mL for sDNA and 9.2 ng/mLfor hsDNA,*** method can be applied to determination of trace amounts of DNA.

关键词： bleomycinA5, nucleic acids, resonance Rayleigh scattering, fluorescence quenching, absorption spectrum.

Resonance Rayleigh scattering spectral characteristics of interaction of nucleic acids with some cationic surfactants and their analytical applications

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Science China Chemistry 2002年第2期45卷 173-183页

作者：刘绍璞范莉胡小莉罗红群 1. Institute of Environmental Chemistry Southwest China Normal University 400715 Chongqing China

In near neutral medium, the resonance Rayleigh scattering (RRS) intensities of an alone cationic surfactant and nucleic acid are very weak. However, when they combine with each other to form a complex, the RRS intensity of the solution is enhanced greatly. In this paper the reactions of five cationic surfactants with nucleic acids have been studied. The results show that the reaction conditions and RRS spectral characteristics of these reactions are similar, but their sensitivities are obviously different. Among them, the sensitivity of cetyldimethyl benzylammonium chloride (CDBAC) with an aryl and large molecular weight is the highest, while that of cetyltrimethylammonium bromide (CTAB) without aryl and with small molecular weight is the lowest. The detection limits for ctDNA and yRNA of the former are 6.6 and 29.4 ng@mL?1, while that of the latter are 13.3 and 53.6 ng@mL?1. The method has better selectivity and can be applied to the determination of trace amounts of nucleic acids. Furthermore, it is discovered in the investigation that not only the RRS intensity is related to the structure and molecular weight of the cationic surfactants, but also the change of the RRS intensity is closely related to the conformational change of nucleic acid. Therefore, the RRS method can be expanded to become a useful way to study the nucleic acid conformation.

关键词： resonance Rayleigh scattering, nucleic acids, cationic surfactant, determination.

Mechanism of exogenous nucleic acids and their precursors improving the repair of intestinal epithelium after 7-irradiation in mice

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World Journal of Gastroenterology 2000年第5期6卷 709-717页

作者： Da Xiang Cui~1 Guei Ying Zeng~2 Feng Wang~1 Jun Rong Xu~1 Dong Qing Ren~2 Yan Hai Guo~1 Fu Rong Tian~2 Xiao Jun Yan~1 Yu Hou~1 Cheng Zhi Su~1 1 Institute of Genetic Diagnosis of the Fourth Military Medical University,Xi’an 710032,China 2 Department of Irradiation Medicine of the Fourth Military Medical University,Xi’an 710032,China Da Xiang Cui Feng Wang Jun Rong Xu Yan Hai Guo Xiao Jun Yan Yu Hou Cheng Zhi Su Institute of Genetic Diagnosis of the Fourth Military Medical University Xi’an 710032 China Guei Ying Zeng Dong Qing Ren Fu Rong Tian Department of Irradiation Medicine of the Fourth Military Medical University Xi’an 710032 China

AIM To clone expressed genes associated withrepair of irradiation-damaged mice intestinalgland cells treated by small intestinal RNA,andto explore the molecular mechanism ofexogenous nucleic acids improving repair ofintestinal *** The animal mode of test group andcontrol group was established,forty-five micebeing irradiated by γ ray were treated with smallintestinal RNA as test group,forty mice beingirradiated by γ ray were treated withphysiological saline as control group,five micewithout irradiation were used as normal control,their jejunal specimens were collectedrespectively at 6h,12h,24h,4d and 8d *** by using LD-PCR based onsubtractive hybridization,these gene fragmentsdifferentially expressed between test group andcontrol group were obtained,and then werecloned into T vectors as well as *** sequences were ***,if being new sequences,they were submitted to *** Ninety clones were associated withrepair of irradiation-damaged intestinal glandcells treated by intestinal *** clonesfrom test group of 6h,12h,24h,4d and 8dwere respectively 18,22,25,13,*** screening against GeneBank,18 of which werenew sequences,the others were dramaticallysimilar to the known sequences,mainly similarto hsp,Nmi,Dutt1,alkaline phosphatase,homeobox,anti-CEA ScFv antibody,arginine/serine kinase and BMP-4,*** genefragments were new sequences,their acceptnumbers in GeneBank were *** Ninety clones were obtained tobe associated with repair of irradiation-damagedmice intestinal gland cells treated by smallintestinal RNA,which may be related toabnormal expression of genes and matchedproteins of hsp,Nmi,Duttl,Na,K-ATPase,alkalineph-osphatase,glkA,single strandedreplicative centromeric gene as well as 18 newsequences.

关键词： radiation ionizing intestine small/injuries RNA gene expression nucleic acids/therapeutic use polymerase chain reaction repair intestinal epithelium mice

Liquid biopsy in patients with pancreatic cancer: Circulating tumor cells and cell-free nucleic acids

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World Journal of Gastroenterology 2016年第25期22卷 5627-5641页

作者： Taisuke Imamura Shuhei Komatsu Daisuke Ichikawa Tsutomu Kawaguchi Mahito Miyamae Wataru Okajima Takuma Ohashi Tomohiro Arita Hirotaka Konishi Atsushi Shiozaki Ryo Morimura Hisashi Ikoma Kazuma Okamoto Eigo Otsuji Division of Digestive Surgery Department of Surgery Kyoto Prefectural University of Medicine

Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called "liquid biopsy" has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field.

关键词： Pancreatic cancer Biomarker Liquid biopsy Circulating tumor cells Cell-free nucleic acids

Application of peptide nucleic acids containing azobenzene self-assembled electrochemical biosensors in detecting DNA sequences

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Science China Chemistry 2009年第7期52卷 1009-1013页

作者： LIU Sheng CHEN Miao LI JinDu ZHANG HaoBo WANG JinQing YANG ShengRong State Key Laboratory of Solid Lubrication Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou 730000China Graduate University of Chinese Academy of Sciences Beijing 100039China

Hybridization of peptide nucleic acids probe containing azobenzene (NH2-TNT4, N-PNAs) with DNA was performed by covalently immobilizing of NH2-TNT4 in sequence on the 3-mercaptopropionic acid self-assembled monolayer modified gold electrode with the helps of N-(3-dimethylaminopropy1)-N'-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), and the hybrid was coded as N-PNAs/DNA. Using [Fe(CN)6]4-/3- (1:1) as the electrochemical indicator, the electrochemical properties of the N-PNAs self-assembled monolayer (N-PNAs-SAMs) and N-PNAs/DNA hybridization system under the conditions of before and after UV light irradiation were characterized with cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrochemical impedance spectra (EIS). Results showed that the redox currents decreased with the increase of irradiation time, suggesting that the ability of the charge transfer on the electrode surface was weakened and the conformation of hybrid system had been changed, and the control of PNAs/DNA hybridization could be realized by UV light irradiation.

关键词： azobenzene monomer peptide nucleic acid hybridization gold electrode electrochemical biosensors